Current Oncology

Molecular Profiling and Treatment Outcomes in Uterine Serous Carcinoma: Prognostic Role of Estrogen Receptor Expression

Background: Uterine serous carcinoma (USC) represents a rare but aggressive subtype of endometrial cancer, accounting for a disproportionate number of disease-related deaths. Although molecular classification has improved risk stratification, prognostic heterogeneity highlights the need for new prognostic markers. Methods: We retrospectively analyzed 83 patients with USC treated at our institution between 1 January 2015 and 31 December 2023. Clinicopathological characteristics, treatment strategies, molecular biomarkers accessed by immunohistology (TP53, ER, PR, HER2, and MMR status), and survival outcomes were collected. Patients were first staged by FIGO 2009 and retrospectively reclassified by FIGO 2023. Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) were assessed using Kaplan–Meier and Cox regression analyses. Results: The majority of patients were presented with advanced disease (FIGO stage IIIC-IV). TP53 mutations were found in 88% of cases, HER2 amplification in 18%, and ER expression in 57.8%. ER-positive patients showed significantly improved DFS in the adjuvant setting compared with ER-negative patients, whereas no significant associations were observed for first-line PFS or OS in multivariable analyses. HER2 amplification was not associated with inferior survival in our cohort. The advanced stage remained an independent predictor of worse OS. Conclusions: USC is a biologically heterogeneous disease, and its treatment should be guided by its molecular profile. ER expression identifies a subset of patients with improved DFS, suggesting potential prognostic relevance in this high-risk histology.

Evaluating the Cost-Effectiveness of Cervical Cancer Screening and Treatment in Western Romania

Background and Objectives: As a leading European country in terms of cervical cancer incidence and mortality, there has been a pressing need for Romania to upgrade its cervical cancer management. The criteria set by the International Federation of Gynecology and Obstetrics indicate that different treatments should have a similar trend concerning progression-free survival and overall survival at all the various stages of cervical cancer. This study aimed to assess the cost-effectiveness (CE) of the primary treatment plans related to the survival rate for cervical cancer screening in the western part of Romania and provide some recommendations. Materials and Methods: Descriptive statistics and a correlation model were used to examine costs. AI models have been developed to forecast the CE of different treatments using the above-mentioned studies on overall survival rates and treatment-related toxicity rates for five years. The costs of cervical cancer treatment were sourced from the public health department, the oncology clinic in the western region of Romania, and the County Hospital available for each stage. Results: Treatment expenses vary by cancer stage, with a significant increase from stages IA/IB to IIA, stabilizing between IIA and IIIC (about €7800–€8300), followed by a steep decline in IVA and a more pronounced decrease in IVB and in situ. The results highlight certain treatment combinations and their costs, indicating that the highest costs (exceeding €8000) are linked to multimodal treatments, which encompass surgery, chemotherapy, radiotherapy, and brachytherapy. Conclusions: Advanced cancer stages (IIA–IIIC) entail the highest treatment costs due to intricate, multimodal therapy, whereas early stages (IA, IB, in situ) and late terminal stages (IVB) are linked to considerably reduced treatment costs.

HPV Sampling Options for Cervical Cancer Screening: Preferences of Urban-Dwelling Canadians in a Changing Paradigm

Introduction: Of women in Canada diagnosed with invasive cervical cancer, 50% have not been screened according to guidelines. Interventions involving self-collected samples for human papillomavirus (hpv) screening could be an avenue to increase uptake. To guide the development of cervical cancer screening interventions, we assessed (1) preferred sample collection options, (2) sampling preferences according to previous screening behaviours, and (3) preference for self-sampling among women not screened according to guidelines, as a function of their reasons for not being screened. Methods: Data were collected in an online survey (Montreal, Quebec; 2016) and included information from female participants between the ages of 21 and 65 years who had not undergone hysterectomy and who had provided answers to survey questions about screening history, screening interval, and screening preferences (n = 526, weighted n = 574,392). Results: In weighted analyses, 68% of all women surveyed and 82% of women not recently screened preferred screening by self-sampling. Among women born outside of Canada, the United States, or Europe, preference ranged from 47% to 60%. Nearly all women (95%–100%) who reported fear or embarrassment, dislike of undergoing a Pap test, or lack of time or geography-related availability of screening as one of their reasons for not being screened stated a preference for undergoing screening by self-sampling. Conclusions: The results demonstrate a strong preference for self-sampling among never-screened and not-recently-screened women, and provides initial evidence for policymakers and researchers to address how best to integrate self-sampling hpv screening into both organized and opportunistic screening contexts.

Discovery of a Ferroptosis-Related lncRNA–miRNA–mRNA Gene Signature in Endometrial Cancer Through a Comprehensive Co-Expression Network Analysis

Background: As a newly recognized type of cell death implicated in cancer, ferroptosis plays multiple roles in tumor biology. Here, we sought to construct a prognostic framework for EC on the basis of ferroptosis-related long non-coding RNAs (FerlncRNAs), microRNAs (FermiRNAs), and mRNAs (FRGs) for endometrial cancer (EC). Methods: Transcriptomic profiles of tumors and matched clinical data for 544 EC patients were retrieved from TCGA-UCEC. A prognostic framework was generated through Cox regression, integrating ferroptosis-linked lncRNAs, miRNAs, and mRNAs. EC cases were stratified into groups with high or low predicted risk based on ferroptosis-related gene expression. The model’s prognostic utility was examined through Kaplan–Meier (K–M) analysis and receiver operating characteristic curves. Results: A prognostic model based on 16 RNAs, including 10 FerlncRNAs, 2 FermiRNAs, and 4 FRGs, was developed. Analysis using K–M plots showed that high-risk patients experienced shorter overall survival than their low-risk counterparts (p < 0.001). The model’s area under curve (AUC) values were 0.731, 0.749, and 0.768 at 1-, 3-, and 5-year time points, surpassing those of standard clinical parameters. Furthermore, in an external validation cohort, these signature RNAs were associated with EC prognosis. Conclusions: The novel ferroptosis-related lncRNA–miRNA–mRNA prognostic model provides a basis to assess clinical prognosis in EC patients.

Is There a Role for Risk-Reducing Bilateral Breast Surgery in BRCA1/2 Ovarian Cancer Survivors? An Observational Study

Background: Risk-reducing surgeries are an option for cancer risk management in BRCA1/2 individuals. However, while adnexectomy is commonly recommended in breast cancer (BC) survivors, risk-reducing bilateral breast surgery (RRBBS) is controversial in ovarian cancer (OC) survivors due to relapse rates and mortality. Methods: We conducted a retrospective analysis of BRCA1/2-OC survivors, with OC as first cancer diagnosis. Results: Median age at OC diagnosis for the 69 BRCA1/2-OC survivors was 54 years. Median overall survival was 8 years, being significantly higher for BRCA2 patients than for BRCA1 patients (p = 0.011). Nine patients (13.2%) developed BC at a median age of 61 years. The mean overall BC-free survival was 15.5 years (median not reached). Eight patients (11.8%) underwent bilateral mastectomy (5 simultaneous with BC treatment; 3 RRBBS) at a median age of 56.5 years. The median time from OC to bilateral mastectomy/RRBBS was 5.5 years. Conclusions: This study adds evidence regarding a lower BC risk after BRCA1/2-OC and higher survival for BRCA2-OC patients. A comprehensive analysis of the competing risks of OC mortality and recurrence against the risk of BC should be individually addressed. Surgical BC risk management may be considered for longer BRCA1/2-OC disease-free survivors. Ultimately, these decisions should always be tailored to patients’ characteristics and preferences.

Blockade of ALDH in Cisplatin-Resistant Ovarian Cancer Stem Cells In Vitro Synergistically Enhances Chemotherapy-Induced Cell Death

Epithelial ovarian cancer (EOC) is the leading cause of gynecological cancer-related death. The high mortality and morbidity associated with EOC are mostly due to late diagnosis and chemotherapy drug resistance. Currently, the standard first-line chemotherapy regimen is systemic administration of platinum-based chemotherapy combined with a taxane. A major problem besides cisplatin resistance (occurring in nearly one-third of patients) is the greater toxicity of the drug combinations. A synergistic treatment with drug supporting activity could maximize the cytotoxic effects of chemotherapeutic agents on tumor cells while decreasing the dosage of each drug to potentially reduce toxicity. The ALDH-blocking agent Disulfiram (DSF), a clinically approved drug used for alcoholism treatment, has displayed promising anti-cancer activity. We previously described that blocking ALDH activity enhances the induction of apoptosis, especially in ovarian cancer stem cells treated with chemotherapeutic agents. In this study, we further investigated the synergistic effect of DSF in combination with cytotoxic chemotherapeutic drugs. The concentration of each chemotherapeutic agent could be significantly reduced with sustained efficacy on tumor cell apoptosis in cell lines in vitro (Dose-Reduction Index at IC50 from 1 to 50). Moreover, the potential chemo-sensitizing effects of DSF on ALDH-associated cisplatin-resistant ovarian cancer stem cells were also investigated and shown that in contrast to its high resistance to cisplatin, the cisplatin-resistant cells remain very sensitive to DSF-induced cytotoxicity (apoptosis and necrosis: cisplatin-resistant cells vs. parental cells: 60.4% vs. 20.5%). In combination with DSF and cisplatin, relatively more apoptosis and necrosis were induced in cisplatin-resistant cells than in their parental cells (apoptosis and necrosis: cisplatin-resistant cells vs. parental cells: 81.5% vs. 50.1%). A transcriptome analysis identified that ALDH was mainly enriched in the cancer-associated fibroblasts and showed that ALDH plays roles in responding to oxidative stress, metabolisms, and energy transition in the ALDH-associated cisplatin-resistant ovarian cancer stem cells. In conclusion, our data demonstrate a key role of ALDH-associated cisplatin-resistant cancer stem cells and identifies DSF as a potential adjuvant for a rational protocol design by computational quantitative assessment in vitro on ovarian cancer cell lines. Our work contributes to resolving the ALDH-associated cisplatin resistance and provides a resource for the development of novel chemotherapeutic regimens.

Germline Mutations in DNA Repair Genes in Patients with Pancreatic Neuroendocrine Neoplasms: Diagnostic and Therapeutic Implications

Pancreatic neuroendocrine neoplasms (pNENs) are the second most common type of pancreatic cancer after pancreatic ductal adenocarcinoma. Germline mutations in DNA repair genes drive several hereditary and sporadic cancers; however, their role in pNENs remains poorly defined. This pilot study aimed to assess the frequency and clinical relevance of germline DNA repair gene mutations in patients with pNENs, both with and without a family history of cancer. Germline DNA from 57 Polish patients with pNENs was analyzed using targeted next-generation sequencing to identify variants in a panel of DNA repair genes. Variant classification followed the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines. Germline mutations were identified in 14 patients (24.6%), both with and without a family history of malignancy. Two patients carried pathogenic variants in BRCA2 and CHEK2, while seven carried variants of uncertain significance (VUS). The identified variants have been implicated in various cancer types, including breast, ovarian, prostate, gastric, colorectal, and pancreatic cancers. These findings indicate that germline mutations in DNA repair genes may contribute to the pathogenesis of pNENs, even in patients without a family history. Broader germline testing and population-specific studies are needed to clarify the genetic landscape and clinical implications of these alterations.

Treatment Patterns, Clinical Outcomes and Quality of Life in BRCA1/2-Associated Breast Cancer Patients: A Retrospective Analysis

Background: Breast cancer (BC) patients with germline BRCA1/2 pathogenic variants (PVs) often face unique challenges compared to non-carriers. However, the impact of PVs on treatment patterns, clinical outcomes, and quality of life (QoL) remains insufficiently explored. This study aims to assess these factors in these individuals. Methods: A retrospective analysis was conducted using data from the Medical University of Vienna Center for Familial Breast and Ovarian Cancer between 2011 and 2021. Among 1285 individuals identified, 338 were included (120 BRCA1 PVs, 47 BRCA2 PVs, and 171 non-carriers). Clinical data including treatment patterns and outcomes were collected; QoL was assessed in BRCA1/2 PV carriers using the SF-12 questionnaire. Results: Among 338 BC patients, BRCA1 PV carriers were significantly younger at disease onset and more likely to present with triple-negative BC, with higher Ki-67 (>10%) than BRCA2 or non-carriers. Platinum-based chemotherapy was more frequently administered to BRCA PV carriers for neoadjuvant treatment (OR 7.7, p < 0.001), and therapeutic bilateral mastectomy was more common in BRCA1 carriers (44.7%) compared to BRCA2 (37.8%, p = 0.114) and non-carriers (25.2%, p = 0.003). Epirubicin was the primary agent for adjuvant chemotherapy across all groups compared to other chemotherapeutic agents. QoL assessments revealed significant physical health challenges, particularly among those who underwent neoadjuvant chemotherapy and surgery, while mental health scores remained relatively high. Conclusions: This study highlights the distinct treatment patterns and tumor characteristics associated with BRCA1/2 carriers, including the impact of treatments on quality of life. Nevertheless, our findings ought to be interpreted with caution due to the small sample size. Larger prospective studies with more complete treatment data, including PARP inhibitor use, and further research on supportive care strategies are needed for this high-risk population.

Integrative Genomic and Clinicopathologic Characterization of Pure Primary Ovarian Large Cell Neuroendocrine Carcinoma: A Case Report and Molecular Insight

Primary ovarian large cell neuroendocrine carcinoma is an extremely rare and aggressive gynecologic malignancy with poorly defined molecular characteristics and no standard treatment protocols. We present a case of pure ovarian LCNEC in a postmenopausal woman who underwent optimal cytoreductive surgery followed by platinum-based chemotherapy. Histopathologic and immunohistochemical analyses confirmed the diagnosis. Next-generation sequencing (NGS) revealed a pathogenic BRCA2 frameshift mutation (c.7177dupA), an ATM nonsense mutation, and Tier II mutations in TP53 and PTEN. The tumor exhibited homologous recombination deficiency (HRD), microsatellite instability-high (MSI-H), and an exceptionally high tumor mutational burden (TMB) of 277.49 mutations/Mb. These molecular alterations closely resemble those observed in high-grade neuroendocrine carcinomas of cervical and endometrial origin, suggesting a convergent genomic profile across gynecologic neuroendocrine carcinomas (NECs). Our findings underscore the potential of comprehensive genomic profiling in rare tumors such as ovarian LCNEC to refine diagnosis and identify candidates for biomarker-driven therapies, including PARP inhibitors and immune checkpoint inhibitors. This case supports the integration of molecular diagnostics into clinical practice and highlights the need for prospective studies incorporating molecular stratification to inform treatment strategies for rare and aggressive neuroendocrine tumors.

Dynamic Monitoring of Recurrent Ovarian Cancer Using Serial ctDNA: A Real-World Case Series

Recurrent ovarian cancer (OC) is challenging to detect early using current methods like CA-125 and imaging. Circulating tumor DNA (ctDNA) may improve disease monitoring. Here, we assess the real-world clinical utility of serial ctDNA analyses in patients with recurrent OC. We analyzed serial plasma samples (N = 23) from six patients with recurrent OC using a tumor-informed next-generation sequencing assay targeting 68 cancer-related genes developed at the University of Washington. ctDNA variant allele frequencies (VAFs) were correlated with CA-125 levels, radiographic findings, and clinical outcomes. ctDNA levels generally reflected clinical status, accurately mirroring disease progression and therapeutic response. In one patient, rising ctDNA preceded clinical recurrence by four months, despite normal CA-125 and imaging, highlighting its potential advantage. Conversely, some patients exhibited clinical progression with undetectable ctDNA, indicating limitations in assay sensitivity, biological factors, or metastatic sites (e.g., brain metastases). ctDNA and CA-125 showed complementary value in most cases, suggesting potential combined use in clinical monitoring. Our findings demonstrate that ctDNA is a promising biomarker to complement existing monitoring approaches for recurrent OC. In some cases, capable of predicting relapse and treatment response ahead of current clinical indicators. However, identified discordances underscore technical and biological challenges that warrant further investigation. Larger prospective studies are necessary to refine ctDNA’s clinical utility and integration into personalized OC care.

Ten-Year Real-World Outcomes and Clinicopathologic Predictors of Recurrence in Adult Granulosa Cell Tumors: A Turkish Single-Center Experience

Adult granulosa cell tumors (AGCT) are rare ovarian neoplasms with typically indolent behavior but potential for late recurrence. This study aimed to evaluate long-term outcomes and identify clinicopathological predictors of disease-free survival (DFS) in patients with AGCTs. This retrospective cohort study included patients with histologically confirmed AGCTs who were treated or followed at Ege University Faculty of Medicine between January 2012 and 2023. Survival outcomes were analyzed using Kaplan–Meier and Cox regression methods. Among 55 patients with a median follow-up of 113.7 months, the median DFS was 92.3 months, and the median overall survival (OS) was 113.7 months. The 5-year DFS and OS rates were 84.5% and 93.9%, respectively. Recurrence occurred in 23.6% of patients and was significantly linked to advanced FIGO stage, atypical endometrial pathology, and bleomycin–etoposide–cisplatin (BEP)/etoposide–cisplatin (EP)-based adjuvant chemotherapy. Larger tumor size (>10 cm) and stage III disease were also associated with shorter DFS. Univariate analysis showed that stage III disease (HR 7.14, p = 0.006) and tumor size >10 cm (HR 3.59, p = 0.025) were associated with significantly shorter DFS, while absence of endometrial pathology was protective (HR 0.34, p = 0.022). In multivariate analysis, stage III disease remained the only independent predictor of recurrence (HR 4.45, p = 0.046). Advanced-stage disease is an independent predictor of recurrence and should be considered a high-risk feature requiring prolonged follow-up.

In-Hospital Mortality Among Patients Undergoing Percutaneous Pericardiocentesis for Pericardial Effusion with and Without Malignancy

Background: Despite the high prevalence of malignant pericardial effusions (MPEs), the differences in mortality between those undergoing pericardiocentesis for MPE versus non-malignancy pericardial effusions (NMPEs) are not well characterized. To address this knowledge gap, we aim to compare clinical outcomes following pericardiocentesis among patients with MPE and NMPE. Methods: A retrospective analysis was conducted on the US National Inpatient Sample (NIS) to identify all hospitalizations during which pericardiocentesis was performed between 1 January 2016 and 31 December 2020 (total n = 174,776,205). This cohort was further stratified based on the presence or absence of malignancy. The primary outcome of interest was in-hospital mortality. Secondary outcomes included discharge disposition (categorized as non-home discharges), length of stay, and total hospitalization costs. Results: A total of 85,125 patients with pericardial effusions undergoing pericardiocentesis were identified. Patients with an MPE (n = 24,740) were younger and more likely to have a history of malnutrition, prior radiation, palliative care treatments, and do-not-resuscitate (DNR) orders compared to those with an NMPE (n = 60,385). Lung cancer was the most common malignancy (40.3%) in patients with an MPE requiring pericardiocentesis. The in-hospital mortality following pericardiocentesis was 11.8% in patients with malignancy and 8.2% in patients without (odds ratio (OR) for mortality 1.50 (95% confidence interval [CI]: 1.34–1.68, p < 0.001). Lung cancer, non-Hodgkin lymphoma, esophageal cancer, ovarian cancer, and leukemia were associated with a significantly increased risk of death during the same admission. Non-home discharge, length of stay, and total hospitalization cost were marginally greater in those with an MPE. Conclusions: In patients undergoing pericardiocentesis, those with an MPE had significantly higher in-hospital mortality compared to those with an NMPE. Additionally, the MPE group had a marginally longer length of stay and incurred higher total hospital costs. Further research is warranted to explore optimal treatment strategies for MPEs, particularly in patients with a limited life expectancy.

Trend and Cancer-Specific Prevalence of Kidney Stones Among US Cancer Survivors, 2007–2020

Purpose: To evaluate the prevalence and cancer-specific patterns of kidney stones among U.S. cancer survivors compared to non-cancer adults. Methods: This was a serial cross-sectional, descriptive epidemiologic analysis of a US nationally representative sample from the National Health and Nutrition Examination Survey from 2007 to 2020. Weighted prevalence of kidney stones was estimated for both non-cancer adults and cancer survivors by study cycle. Multivariable logistic regression was conducted to examine factors associated with higher probability of kidney stones in both non-cancer adults and cancer survivors. Results: From 2007–2008 to 2017–2020, kidney stone prevalence rose in both non-cancer adults (8.5% to 9.2%, p for trend = 0.013) and cancer survivors (13.1% to 17.3%, p for trend = 0.033). Throughout the study period, prevalence was consistently higher in cancer survivors. The overall prevalence from 2007 to 2020 was 15.8% (95% CI: 14.0–17.5%) in cancer survivors and 9.2% (95% CI: 8.8–9.6%) in non-cancer adults. After adjusting for sociodemographic, lifestyle, and health factors, cancer survivors had higher odds of kidney stones (OR = 1.28, 95% CI: 1.10–1.49). Compared with non-cancer adults, survivors of ovarian (OR = 3.71, 95% CI: 1.77–7.78), kidney (OR = 2.88, 95% CI: 1.46–5.68), bone and soft tissue (OR = 2.86, 95% CI: 1.12–7.30), uterine (OR = 1.94, 95% CI: 1.17–3.22), cervix (OR = 1.68, 95% CI: 1.08–2.61) and prostate (OR = 1.41, 95% CI: 1.06–1.87) cancers were statistically more likely to report kidney stones. The prevalence was numerically highest among survivors of kidney cancer (34.7%), followed by bone and soft tissue (29.9%), ovarian (29.8%), and testicular (26.3%) cancers. Conclusions: The higher prevalence of kidney stones in cancer survivors, with substantial variation by cancer type, highlights the urgent need for effective clinical management of kidney stones in oncology settings and mechanistic research.

Ovarian Mesonephric-like Adenocarcinoma: Its Prevalence in a Japanese High-Volume Cancer Center and a Literature Review on Therapeutic Targets

Background: Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior. This study aims to determine the frequency of ovarian MLA, review the existing literature, and elucidate its clinicopathological characteristics, including the potential therapeutic targets. Methods: We retrospectively reviewed the pathological diagnoses of 501 primary ovarian cancer surgical cases at our institution from 2010 to 2023. MLAs exhibiting typical morphological and immunohistochemical features were included. The frequency and clinicopathological characteristics of these cases were summarized. Additionally, we conducted a literature search using PubMed to collect and summarize previously reported cases of ovarian MLAs. Results: Among the 501 primary ovarian cancer cases, we identified 3 cases (0.6%) of MLA. The patients were 52–76 years old, and the initial FIGO stages were IC1 (two cases) and IIIB (one case). All the cases exhibited HRP, pMMR, PD-L1 negativity (CPS < 1), and low HER2 expression. Two cases experienced metastatic recurrence. A literature review identified 97 cases of MLA. The MLAs frequently exhibited KRAS mutations (90%, 38/42), with a recurrence rate of 39% (26/67). Conclusion: MLAs accounted for 0.6% of malignant ovarian tumors at our institution, all of which were advanced or recurrent cases. These cases showed HRP, pMMR, and PD-L1 negativity, indicating a lack of current therapeutic targets. The literature also reported a high incidence of advanced and recurrent cases, highlighting the need for accurate diagnosis and the development of new treatments. The frequent KRAS mutations suggest a potential therapeutic target for recurrent or metastatic MLA.

Pattern Anlysis of Risk-Reducing Strategies in Unaffected Korean BRCA1/2 Mutation Carriers

The lifetime risk of breast and ovarian cancer increases substantially for individuals with mutations in BRCA1/2. The evidence indicates that BRCA1/2 mutation carriers benefit from early cancer detection and prevention strategies. However, data on the patterns of risk-reducing interventions are lacking. This study investigated the patterns of surveillance and risk-reducing interventions among unaffected BRCA1/2 mutation carriers. A cohort of unaffected BRCA1/2 mutation carriers was identified from the Korean Hereditary Breast cAncer (KOHBRA) study database, and a telephone survey was conducted. The survey included questions on the incidence of new cancers, patterns of cancer (breast, ovarian, prostate, other) surveillance, chemoprevention, risk-reducing surgery, and reasons for participating in risk-reducing strategies. Between November 2016 and November 2020, 192 BRCA1/2 mutation carriers were contacted, of which 83 responded. After excluding 37 responders who refused to participate, 46 participants (15 males, 31 females) were included in the analysis. The mean ± SD follow-up time was 103 ± 17 months (median 107, range 68~154), and the mean ± SD age was 31 ± 8 years. Ten BRCA1/2 mutation carriers developed breast cancer, one developed ovarian cancer, and three developed other cancers. Six BRCA1/2 mutation carriers (19.4%) underwent annual breast cancer surveillance as recommended by guidelines, while none underwent ovarian or prostate cancer surveillance. Three carriers (9.7%) used chemoprevention for breast cancer. Risk-reducing salpingo-oophorectomy was performed on only one BRCA1/2 mutation carrier. The rates of breast/ovarian cancer surveillance, chemoprevention, and risk-reducing surgery were low among unaffected Korean BRCA1/2 mutation carriers. Given this cohort’s relatively high risk of developing breast cancer, strategies to encourage active participation in risk reduction are needed.

Advancing Research Alongside Patient Partners: Next-Generation Best Practices for Effective Collaboration in Health Research

Ovarian Cancer Canada’s Patient Partners in Research (PPiR) is a national volunteer-based program that trains and connects individuals with lived ovarian cancer (OC) experience to diverse research opportunities, to maximize the clinical relevance and real-life impact of OC research in Canada. A steadily increasing demand for patient partners to be involved as research team members and decision-makers led us to co-develop with the PPiR team a series of “best practices” for researcher–patient partnerships. This framework formalizes our evolving approach to patient engagement and begins to address challenges that can arise in research settings focused on less commonly diagnosed yet significant and fatal diseases such as OC: (1) Start early. (2) Foster collaboration among the entire research team. (3) Establish expectations and communicate regularly. (4) Report impact of patient partner contributions. (5) Ensure adequate resources. While there are ongoing challenges associated with patient engagement that need to be addressed, data collected from an anonymous survey of Canadian OC researchers show a marked improvement in perceived benefits of patient engagement over time and validate the best practices presented herein. Developed in the context of OC research, these best practices can be adapted to a variety of health research settings with similar challenges.

The Relation Between Post-Operative Surgical Site Infection and Time to Start Adjuvant Treatment in Ovarian and Uterine Cancers

Surgical site infections (SSIs) occur in 10–15% of patients and are linked to up to 29% of delays in starting adjuvant treatment. This study assessed the association between SSIs in patients with ovarian and uterine cancer and their impact on time to adjuvant therapy and oncologic outcomes. Patients who underwent surgery from 1 January 2015 to 30 September 2017 were included, using institutional National Surgical Quality Improvement Program (NSQIP) data and chart reviews. Among 371 patients (median follow-up 4.1 years), 243 (65.5%) received adjuvant treatment. The median time to start was 39 days for chemotherapy, 61 days for radiotherapy, and 42 days for combined therapy (p < 0.001). Patients with ovarian cancer began treatment sooner than those with uterine cancer (39 vs. 52 days, p < 0.001), but no significant difference was observed between those with or without SSIs. In 238 patients with uterine cancer, those with SSIs had a twofold higher recurrence risk (HR 1.97, p = 0.022) and over threefold lower overall survival (HR 3.45, p = 0.018). Multivariable analysis showed that surgical route and disease stage were independent predictors; SSI was not an independent factor. No survival difference related to SSIs was found in patients with ovarian cancer. Further research is needed to clarify the impact of SSIs on treatment timing and recurrence.

Clinical Outcomes of Poly(ADP–Ribose) Polymerase Inhibitors as Maintenance Therapy in Patients with Ovarian Cancer in the Southeastern Region of Korea

Purpose: In this study, we aimed to retrospectively investigate the real-world clinical efficacy and adverse events of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors in real-world clinical practice among patients with newly diagnosed epithelial ovarian cancer. Methods: We retrospectively reviewed the medical records from hospitals. Patients with epithelial ovarian cancer treated with olaparib or niraparib as frontline maintenance treatment between 1 January 2014 and 31 December 2022 were included. Progression-free survival (PFS) was analyzed using the Kaplan–Meier method, and adverse events associated with PARP inhibitor treatment were investigated. Results: Ninety-six patients treated with PARP inhibitors were identified. The median follow-up period was 21.8 months (95% confidence interval [CI] 19.4–24.0). Twenty (20.1%) patients experienced disease progression, and two patients died. The median PFS was 45.3 months (95% CI 39.4–NA). BRCA1 or BRCA2 gene mutations and primary cytoreductive surgery were associated with better PFS. Adverse events of any grade occurred in 74 (77.1%) patients. Nineteen (19.8%) patients experienced PARP inhibitor therapy interruptions, and 35 (36.5%) patients experienced dose reductions. Only three patients discontinued the drug due to adverse events. Conclusions: In a real-world setting, PARP inhibitors showed efficacy comparable to that reported in published randomized controlled trials and had acceptable safety profiles.

Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with Gastric Cancer Associated with Hereditary Breast and Ovarian Cancer

Helicobacter pylori, a gram-negative, flagellated, helical bacterium, is a common cause of chronic gastric infection worldwide. According to the World Health Organization, H. pylori infection, a specific carcinogenic factor, was the leading cause of gastric cancer (GC) in 2014 worldwide (80%). H. pylori infection causes GC in >98% of patients in East Asian countries, including Japan. However, only some types of GCs are associated with H. pylori infection. Previous clinical studies have revealed that the bacterium secretes cytotoxin-associated gene A antigen, which inhibits the nuclear translocation of the breast cancer susceptibility gene 1 and 2 (BRCA1/2), a factor involved in DNA damage repair. This indicated an association between hereditary breast and ovarian cancers (HBOCs) and the development of GC. However, the detailed mechanisms underlying the development of GC caused by H. pylori infection remain unclear. Using the information on hereditary cancers obtained based on cancer genomic medicine, this study revealed that the incidence of GC was high in families with HBOC, with a preponderance for men from families with HBOC. Furthermore, the use of poly-adenosine diphosphate-ribose polymerase inhibitors in patients with hereditary GC is considered safe and effective. This study provides substantial evidence for guiding the establishment of early treatment for patients with advanced-stage/metastatic GC who harbored BRCA1/2 mutations.

Bone Health and Endocrine Therapy with Ovarian Function Suppression in Premenopausal Early Breast Cancer: A Real-Life Monocenter Experience with Denosumab

Adjuvant endocrine therapy for early breast cancer significantly reduces recurrence but increases bone fragility. Given limited data on denosumab (60 mg every 6 months) in premenopausal patients receiving endocrine therapy for early breast cancer, we conducted a retrospective real-world study at the Gemelli Hospital (September 2018–January 2025). A descriptive analysis was performed. The primary endpoint was to assess efficacy, evaluated by changes in bone mineral density via dual-energy X-ray absorptiometry and by monitoring bone turnover markers, particularly serum C-terminal telopeptide of type I collagen. Safety was evaluated based on adverse endocrine therapy events (osteoporotic fractures) and adverse denosumab events (osteonecrosis of the jaw). Sixty-nine patients were eligible for the study. Endocrine therapy included ovarian function suppression with exemestane (89.8%) or tamoxifen (10.1%). Baseline spinal osteoporosis decreased from 20.3% to 5.8%, osteopenia from 39.1% to 34.8%, with normal T-scores rising from 17.4% to 34.8%. Femoral improvements were similar. Serum C-terminal telopeptide of type I collagen levels (evaluated in 35.8%) showed stable reduction in 97%. Denosumab adherence was 89.9%. One osteonecrosis of the jaw case occurred (1.4%); no fractures were reported. Denosumab demonstrated efficacy in improving bone density and reducing bone turnover, with excellent adherence and favorable safety. Longer follow-up is needed to assess post-discontinuation effects.

Trajectories of Cancer Antigen 125 (CA125) Within 3 and 6 Months After the Initiation of Chemotherapy Treatment for Advanced Ovarian Cancer and Clinical Outcomes: A Secondary Analysis of Data from a Phase III Clinical Trial

Background: A single measurement or a summary of a limited number of measurements of CA125 was considered in the prediction of clinical outcomes for patients with ovarian cancer. We aimed to identify the classes of patients with advanced ovarian cancer based on their CA125 trajectory and to investigate the heterogeneity of clinical outcomes among the patients in the different classes. Methods: CA125 trajectory classes were identified by latent-class mixed models based on values collected within 3 and 6 months post-treatment for 819 women with advanced ovarian cancer enrolled in a randomized trial. Results: Based on their CA125 values during the first 6 months of treatment, the patients with low CA125 levels at baseline that remained low during treatment had the best clinical outcome (a median survival of 83 months and a progression-free survival of 34 months). In contrast, the patients with high CA125 values at baseline with a modest decrease during treatment had the highest risk of death and progression (hazard ratio [95% confidence interval]: 4.83 [3.56, 6.54] for overall survival and 5.15 [3.87, 6.87] for progression-free survival). Conclusions: Longitudinal trajectories of CA125 may provide more direct information for the prognoses of patients with advanced ovarian cancer undergoing chemotherapy treatment.

Optimizing Adjuvant Care in Early Breast Cancer: Multidisciplinary Strategies and Innovative Models from Canadian Centers

The adjuvant treatment landscape for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) early breast cancer (EBC) is rapidly evolving, with a diverse range of therapeutic options—including endocrine therapies, bisphosphonates, ovarian function suppression, olaparib, CDK4/6 inhibitors, and emerging agents such as immunotherapy. While these advances have markedly improved patient outcomes, they also introduce challenges related to implementation, monitoring, and resource allocation. Notably, therapies like CDK4/6 inhibitors require particularly close monitoring, creating logistical and capacity challenges for medical oncologists, whose workloads are already stretched due to rising cancer incidence and treatment complexities. These challenges underscore the need for innovative care delivery solutions to ensure patients with EBC continue to receive optimal care. This paper offers a comprehensive guide—a playbook—of multidisciplinary-team-based care models designed to optimize adjuvant treatment delivery in EBC. Drawing on real-world evidence and successful applications across Canadian centers, we explore models led by nurses, nurse practitioners (NPs), general practitioners in oncology (GPO), and pharmacists. Each model leverages the unique expertise of its team to manage treatment toxicities, facilitate adherence, and enhance patient education, thereby promoting effective and sustainable care delivery. Importantly, these models are not intended to compete with one another, but rather to serve as a flexible recipe book from which breast cancer care teams can draw strategies tailored to their local resources and patient needs. By detailing implementation strategies, benefits, and challenges—in many instances supported by quantitative metrics and economic evaluations—this work aims to inspire care teams nationwide to optimize the adjuvant management of patients with HR+, HER2– EBC.

The Burden and Trends of Gynecological Cancers in Asia from 1980 to 2021, with Projections to 2050: A Systematic Analysis for the Global Burden of Disease Study 2021

Gynecological cancers pose a significant threat to women’s health. This study aimed to investigate the disease burden of cervical, uterine, and ovarian cancers in Asia from 1980 to 2021. The Global Burden of Disease 2021 database (GBD 2021) was used to conduct a cross-sectional study. The incidence, mortality rates, and disability-adjusted life years (DALYs) were obtained as indicators to estimate the burden. The effects of age, period, and cohort on the incidence of gynecological cancers were analyzed via the age-period-cohort web tool (APC-Web). The future trends of the gynecological cancer burden in Asia from 2025 to 2050 were predicted via a Bayesian age-period-cohort model. In 2021, cervical cancer exhibited the highest age-standardized mortality burden (3.1 deaths per 100,000; 95% UI: 2.7–3.4), whereas uterine cancer had the lowest (0.7 deaths per 100,000; 95% UI: 0.6–0.9). Geographically, South Asia has experienced the highest cervical cancer burden, with Seychelles, Mongolia, Cambodia, and Nepal ranking among the most affected nations. In contrast, Central Asia had the highest ovarian cancer burden, led by Georgia, followed by the United Arab Emirates, Seychelles, and Brunei Darussalam. Similarly, the uterine cancer burden was most pronounced in Central Asia, with Georgia, Armenia, Mauritius, and the United Arab Emirates exhibiting elevated rates. Finally, increasing trends in the burden of gynecological cancers were predicted across all age groups from 2025 to 2050, with women aged 60 to 64 years being the most affected. In conclusion, gynecological cancers are significant contributors to the disease burden in Asia. Improved early screening methods are essential to mitigate this increasing burden.

The Value of Thin Layer Cytology in Cancer Patients’ Pericardial Effusions

Objective: Early diagnosis and treatment of metastatic pericardial disease are crucial to prevent the life-threatening complication of cardiac tamponade. Thin Layer Cytology (TLC), a widely adopted technique in cytology, has gained significant acceptance for most specimens. Our study aimed to assess the utility of TLC in diagnosing metastatic neoplasms and their origins in pericardial effusions, as well as monitoring response to chemotherapy. Methods: We examined 184 pericardial fluids collected by pericardiocentesis and processed using the ThinPrep liquid-based technique. Various immunocytochemical markers were used to determine the site of metastatic neoplasms. We also evaluated the response to therapy in 53 patients with lung and breast cancer. Results: Out of 184 specimens, 113 pericardial fluids were diagnosed as positive for malignancy, while 71 were negative. Twenty-three cases of unknown primary site were included in the total positive cases. Ninety cases positive for malignancy had a known primary site of origin, including 31 lung carcinomas, 22 breast carcinomas, 10 ovarian carcinomas, 6 T-cell lymphomas, 3 urinary bladder carcinomas, 4 renal carcinomas, 5 adenocarcinomas of the colon, 5 prostate carcinomas, 2 parotid adenocarcinomas, and 2 melanomas. Regarding the 53 cases with chemotherapy treatment, the cytologic examination of pericardial fluid showed a remarkable reduction in neoplastic burden after the third dose of cisplatin or thiotepa instilled into the pericardial cavity. ThinPrep provided excellent preservation of cytomorphological features, high cellularity per slide, and a clear background. This comprehensive analysis provides crucial information about the types and distribution of cancerous cells present in the samples. Conclusions: Thin Layer Cytology (TLC) is a valuable diagnostic tool for detecting metastatic pericardial malignancy. It allows the examination of exfoliated cells from the pericardial fluid, providing crucial information for diagnosis, management, and monitoring the acute responsiveness to intrapericardial chemotherapy. Immunocytochemistry (IHC) can identify specific markers for various types of cancer, enabling a more accurate diagnosis and guiding further treatment decisions.

Putting Patients First: Pragmatic Trials in Gynecologic Oncology

In November 2024, the Society of Gynecologic Oncology of Canada hosted a 2-day, interdisciplinary Pragmatic Clinical Trials (PCTs) Workshop with the goal of launching an initiative to develop and promote PCTs within the Canadian gynecologic oncology research environment. The programme brought together multiple stakeholders, including patients with ovarian cancer, patient advocates, experts in PCTs, gynecologic oncologists, medical oncologists and clinical fellows. Foundational elements of pragmatism were emphasized in the context of the primary goal of PCTs, showing the real-world effectiveness of interventions in broad patient groups. Examples of how PCT outcomes can inform and influence clinical decision making and health policy were presented in the context of those outcomes that matter most to patients with cancer. The patients and patient advocates had the essential role of helping clinical investigators co-design PCT protocols to answer common, important, and practical questions that focus on outcomes that matter to patients. These endpoints included overall survival, quality of life and promotion of informed patient decision making. Tangible workshop outcomes included the development of several new proposals for PCTs inspirited and directed by the patient voice. Further educational initiatives to engage clinical gynecologic oncology investigators at all stages in their career are being planned.

Mother–Child Approach to Cervical Cancer Prevention in a Low Resource Setting: The Cameroon Baptist Convention Health Services Story

Introduction: The rates of cervical cancer screening in Cameroon are unknown and HPV vaccination coverage for age-appropriate youths is reported at 5%. Objectives: To implement the mother–child approach to cervical cancer prevention (cervical screening by HPV testing for mothers and HPV vaccination for daughters) in Meskine, Far North, Cameroon. Methods: After the sensitization of the Meskine–Maroua region using education and a press-release by the Minister of Public Health, a 5-day mother–child campaign took place at Meskine Baptist Hospital. The Ampfire HPV Testing was free for 500 women and vaccination was free for age-appropriate children through the EPI program. Nurses trained in cervical cancer education conducted group teaching sessions prior to having each woman retrieve a personal sample. Self-collected samples were analyzed for HPV the same day. All women with positive tests were assessed using VIA–VILI and treated as appropriate for precancers. Results: 505 women were screened, and 92 children vaccinated (34 boys and 58 girls). Of those screened, 401 (79.4%) were aged 30–49 years old; 415 (82%) married; 348 (69%) no education. Of the HPV positive cases (101): 9 (5.9%) were HPV 16, 11 (10.1%) HPV 18, 74 (73%) HPV of 13 other types. Those who were both HPV and VIA–VILI positive were treated by thermal ablation (63%) or LEEP (25%). Conclusion: The mother–child approach is an excellent method to maximize primary and secondary prevention against cervical cancer.

Ritonavir’s Evolving Role: A Journey from Antiretroviral Therapy to Broader Medical Applications

Ritonavir is a protease inhibitor initially developed for HIV treatment that is now used as a pharmacokinetic booster for other antiretrovirals due to it being a cytochrome P450 3A4 enzyme and P-glycoprotein inhibitor. Consequently, ritonavir is of special interest for repurposing in other diseases. It had an important role in battling the COVID-19 pandemic as a part of the developed drug Paxlovid® in association with nirmatrelvir and has shown effects in hepatitis and other pathogenic diseases. Ritonavir has also shown promising results in overcoming drug resistance and enhancing the efficacy of existing chemotherapeutic agents in oncology. Evidence of cancer repurposing potential was demonstrated in cancers such as ovarian, prostate, lung, myeloma, breast, and bladder cancer, with several mechanisms of action presented. In vitro studies indicate that ritonavir alone can inhibit key pathways involved in cancer cell survival and proliferation, causing apoptosis, cell cycle arrest, endoplasmic reticulum stress, and metabolic stress due to the inhibition of molecules like heat shock protein 90 and cyclin-dependent kinases. Ritonavir also causes resistant cells to become sensitized to anticancer drugs like gemcitabine or docetaxel. These findings indicate that repurposing ritonavir, either on its own or in combination with other medications, could be a promising approach for treating various diseases. This is particularly relevant in cancer therapy, where ritonavir repurposing is the central focus of this review.

Targeting TOP2A in Ovarian Cancer: Biological and Clinical Implications

The enzyme topoisomerase II alpha (TOP2A) plays a critical role in DNA replication and cell proliferation, making it a promising target for cancer therapy. In epithelial ovarian cancer (EOC), TOP2A overexpression is associated with poor prognosis and resistance to conventional treatments. This review explores the biological functions of TOP2A in EOC and discusses its potential as a therapeutic target. We highlight studies on the mechanisms through which TOP2A contributes to tumor progression and recurrence. Additionally, we evaluate the clinical implications of targeting TOP2A, including the use of TOP2A inhibitors and their combination with novel drugs. We provide a comprehensive overview of the current understanding and future directions for targeting TOP2A in the management of EOC.

Assessment of the American College of Surgeons Surgical Risk Calculator (ACS-SRC) for Prediction of Early Postoperative Complications in Patients Undergoing Cytoreductive Surgery for Ovarian Peritoneal Carcinomatosis

Ovarian cancer (OC) is diagnosed at a locally advanced stage in two-thirds of cases. The first line of treatment consists of cytoreductive surgery (CRS) combined with neoadjuvant and/or adjuvant chemotherapy. However, CRS can be associated with high rates of postoperative complications (POCs), and detection of fragile patients at high risk of POCs is important. The American College of Surgeons Surgical Risk Calculator (ACS-SRC) provides a predictive model for early POCs (30 days) for any given surgical procedure. This study aimed to evaluate the performance of the ACS-SRC in predicting the occurrence of early POCs for patients undergoing CRS for OC. This was a retrospective study that included patients undergoing CRS for advanced OC between January 2010 and December 2022. Early POCs were reviewed, and the rate of POCs was compared with those predicted by the ACS-SRC to evaluate its accuracy (i.e., discrimination and calibration). A total of 218 patients were included, 112 of whom underwent extensive surgery/resection. A total of 94 complications were recorded. This cohort demonstrated correct calibration of the ACS-SRC for the prediction of surgical site infection, readmission, and the need for nursing care post-discharge (NCPD; transfer to revalidation center or need for nursing care at home). Using both the discrimination and calibration methods, the score only predicted NCPD. In this study, the ACS-SRC was shown to be of little value for patients undergoing cytoreductive surgery for ovarian peritoneal carcinomatosis, as it only accurately predicted NCPD.

Peripheral Neuropathy Instruments for Individuals with Cancer: A COSMIN-Based Systematic Review of Measurement Properties

Although the literature on patient-reported outcomes (PROMs) continues to expand, challenges persist in selecting reliable and valid instruments for assessing peripheral neuropathy (PN) in patients with cancer. This systematic review aimed to identify all validated self-report PN scales and critically appraise their measurement properties. This review was conducted using the COSMIN methodology for PROMs and the PRISMA statement. Five databases were searched from inception to August 2024, identifying 46 eligible studies and 16 PROMs. Evidence quality ranged from “very low” to “moderate”, with notable inconsistencies in the content and structural validity phases of most instruments. Instruments such as the Chemotherapy-induced peripheral neuropathy assessment tool and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity demonstrated moderate quality and potential utility in clinical practice, while others, including the Location-based assessment of sensory symptoms in cancer and the Measure of Ovarian Symptoms and Treatment, had insufficient evidence to support their use. Importantly, all PROMs focused on chemotherapy-induced peripheral neuropathy, highlighting a significant gap in instruments addressing other PN causes, such as radiotherapy or tumor-related nerve damage. Further research should prioritize developing and validating instruments for distinct cancer populations, ensuring robust psychometric properties and clinical applicability.

Postoperative Complications of Upfront Ovarian Cancer Surgery and Their Effects on Chemotherapy Delay

Background: Extensive surgery on advanced-stage epithelial ovarian cancer is associated with increased postoperative morbidity, which may cause a delay in or omission of chemotherapy. We examined postoperative complications and their effects on adjuvant treatment in patients undergoing primary debulking surgery (PDS). Methods: Stage IIIC-IV epithelial ovarian cancer patients who underwent PDS between January 2013 and December 2020 were included. Patients were divided into two groups according to the radicality of the operation, i.e., extensive or standard surgery, and their outcomes were compared. Results: In total, 172 patients were included; 119 underwent extensive surgery, and 53 had standard surgery. Clavien–Dindo grade 3–5 (CDC 3+) complications were detected in 41.2% of patients after extensive operations and in 17% after standard surgery (p = 0.002). The most common CDC 3+ complication was pleural effusion. Despite the difference in the complication rates, the delay in chemotherapy did not differ between the extensive and standard groups (p = 0.98). Conclusions: Complications are common after PDS. Extensive surgery increases the complication rate, but most complications can be treated effectively; therefore, a delay in adjuvant treatment is rare.

An Overview of Long-Acting GnRH Agonists in Premenopausal Breast Cancer Patients: Survivorship Challenges and Management

Managing breast cancer in premenopausal women poses unique challenges due to its considerable effect on both morbidity and mortality. Goserelin, a gonadotropin-releasing hormone agonist, has emerged among the various modalities as a preferred option for ovarian function suppression, owing to its efficacy in reducing ovarian estrogen production in premenopausal women with hormone receptor-positive breast cancer. Recent studies have affirmed the efficacy and safety of long-acting (LA) goserelin 10.8 mg every 12 weeks, offering comparable outcomes to monthly injections. This flexibility enables personalized treatment approaches, potentially enhancing patient satisfaction. Off-label utilization of goserelin LA surged during the coronavirus disease pandemic, prompting initiatives to broaden its use for breast cancer treatment. Switching to goserelin LA can streamline treatment, boost adherence, and optimize resource utilization. With the recent approval of goserelin 10.8 mg LA by Health Canada on 6 May 2024, for use in breast cancer, Canada is the latest to join over 60 countries worldwide to expand the accepted indications for goserelin LA and ensure its availability to potentially enhance healthcare delivery, patient care, and breast cancer outcomes. Goserelin LA offers premenopausal patients a means to more effectively manage the constraints imposed by breast cancer treatment and its impact on survivorship.

Comparison of Weekly Paclitaxel Regimens in Recurrent Platinum-Resistant Ovarian Cancer: A Single Institution Retrospective Study

Weekly paclitaxel (WP) is a chemotherapeutic cornerstone in the management of patients with platinum-resistant ovarian carcinoma. Multiple WP dosing regimens have been used clinically and studied individually. However, no formal comparison of these regimens is available to provide objective guidance in clinical decision making. The primary objective of this study was to compare the cumulative dose of paclitaxel delivered using 80 mg/m2/week, administered using either a 3 weeks out of 4 (WP3) or a 4 weeks out of 4 (WP4) regimen. The secondary objective was to evaluate the clinical outcomes associated with both regimens, including efficacy and toxicity parameters. Our retrospective cohort comprised 149 patients harboring platinum-resistant ovarian cancer treated at the CHU de Québec from January 2012 to January 2023. WP3 and WP4 reached a similar cumulative dose (1353.7 vs. 1404.2 mg/m2; p = 0.29). No significant differences in the clinical outcomes were observed. The frequency of dose reduction was significantly higher for WP4 than WP3 (44.7% vs. 4.9%; p < 0.01), mainly due to treatment intolerance from toxicity (34.0% vs. 3.9%; p < 0.01). Our data suggest that a WP3 regimen delivers a similar cumulative dose to WP4, hence offering a better tolerability profile without compromising efficacy.

Re-Evaluating Chemotherapy Dosing Strategies for Ovarian Cancer: Impact of Sarcopenia

We investigated the impact of sarcopenia on adjuvant chemotherapy dosing in advanced epithelial ovarian cancer (EOC). The chemotherapy dosing and toxicity of 173 eligible patients who underwent cytoreductive surgery and adjuvant chemotherapy at a single institution were analyzed. Patients with a skeletal muscle index less than 39 cm2/m2 measured on a CT scan were considered sarcopenic. Sarcopenic and non-sarcopenic patients were compared with regard to relative dose intensity (RDI), completion of scheduled chemotherapy, toxicity, and survival. A total of 62 (35.8%) women were sarcopenic. Sarcopenic women were less likely to complete at least six cycles of chemotherapy (83.9% vs. 95.5%, p = 0.02). The mean RDI for both carboplatin (80.4% vs. 89.4%, p = 0.03) and paclitaxel (91.9% vs. 104.1%, p = 0.03) was lower in sarcopenic patients compared to non-sarcopenic patients. Despite these differences in chemotherapy, there was no difference in neutropenia or median overall survival (3.99 vs. 4.57 years, p = 0.62) between the sarcopenic and non-sarcopenic women, respectively. This study highlights the importance of considering lean body mass instead of body weight or surface area in chemotherapy dosing formulas for sarcopenic women with advanced EOC. Further research is needed to optimize chemotherapy strategies based on individual body composition, potentially leading to improved dosing strategies in this population.

Long-Term Follow-Up of Tamoxifen Treatment and the Use of Imaging in Psammocarcinoma: A Case Report, Review of the Literature and Discussion of Diagnostic and Therapeutic Challenges

Psammocarcinoma (PsC) represents a rare form of low-grade serous tumor of the ovary or peritoneum. Although ovarian cancer generally has a poor prognosis in its late stages, PsC seems to have a more indolent course. We present a patient with a history of unspecific abdominal pain for more than a year, with sudden acute onset of severe inguinal pain. On admission to the hospital, a computed tomography (CT) revealed a pelvic mass of suspected ovarian origin. Radical surgery was attempted but not achieved due to widespread tumor growth. Histopathological evaluation revealed estrogen receptor-positive stage III PsC. Tamoxifen treatment was thus initiated, still maintaining stable disease 10 years later. The patient has undergone extensive radiological work-up, including CT, chest X-ray, 18F-fluoro-deoxy-glucose positron emission tomography (PET)/CT, 99mTc- hydroxymethylene diphosphonate (HDP) bone scintigraphy, 18F-fluoro-thymidine (FLT) PET/CT, Tc-99m depreotide scintigraphy and magnetic resonance imaging. In conclusion, we demonstrate that PsC has characteristic radiological features and different imaging modalities can be suitable in different clinical situations. In contrast to most other ovarian cancers, PsC does not always warrant adjuvant chemotherapy, even in advanced stages. This emphasizes the need for a deeper knowledge of the biological behavior of this rare tumor, to select the optimal treatment strategy.

Fertility Assessment after Ovarian Transposition in Children and Young Women Treated for a Malignant Tumor

Ovarian transposition (OT) has been proposed as a protective measure against radiation-induced damage to ovarian function and fertility. Despite its historical use, limited research has focused on evaluating endocrine and exocrine ovarian function after OT performed in adolescents and young adults (AYAs) before or during puberty. The purpose of our study was to investigate the fertility, pubertal development, and ovarian function of women with a previous history of OT during childhood, adolescence or young adulthood. In an observational bicentric retrospective study, we included 32 young female cancer patients who underwent OT before the age of 26 between 1990 and 2015 at Lyon Léon Bérard Cancer Center or Nancy University Hospital. The mean age at the time of OT was 15.6 years with a cancer diagnosis at 15 ± 4.8 years. Among the 10 women attempting pregnancy post-treatment, 60% achieved successful pregnancies. After a mean follow-up of 9.6 ± 7 years, 74% (17 out of 23) of women recovered spontaneous menstrual cycles (seven out of eight evaluable women with OT before or during puberty). Notably, 35% of women who did not attempt pregnancy demonstrated adequate ovarian reserve. Ovarian reserve and function recovery were influenced by the specific chemotherapy received. Importantly, our findings suggest that OT’s effectiveness on ovarian activity resumption does not significantly differ when performed before or during puberty compared to pubertal stages. This study contributes valuable insights into the long-term reproductive outcomes of young women undergoing OT, emphasizing its potential efficacy in preserving ovarian function and fertility across different developmental stages.

Immunogenicity of Non-Mutated Ovarian Cancer-Specific Antigens

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

Real-World Safety of Niraparib for Maintenance Treatment of Ovarian Cancer in Canada

Niraparib was recently funded in Canada for the maintenance treatment of ovarian cancer following platinum-based chemotherapy. However, the drug’s safety profile in the real world remains uncertain. We conducted a cohort study to describe the patient population using niraparib and the proportion that experienced adverse events between June 2019 and December 2022 in four Canadian provinces (Ontario, Alberta, British Columbia [BC], and Quebec). We used administrative data and electronic medical records from Ontario Health, Alberta Health Services, and BC Cancer, and registry data from Exactis Innovation. We summarized baseline characteristics using descriptive statistics and reported safety outcomes using cumulative incidence. We identified 514 patients receiving niraparib. Mean age was 67 years and most were initiated on a daily dose of 100 or 200 mg/day. Grade 3/4 anemia, neutropenia, and thrombocytopenia occurred in 11–16% of the cohort. In Ontario, the three-month cumulative incidence of grade 3/4 thrombocytopenia was 11.6% (95% CI, 8.3–15.4%), neutropenia was 7.1% (95% CI, 4.6–10.4%), and anemia was 11.3% (95% CI, 8.0–15.2%). Cumulative incidences in the remaining provinces were similar. Initial daily dose and proportions of hematological adverse events were low in the real world and may be related to cautious prescribing and close monitoring by clinicians.

High-Grade Serous Ovarian Cancer during Pregnancy: From Diagnosis to Treatment

Background: Due to the rarity of ovarian cancer diagnosed during pregnancy, the literature on the treatment of subtypes of epithelial ovarian cancer in pregnancy is sparse. The aim of our review was to analyze cases of high-grade serous ovarian cancer in pregnancy. Methods: The PubMed and Scopus databases were searched for relevant articles published in English between January 2000 and December 2023. The references of all the relevant reviews found were also checked to avoid omitting eligible studies. Information on the all retrieved cases was extracted and reviewed in detail. The most important detail was the subtype of high-grade serous ovarian cancer, which was referred to as serous adenocarcinoma (grade 2 or grade 3) in older cases. Results: We found eleven cases with relevant details of high-grade serous ovarian cancer diagnosed in pregnancy. Despite the small number of cases we found, our study demonstrated the importance of an accurate initial vaginal ultrasound at the first examination in pregnancy and the safety of diagnostic surgery and chemotherapy in pregnancy. Conclusions: There have not been long-term follow-ups of patients’ oncologic and obstetric outcomes. As patients should be comprehensively informed, more detailed case reports or series with longer follow-up periods are needed.

Review on the Role of BRCA Mutations in Genomic Screening and Risk Stratification of Prostate Cancer

(1) Background: Somatic and germline alterations can be commonly found in prostate cancer (PCa) patients. The aim of our present study was to perform a comprehensive review of the current literature in order to examine the impact of BRCA mutations in the context of PCa as well as their significance as genetic biomarkers. (2) Methods: A narrative review of all the available literature was performed. Only “landmark” publications were included. (3) Results: Overall, the number of PCa patients who harbor a BRCA2 mutation range between 1.2% and 3.2%. However, BRCA2 and BRCA1 mutations are responsible for most cases of hereditary PCa, increasing the risk by 3–8.6 times and up to 4 times, respectively. These mutations are correlated with aggressive disease and poor prognosis. Gene testing should be offered to patients with metastatic PCa, those with 2–3 first-degree relatives with PCa, or those aged < 55 and with one close relative with breast (age ≤ 50 years) or invasive ovarian cancer. (4) Conclusions: The individualized assessment of BRCA mutations is an important tool for the risk stratification of PCa patients. It is also a population screening tool which can guide our risk assessment strategies and achieve better results for our patients and their families.

A Survival Analysis of Patients with Recurrent Epithelial Ovarian Cancer Based on Relapse Type: A Multi-Institutional Retrospective Study in Armenia

Background: Annually, approximately 200 new ovarian cancer cases are diagnosed in Armenia, which is considered an upper-middle-income country. This study aimed to summarize the survival outcomes of patients with relapsed ovarian cancer in Armenia based on the type of recurrence, risk factors, and choice of systemic treatment. Methods: This retrospective case-control study included 228 patients with relapsed ovarian cancer from three different institutions. Results: The median age of the patients was 55. The median follow-up times from relapse and primary diagnosis were 21 and 48 months, respectively. The incidence of platinum-sensitive relapse was 81.6% (186), while platinum-resistant relapse was observed in only 18.4% (42) of patients. The median post-progression survival of the platinum-sensitive group compared to the platinum-resistant group was 54 vs. 25 months (p < 0.001), respectively, while the median survival after relapse was 25 vs. 13 months, respectively; three- and five-year post-progression survival rates in these groups were 31.2% vs. 23.8%, and 15.1% vs. 9.5%, respectively (p = 0.113). Conclusions: Overall, despite new therapeutic approaches, ovarian cancer continues to be one of the deadly malignant diseases affecting women, especially in developing countries with a lack of resources, where chemotherapy remains the primary available systemic treatment for the majority of patients. Low survival rates demonstrate the urgent need for more research focused on this group of patients with poor outcomes.

Ovarian Cancer in the Older Manitoban Population—Treatment Tolerance and Cancer-Related Outcomes: A Manitoba Ovarian Cancer Outcomes (MOCO) Group Study

Background: In Canada, individuals with gynecologic reproductive organs (ovaries, fallopian tubes, uterus) over the age of 70 comprise a large proportion of epithelial ovarian cancer patients. These patients often have co-morbidities, polypharmacy, or decreased functional status that may impact treatment initiation and tolerance. Despite this, there is limited evidence to guide treatment for older patients diagnosed with ovarian epithelial carcinoma. Methods: This is a retrospective study with data from Manitoba, Canada. The data were obtained from the Manitoba Ovarian Cancer Database, the Manitoba Cancer Registry, and electronic health records. All individuals with epithelial ovarian, fallopian tube, or peritoneal cancer diagnosed between 2009 and 2018 were identified. Patients aged > 70 at the time of diagnosis were included in the study cohort. Results: Four hundred and forty individuals were included. The majority had advanced stage disease (56%). Moreover, 59% of patients received no chemotherapy. Of the patients who received chemotherapy, 20% received <2 cycles and 21% required a dose reduction due to toxicity. Univariable and multivariable analysis identified advanced stage (p < 0.001), treatment modality (p < 0.001), and advanced age at diagnosis (p < 0.001) with poorer overall survival. Conclusions: Our study demonstrated a high rate of chemotherapy dose reduction and discontinuation in the elderly epithelial ovarian cancer population. Further research is needed to identify risk factors for treatment discontinuation and intolerance in this population.

Novel Therapeutics in Ovarian Cancer: Expanding the Toolbox

Despite high response rates to initial therapy, most patients with ovarian cancer will ultimately recur and go on to develop resistance to standard treatments. Novel therapies have been developed to overcome drug resistance and alter the tumor immune microenvironment by targeting oncogenic pathways, activating the innate immune response, and enhancing drug delivery. In this review, we discuss the current and future roles of chemotherapy, targeted agents such as poly (ADP-ribose) polymerase (PARP) inhibitors, bevacizumab, and mirvetuximab in the treatment of ovarian cancer. We explore the emerging role of therapeutic targets, including DNA repair pathway inhibitors and novel antibody–drug conjugates. Furthermore, we delve into the role of immunotherapeutic agents such as interleukins as well as immune-promoting agents such as oncolytic viruses and cancer vaccines. Innovative combination therapies using these agents have led to a rapidly evolving treatment landscape and promising results for patients with recurrent ovarian cancer.

Prediction of Chemoresistance—How Preclinical Data Could Help to Modify Therapeutic Strategy in High-Grade Serous Ovarian Cancer

High-grade serous ovarian cancer (HGSOC) is one of the most lethal tumors generally and the most fatal cancer of the female genital tract. The approved standard therapy consists of surgical cytoreduction and platinum/taxane-based chemotherapy, and of targeted therapy in selected patients. The main therapeutic problem is chemoresistance of recurrent and metastatic HGSOC tumors which results in low survival in the group of FIGO III/IV. Therefore, the prediction and monitoring of chemoresistance seems to be of utmost importance for the improvement of HGSOC management. This type of cancer has genetic heterogeneity with several subtypes being characterized by diverse gene signatures and disturbed peculiar epigenetic regulation. HGSOC develops and metastasizes preferentially in the specific intraperitoneal environment composed mainly of fibroblasts, adipocytes, and immune cells. Different HGSOC subtypes could be sensitive to distinct sets of drugs. Moreover, primary, metastatic, and recurrent tumors are characterized by an individual biology, and thus diverse drug responsibility. Without a precise identification of the tumor and its microenvironment, effective treatment seems to be elusive. This paper reviews tumor-derived genomic, mutational, cellular, and epigenetic biomarkers of HGSOC drug resistance, as well as tumor microenvironment-derived biomarkers of chemoresistance, and discusses their possible use in the novel complex approach to ovarian cancer therapy and monitoring.

Association between Endometriosis and the Risk of Ovarian, Endometrial, Cervical, and Breast Cancer: A Population-Based Study from the U.S. National Inpatient Sample 2016–2019

Objective: We investigated the potential relationship between endometriosis and risk of ovarian, endometrial, cervical, and breast cancers using the National Inpatient Sample (NIS) database. Methods: We utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016–2019). Univariate and multivariate regression analyses (adjusted for age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate the association between endometriosis and gynecologic cancers and summarized as odds ratios (ORs) with 95% confidence intervals (CIs). Results: In the examined dataset, there were 1164 and 225,323 gynecologic cancer patients with and without endometriosis, respectively. Univariate analysis showed endometriosis was significantly associated with a higher risk of ovarian (OR = 3.42, 95% CI: 3.05–3.84, p < 0.001) and endometrial (OR = 3.35, 95% CI: 2.97–3.79, p < 0.001) cancers. There was no significant association between endometriosis and cervical cancer (OR = 1.05, 95% CI: 0.85–1.28, p = 0.663). Interestingly, endometriosis was significantly associated with a low risk of breast cancer (OR = 0.12, 95% CI: 0.10–0.17, p < 0.001). Multivariate analysis after Bonferroni correction (p < 0.006) showed that endometriosis was significantly associated with a high risk of ovarian (adjusted OR = 3.34, 95% CI: 2.97–3.75, p < 0.001) and endometrial (adjusted OR = 3.61, 95% CI: 3.12–4.08, p < 0.001) cancers. Conversely, there was no significant association between endometriosis and cervical cancer (OR = 0.80, 95% CI: 0.65–0.99, p = 0.036). Conclusions: Patients with endometriosis exhibited unique gynecologic cancer risk profiles, with higher risks for ovarian and endometrial cancers, and no significant risk for cervical cancer. The observed connection between endometriosis and a reduced risk of breast cancer remains a perplexing phenomenon, which cannot be put into context to date.

Specialty Care and Counselling about Hereditary Cancer Risk Improves Adherence to Cancer Screening and Prevention in Newfoundland and Labrador Patients with BRCA1/2 Pathogenic Variants: A Population-Based Retrospective Cohort Study

Pathogenic variants (PVs) in BRCA1 and BRCA2 increase the lifetime risks of breast and ovarian cancer. Guidelines recommend breast screening (magnetic resonance imaging (MRI) and mammogram) or risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO). We sought to (1) characterize the population of BRCA1/2 PV carriers in Newfoundland and Labrador (NL), (2) evaluate risk-reducing interventions, and (3) identify factors influencing screening and prevention adherence. We conducted a retrospective study from a population-based provincial cohort of BRCA1/2 PV carriers. The eligibility criteria for risk-reducing interventions were defined for each case and patients were categorized based on their level of adherence with recommendations. Chi-squared and regression analyses were used to determine which factors influenced uptake and level of adherence. A total of 276 BRCA1/2 PV carriers were identified; 156 living NL biological females composed the study population. Unaffected females were younger at testing than those with a cancer diagnosis (44.4 years versus 51.7 years; p = 0.002). Categorized by eligibility, 61.0%, 61.6%, 39.0%, and 75.7% of patients underwent MRI, mammogram, RRM, and RRSO, respectively. Individuals with breast cancer were more likely to have RRM (64.7% versus 35.3%; p < 0.001), and those who attended a specialty hereditary cancer clinic were more likely to be adherent to recommendations (73.2% versus 13.4%; p < 0.001) and to undergo RRSO (84.1% versus 15.9%; p < 0.001). Nearly 40% of the female BRCA1/2 PV carriers were not receiving breast surveillance according to evidence-based recommendations. Cancer risk reduction and uptake of breast imaging and prophylactic surgeries are significantly higher in patients who receive dedicated specialty care. Organized hereditary cancer prevention programs will be a valuable component of Canadian healthcare systems and have the potential to reduce the burden of disease countrywide.

Ovarian Cancer: From Precursor Lesion Identification to Population-Based Prevention Programs

Epithelial ovarian cancer (EOC) is a heterogeneous group of malignancies, including high-grade serous ovarian cancer (HGSC). HGSC is often diagnosed at advanced stages and is linked to TP53 variants. While BRCA variants elevate risk, most HGSC cases occur in individuals without known genetic variants, necessitating prevention strategies for people without known high-risk genetic variants. Effective prevention programs are also needed due to the lack of traditional screening options. An emerging primary prevention strategy is opportunistic salpingectomy, which involves removing fallopian tubes during another planned pelvic surgery. Opportunistic salpingectomy offers a safe and cost-effective preventative option that is gaining global adoption. With the publication of the first cohort study of patients who underwent salpingectomy, specifically for cancer prevention, attention has turned to broadening opportunities for salpingectomy in addition to more targeted approaches. Prevention opportunities are promising with increasing adoption of salpingectomy and the increased understanding of the etiology of the distinct histotypes of ovarian cancer. Yet, further research on targeted risk-reducing salpingectomy with thoughtful consideration of equity is necessary to reduce death and suffering from ovarian cancer.

Beyond Sterilization: A Comprehensive Review on the Safety and Efficacy of Opportunistic Salpingectomy as a Preventative Strategy for Ovarian Cancer

Ovarian cancer (OC) is Canada’s third most common gynecological cancer, with an estimated 3000 new cases and 1950 deaths projected in 2022. No effective screening has been found to identify OC, especially the most common subtype, high-grade serous carcinoma (HGSC), at an earlier, curable stage. In patients with hereditary predispositions such as BRCA mutations, the rates of HGSC are significantly elevated, leading to the use of risk-reducing salpingo-oophorectomy as the key preventative intervention. Although surgery has been shown to prevent HGSC in high-risk women, the associated premature menopause has adverse long-term sequelae and mortality due to non-cancer causes. The fact that 75% of HGSCs are sporadic means that most women diagnosed with HGSC will not have had the option to avail of either screening or prevention. Recent research suggests that the fimbrial distal fallopian tube is the most likely origin of HGSC. This has led to the development of a prevention plan for the general population: opportunistic salpingectomy, the removal of both fallopian tubes. This article aims to compile and review the studies evaluating the effect of opportunistic salpingectomy on surgical-related complications, ovarian reserve, cost, and OC incidence when performed along with hysterectomy or instead of tubal ligation in the general population.

Combined Interval Cytoreductive Surgery and Carboplatin-Based Hyperthermic Intraperitoneal Chemotherapy in Advanced Primary High-Grade Serous Ovarian Cancer

Combining interval cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in advanced epithelial ovarian carcinoma (EOC). Although limited, growing evidence regarding carboplatin-based HIPEC highlights its potential. This retrospective study included all patients with advanced primary high-grade serous ovarian cancer who underwent interval CRS combined with carboplatin-based HIPEC at our Canadian tertiary care center between 2014 and 2020. We identified 40 patients with a median age of 61 years. The median peritoneal cancer index was 13 and complete cytoreduction was achieved in 38 patients (95%). Median hospital stay was 13 days and there were four admissions to the intensive care unit (10%) and six readmissions (15%). Severe adverse events occurred in eight patients (20%) and there was no perioperative death. Recurrence was seen in 33 patients (82%) with a median DFS of 18.0 months and a median overall survival of 36.4 months. Multivariate analyses showed that age, peritoneal cancer index, completeness of cytoreduction, occurrence of severe complications, and bowel resection did not significantly impact DFS or OS in our cohort. Interval CRS combined with carboplatin-based HIPEC for advanced primary EOC is associated with acceptable morbidity and oncological outcomes. Larger studies are required to determine the long-term outcomes.

Adjuvant Treatment of Stage I–II Serous Endometrial Cancer: A Single Institution 20-Year Experience

Background: Serous endometrial carcinoma (SEC) is a high-risk subtype of endometrial cancer. The effectiveness of multiple adjuvant therapies, namely chemotherapy (CT), radiotherapy (RT), and sequential/concurrent chemotherapy with radiotherapy (CRT), have previously been investigated. However, optimal management of early-stage SEC remains unclarified. Methods: All cases of early-stage SEC (FIGO 2009 stages I–II) treated in our institution from 2002 to 2019 were identified. Patient data were documented until September 2023. Overall survival (OS) and disease-free survival (DFS) were computed using Kaplan–Meier estimates and Cox’s proportional hazard model; descriptive statistical analysis was performed. Results: A total of 50 patients underwent total hysterectomy-bilateral salpingo-oophorectomy and omentectomy, displaying stage IA (60%), IB (24%), and II (16%) disease. The median follow-up was 90.9 months. Patients underwent adjuvant CRT (n = 36, 72%), CT (n = 6, 12%), or RT (n = 6, 12%). Two patients were observed and excluded from analyses. The 42 patients who received radiotherapy had pelvic external beam radiotherapy (n = 10), vaginal brachytherapy (n = 21), or both (n = 11). CRT had better OS (HR 0.14, 95%CI 0.04–0.52, p < 0.005) and DFS (HR 0.25, 95%CI 0.07–0.97, p = 0.05) than CT alone. RT displayed no OS or DFS benefits compared to CT/CRT. Recurrences were mostly distant. Acute and late G3-4 toxicities were primarily hematologic. Conclusions: Our data underline the challenge of treating SEC. CRT appears to be superior to CT alone but not to RT. Most recurrences were distant, highlighting the need for optimized systemic treatment options.

Oncologic and Operative Outcomes of Robotic Staging Surgery Using Low Pelvic Port Placement in High-Risk Endometrial Cancer

Upper para-aortic lymph node dissection (PALND) is one of the most challenging gynecologic robotic procedures. This study aimed to evaluate the oncologic and operative outcomes of robotic staging surgery, including upper PALND, using low pelvic port placement (LP3) in 22 patients with high-risk endometrial cancer. High-risk was defined as patients who showed deep myometrial invasion with grade III, cervical involvement, or high-risk histology. The mean patient age and body mass index were 58 years and 24 kg/m2. The mean operative time was 263 min. The mean number of total LNs and upper PALNs obtained was 31 and 10. Two patients received lymphangiography to reduce the amount of drained lymphatic fluid after surgery. The recurrence rate was 13.6% (3/22). There were two LN recurrences and one at the peritoneum in the intra-abdominal cavity. Robotic staging surgery using LP3 was feasible for performing PALND as well as procedures in the pelvic cavity simultaneously. It provides important techniques for performing optimal surgical procedures when surgeons decide to perform comprehensive PALND in instances of isolated recurrence or unexpected LN enlargement as well as high-risk endometrial cancer. Consequently, surgeons can achieve surgical consistency and reproducibility for PALND, leading to improved operative and survival outcomes in high-risk endometrial cancer.

Endocrine Therapy for Endometrial Carcinoma: Current Evidence, Resistance Mechanisms, and Biomarker-Driven Patient Selection

The treatment landscape for endometrial carcinoma (EC) is undergoing a paradigm shift from traditional histopathological dualism to precision medicine grounded in the Cancer Genome Atlas (TCGA) molecular classification. The “No Specific Molecular Profile” (NSMP) subgroup, the largest molecular cohort, has emerged as a particularly promising target for endocrine-based strategies. While endocrine therapy (ET) has been a mainstay for over 60 years due to its favorable safety profile, its efficacy as monotherapy remains modest. This review provides a comprehensive overview of current endocrine strategies, including traditional agents like progestins and aromatase inhibitors, and focuses on novel combination therapies designed to overcome resistance. Recent clinical trials have demonstrated that integrating molecularly targeted agents, such as CDK4/6 and mTOR inhibitors, significantly improves clinical outcomes. Specifically, patients with TP53 wild-type status and CTNNB1 mutations exhibit exceptional responses to these combinations. Furthermore, we discuss the potential of next-generation selective estrogen receptor degraders (SERDs) and the importance of refining patient selection through robust predictive biomarkers. Driven by molecular insights, endocrine therapy is transitioning from a secondary palliative option into a definitive cornerstone of precision oncology, offering a personalized and effective treatment for patients with advanced or recurrent endometrial carcinoma.

Molecular Classification Guides Fertility-Sparing Treatment for Endometrial Cancer and Atypical Hyperplasia Patients

Objectives: The objective of this study was to investigate the significance of molecular classification in guiding treatment decisions for patients with endometrial cancer (EC) or atypical hyperplasia (AH) undergoing fertility-sparing treatment (FST), particularly for those with non-NSMP subtypes. Methods: We conducted a retrospective cohort study involving EC/AH patients undergoing FST and molecular classification using next-generation sequencing at Peking University People’s Hospital between June 2020 and September 2023. Results: A total of 118 EC/AH patients were included, including 92 cases with NSMP, 11 with MMRd, 11 with POLEmut, and 4 with p53abn. (1) Of the 11 patients with MMRd, 6 achieved a complete response (CR) with 1 case receiving progestin, 3 cases showed insensitivity to the initial progestin before transitioning to a combined regimen of progestin and a PD-1 inhibitor, and 2 cases initially received progestin plus a PD-1 inhibitor. There were no significant differences in the cumulative CR rates between the MMRd and NSMP subgroups but a trend of a lower relapse-free-survival (RFS) rate for the MMRd subgroup (p = 0.074). (2) Of the 11 cases with POLEmut, 10 achieved CR but 4 relapsed. There was also a trend for a lower RFS rate in the POLEmut patients (p = 0.069) compared with the NSMP subgroup. (3) Three of the four patients with p53mut achieved CR after treatment with the GnRHa plus LNG-IUS regimen. Conclusion: The selection of appropriate regimens may improve FST outcomes in EC/AH patients with molecular classification of non-NSMP subtypes. Immunotherapy is an effective fertility-preserving approach for patients with MMRd.

CD8+CD28+PD1− T Cells as a Prognostic Biomarker in Endometrial Cancer

Endometrial cancer (EC) is an immunogenic tumor, with CD8+ T cells playing a pivotal role in antitumor immunity. Overexpression of PD1 suppresses T cell function by inhibiting CD28, a critical co-stimulatory molecule. Classifying CD8+ T cells based on PD1 and CD28 expression provides valuable insights into the immune microenvironment of EC. Peripheral blood samples from 120 EC patients and tumor tissue samples from 81 EC patients were analyzed via flow cytometry. CD8+ T cells were categorized according to PD1 and CD28 expression, and their associations with clinical characteristics were systematically evaluated. Peripheral CD28−/CD8+ and PD1+/CD8+ T cell proportions were significantly associated with several high-risk factors, including deep myometrial invasion, and LVSI, as well as metabolic disorders such as dyslipidemia. Peripheral CD28+PD1−/CD8+ T cells were associated with stage, grade, and LVSI, inversely correlated with age, and elevated in patients with hypertension or dyslipidemia. Tumor-infiltrating CD28+PD1−/CD8+ T cells were associated with tumor grade and LVSI, with multivariate analysis identifying low proportions as an independent predictor of relapse. In summary, CD8+CD28− and CD8+PD1+ T cells are linked to high-risk clinical features in EC, while tumor-infiltrating CD8+CD28+PD1− T cells serve as a key independent prognostic marker for relapse. Additionally, CD8+CD28−, CD8+PD1+, and CD8+CD28+PD1− T cell proportions in PBMC are closely associated with metabolic disorders, emphasizing their potential as biomarkers for immune and metabolic interactions in EC.

The “Sandwich” Schedule: A Well-Tolerated Adjuvant Treatment Both in Intermediate–High- and High-Risk Endometrial Cancer

(1) Background: In intermediate–high- and high-risk endometrial cancer (EC), radiotherapy (RT) and chemotherapy (CT) play a basic role. However, there is controversy regarding the optimal timing of their combination. The “sandwich” schedule involves adjuvant CT followed by RT and subsequent CT. The aim of this study is to assess the tolerability and efficacy of the “sandwich” schedule. (2) Methods: A retrospective study was conducted in two gynecological oncology units in Torino, Italy, from 1 January 2003 until 31 December 2021. Intermediate–high- and high-risk patients with available clinical data were included. Compliance with treatment, CT and RT toxicities, disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed. (3) Results: A total of 118 patients were selected: 27.1% FIGO I-II stages and 72.9% III-IV. Most of the patients (75.4%) received a carboplatin–paclitaxel combination, and as much as 94.9% of CT cycles were completed. Chemotherapy-related G3-4 toxicities were detected in 5.3% of the patients, almost half of which were hematological. Grade 2 gastrointestinal and genitourinary toxicities were reported in 8.4% and 4.2% of cases, respectively. With a median follow-up of 46 months, DFS was 77.6%, CSS was 70% and 5-year OS was 54%. (4) Conclusions: The “sandwich” schedule for CT and RT combination is an effective adjuvant treatment with low toxicity both in intermediate–high- and high-risk EC.

Diagnostic Performance of Preoperative Imaging in Endometrial Cancer

Background: Endometrial cancer is one of the most common gynecological malignancies. Because the findings mentioned in radiogram interpretation reports issued by diagnostic radiologists influence treatment strategies, we aimed to evaluate the diagnostic accuracy of preoperative computed tomography (CT) and magnetic resonance imaging (MRI) interpretation results in clinically relevant settings. Methods: The clinical records of patients diagnosed with endometrial cancer treated at Tohoku University Hospital from January 2012 to December 2021 were reviewed. The preoperative and pathologically estimated cancer stages were compared based on the results mentioned in the radiogram interpretation report. Results: The preoperative and postoperative cancer stages were concordant in 70.0% of the patients. By contrast, the cancer stage was underdiagnosed and overdiagnosed in 21.7% and 8.2% of the patients, respectively. The sensitivities of MRI for deep myometrial invasion, cervical stromal invasion, vaginal invasion, and adnexal metastasis were 65.1%, 58.2%, 33.3%, and 18.4%, respectively. The sensitivity and specificity for pelvic lymph node metastasis using a combination of CT and MRI were 40.9% and 98.4%, respectively. Those for para-aortic lymph node metastases using CT were 37.0% and 99.5%, respectively. Conclusions: The low sensitivity observed in this study clarified the limitations of preoperative diagnostic performance in current clinical practice.

The Quality of Life after Endometrial Cancer Study: Baseline Characteristics and Patient-Reported Outcomes

Endometrial cancer (EC) patients make up the second largest group of female cancer survivors. Patient-reported outcomes (PROs) including quality of life (QOL) and sexual function and satisfaction (SF and S) are critical facets of survivorship. This prospective, longitudinal study assesses associations between baseline characteristics and PROs after treatment. Herein, we report the baseline clinical characteristics and PROs prior to treatment initiation. Outcomes post-treatment over time will be reported separately. Patients with planned surgery for EC were prospectively enrolled in 2019–2021 and administered the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 30 (QLQ-C30), EORTC QLQ EC Module (EN24), Patient-Reported Outcomes Measurement Information System (PROMIS), and the Mayo Clinic lower extremity lymphedema (LEL) questionnaire. This study enrolled 198 patients with a mean (SD) age of 63.6 (9.8) years and body mass index of 35.5 (8.3) kg/m2. No significant differences in the PROs for the QOL were seen when compared to the reference means (SD) except for the lower interest in sexual activity (31.9 (9.8) vs. 47.5 (SE0.70)) and lower fatigue (21.3 (19.8) vs. 31.7 (25.9)). Increased obesity was associated with an increased likelihood of LEL (p < 0.01) and multiple QOL scales, including poorer global health status (p < 0.01) and physical functioning (p < 0.01). Prior to treatment initiation for EC, the patients had a similar QOL compared to that of the general population. The patients with increasing obesity, a known risk factor for EC, had worse overall global health status and physical functioning. A better understanding of these QOL measures is imperative for earlier identification and intervention of patients at risk of chronic impairments from EC treatment.

Understanding Characteristics, Treatment Patterns, and Clinical Outcomes for Individuals with Advanced or Recurrent Endometrial Cancer in Alberta, Canada: A Retrospective, Population-Based Cohort Study

Endometrial cancer (EC) incidence has increased in recent decades. However, population-based outcomes data are limited. In this retrospective cohort study, we examined characteristics, treatment patterns, and clinical outcomes, including time to next treatment (TNNT) and overall survival (OS), among advanced/recurrent (A/R) EC patients between 2010 and 2018 in Alberta, Canada. Kaplan–Meier statistics evaluated TTNT and OS, stratified by patient (A/R) and treatment. A total of 1053 patients were included: 620 (58.9%) advanced and 433 (41.1%) recurrent. A total of 713 (67.7%) patients received first-line therapy: 466 (75.2%) advanced and 247 (57.0%) recurrent. Platinum-based chemotherapy (PBCT) was the most common first-line regimen (overall: 78.6%; advanced: 96.1%; recurrent: 45.3%). The median TTNT and OS from first-line therapy were 19.9 months (95% confidence interval [CI]: 17.5–23.5) and 35.9 months (95% CI: 31.5–53.5), respectively. Following first-line PBCT, the median OS from second-line chemotherapy (N = 187) was 10.4 months (95% CI: 8.9–13.3) and higher for those rechallenged with PBCT (N = 72; 38.5%) versus no rechallenge (N = 115; 61.5%) (13.3 months [95% CI: 11.2–20.9] vs. 6.4 months [95% CI: 4.6–10.4; p < 0.001]). The findings highlight poor outcomes in A/R EC, particularly following first-line therapy, and that additional tolerable therapeutic options are needed to improve patient outcomes.

Risk Stratified Follow-Up for Endometrial Cancer: The Clinicians’ Perspective

Risk-stratified follow-up for endometrial cancer (EC) is being introduced in many cancer centres; however, there appears to be diversity in the structure and availability of schemes across the UK. This study aimed to investigate clinicians’ and clinical specialist nurses’ (CNS) experiences of follow-up schemes for EC, including patient-initiated follow-up (PIFU), telephone follow-up (TFU) and clinician-led hospital follow-up (HFU). A mixed-methods study was conducted, consisting of an online questionnaire to CNSs, an audience survey of participants attending a national “Personalising Endometrial Cancer Follow-up” educational meeting, and qualitative semi-structured telephone interviews with clinicians involved in the follow-up of EC. Thematic analysis identified three main themes to describe clinicians’ views: appropriate patient selection; changing from HFU to PIFU schemes; and the future of EC follow-up schemes. Many participants reported that the COVID-19 pandemic impacted EC follow-up by accelerating the transition to PIFU/TFU. Overall, there was increasing support for non-HFU schemes for patients who have completed primary treatment of EC; however, barriers were identified for non-English-speaking patients and those who had communication challenges. Given the good long-term outcome associated with EC, greater focus is needed to develop resources to support patients post-treatment and individualise follow-up according to patients’ personal needs and preferences.

HE4 Tissue Expression as A Putative Prognostic Marker in Low-Risk/Low-Grade Endometrioid Endometrial Cancer: A Review

Low-grade stage I endometrioid endometrial carcinomas should have an excellent prognosis, but a small subset of these cancers can relapse. The search for putative immunohistochemical prognostic markers for relapse in low-risk/low-grade endometrioid endometrial cancers remains open. Among the candidate molecules that may implicate the roles of immunohistochemical risk markers, we focused our attention on human epididymis protein 4 (HE4) after a review of the literature. Few authors have devoted themselves to this topic, and none have found a correlation between the tissue expression of HE4 and the molecular classification of endometrial cancer. Five different variants of HE4 mRNA and multiple protein isoforms of HE4 were identified many years ago, but current HE4 assays only measure the total HE4 expression and do not distinguish the different proteins encoded by different mRNA variants. It is important to have an approach to distinguish specific variants in the future.

Evaluation of Patient-Reported Symptoms and Functioning after Treatment for Endometrial Cancer

The overall survival of women with endometrial cancer is excellent after management. Different management strategies are associated with variable patient-reported outcomes (PROs). Evaluating PROs in the follow-up period can aid in better counseling and intervention for PRO improvement. This study aimed to evaluate the properties of the Slovenian translation of the EORTC QLQ-EN24 assessment scale. Women treated at the University Medical Centre Maribor, Slovenia, between January 2016 and December 2019 were invited to report their symptoms using the EORTC QLQ-EN24 questionnaire. Data were correlated with treatment modalities and clinical characteristics. The median age of participants in our study was 61 years old. PROs were not specific to therapy or clinical characteristics. Overall, women who more frequently reported gastrointestinal symptoms, muscular pain, or back pain also had statistically more frequently decreased levels of PROs in other assessed areas. Women who reported sexual or vaginal problems more often reported significantly poorer body images. Sexual activity within 4 weeks prior to completing the scale was reported by 39% of women. Sexual functioning assessments also showed important correlations between sexual interest, enjoyment, and activity. Individualized follow-ups addressing PROs should be offered to better address concerns and improve long-term outcomes in women with endometrial cancer.

Mismatch Repair Universal Screening of Endometrial Cancers (MUSE) in a Canadian Cohort

Background: Approximately 2–6% of endometrial cancers (ECs) are due to Lynch Syndrome (LS), a cancer predisposition syndrome caused by germline pathogenic variants (PVs) affecting the DNA mismatch repair (MMR) pathway. Increasingly, universal tissue-based screening of ECs has been proposed as an efficient and cost-effective way to identify families with LS, though few studies have been published on Canadian cohorts. The purpose of this study was to evaluate the feasibility and overall performance of a universal immunohistochemistry (IHC) screening program for women with EC within a single Canadian university hospital centre. Methods and Results: From 1 October 2015 to 31 December 2017, all newly diagnosed ECs (n = 261) at our centre were screened for MMR protein deficiency by IHC. MMR deficiency was noted in 69 tumours (26.4%), among which 53 had somatic MLH1 promoter hypermethylation and were considered “screen-negative”. The remaining MMR-deficient cases (n = 16) were considered “screen-positive” and were referred for genetic counselling and testing. Germline PVs were identified in 12/16 (75%). One additional PV was identified in a screen-negative individual who was independently referred to the Genetics service. This corresponds to an overall LS frequency of 5.0% among unselected women with EC, and 6.4% among women diagnosed under age 70 years. Our algorithm detected MMR gene pathogenic variants in 4.6% and 6.2% of unselected individuals and individuals under age 70 years, respectively. Four germline PVs (30.8%) were identified in individuals who did not meet any traditional LS screening criteria. Conclusions: Universal IHC screening for women with EC is an effective and feasible method of identifying individuals with LS in a Canadian context.

Open Surgery including Lymphadenectomy without Adjuvant Therapy for Uterine-Confined Intermediate- and High-Risk Endometrioid Endometrial Carcinoma

Minimally invasive surgery may not be an appropriate surgical approach in intermediate- and high-risk endometrial carcinoma, even though adjuvant therapy is given. The objective of this study was to evaluate the results of open surgery including lymphadenectomy without adjuvant therapy in patients with uterine-confined intermediate- and high-risk endometrioid endometrial carcinoma. Two hundred fifty-six patients with uterine-confined endometrioid endometrial carcinoma were treated with open surgery, including pelvic with or without para-aortic lymphadenectomy. Of the 81 patients with uterine-confined intermediate- or high-risk disease, 77 were treated with systematic lymphadenectomy without adjuvant therapy. Seven patients developed recurrence, comprising 5.5% (3/55) and 18.2% (4/22) of the intermediate- and high-risk patients, respectively. The time to recurrence was 1–66 months. The sites of recurrence were the vaginal apex (n = 2), lung (n = 2), vaginal sidewall (n = 1), pelvic lymph nodes (n = 1), and para-aortic to supraclavicular nodes (n = 1). Of these, five patients were alive without disease after salvage treatment, but two understaged high-risk patients died of disease. The five-year disease-specific survival rates of intermediate- and high-risk patients were 100% and 90%, respectively. The present study indicated that patients with uterine-confined intermediate- and high-risk endometrioid endometrial carcinoma had excellent survival when treated with open surgery, including lymphadenectomy alone. The safety of omitting adjuvant therapy should be evaluated in prospective randomized trials comparing open surgery with minimally invasive surgery.

Could the Long-Term Oncological Safety of Laparoscopic Surgery in Low-Risk Endometrial Cancer also Be Valid for the High–Intermediate- and High-Risk Patients? A Multi-Center Turkish Gynecologic Oncology Group Study Conducted with 2745 Endometrial Cancer Cases. (TRSGO-End-001)

This study was conducted to compare the long-term oncological outcomes of laparotomy and laparoscopic surgeries in endometrial cancer under the light of the 2016 ESMO-ESGO-ESTRO risk classification system, with particular focus on the high–intermediate- and high-risk categories. Using multicentric databases between January 2005 and January 2016, disease-free and overall survivals of 2745 endometrial cancer cases were compared according to the surgery route (laparotomy vs. laparoscopy). The high–intermediate- and high-risk patients were defined with respect to the 2016 ESMO-ESGO-ESTRO risk classification system, and they were analyzed with respect to differences in survival rates. Of the 2745 patients, 1743 (63.5%) were operated by laparotomy, and the remaining were operated with laparoscopy. The total numbers of high–intermediate- and high-risk endometrial cancer cases were 734 (45%) patients in the laparotomy group and 307 (30.7%) patients in the laparoscopy group. Disease-free and overall survivals were not statistically different when compared between laparoscopy and laparotomy groups in terms of low-, intermediate-, high–intermediate- and high-risk endometrial cancer. In conclusion, regardless of the endometrial cancer risk category, long-term oncological outcomes of the laparoscopic approach were found to be comparable to those treated with laparotomy. Our results are encouraging to consider laparoscopic surgery for high–intermediate- and high-risk endometrial cancer cases.

What Has Changed in the Management of Uterine Serous Carcinomas? Two Decades of Experience

Uterine serous carcinoma accounts for 3–10% of endometrial cancers, but it is the most lethal histopathological subtype. The molecular characterization of endometrial carcinomas has allowed novel therapeutic approaches for these patients. We undertook a retrospective analysis of patients with uterine serous carcinomas treated in our hospital within the last two decades to identify possible changes in their management. The patients and their characteristics were evenly distributed across the two decades. Treatment modalities did not change significantly throughout this period. After adjuvant treatment, patients’ median disease-free survival was 42.07 months (95% CI: 20.28–63.85), and it did not differ significantly between the two decades (p = 0.059). The median overall survival was 47.51 months (95% Cl: 32.18–62.83), and it significantly favored the first decade’s patients (p = 0.024). In patients with de novo metastatic or recurrent disease, median progression-free survival was 7.8 months (95% Cl: 5.81–9.93), whereas both the median progression-free survival and the median overall survival of these patients did not show any significant improvement during the examined time period. Overall, the results of our study explore the minor changes in respect of uterine serous carcinoma’s treatment over the last two decades, which are reflected in the survival outcomes of these patients and consequently underline the critical need for therapeutic advances in the near future.

HPV and Cervical Cancer—Biology, Prevention, and Treatment Updates

One of the most significant breakthroughs in cancer research has been the identification of persistent infection with certain human papillomaviruses (HPV) genotypes as the cause of cervical cancer. Since then, a range of diagnostic and therapeutic methods has been developed based on this discovery. This article aims to describe the latest updates in the biology, prevention, and treatment of HPV-related cervical cancer. The current state of knowledge regarding vaccinations, diagnostic tests, and cervical cancer therapies is presented. The latest WHO guidelines on vaccinations are presented, as well as announcements of upcoming changes. The final part of the article summarizes promising new diagnostic and treatment methods, as well as perspectives and the latest research findings on self-administered diagnostic tests, the use of therapeutic vaccines, and circulating cell-free DNA in diagnosis. Despite the significant progress made in recent years, the strategy based on vaccination and testing remains the cornerstone in the fight against HPV-related cervical cancer.

Advances in Therapeutic Vaccines Against HPV: A Review of Human Clinical Trials

Cervical cancer remains a major public health concern, particularly in low- and middle-income countries (LMICs) where access to preventive measures is limited. Persistent infection with high-risk human papillomavirus (HPV) types, mainly HPV16 and HPV18, is the key cause of cervical cancer. While prophylactic HPV vaccines effectively prevent new infections, they offer no therapeutic benefit for individuals with established lesions. This review evaluates the clinical evidence on therapeutic HPV vaccines, focusing on their ability to promote viral clearance. A bibliographic search was conducted in PubMed, selecting human studies reporting outcomes on HPV clearance. Seventeen clinical trials were identified, including DNA-based (VGX-3100, GX-188E), viral-vector (MVA E2, TG4001), peptide-based (Pepcan), and bacterial-vector (GLT 001) vaccines. Among them, DNA-based vaccines, particularly VGX-3100, showed the most consistent results, whereas several protein- or vector-based approaches demonstrated variable outcomes. Early therapeutic HPV vaccine trials faced setbacks due to limited efficacy, delivery approaches, and study design challenges, preventing progression to late-phase development. Recent DNA-based candidates, however, are advancing through phase II/III trials. While none have yet to be approved for commercial use, these vaccines elicit virus-specific T-cell responses and can induce regression of precancerous lesions, offering a promising addition to prophylactic vaccination and screening. Variability in study designs and endpoints underlines the need for standardized protocols and further phase III trials. Overall, therapeutic HPV vaccines represent a rapidly advancing field with the potential to complement prophylactic vaccination and screening, thereby strengthening global cervical cancer control efforts, particularly in LMICs.

Design and Development of a Device (Sifilotto®) for Tumour Tracking in Cervical Cancer Patients Undergoing Robotic Arm LINAC Stereotactic Body Radiation Therapy Boost: Background to the STARBACS Study

Standard of Care (SOC) for locally advanced cervical cancer is represented by external beam radiation therapy concurrent with platinum-based chemotherapy and immunotherapy (cCIRT) followed by brachytherapy boost and immunotherapy maintenance. In some instances, it is impossible to perform brachytherapy due to patient and/or cancer issues. In these circumstances, an external beam boost could be delivered. Using a robotic arm LINAC, it is mandatory to use intramucosal implanted fiducials which are needed for tumour tracking. To avoid invasive procedures, we developed an original intravaginal 3D-printed universal device containing gold fiducials embedded within it. In this paper, we describe the step-by-step procedure that allowed us to obtain the utility model patent, including the in vivo test (feasibility, reproducibility, device compliance) on seven patients within the study protocol “STereotActic Radiotherapy Boost in locally Advanced Cervical carcinoma patientS” (STARBACS).

Neoadjuvant and Adjuvant Systemic Therapy for Newly Diagnosed Stage II–IV Epithelial Ovary, Fallopian Tube, or Primary Peritoneal Carcinoma: A Practice Guideline

Background: This study aims to provide guidance for the use of neoadjuvant and adjuvant systemic therapy in women with newly diagnosed stage II–IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma. Methods: EMBASE, MEDLINE, and Cochrane Library were investigated for relevant systematic reviews and phase III trials. Articles focusing on consolidation and maintenance therapies were excluded. Results: For women with potentially resectable disease, primary cytoreductive surgery, followed by six to eight cycles of intravenous three-weekly paclitaxel and carboplatin is recommended. For those with a high-risk profile for primary cytoreductive surgery, neoadjuvant chemotherapy can be an option. Adjuvant chemotherapy with six cycles of dose-dense weekly paclitaxel plus three-weekly carboplatin can be considered for women of Japanese descent. In women with stage III or IV disease, the incorporation of bevacizumab concurrent with paclitaxel and carboplatin is not recommended for use as adjuvant therapy unless bevacizumab is continued as maintenance therapy. Intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel can be considered for stage III optimally debulked women who did not receive neoadjuvant chemotherapy. However, intraperitoneal administration of chemotherapy with bevacizumab should not be considered as an option for stage II–IV optimally debulked women. Discussion: The recommendations represent a current standard of care that is feasible to implement and valued by both clinicians and patients.

An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline: Consolidation or Maintenance Systemic Therapy for Newly Diagnosed Stage II, III, or IV Epithelial Ovary, Fallopian Tube, or Primary Peritoneal Carcinoma

Objective: To provide recommendations on systemic therapy options in consolidation or maintenance therapy for women with newly diagnosed stage II, III, or IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma including all histological types. Methods: Consistent with the Program in Evidence-based Program’s standardized approach, MEDLINE, EMBASE, PubMed, Cochrane Library, and PROSPERO (the international prospective register of systematic reviews) databases, and four relevant conferences were systematically searched. The Working Group drafted recommendations and revised them based on the comments from internal and external reviewers. Results: We have one recommendation for consolidation therapy and eight recommendations for maintenance therapy. Overall, consolidation therapy with chemotherapy should not be recommended in the target population. For maintenance therapy, we recommended olaparib (Recommendation), niraparib (Weak Recommendation), veliparib (Weak Recommendation), and bevacizumab (Weak Recommendation) for certain patients with newly diagnosed stage III–IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, respectively. We do not recommend some agents as maintenance therapy in four recommendations. We are unable to specify the patient population by histological types for different maintenance therapy recommendations. When new evidence that can impact the recommendations is available, the recommendations will be updated as soon as possible.

Surgically Treated Cervical Cancer in Manitoba: A Retrospective Study of the Impact of Geography on Care

Background/Objectives: Cervical cancer outcomes based on geographic location of residence reveal inconsistent patterns, and most of the evidence is from the United States. This retrospective study aimed to investigate whether there existed a difference in overall survival (OS) and recurrence-free survival (RFS) between individuals living within a Canadian city with a tertiary care centre versus those living remotely within a large catchment area (up to >1000 km travel distance), including a sizeable rural component. Methods: Surgically treated cervical cancer patients from 2000 to 2016 were included. Patients were treated with either radical hysterectomy, trachelectomy, or simple hysterectomy. Adjuvant treatment was provided depending on surgical pathology. OS and RFS were estimated using Kaplan–Meier curves and cumulative incidence curves. Results: Two hundred and eighty-two patients with surgically treated cervical cancer were included: 185 patients living within urban city limits and 97 patients living rurally. There were no significant baseline differences between groups. No significant difference in OS or RFS was found, even after adjusting for death as a competing risk for RFS. The median time to surgery for residents living within versus outside the city was 84 vs. 66 days, respectively, although this difference was not statistically significant (p = 0.3179). Conclusions: This is the first Canadian study to examine an association between survival and distance to care for cervical cancer.

Diabetes, Obesity, and Endometrial Cancer: A Review

Endometrial cancer is the fourth most diagnosed cancer in U.S. women. Diabetes and obesity are established independent risk factors for EC, but their combined effect is less defined. This review investigates the literature on these comorbidities as risk factors and modifiers of EC. Multiple cohort and case–control investigations have shown an increased relative risk (RR) and odds ratio (OR) when diabetes and obesity coexist. In one prospective cohort, the RR of EC in diabetic women was 1.94 [95% CI, 1.23–3.08], but increased to 6.39 [95% CI, 3.28–12.06] with obesity; with low physical activity added, RR rose to 9.61 [95% CI, 4.66–19.83]. Case–control studies similarly show an OR of 1.4 [95% CI, 0.9–2.4] for diabetes alone, vs. 5.1 [95% CI, 3.0–8.7] with BMI > 30 and diabetes. Mechanistically, both conditions promote a pro-cancerous microenvironment through metabolic and inflammatory pathways. They also worsen treatment outcomes, with greater surgical complications, thromboembolic events (p < 0.01), prolonged hospitalizations 6.2 days versus 4.5 days (p < 0.03), and poorer survival with an elevated cancer-specific mortality (HR = 2.65, 95% CI 1.60–4.40). These findings underscore the urgent need for targeted interventions and translational research on how these comorbidities impact the pathophysiologic processes of EC.

Voices from the Margins: Barriers and Facilitators to HPV Self-Sampling Among Structurally Marginalized People with a Cervix in the Greater Toronto Area and Ontario

Sex workers and formerly incarcerated people with a cervix face significant structural, interpersonal, and emotional barriers to cervical cancer screening, despite being at elevated risk for HPV infection. HPV self-sampling (HPV-SS) is a validated, user-directed method that has the potential to address these barriers, yet it remains excluded from Ontario’s organized screening program. This qualitative study explored the lived experiences of structurally marginalized individuals with a cervix who were offered HPV-SS as part of a mixed-methods pilot in the Greater Toronto Area. Five virtual focus groups were conducted with 34 participants, including both those who used the HPV-SS kit and those who declined it. Using inductive thematic analysis, we identified barriers to traditional screening including fear, stigma, mistrust of healthcare providers, logistical constraints, and a lack of accessible information. HPV-SS was widely described as more acceptable, empowering, and emotionally manageable, offering participants autonomy, privacy, and control over their care. Concerns included swab design, uncertainty about correct use, and unclear follow-up after positive results. Participants offered concrete, community-informed recommendations to improve HPV-SS implementation, including opt-in distribution models, gender-affirming language, and trauma-informed educational materials. The findings highlight the urgent need to integrate HPV-SS into organized screening programs to advance equitable access to cervical cancer prevention for marginalized populations.

Innovations in the Management of Vaginal Cancer

Primary vaginal cancer is a rare gynecologic malignancy. Given the rarity of the disease, standardized approaches to management are limited, and a great variety of therapeutic conditions are endorsed. This paper reviews advances in surgical approaches, radiation, chemoradiation, and immunotherapy. Advances in surgical management including the increasing use of laparoscopic and endoscopic approaches, as well as the novel techniques in vaginal reconstruction, are reviewed. Concurrent chemoradiation remains a mainstay of treatment for vaginal cancer and has improved local control of disease and overall survival. Additionally, with metastatic disease or situations where toxicity from CCRT is unacceptable, systemic therapies including immunotherapy approaches are reviewed.

The Effect of Prophylactic Hepatoprotective Therapy on Drug-Induced Liver Injury in Patients Undergoing Chemotherapy for Cervical Cancer: A Retrospective Analysis Based on Propensity Score Matching

This retrospective study aimed to assess the effectiveness of prophylactic hepatoprotective therapy in decreasing the incidence of drug-induced liver injury (DILI) among patients with cervical cancer undergoing chemotherapy. The analysis was performed on patients with cervical cancer who received chemotherapy at a tertiary hospital between September 2019 and August 2020. Propensity score matching (PSM) was utilized to equilibrate baseline characteristics between the treatment group, which received prophylactic hepatoprotective drugs, and the control group, which did not receive prophylaxis. The incidence and severity of liver injury were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Out of the 609 patients initially screened, 299 were included following PSM, with 105 in the treatment group and 194 in the control group. There were no significant differences in the incidence of liver injury (21.90% vs. 18.04%, p = 0.420) or its severity (p = 0.348) observed between the groups. Furthermore, none of the subgroups exhibited a significant reduction in DILI risk with prophylaxis. However, the number of patients experiencing an increase in their grade of liver injury was significantly higher in the treatment group (18.10% vs. 13.40%, p = 0.002), with these patients also exhibiting increased levels of alkaline phosphatase (ALP) and direct bilirubin (DBIL) post-chemotherapy (p < 0.05). Hepatoprotective drugs are not associated with a reduced risk of DILI and may in fact increase risk.

Cervical Cancer Screening Cascade: A Framework for Monitoring Uptake and Retention Along the Screening and Treatment Pathway

Background: Cervical cancer is a major global health concern, causing approximately 350,000 deaths annually. It is also preventable through effective prevention and early detection. To facilitate elimination, the World Health Organization (WHO) set targets for HPV vaccination, screening, and treatment. Achieving these goals requires frameworks to monitor screening program performance. As many regions transition to HPV primary screening, a standardized Cervical Cancer Screening Cascade can track performance, identify gaps in follow-up, and optimize resource allocation. Methods: This paper introduces a structured cascade developed to monitor uptake, retention, and outcomes in HPV-based screening programs. The Cascade was created through collaboration between public health experts, clinicians, and researchers at the University of British Columbia (UBC), the Women’s Health Research Institute, and BC Cancer. Results: The Cascade outlines four phases: screening, triage, detection, and treatment. Each phase includes two substages: “uptake” and “results,” with an additional substage in screening (“invitation”). “Screening” assesses invitation effectiveness and participation. “Triage” tracks follow-up after a positive screen. “Detection” evaluates attendance at diagnostic appointments, and “Treatment” measures the treatment rate for those with precancerous lesions. Conclusions: The Cascade can guide emerging and existing HPV screening programs within Canada and other similarly resourced settings and serve as a benchmark tool for programs to assess their progress towards cervical cancer elimination.

Is Moderately Hypofractionated Radiotherapy a Safe and Effective Strategy for Cervical Cancer?—A Review of Current Evidence

Cervical cancer (CC) remains a leading cause of cancer-related mortality, particularly in low- and middle-income countries (LMICs), despite advancements in HPV vaccination and screening. Radiotherapy (RT) plays a critical role in managing CC, but conventional fractionated radiotherapy (CFRT) is limited by long treatment durations, which reduce patient adherence, increase the risk of treatment interruptions, and impair healthcare access in LMICs. Moderately hypofractionated radiotherapy (MHRT) may offer a promising alternative, delivering higher doses per fraction with fewer total fractions, thus shortening treatment duration and alleviating the burden on both patients and healthcare systems. Early clinical data suggest that MHRT achieve acceptable short- to medium-term tumor control with manageable toxicity. However, the small sample sizes and limited follow-up in published studies preclude definitive conclusions about long-term efficacy and safety. This review synthesizes the existing clinical evidence to outline the potential benefits and inherent limitations of MHRT in CC management and highlight the need for future large-scale, long-term randomized controlled trials with rigorous quality assurance protocols. These findings also have implications for the potential implementation of MHRT in LMICs.

Towards Cervical Cancer Elimination: Insights from an In-Depth Regional Review of Patients with Cervical Cancer

Cervical cancer is a largely preventable disease, with over 90% of cases caused by persistent infection with human papillomavirus (HPV). Despite the availability of HPV vaccination and cervical screening, incidence rates in Canada have been rising since 2015, particularly among underserved populations. This study investigates contributing factors behind cervical cancer diagnoses in Eastern Ontario over a two-year period to identify gaps leading to failures in prevention and screening. A retrospective chart review was conducted for cervical cancer cases diagnosed between January 2022 and December 2023 at two regional cancer centres in Eastern Ontario. Cases were categorized as screen-detected, inadequately screened, or system failure, based on prior screening history and care processes. Data was collected on patient, screening, and cancer characteristics. Of 132 cases, 22 (16.7%) were screen-detected, 73 (55.3%) were inadequately screened, and 37 (28.0%) were attributed to healthcare system failure. Later-stage disease was significantly more common in the latter two groups. Thirty-one (23.5%) cases presented with palliative diagnoses, and 18 (13.6%) individuals died within 2.5 years. Inadequate screening was associated with rurality, deprivation, and lack of a primary care provider. System failures included false-negative Pap tests, loss to follow-up, and misapplication of screening guidelines. This study evaluated failures in cervical cancer prevention, which led to cervical cancer diagnoses in Eastern Ontario. Gaps included suboptimal screening participation, lack of access to care, health care system breakdowns, and limitations of the Pap test. Findings provide concrete suggestions for eliminating cervical cancer in Canada.

HPV Testing, Self-Collection, and Vaccination: A Comprehensive Approach to Cervical Cancer Prevention

This white paper, prepared by a consortium of Canadian national and provincial organizations and experts, outlines urgent strategies to curb the rising incidence of HPV-related cancers, of which, cervical cancer is currently the fastest-growing cancer in Canada. Despite school-based vaccination programs, the national HPV vaccine uptake remains suboptimal at about 64%, far below the 90% coverage target by 2025 necessary to eliminate cervical cancer by 2040. The report emphasizes a multi-pronged approach: support access to HPV vaccination with expanded funding policies and education around school-based programs while addressing inequities in underserved populations. HPV testing is highlighted as the preferred method for cervical cancer screening, offering higher sensitivity than Pap smears. Self-collection is presented as an innovative strategy to reduce barriers, particularly for marginalized groups, with promising evidence from Canadian pilots and international models. Crucially, we call for investment in comprehensive, population-based databases to track vaccination, screening participation, and follow-up care. Robust registries would allow targeted outreach to under- or never-screened individuals, ensure timely follow-up of abnormal results, and measure the impact of prevention programs across Canada. With vaccination, equitable access to HPV testing, integration of self-collection, and strong data systems, Canada can achieve its goal of eliminating cervical cancer within two decades.

Comparative Efficacy of Photodynamic Therapy and Cold Knife Conization for Cervical High-Grade Squamous Intraepithelial Lesions

(1) Background: Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) offers a non-invasive alternative for managing cervical intraepithelial neoplasia. This comparative study assessed the efficacy and safety of 5-ALA PDT versus cervical conization in treating HSIL. (2) Methods: A total of 137 patients with HSIL and HPV infection, confirmed by pathological biopsy, were included. Based on patient preference and gynecological evaluation, participants were allocated into the PDT group and the CKC group. Follow-up assessments were conducted at 6 months post-treatment, involving HPV testing, cytology, and colposcopy. Additionally, any discomfort or side effects experienced during treatment were documented, along with a preliminary analysis of treatment costs and duration. (3) Results: The overall lesion remission rates were 88.0% for the PDT group and 89.6% for the CKC group, while HPV clearance rates were 80.0% and 82.7%, respectively. Although no statistically significant difference in efficacy was observed between the two groups, the PDT group exhibited a notably lower incidence of side effects. Nevertheless, the PDT group was associated with higher costs and longer treatment duration. (4) Conclusions: These findings indicate that 5-ALA PDT achieves comparable efficacy to CKC in the treatment of HSIL. Therefore, PDT may serve as a valuable therapeutic option for patients seeking fertility preservation or less invasive management strategies.

Barriers and Facilitators to Cervical Cancer Screening in Northern Uganda: Qualitative Insights from Healthcare Workers and Administrators

Background: Cervical cancer (CC) is the most common cancer among Ugandan women and the leading cause of cancer mortality. Screening has proven to be a cost-effective method in reducing its burden, yet uptake among women of reproductive age remains alarmingly low, with national adherence rates under 10%. Objective: This study explored healthcare workers’ (HWs) perspectives on barriers and facilitators to screening and attitudes toward implementing human papillomavirus (HPV) DNA testing with self-collection. Methods: A qualitative research design was employed. Twenty semi-structured interviews were conducted with purposively sampled healthcare providers and administrators across different cadres at a referral hospital and three peripheral health centres in Northern Uganda. Interviews were analysed thematically using the Social Ecological Model. Data collection and analysis proceeded iteratively until thematic saturation. Reporting follows the Consolidated Criteria for Reporting Qualitative Research (COREQ). Results: Participants described individual and interpersonal barriers such as limited awareness, poor preventive health-seeking, fear of results, stigma, and limited male involvement. Organisational barriers included staff shortages, weak referral practices, and stock-outs of supplies, while policy constraints included limited governmental support and competing priorities. Facilitators included targeted health education, routine referrals from all service entry points, outreach screening, and donor support. Most respondents favoured scaling up of self-collected HPV testing, citing higher acceptability and feasibility for outreach, contingent on sustained supplies, laboratory capacity, and training. Conclusions: Multi-level interventions are needed to strengthen facility workflows, staff capability, community engagement, and reliable supply chains. Expanding access to self-collected HPV testing may overcome major barriers and represents a promising strategy to increase screening uptake in Uganda and similar low resource settings.

Machine Learning-Based Prognostic Modelling Using MRI Radiomic Data in Cervical Cancer Treated with Definitive Chemoradiotherapy and Brachytherapy

Background: This study aims to evaluate the contribution of clinical and radiomic features to machine learning-based models for survival prediction in patients with locally advanced cervical cancer. Methods: Clinical and radiomic data from 161 patients were retrospectively collected from a single center. Radiomic features were obtained from contrast-enhanced magnetic resonance imaging (MRI) T1-weighted (T1W), T2-weighted (T2W), and diffusion-weighted (DWI) sequences. After data cleaning, feature engineering, and scaling, survival prediction models were created using the CatBoost algorithm with different data combinations (clinical, clinical + T1W, clinical + T2W, clinical + DWI). The performance of the models was evaluated using test accuracy, precision, recall, F1-score, ROC curve, and Bland–Altman analysis. Results: Models using both clinical and radiomic features showed significant improvements in accuracy and F1-score compared to models based solely on clinical data. In particular, the CatBoost_CLI + T2W_DMFS model achieved the best performance, with a test accuracy of 92.31% and an F1-score of 88.62 for distant metastasis-free survival prediction. ROC and Bland–Altman analyses further demonstrated that this model has high discriminative power and prediction consistency. Conclusions: The CatBoost algorithm shows high accuracy and reliability for survival prediction in locally advanced cervical cancer when clinical and radiomic features are combined. The addition of radiomics data significantly improves model performance.

PET/CT Imaging Characteristics of Gastric-Type Endocervical Adenocarcinoma: Findings from a Small Exploratory Series

Objective: To identify distinctive 18F-FDG positron emission tomography (PET)/computer tomography (CT) features of gastric-type endocervical adenocarcinoma (GAS) that differentiate it from squamous cell carcinoma (SCC) and usual-type endocervical adenocarcinoma (UEA), as well as to correlate these findings with pathological characteristics. Methods: Patients treated between December 2018 and December 2024 were retrospectively reviewed. The study included 12 GAS, 48 SCC, and 30 UEA cases. Evaluated parameters included tumor morphology, cystic components, uterine cavity fluid, N/M staging, tumor diameter, the cervical lesion maximum standardized uptake value (SUVmax), and the tumor-to-liver maximum standardized uptake ratio (T/L SUVmax). Results: GAS predominantly exhibited diffuse infiltrative growth (11/12), in contrast to mass-like growth observed in SCC (37/48) and UEA (24/30) (both p < 0.001). Cystic components, uterine cavity fluid, and peritoneal metastasis occurred significantly more frequently in GAS (12/12, 11/12, 5/12, respectively) compared to SCC and UEA (all p < 0.001). Elevated CA19-9 levels were more common in GAS (9/12) compared with SCC (p < 0.001). Tumor diameter did not differ significantly among the groups (p > 0.05). SUVmax and T/L SUVmax values were significantly lower in GAS (7.5 ± 3.8 and 2.5 ± 1.6, respectively) than in UEA (19.1 ± 11.4 and 5.7 ± 3.4) and SCC (17.4 ± 6.7 and 5.5 ± 2.6) (all p < 0.001). Conclusion: The clinical characteristics of GAS include infiltrative tumor growth, fluid accumulation in the uterine cavity, frequent formation of microcystic or macrocystic components, peritoneal metastasis, and elevated CA19-9 levels. In this cohort, SUVmax and T/L SUVmax values in GAS were significantly lower than those observed in SCC and UEA.

Cervical Cancer Elimination Requires Systems, Trust, and Action

Cervical cancer has a clear and achievable path to elimination [...]

Challenges in Implementing Comprehensive Precision Medicine Screening for Ovarian Cancer

Precision medicine has revolutionised targeted cancer treatments; however, its implementation in ovarian cancer remains challenging. Diverse tumour biology and extensive heterogeneity in ovarian cancer can limit the translatability of genetic profiling and contribute to a lack of biomarkers of treatment response. This review addresses the barriers in precision medicine for ovarian cancer, including obtaining adequate and representative tissue samples for analysis, developing functional and standardised screening methods, and navigating data infrastructure and management. Ethical concerns related to patient consent, data privacy and health equity are also explored. We highlight the socio-economic complexities for precision medicine and propose strategies to overcome these challenges with an emphasis on accessibility and education amongst patients and health professionals and the development of regulatory frameworks to support clinical integration. Interdisciplinary collaboration is essential to drive progress in precision medicine to improve disease management and ovarian cancer patient outcomes.

Pembrolizumab-Induced Simultaneous and Refractory Systemic Capillary Leak and Cytokine Release Syndromes: A Case Report

Systemic Capillary Leak Syndrome (SCLS) and Cytokine Release Syndrome (CRS) have both been described as rare but severe adverse reactions induced by Programmed cell death protein 1 (PD-1) inhibitors such as pembrolizumab. We report the case of a 40-year-old woman undergoing treatment with pembrolizumab for a stage 4 cervical squamous cell carcinoma who presented with anasarca, hypotension, hemoconcentration and signs of multisystemic inflammation. After elimination of alternative causes such as nephrotic syndrome, cardiac dysfunction and cirrhosis, she was diagnosed with both pembrolizumab-induced SCLS and CRS. She was successfully treated with a multimodal treatment approach including intravenous immunoglobulins, steroids, diuretics and axitinib for SCLS as well as ruxolitinib for CRS. After several months of hospitalization, her symptoms finally improved with this treatment regimen, and she was able to attain euvolemic state and be discharged from the hospital. This case highlights certain rare and severe adverse effects of treatment with PD-1 inhibitors. Furthermore, it proposes a novel therapeutic approach for similar cases based upon probable underlying physiopathological mechanisms in SCLS and CRS.

Evaluation of Cervical Cancer Screening in Japan: Challenges and Future Directions for Negative Intraepithelial Lesion or Malignancy/High-Risk Human Papillomavirus Positive Case Management

Cervical cancer screening is crucial for early detection and prevention. In Japan, women with negative intraepithelial lesion or malignancy (NILM) and high-risk human papillomavirus (HR-HPV) positivity are recommended retest for 12 months, rather than immediate colposcopy. International guidelines differ, and often prioritize early colposcopy for persistent HPV16/18 infections. This study evaluates Japan’s current screening approach, and identifies areas for improvement. A retrospective cohort study analyzed cervical cancer screening data from Saga Prefecture (2019–2021), assessing follow-up adherence, colposcopy referral rates, and CIN2+ and CIN3+ detection among NILM/HR-HPV+ cases. Among 27,789 individuals screened, 2248 (8.1%) were NILM/HR-HPV+. Follow-up adherence after 12 months was 54.4%. Of these, 132 with cytological abnormalities underwent colposcopy, revealing CIN2+ in 27.3% of cases. Additionally, 561 women with persistent NILM/HR-HPV+ underwent colposcopy, with CIN2+ in 7.6% and CIN3+ in 3.9% of cases. Japan’s current NILM/HR-HPV+ management strategy could delay the detection of high-grade cervical lesions. International guidelines favor earlier colposcopy referrals, particularly for HPV16/18+ cases. To improve cervical cancer prevention, Japan should consider a risk-based stratification model, enhance follow-up adherence, expand colposcopy access, and develop a national patient tracking system. Adopting primary HPV-based screening could attain the best global practices, facilitating earlier detection and reducing cervical cancer.

Tumor Invasion Distance Based on MRI Is a Novel Prognostic Indicator for I-IIIB Cervical Cancer Patients Treated with Radiotherapy

Aims:This study aimed to identify the prognostic value of tumor invasion distance (TID) based on MRI findings in cervical-cancer (CC) patients treated with radiotherapy (RT). Methods: A total of 218 CC patients diagnosed at Fujian Cancer Hospital from December 2018 to December 2019 were included in the study. Cox regression analyses were conducted to identify independent prognostic factors for overall survival (OS), including low 1/3 vaginal involvement, a longer TID, and RT without chemotherapy. These factors were subsequently used to construct a nomogram for individualized risk prediction. Kaplan–Meier survival analysis was employed to evaluate survival outcomes and establish a risk stratification system. The performance of the new stratification was assessed using the linear trend χ2 test, Akaike information criterion, and Harrell’s concordance index. Results: A longer TID was associated with worse 3-year OS (p < 0.001, HR: 3.42, 95% CI: 1.67–7.00). A longer TID, lower 1/3 vaginal involvement, and concurrent chemotherapy were independent prognostic survival factors for CC patients. Compared with the 2018 FIGO staging system, the new risk stratification system provided better monotonicity with a higher linear trend χ2 value (28.03 vs. 9.35), better discriminatory ability with smaller Akaike information criterion (312 vs. 331), and a greater Harrell C statistic (0.74 vs. 0.65) for predicting 3-year OS. Conclusions: This was the first study to demonstrate the prognostic value of TID in CC patients who received RT. The new risk stratification system based on TID could complement the 2018 FIGO staging system in identifying high-risk patients for more intense treatment and care. Further prospective research with larger samples is warranted to confirm the significance of TID for CC patients treated with RT.

Breaking Barriers: Empowering Cervical Cancer Screening with HPV Self-Sampling for Sex Workers and Formerly Incarcerated Women in Toronto

Background: Although cervical cancer (CC) is highly preventable through appropriate screening methods like the Papanicolaou (Pap) test, which enables early detection of malignant and precancerous lesions, access to such screening has not been equitable across social groups. Sex workers and people with records of incarceration are among the most under-screened populations in Ontario. Little is known about the acceptability and feasibility of HPV self-sampling (HPV-SS) as an alternative cervical cancer screening method for these groups. This online, community-based mixed-methods pilot study aimed to address this knowledge gap. Methods: Eighty-four under- and never-screened sex workers and ex-prisoners aged 25–69 years and residing in the Greater Toronto Area, were recruited by community peer associates. Participants completed an online survey and viewed short videos about CC and screening with Pap and HPV-SS. Those who opted for HPV-SS conducted the test at one of two collaborating organizations. Results: The median age of participants was 36.5 years. Most had limited knowledge about CC and screening. Approximately 13% identified as non-binary, and 5% as two-spirit or trans men, with the majority having completed secondary education. Of the participants, 88% chose HPV-SS, and one-third tested positive for high-risk HPV types. The ability to self-sample without judgment from healthcare providers was noted as a key advantage. However, there was a need for training on proper HPV-SS techniques. Conclusions: To improve cervical cancer screening among sex workers, increasing awareness through participatory community co-creation of sexual health education is essential. Additionally, offering HPV-SS as a screening option is crucial, given its demonstrated acceptability and feasibility within this population, many of whom lack a primary care provider and face discriminatory attitudes in healthcare settings.

Molecular Prognostic Factors in Uterine Serous Carcinomas: A Systematic Review

Uterine serous carcinomas are an aggressive minority of endometrial cancers. They are characterized by mutations in TP53 and extensive copy number alterations and are primarily classified in the copy number-high/p53abn molecular prognostic group, highlighting a unique molecular profile that is crucial for understanding their behavior and treatment responses. Clinical studies have shown that molecular categorization via biomarkers can facilitate proper treatment selection, and this is now widely used. In this context, the scope of this systematic review is to identify molecular characteristics with prognostic significance for these neoplasms to further inform on their treatment needs. We performed a comprehensive literature search of all articles written in English using the PubMed/Medline and Cochrane databases through February 2025. Our review led to the inclusion of 95 studies, from which we identified a total of 66 distinct molecular characteristics along with new cancer signatures that may impact prognosis. These findings have the potential to inform clinical practice by aiding in the development of tailored treatment strategies for patients with uterine serous carcinoma, ultimately improving outcomes in this challenging malignancy.

The Complex Tumor Microenvironment in Ovarian Cancer: Therapeutic Challenges and Opportunities

The tumor microenvironment (TME) in ovarian cancer (OC) has much greater complexity than previously understood. In response to aggressive pro-angiogenic stimulus, blood vessels form rapidly and are dysfunctional, resulting in poor perfusion, tissue hypoxia, and leakiness, which leads to increased interstitial fluid pressure (IFP). Decreased perfusion and high IFP significantly inhibit the uptake of therapies into the tumor. Within the TME, there are numerous inhibitor cells, such as myeloid-derived suppressor cells (MDSCs), tumor association macrophages (TAMs), regulatory T cells (Tregs), and cancer-associated fibroblasts (CAFs) that secrete high numbers of immunosuppressive cytokines. This immunosuppressive environment is thought to contribute to the lack of success of immunotherapies such as immune checkpoint inhibitor (ICI) treatment. This review discusses the components of the TME in OC, how these characteristics impede therapeutic efficacy, and some strategies to alleviate this inhibition.

The Development and Testing of a Patient Decision Aid for Individuals with Homologous Recombinant Proficient Ovarian Cancer Who Are Considering Niraparib Maintenance Therapy

New treatments for ovarian cancer are available that require trade-offs between progression-free survival and quality of life. The aim of this study was to develop a decision aid for patients with homologous recombinant proficient (HRP) tumors, as the benefit–harm ratio of niraparib needs consideration. This decision aid was created with a systematic and iterative development process based on the Ottawa Decision Support Framework. The decision aid was user-tested for acceptability, usability, and comprehensibility using a survey completed by a sample of patients with ovarian cancer and oncologists. This decision aid follows the International Patient Decision Aids Standards (IPDAS) criteria in its development. User-test respondents (n = 13 patients; 13 physicians) reported that the decision aid used language that was easy to follow (69% patients; 85% physicians), was an appropriate length (69% patients; 62% physicians) and provided the right amount of information (54% patients; 54% physicians). Most respondents (92% patients; 62% physicians) would recommend this decision aid for HRP patients considering niraparib. This is the first decision aid for patients with HRP ovarian cancers who are considering niraparib maintenance therapy. It is available on-line and is being further evaluated in a pragmatic clinical trial in Saskatchewan.

Trends in Early-Stage Cervical Cancer Management in the US: A National Cancer Database Analysis

The Laparoscopic Approach to Cervical Cancer (LACC) trial was published in 2018 and demonstrated that minimally invasive surgery (MIS) yields inferior survival outcomes in early-stage cervical cancer compared to open surgery. This study investigates how the results of the LACC trial have impacted the selection of the primary treatment modality and adjuvant radiation utilization in early-stage cervical cancer. Using the National Cancer Database (NCDB), we compared patients with stage IA2-IB1 cervical cancer before (1/2016–12/2017) and after (1/2019–12/2020) the LACC trial. A total of 7930 patients were included: 4609 before and 3321 after the LACC trial. There was a decline in MIS usage from 67% pre-LACC to 35% thereafter (p < 0.001). In both the pre- and post-LACC periods, patients undergoing radical MIS more frequently had small volume disease (pre-LACC tumors ≤ 2 cm, 48% MIS vs. 41% open, p = 0.023; post-LACC stage IA2, 22% vs. 15%, p = 0.002). Pre-LACC, MIS radical hysterectomy was associated with White race (82% vs. 77%, p = 0.001) and private insurance (63% vs. 54%, p = 0.004), while there was no difference in socioeconomic factors in the post-LACC period. Although the proportion of patients treated with primary chemoradiation remained stable, the post-LACC cohort had a younger median age (52.47 vs. 56.37, p = 0.005) and more microscopic disease cases (13% vs. 5.4%, p = 0.002). There was no difference in the rate of radiation after radical hysterectomy before and after the trial (26% vs. 24%, p = 0.3). Conclusions: Post-LACC, patients were less likely to undergo MIS but received adjuvant radiation at similar rates, and primary chemoradiation patients were younger and more likely to have microscopic disease.

A Systematic Review of SBRT Boost for Cervical Cancer Patients Who Cannot Benefit from Brachytherapy

Stereotactic body radiation therapy has emerged as a promising alternative to brachytherapy, delivering high doses to tumors with precision while sparing surrounding organs. This systematic review evaluates the role of SBRT as a boost for patients who are ineligible for brachytherapy. A total of 17 studies, involving 288 patients, were analyzed, focusing on dosimetric parameters and toxicity. The radiation regimens varied in dose and fractionation schedules, with external beam doses ranging from 44 to 61.6 Gy, and SBRT boost doses ranging from 5 to 30 Gy. The total EQD2 doses were between 50.5 and 92.4 Gy. The results indicate adequate tumor control with SBRT, with local control rates ranging from 57% to 95.5%. The acute genitourinary and gastrointestinal toxicities were mostly grade 1 or 2, while late toxicities were less common. The overall survival rates varied between 34% and 96%. These results suggest that SBRT boost offers a viable option for cervical cancer patients ineligible for brachytherapy, with acceptable toxicity and promising survival outcomes. Nevertheless, the scarcity of data, which mainly originate from small studies with patients having varied stages of disease, as well as the lack of long-term follow up with SBRT, should encourage clinicians to utilize brachytherapy whenever suitable as a boost in these patient cohorts.

COVID-19 Pandemic Impact on Delays in Diagnosis and Treatment for Cervical Cancer in Montreal, Canada

Introduction. The COVID-19 pandemic has been responsible for a major reorganization of healthcare systems, with less access for cancer screening. Few data exist on the impact of cervical cancer treatment during the pandemic. Methods. The purpose of this study was to compare the cervical cancer stage at diagnosis and the surgical and medical treatment delays before and during the COVID-19 pandemic. This is a retrospective cohort study of all cervical cancers diagnosed at any stages between 1 January 2018 and 28 February 2022 at the Centre Hospitalier de l’Université de Montréal. Stage at diagnosis, time to initial referral, time from diagnosis to treatment before and during the COVID-19 pandemic were compared. Results. A total of 244 cervical cancers were diagnosed during the study period. No differences were observed between the number of cases diagnosed before and after pandemic (p = 0.237). Most patients and disease characteristics did not differ between the study periods, but the patients were significantly younger (p = 0.007), with higher BMI (p = 0.024) in the pandemic period. The mean time between initial diagnosis and referral was longer during the pandemic by 13 days (p = 0.042). The mean time between diagnosis and MRI and diagnosis and PET CT was not longer during the pandemic (p = 0.481 and p = 0.384). There were no significant differences in the mean time from the initial referring to the first visit at the CHUM (p = 0.895) or in the mean time from diagnosis to treatment (0.668) and duration of treatment (p = 0.181) Conclusion. Minor delays were observed during the COVID-19 pandemic. Cervical cancer patients treated at the CHUM, a tertiary and quaternary Canadian public health center, were globally referred and treated similarly, as those who were treated before pandemic.

Clinical Impact of MRI-Guided Intracavitary–Interstitial Brachytherapy in the Curative Management of Advanced-Stage Cervical Cancer

This study investigates the clinical efficacy of MRI-based adaptive brachytherapy (IGABT) using combined intracavitary and interstitial techniques in the curative treatment of patients with advanced cervical cancer (LACC). A retrospective analysis was conducted on 149 LACC patients treated at a single center. The therapeutic protocol included intensity-modulated external beam radiotherapy (IMRT) and IGABT. Dosimetric parameters were evaluated for relevance for local control (LC), progression-free survival (PFS), and overall survival (OS) using Kaplan–Meier estimation, Cox regression, and log-rank test. Patients predominantly presented with stage III/IV tumors (81%, FIGO 2018). The median high-risk clinical target volume (hrCTV) was 34 cm3, with a median D90% dose of 88.9 GyEQD2. At 24 months, OS, PFS, and LC rates were 86%, 57%, and 81%, respectively. FIGO stage, tumor volume, and histology were significant predictors of PFS. Higher total hrCTV doses were strongly correlated with improved LC and PFS, emphasizing the importance of precise dosimetric optimization in IGABT and confirming the critical role of IGABT in achieving very good LC rates for LACC. The reported LC rates are comparable to landmark studies, such as INTERLACE and KEYNOTE-A18. This study validates the effectiveness of MRI-guided IGABT in enhancing local tumor control in advanced-stage cervical cancer while providing insights into the prognostic implications of dosimetric parameters such as hrCTV and point A. Future research should address the persistent challenge of distant metastases by exploring the integration of novel systemic treatment options.

Comprehensive Evaluation of Inflammatory Biomarkers in Cervical Cancer Treated with Chemoradiotherapy

Objective: Inflammatory biomarkers have been shown to possess both prognostic and predictive significance in various cancers. Among the emerging biomarkers, the pan-immune-inflammation value (PIV) has recently been introduced as a novel indicator representing both the immune response and the systemic inflammatory state. This study aims to comprehensively evaluate the predictive value of inflammatory biomarkers on survival outcomes in cervical cancer patients undergoing chemoradiotherapy. Methods: A total of 90 patients who had undergone chemoradiotherapy for cervical cancer were included. Data on demographics, treatment protocols, pre-treatment blood parameters, and survival outcomes were collected. The association between inflammatory biomarkers and survival outcomes was investigated through univariate and multivariate analyses. Results: The univariate analysis identified the following as predictors of progression-free survival (PFS): neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR), systemic immune-inflammation index (SII), PIV, C-reactive protein (CRP), albumin, and tumor size. Multivariate analysis revealed that only the PIV significantly predicted PFS (HR 3.05, 95% CI 1.0 to 9.3, p = 0.04). In the univariate analysis, several variables were predictive of overall survival (OS), including NLR, PLR, MLR, SII, PIV, CRP, LDH, albumin, tumor size, and Eastern Cooperative Oncology Group Performance Status (ECOG PS). Multivariate analysis revealed CRP (HR 3.41, 95% CI 1.5 to 7.7, p = 0.003) and ECOG PS (HR 4.78, 95% CI 1.3 to 17.3, p = 0.01) predictive of OS, with PIV approaching statistical significance (HR 2.56, 95% CI 0.8 to 7.6, p = 0.09). Conclusions: This study provides the first comprehensive analysis of the association between cervical cancer and various inflammatory biomarkers. Many of these biomarkers have demonstrated predictive value for survival outcomes in patients with cervical cancer undergoing definitive chemoradiotherapy. Among the biomarkers evaluated, CRP and PIV were identified as the most predictive, warranting further exploration in future research.

Addressing Underscreening for Cervical Cancer among South Asian Women: Using Concept Mapping to Compare Service Provider and Service User Perspectives of Cervical Screening in Ontario, Canada

Cervical cancer is largely preventable through screening and treatment of cervical lesions. In the province of Ontario, South Asian women have some of the lowest rates of screening. The roles of service providers—those in healthcare and community services—and their interactions with screen-eligible people can greatly impact the uptake of screening. In our study, we used concept mapping (CM) to engage over 70 South Asian service users (i.e., those eligible for cervical screening) and service providers to identify a range of ideas and experiences that impact uptake of cervical screening for South Asian women, which were then rated by 45 participants in terms of ‘importance’ and ‘ease to address’ to encourage participation in cervical screening. Overall, ideas related to knowledge and education were rated as most important and easiest to address by both groups. Some differences were seen with South Asian service users valuing the importance of addressing ‘cultural beliefs and influences specific to sexual health’ more than service providers, while service providers valued the importance of addressing ‘lack of comfort and supportive relationships’ more than South Asian service users. Future interventions should target the knowledge and education needs of service users and increase service providers’ awareness of cultural beliefs and influences specific to sexual health.

Pan-Canadian Analysis of Practice Patterns in Small Cell Carcinoma of the Cervix: Insights from a Multidisciplinary Survey

Small-cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare cancer with poor prognosis, with limited data to guide its treatment. The objective of this study was to evaluate practice patterns in the management of SCNECC. A 23-question online survey on management of SCNECC was disseminated to Canadian gynecologic oncologists (GO), radiation oncologists (RO) and medical oncologists (MO). In total, 34 practitioners from eight provinces responded, including 17 GO, 13 RO and four MO. During staging and diagnosis, 74% of respondents used a trimodality imaging approach, and 85% tested for neuroendocrine markers. In early-stage (1A1-1B2) SCNECC, 87% of practitioners used a surgical-based approach with various adjuvant and neoadjuvant treatments. In locally advanced (1B3-IVA) SCNECC, 53% favored primary chemoradiation, with cisplatin and etoposide, with the remainder using surgical or radiation-based approaches. In metastatic and recurrent SCNECC, the most common first-line regimen was etoposide and platinum, and 63% of practitioners considered clinical trials in the first line setting or beyond. This survey highlights diverse practice patterns in the treatment of SCNECC. Interdisciplinary input is crucial to individualizing multimodality treatment, and there is a need for prospective trials and intergroup collaboration to define the optimal approach towards managing this rare cancer type.

Progress and Challenges in Canada’s Path Toward the Elimination of Cervical Cancer

Cervical cancer is almost entirely preventable and treatable when detected early, making its elimination within reach for Canada and the world. However, cervical cancer is now the fastest-increasing cancer (+3.7% per year since 2015) in Canada as of 2023, marking the first significant increase in cervical cancer incidence since 1984. The human papillomavirus (HPV) vaccine and cervical screening are key preventive measures, with targets set by the WHO and the Canadian Partnership Against Cancer (CPAC) to eliminate cervical cancer in Canada by 2030 and 2040, respectively. These targets include increasing HPV vaccination rates, implementing primary HPV screening, and improving follow-up for abnormal HPV+ results. However, Canada’s progress has been impeded by significant challenges. As of the most recent data, HPV vaccine coverage rates in Canada range from 47% to 81%, with an estimated national HPV vaccination completion rate of 64% in Canada, far below the target of 90% by 2025 set by the CPAC. With the exception of British Columbia and Prince Edward Island, the adoption of HPV DNA testing as the primary screening method has been slow across the Canadian provinces and territories despite its superior sensitivity compared with traditional cytology. This article reviews the current state of HPV vaccination and screening in Canada, emphasizing the need for coordinated efforts, transparency, and resource sharing to overcome barriers. Key recommendations include the dissemination of accessible educational materials, partnerships, and collaboration, including nationwide task forces and roundtables, and the implementation of standardized guidelines for HPV screening. Achieving cervical cancer elimination requires a united approach involving federal, provincial, and territorial health authorities, researchers, clinicians, NGOs, community groups, and patients’ voices working together to ensure consistent, effective, timely, and meaningful cervical cancer prevention strategies are used across the country.

Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP): A Systematic Review of the Literature in the Last 20 Years

Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP) is a rare uterine tumor primarily affecting perimenopausal and postmenopausal women, typically aged between 45 and 55 years. Characterized by ambiguous histological features, STUMPs present diagnostic challenges as they cannot be definitively classified as benign or malignant based on morphology alone. This systematic review aims to elucidate the clinical, pathological, immunohistochemical, and treatment-related characteristics of STUMPs through an analysis of the literature from the past 20 years. The study follows PRISMA guidelines, utilizing comprehensive searches of PubMed and Scopus databases, yielding 32 studies that meet the inclusion criteria. From the analysis of these studies, it was revealed that the clinical presentations vary from common symptoms such as abnormal uterine bleeding and pelvic pain to incidental detection of uterine mass. Histologically, STUMPs demonstrate features overlapping with both leiomyomas and leiomyosarcomas, including mild nuclear atypia, low mitotic indices, and focal necrosis. Immunohistochemical markers such as p16 and p53 have been investigated for prognostic significance. Elevated p16 expression, often associated with aggressive behavior, was observed in a subset of STUMPs. Surgical management, typically involving hysterectomy or tumorectomy, is the primary treatment, though the extent of resection is variable. Adjuvant therapies are not routinely recommended, but long-term surveillance is advised, especially for high-risk patients. Recurrence rates for STUMPs are approximately 12%, with factors such as high mitotic counts and coagulative necrosis indicating higher risk. This review highlights the complexity of STUMP diagnosis and management, emphasizing the need for more precise diagnostic criteria and individualized treatment strategies. Understanding the morphological, immunohistochemical, and clinical behavior of STUMPs can improve patient outcomes and guide future research in this diagnostically challenging area.

Does Prior Experience Matter? Intention to Undergo Cervical Cancer Screening among Rural Women in South-Central Ethiopia

Early screening for cervical cancer has substantially reduced the morbidity and mortality attributed to it. This study aimed to assess factors that affect the intention to undergo cervical cancer screening among rural women attending primary healthcare facilities in south-central Ethiopia. A health-facility-based, cross-sectional study design was employed for which the calculated required sample size was 427. An interviewer-administered structured questionnaire was adapted from previously published research and used to collect data. Statistical Package for Social Sciences (SPSS) version 27 was used for the statistical analysis. A logistic regression model was used to determine the factors that influenced the women’s intention to undergo cervical cancer screening. A total of 420 women participated in this study, with a response rate of 98%. The mean score from the questionnaire that was used to assess the women’s intention to undergo cervical cancer screening was 10.25 (SD ± 2.34; min 3, max 15). The absence of previous screening experience (AOR: 0.498; 95% CI 0.27–0.92) and high degree of perceived behavioural control (AOR, 0.823; 95% CI 0.728–0.930) were significantly negatively associated with women’s intention to undergo cervical cancer screening. Previous screening experience and perceived behavioural control significantly influenced the intention to undergo cervical cancer screening. Women in rural areas could, therefore, benefit from awareness-creation programmes that focus on these factors.

Important and Feasible Actions to Address Cervical Screening Participation amongst South Asian Women in Ontario: A Concept Mapping Study with Service Users and Service Providers

Regular cervical screening can largely prevent the development of cervical cancer and innovative methods are needed to better engage people in screening. In Ontario, Canada, South Asian women have some of the lowest rates of screening in the province. In this study, we used concept mapping to engage two stakeholder groups—South Asian service users and service providers—to identify and prioritize points of intervention to encourage the uptake of cervical screening. After participants brainstormed a master list of statements, 45 participants rated the statements based off ‘importance’ and ‘ease to address’ in relation to encouraging cervical screening. A bivariate plot (X-Y graph) that shows the average rating values for each statement across the two rating variables (a ‘go-zone’ display) was produced to display priorities for implementation. Statements that were considered high priority to address reflected issues around education and awareness including understanding and communication related to cervical screening and preventative care, as well as the need for trusted sources of information. Statements that were considered high priority but challenging to implement were centered around fear, stigma, discomfort, family and personal priorities. This study highlighted that stigma, norms and social relations that impact the uptake of screening must be addressed in order for education and awareness raising to be effective and to move people from conviction around screening to action.

Paclitaxel as HIPEC-Drug after Surgical Cytoreduction for Ovarian Peritoneal Metastases: A Randomized Phase III Clinical Trial (HIPECOVA)

Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I–II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien–Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.

Impact of PET/CT Imaging with FDG in Locally Advanced Cervical Carcinoma—A Literature Review

Positron emission tomography (PET) and computed tomography (CT) have evolved as a pivotal diagnostic modality in the field of oncology. With its increasing application in staging and ready availability, it becomes imperative for committed radiation oncologists to possess a complete analysis and understanding of integration of molecular imaging, which can be helpful for radiation planning, while also acknowledging its possible limitations and challenges. A significant obstacle lies in the synthesis and design of tumor-specific bmolecules for diagnosing and treating cancer. The utilization of radiation in medical biochemistry and biotechnology, encompassing diagnosis, therapy, and control of biological systems, is encapsulated under the umbrella term “nuclear medicine”. Notably, the application of various radioisotopes in pharmaceutics has garnered significant attention, particularly in the realm of delivery systems for drugs, DNA, and imaging agents. The present article provides a comprehensive review of use of novel techniques PET and CT with major positron-emitting radiopharmaceuticals currently in progress or utilized in clinical practice with their integration into imaging and radiation therapy.

Significance of Concurrent Chemoradiotherapy as Primary Treatment in Patients with Metastatic Cervical Cancer

(1) This study investigated the prognostic impact of tumor size in patients with metastatic cervical cancer. (2) Methods: Seventy-three cervical cancer patients in our institute were stratified into two groups based on distant metastasis: para-aortic lymph node metastasis alone (IIIC2) or spread to distant visceral organs with or without para-aortic lymph node metastasis (IVB) to identify primary tumor size and concurrent chemoradiotherapy. (3) Results: The overall survival (OS) for patients with a tumor >6.9 cm in size was significantly poorer than that for patients with a tumor ≤6.9 cm in the IVB group (p = 0.0028); the corresponding five-year OS rates in patients with a tumor ≤6.9 and >6.9 cm were 53.3% and 13.4%, respectively. In the multivariate analysis, tumor size and primary treatment were significantly associated with survival in metastatic cervical cancer. (4) Conclusions: Tumor size ≤6.9 cm and concurrent chemoradiotherapy as the primary treatment were favorable prognostic factors for patients with metastatic cervical cancer.

Exceptional Response to Trastuzumab Deruxtecan (T-DXd) in HER2-Positive Metastatic Endometrial Cancer

Objectives: Endometrial cancer is the most common gynaecologic malignancy, and its mortality rate is rising. Advanced or recurrent disease remains challenging because historically there have been limited therapeutic options. We aim to describe a complete and durable response to the HER2-directed antibody–drug conjugate trastuzumab deruxtecan (T-DXd) in a heavily pretreated patient with HER2-positive, mismatch-repair-deficient metastatic serous endometrial cancer. Methods: A 72-year-old woman underwent hysterectomy, bilateral salpingo-oophorectomy, and staging procedures for FIGO stage IIIA, high-grade serous papillary endometrial carcinoma. Tumour profiling revealed dMMR, a p53 abnormal pattern, and HER2 overexpression (IHC 3+). She received carboplatin/paclitaxel plus avelumab, followed by pegylated liposomal doxorubicin and weekly paclitaxel. After progression on paclitaxel, off-label T-DXd was initiated. Molecular data (FoundationOne CDx) were collected, along with and serial imaging and CA125 assessments. Results: The patient developed cough after two cycles of T-DXd; interstitial lung disease was excluded, and treatment resumed with steroid cover. By December 2024, PET/CT demonstrated complete metabolic response, with resolution of vaginal-vault and para-aortic lesions and normalisation of CA125. Real-world progression-free survival exceeded eight months, with ongoing symptom improvement. Treatment was generally well tolerated; the principal adverse event was grade 3 neutropenia requiring dose reduction. No cardiotoxicity or interstitial lung disease occurred. Conclusions: This case illustrates that T-DXd can induce deep and durable remission in HER2-positive, dMMR metastatic serous endometrial cancer after multiple lines of therapy. It adds real-world evidence supporting further investigation of HER2-directed antibody–drug conjugates in gynaecologic malignancies, and underscores the need for confirmatory trials and refined biomarker-driven patient selection.

Molecular Differences between Squamous Cell Carcinoma and Adenocarcinoma Cervical Cancer Subtypes: Potential Prognostic Biomarkers

The most frequently diagnosed histological types of cervical cancer (CC) are squamous cell carcinoma (SCC) and adenocarcinoma (ADC). Clinically, the prognosis of both types is controversial. A molecular profile that distinguishes each histological subtype and predicts the prognosis would be of great benefit to CC patients. Methods: The transcriptome of CC patients from The Cancer Genome Atlas (TCGA) was analyzed using the DESeq2 package to obtain the differentially expressed genes (DEGs) between ADC and SCC. The DEGs were validated on a publicly available Mexican-Mestizo patient transcriptome dataset (GSE56303). The global biological pathways involving the DEGs were obtained using the Webgestalt platform. The associations of the DEGs with Overall Survival (OS) were assessed. Finally, three DEGs were validated by RT-qPCR in an independent cohort of Mexican patients. Results. The molecular profiles of ADC and SCC of the CC patients of the TCGA database and the Mexican-Mestizo cohort (GSE56303) were determined obtaining 1768 and 88 DEGs, respectively. Strikingly, 70 genes were concordant—with similar Log2FoldChange values—in both cohorts. The 70 DEGs were involved in IL-17, JAK/STAT, and Ras signaling. Kaplan-Meier OS analysis from the Mexican-Mestizo cohort showed that higher GABRB2 and TSPAN8 and lower TMEM40 expression were associated with better OS. Similar results were found in an independent Mexican cohort. Conclusions: Molecular differences were detected between the ADC and SCC subtypes; however, further studies are required to define the appropriate prognostic biomarker for each histological type.

Comparison of Prognosis between Minimally Invasive and Abdominal Radical Hysterectomy for Patients with Early-Stage Cervical Cancer

Minimally invasive surgery (MIS) is performed to treat cervical cancer patients; however, a recent study showed that MIS was associated with higher recurrence and death rate compared with abdominal radical hysterectomy (ARH). In the current study, the prognosis of patients with early-stage cervical cancer who underwent MIS with vaginal closure or ARH was evaluated. One hundred and eighty-two patients underwent radical hysterectomy for cervical cancer with stage of IA2, IB1, and IIA1. MIS was performed by laparoscopy or a robot using the vaginal closure method. Disease-free survival (DFS) and overall survival (OS) were evaluated between the groups. Among the patients, 67 underwent MIS and 115 underwent ARH. The recurrence rate was 4.5% in MIS patients and 3.5% in ARH patients with a median follow-up (interquartile range) of 36 (18–60) and 78 (48–102) months, respectively. DFS and OS were not different between the groups (3y-DFS, 95.3% vs. 96.1%, p = 0.6; 3y-OS, 100% vs. 100%, p = 0.06). In early-stage cervical cancer patients, MIS with vaginal closure did not increase the risk for recurrence or death. Surgical techniques and procedures to avoid spillage of tumor cells could be important for a better prognosis.

Advances in Radiation Oncology for the Treatment of Cervical Cancer

Background: Over the past two decades, there has been significant advancement in the management of cervical cancer, particularly in the domain of definitive chemoradiotherapy for locally advanced cervical cancer (LACC). Indeed, radiation treatment paradigms have shifted from a two-dimensional (2D) approach solely based on anatomical bony landmarks, to an image-guided three-dimensional (3D) approach, with the goal of delivering doses more precisely to clinical targets with an increased sparing of organs-at-risk. Methods: This is a narrative review on the advances in radiation technologies for the treatment of cervical cancer. Using the PubMed database, we identified articles published in English up until November 18, 2021 on the treatment of LACC with external beam radiotherapy (EBRT) and brachytherapy. A search of the Clinicaltrials.gov and Clinicaltrialsregister.eu retrieved information on ongoing clinical trials on the topic of combined immunotherapy and radiotherapy in cervical cancer. Results: We highlight the historical evolution from the use of 2D radiotherapy to 3D-conformal radiotherapy, and then intensity modulated radiotherapy (IMRT) for the delivery of EBRT. We also discuss advances in brachytherapy, notably the transition to 3D image-guided adaptive brachytherapy (3D-IGABT). In this context, we highlight large cohort studies that were recently constructed and have shown significant improvement in local control and treatment-related toxicities with 3D-IGABT. Finally, we discuss other advances in the field, notably the use of stereotactic body radiotherapy (SBRT) as a substitute to brachytherapy, and the addition of immunotherapy to chemoradiation. Conclusions: The use of IG-IMRT and 3D-IGABT have considerably improved treatment outcomes and toxicity profiles for patients with LACC, and are now considered the gold standard in many countries. The use of SBRT boost as a replacement for brachytherapy has been associated with increased toxicity and decreased efficacy and should be used with caution in the context of clinical trials. New experimental approaches include the addition of immunotherapy to chemoradiation regimens.

Brain Metastases in Gynaecologic Cancer: A Retrospective Cohort Study Evaluating Treatment Outcomes, Prognostic Factors, and Overall Survival

(1) Background: The objectives of this study were to assess survival of patients with a diagnosis of brain metastases secondary to gynaecologic malignancy and the impact of clinicopathological factors on prognosis in this population. (2) Methods: A retrospective cohort of patients with gynaecologic cancers diagnosed with brain metastases treated with radiation at a tertiary care centre from 1 January 2004 until 30 September 2023 was studied. Kaplan–Meier method and log-rank test were used to evaluate survival, and cox regression was used to identify significant predictive factors of survival. (3) Results: In total, 103 patients were included in this study. Median age at diagnosis of brain metastases was 59 (range 30–94). Median survival time following diagnosis of brain metastases was 3.6 months (range 0.4–183.8). Survival was significantly longer for patients treated with surgery combined with radiation compared to radiation alone and with stereotactic radiosurgery (SRS) compared to whole brain radiation therapy (WBRT). Cox regression revealed that primary ovarian malignancy, extracranial disease at diagnosis, and ≥3 brain metastases were associated with poorer prognosis, and complete response to prior treatment was associated with more favourable prognosis. (4) Conclusions: Data from this study will assist in providing evidence-based prognostic information to patients with gynaecologic malignancy diagnosed with brain metastases.

Preoperative Cognitive Function and Physical Frailty Predict Decision Satisfaction and Postoperative Adherence in Older Gynecologic Oncology Patients: A Prospective Observational Study

With increasing life expectancy, a growing proportion of patients undergoing surgery for gynecologic cancers are older adults, underscoring the need for reliable predictors of postoperative recovery and patient engagement. Cognitive function and physical frailty are recognized determinants of surgical outcomes, yet their relative impact on patient centered outcomes remains insufficiently explored. This prospective observational study included 68 women aged 65 years and older who underwent abdominal surgery for gynecologic malignancies. Preoperative cognitive function was assessed using the Montreal Cognitive Assessment, and physical frailty was evaluated with the Clinical Frailty Scale. Postoperative outcomes included early recovery parameters, complications, surgical decision satisfaction, and home-based adherence. Higher cognitive scores were associated with earlier mobilization, shorter hospital stay, better postoperative adherence, and greater decision satisfaction, whereas higher frailty scores were associated with delayed recovery and increased complication risk. In regression analyses, preoperative cognitive function was significantly associated with both postoperative adherence and surgical decision satisfaction, whereas physical frailty was not. These findings indicate that preoperative cognitive screening may have predictive value for patient centered recovery behaviors and decision satisfaction in this setting; however, the prediction estimates should be considered exploratory and warrant validation in larger, multicenter cohorts.

Exploring the Role of Hypoxia and HIF-1α in the Intersection of Type 2 Diabetes Mellitus and Endometrial Cancer

Diabetes and Cancer are the most complex chronic diseases, accounting for significant global mortality and morbidity. The association between Type 2 DM (T2DM) and endometrial cancer (EC) is multifaced, sharing numerous risk factors, including insulin resistance, obesity, hypoxia, and oxidative stress. Hypoxia plays a vital role in T2DM pathogenesis by altering the insulin level and pancreatic β-cell failure through an imbalance between antioxidant enzymes and cellular oxidative levels, while chronic inflammation contributes to EC malignancy. HIF-1α is a potent transcription factor involved in modulating cellular responses to hypoxia within the disease environment. Targeting the HIF-1α signaling cascade, a major metabolic regulator may contribute to advanced therapeutic advances. This review focuses on the association between T2DM and EC, especially focusing on hypoxia and HIF signaling pathways. These intersect with key pathways involved in T2DM and EC pathology, such as insulin signaling, PI3K/AKT, mTOR pathway, MUC1/HIF-1α pathway, and hormonal imbalance. Understanding this complex relationship paves the way for future researchers to develop HIF-1α-targeted therapies that could lead to novel combination therapies to treat these comorbid conditions.

High-Dose-Rate Three-Dimensional Image-Guided Adaptive Brachytherapy (3D IGABT) for Locally Advanced Cervical Cancer (LACC): A Narrative Review on Imaging Modality and Clinical Evidence

Background: Brachytherapy (BT) is a critical component of radiotherapy for locally advanced cervical cancer (LACC), and it has rapidly developed in recent decades. Since the advent of three-dimensional image-guided adaptive brachytherapy (3D-IGABT), magnetic resonance imaging (MRI) has emerged as the primary modality for image guidance. Meanwhile, other imaging modalities, such as computed tomography, 18F-fluorodeoxyglucose positron emission tomography, ultrasound, and their combinations have also been widely studied. Materials and methods: We reviewed studies on different imaging modalities utilized for target delineation and planning. Emerging techniques in IGABT like real-time image guidance and 3D printing were also included. We summarized research on their feasibility and concentrated on their clinical outcomes. Results: MRI-guided BT was the gold standard, and CT-guided BT was the most widely applied. Other modalities have shown feasibility and promising efficacy in dosimetry studies and preliminary outcomes. The longer-term clinical outcomes associated with these approaches require further elucidation. Conclusions: As 3D-IGABT was validated by promising clinical outcomes, the future of BT for LACC is expected to progress toward the refinement of more effective image-guided procedures. Moreover, achieving operational consensus and driving technological advancements to mitigate the inherent limitations associated with different imaging modes remain essential.

Patient-Initiated Follow-Up in Ovarian Cancer

This study aimed to assess the feasibility of patient-initiated follow-up (PIFU) in combination with regular tumour marker monitoring as an alternative to conventional hospital follow-up for ovarian cancer survivors. Women who had recently completed treatment for ovarian cancer and had a raised pre-treatment tumour marker were recruited. Participants were allocated to PIFU (intervention group) or conventional hospital follow-up (control group) according to their own preference. Both groups had regular tumour marker monitoring. The change in fear of cancer recurrence (FCR) score as measured by the FCR inventory, and the supportive care need (SCN) scores as measured by the SCN survey at baseline and at 6 months between PIFU and hospital follow-up were compared. Out of 64 participants, 37 (58%) opted for hospital follow-up and 27 (42%) opted for PIFU. During the 6-month study period, there was no significant difference in the change of FCR between the two groups (p = 0.35). There was a significant decrease in the sexuality unmet needs score in the intervention group from baseline to 6-month FU (mean difference −8.7, 95% confidence interval −16.1 to −1.4, p = 0.02). PIFU with tumour marker monitoring is a feasible follow-up approach in ovarian cancer survivorship care. FCR and SCN were comparable between PIFU and conventional hospital follow-up.

Histological and Genetic Diversity in Ovarian Mucinous Carcinomas: A Pilot Study

Tumor heterogeneity remains an ongoing challenge in the field of cancer therapy. Intratumor heterogeneity significantly complicates the diagnosis of cancer and presents challenging clinical problems due to resistance to drug therapy. This study aimed to elucidate the genetic changes histologically (mucinous cystadenoma (MCA), mucinous borderline tumor (MBT), and mucinous ovarian carcinoma (MOC)) in a portion of mucinous ovarian tumors within the same sample. Seven tumor samples obtained from different patients were used to evaluate the genetic mutations in each component. Intratumor genetic heterogeneity was observed in all patients; among them, BRAF (V600E) and p53 (T118I, P142S, T150I, and T170M) point mutations were observed in the MBT component, while KRAS (G12D and G13D) and PIK3CA (E545K) mutations were found in the MOC component. The current findings suggest that diverse genetic alterations occur in mucinous tumors, according to tumor histology. Tumor heterogeneity and genetic diversity in mucinous ovarian tumors might be the cause of treatment failure. Knowledge of intertumor heterogeneity may lead to an increased understanding of the tumor response to treatment.

A Nomogram for Preoperative Prediction of the Risk of Lymph Node Metastasis in Patients with Epithelial Ovarian Cancer

Objective: To develop a nomogram for predicting lymph node metastasis (LNM) in patients with epithelial ovarian cancer (EOC). Methods: Between December 2012 and August 2022, patients with EOC who received computed tomography (CT) and serological examinations and were treated with upfront staging or debulking surgery were included. Systematic pelvic and para-aortic lymphadenectomy was performed in all patients. Univariate and multivariate analysis was used to identify significant risk factors associated with LNM. A nomogram was then constructed to assess the risk of LNM, which was evaluated with respect to its area under the receiver operating characteristic curve (AUC), calibration, and clinical usefulness. Results: Of 212 patients enrolled in this study, 78 (36.8%) had positive LNs. The nomogram integrating CT-reported LN status, child-bearing status, tumour laterality, and stage showed good calibration and discrimination with an AUC of 0.775, significantly improving performance over the CT results (0.699, p = 0.0002) with a net reclassification improvement of 0.593 (p < 0.001) and integrated discrimination improvement of 0.054 (p < 0.001). The decision curve analysis showed the nomogram was of clinical use. Conclusions: A nomogram was constructed and internally validated, which may act as a decision aid in patients with EOC being considered for systemic lymphadenectomy.

Ultra-High-Risk Gestational Choriocarcinoma of the Ovary Associated with Ectopic Pregnancy

Gestational choriocarcinoma of the ovary is an exceptionally rare and highly aggressive tumor. Preoperative diagnosis of extrauterine choriocarcinoma is difficult due to nonspecific clinical presentation and its resemblance to ectopic pregnancy. Without molecular genetic analysis, it is not possible to reliably differentiate gestational from non-gestational choriocarcinoma. Here, we present a case of a 44-year-old woman who presented to our emergency department with complaints of pelvic pain, vaginal bleeding, and amenorrhea. Because of a recent history of conservatively managed ectopic pregnancy, the patient underwent emergency laparoscopy. Right-sided salpingo-oophorectomy was performed due to intraoperatively suspected ovarian ectopic pregnancy. Histopathology results revealed the diagnosis of ovarian choriocarcinoma of possible gestational origin. It was classified as FIGO stage IV and WHO ultra-high-risk, and she underwent multi-agent chemotherapy without major complications. She has remained in complete remission after a 12-month follow-up. Considering the rarity of this diagnosis, we conducted a literature review including all published cases of suspected gestational choriocarcinomas of the ovary. We conclude that due to the rarity of this entity, preoperative differentiating between ovarian ectopic pregnancy and ovarian choriocarcinoma is extremely challenging, and without molecular genetic analysis, it is not possible to identify the genetic origin of the tumor.

Risk Factors for Nodal Failure in Patients with FIGO IIIC Cervical Cancer Receiving Definitive Image-Guided Radiotherapy

Background: Nodal failure is a major failure pattern for patients with FIGO IIIC cervical cancer, which is further associated with worse survival. This study was designed to investigate risk factors for nodal failure in FIGO IIIC cervical cancer patients. Methods: The characteristics of positive lymph nodes (LNs) and relevant clinical factors of 162 FIGO IIIC cervical cancer patients were collected. The chi-square test and logistic regression model were used to identify risk factors for nodal failure. Results: In total, 368 positive LNs were identified, including 307 pelvic LNs and 61 para-aortic LNs. The nodal failure rates for all LNs, pelvic LNs, and para-aortic LNs were 9.2%, 7.8%, and 16.4%, respectively. After 20 fractions of RT, a nodal short diameter (D20F) ≥ 0.95 cm and a ratio of nodal shrinkage (ΔV20F) < 0.435 resulted; <4 cycles of chemotherapy indicated higher nodal failure rates for all LNs. For pelvic LNs, ΔV20F < 0.435 and <4 cycles of chemotherapy were associated with a higher incidence of nodal failure. For para-aortic LNs, ΔV20F < 0.435 was the only risk factor for nodal failure. Conclusions: Para-aortic LNs were more likely to experience nodal failure than pelvic LNs. Nodal shrinkage during radiotherapy and cycles of chemotherapy were associated with nodal failure in patients with FIGO IIIC cervical cancer.

Age-Specific Trends of Invasive Cervical Cancer Incidence in British Columbia, Canada, 1971–2017

This study examined invasive cervical cancer (ICC) incidence trends in British Columbia (BC) by age and stage-at-diagnosis relative to World Health Organization ICC elimination targets (4 per 100,000 persons). Incident ICC cases (1971–2017) were obtained from the BC Cancer Registry. Annual age-standardized incidence rates (ASIRs) per 100,000 persons were generated using the direct method. ASIRs were examined among all ages 15+ years and eight age groups using Joinpoint Regression with the Canadian 2011 standard population. Standardized rate ratios (SRRs) compared stage II–IV (late) versus stage I (early) ASIRs by age (2010–2017). ICC ASIRs did not reach the elimination target. ASIRs declined from 18.88 to 7.08 per 100,000 persons (1971–2017). Stronger declines were observed among ages 45+ years, with the largest decline among ages 70–79 years (AAPC = −3.2%, 95% CI = −3.9% to −2.6%). Among ages 25–69 years, varying levels of attenuation in declining trends and stabilization were observed since the 1980s. SRRs indicated higher rates of late-stage ICC among ages 55+ years (SRR−55–69 years = 1.34, 95% CI = 1.08–1.71). Overall, ICC incidence declined in BC since 1971 but did not reach the elimination target. The pace of decline varied across age groups and increased with age. Continued efforts are needed to progress cervical cancer elimination among all age groups.

Germline BRCA1/2 Variants in Polish Patients with Family History of Breast and Ovarian Cancer: Prevalence, CNV Detection, and Identification of a Novel Loss-of-Function Mutation

Background/Objectives: Pathogenic and likely pathogenic variants in the BRCA1 and BRCA2 genes are associated with a significantly increased risk of breast and/or ovarian cancer. We investigated genetic variants in a cohort of 450 unaffected individuals with a family history of breast and/or ovarian cancer, involving at least one first-degree relative. Methods: Next-generation sequencing (NGS) was used to analyze the coding regions of these two genes, with copy number variation (CNV) analysis. Results: A total of 16 unique to our cohort variants classified as pathogenic or likely pathogenic were identified in 22 patients, including one novel loss-of-function variant in BRCA1 gene. Furthermore, we identified a deletion of exon 21 in the BRCA1 gene in two patients. Conclusions: These results emphasize the difficulties involved in molecular diagnostics and indicate the need for further research into new predictive models for patients with hereditary breast and ovarian cancer.

Population-Based Survival Analysis of Stage IVB Small-Cell Neuroendocrine Carcinoma in Comparison to Major Histological Subtypes of Cervical Cancer

The aim of the current study is to investigate the survival outcome of stage IVB SCNEC of the uterine cervix in comparison to major histological subtypes of cervical cancer. A population-based retrospective cohort study was conducted using the Osaka Cancer Registry data from 1994 to 2018. All FIGO 2009 stage IVB cervical cancer patients who displayed squamous cell carcinoma (SCC), adenocarcinoma (A), adenosquamous cell carcinoma (AS), or small-cell neuroendocrine carcinoma (SCNEC) were first identified. The patients were classified into groups according to the types of primary treatment. Then, their survival rates were examined using the Kaplan–Meier method. Overall, in a total of 1158 patients, clearly differential survival rates were observed according to the histological subtypes, and SCNEC was associated with shortest survival. When examined according to the types of primary treatments, SCNEC was associated with significantly decreased survival when compared to SCC or A/AS, except for those treated with surgery. In patients with FIGO 2009 stage IVB cervical cancer, SCNEC was associated with decreased survival when compared to SCC or A/AS. Although current treatments with either surgery, chemotherapy or radiotherapy have some therapeutic efficacies, to improve the prognosis, novel effective treatments specifically targeting cervical SCNEC need to be developed.

Perceptions of Cancer in Parents of Adolescent Daughters in Northwest Cameroon

Background: Cancer is a rapidly rising cause of morbidity and mortality in sub-Saharan Africa. Cervical cancer, in particular, is still one of the leading causes of mortality for women in this setting. The uptake of healthcare services is in part influenced by patients’ belief systems. We sought to better understand the perception of cancer in the Kom tribe of Northwest Cameroon. Methods: A qualitative research study was completed using a semi-structured interview guide and one-on-one interviews with 45 parents of girls aged 9–14 years. These girls were candidates for free HPV vaccination to prevent cervical cancer. The interviews were recorded, transcribed, and analyzed using ATLAS.ti 9. Results: Thirty-five mothers and ten fathers with a median age of 42 yo were interviewed from Mbingo, Belo, Njinikom, and Fundong. Half of the parents were farmers, with three being herbalists or traditional medicine doctors. Seventy-seven percent had either no or only primary school education. None had had cancer. All knew at least one person with cancer. The most common word for cancer in the Kom language is “ngoissu”. It can refer to a bad infection or cancer. The occurrence of ngoissu is the result of either a curse placed on you, ancestral retribution, or transgressing the ngoulatta (snail shell spoken over and usually placed in a garden). The implications are that treatment of ngoissu must involve the traditional doctor who determines the spiritual issue and prescribes a remedy (like a herb or tea) and/or an incantation. Within the context of cancer, this can lead to a delay in diagnosis until the disease is no longer curable by conventional therapies. Conclusion: Ways to bridge biomedical healthcare services and traditional medicine are needed, especially in tribal contexts where the latter is an integral part of daily life.

Implementation of a Cervical Cancer Screening Intervention for Under- or Never-Screened Women in Ontario, Canada: Understanding the Acceptability of HPV Self-Sampling

With appropriate screening, cervical cancer can be prevented. In Ontario, Canada, some groups of women have low screening rates. South Asian, Middle Eastern and North African women are particularly at risk of under-screening. Currently, cytology-based screening is used in Ontario, although the growing evidence and adoption of HPV testing for cervical screening has encouraged many jurisdictions around the world to move towards HPV testing, with the option of self-sampling. We conducted an intervention beginning in June 2018, where we recruited over 100 under- or never-screened (UNS) women who identify as South or West Asian, Middle Eastern or North African from the Greater Toronto Area, to understand the uptake and acceptability of HPV self-sampling as an alternative to a Pap test. Participants self-selected if they tried the kit or not and completed both quantitative and qualitative research activities. This paper focuses on the qualitative arm of the study, where follow-ups and five focus groups were conducted with those who tried the kit (three groups) and those who did not (two groups), as well as eight key informant interviews with community champions and others who were involved in our recruitment. We used the Consolidated Framework for Implementation Research (CFIR) to guide our data collection and analysis. Major themes around convenience, privacy and comfort came from the data as important drivers of the uptake of the intervention. The role of community champions and peers in engaging and educating UNS women, as well as having self-confidence to collect the sample, also came out as factors impacting uptake and plans for continued use. Overall, the intervention showed that HPV self-sampling is an acceptable alternative to a Pap test for some but not all UNS women in Ontario.

Are Canadian Women Prepared for the Transition to Primary HPV Testing in Cervical Screening? A National Survey of Knowledge, Attitudes, and Beliefs

As Canadian provinces and territories prepare to transition to HPV-based primary screening for cervical cancer, failure to identify and address potential barriers to screening could hinder program implementation. We examined screening-eligible Canadians’ attitudes towards and knowledge of cervical screening. A nationally representative sample of screening-eligible Canadians (N = 3724) completed a web-based survey in the summer of 2022. Oversampling ensured that half of the sample were underscreened for cervical cancer (>3 years since previous screening or never screened). The participants completed validated scales of cervical cancer, HPV, and HPV test knowledge and HPV test and self-sampling attitudes and beliefs. Between-group differences (underscreened vs. adequately screened) were calculated for scales and items using independent sample t-tests or chi-square tests. The underscreened participants (n = 1871) demonstrated significantly lower knowledge of cervical cancer, HPV, and the HPV test. The adequately screened participants (n = 1853) scored higher on the Confidence and Worries subscales of the HPV Test Attitudes and Beliefs Scale. The underscreened participants scored higher on the Personal Barriers and Social Norms subscales. The underscreened participants also endorsed greater Autonomy conferred by self-sampling. Our findings suggest important differential patterns of knowledge, attitudes, and beliefs between the underscreened and adequately screened Canadians. These findings highlight the need to develop targeted communication strategies and promote patient-centered, tailored approaches in cervical screening programs.

2023 Canadian Colposcopy Guideline: A Risk-Based Approach to Management and Surveillance of Cervical Dysplasia

This guideline provides evidence-based guidance on the risk-based management of cervical dysplasia in the colposcopy setting in the context of primary HPV-based screening and HPV testing in colposcopy. Colposcopy management of special populations is also discussed. The guideline was developed by a working group in collaboration with the Gynecologic Oncology Society of Canada (GOC), Society of Colposcopists of Canada (SCC) and the Canadian Partnership Against Cancer (CPAC). The literature informing these guidelines was obtained through a systematic review of the relevant literature via a multi-step search process led by information specialists. The literature was reviewed up to June 2021 with manual searches of relevant national guidelines and more recent publications. Quality of the evidence and strength of recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. The intended users of this guideline include gynecologists, colposcopists, screening programs and healthcare facilities. Implementation of the recommendations is intended to promote equitable and standardized care for all people undergoing colposcopy in Canada. The risk-based approach aims to improve personalized care and reduce over-/under-treatment in colposcopy.

Safety and Efficacy of 2D Brachytherapy vs. 3D Image-Guided Adaptive Brachytherapy for Locally Advanced Cervical Cancer—A Single Institution Retrospective Study

Background: The treatment paradigm for locally advanced cervical cancer (LACC) has shifted from two-dimensional-brachytherapy (2D-BT) to three-dimensional-image-guided adaptive BT (3D-IGABT). In this retrospective study, we report our experience with the change from 2D-BT to 3D-IGABT. Methods: We reviewed 146 LACC patients (98 3D-IGABT and 48 2D-BT) who received chemoradiation between 2004 and 2019. The multivariable odds ratio (OR) for treatment-related toxicities and hazard ratios (HR) for locoregional control (LRC), distant control (DC), failure-free survival (FFS), cancer-specific survival (CSS) and overall survival (OS) are reported. Results: The median follow-up was 50.3 months. There was a significant decrease in overall late toxicities in the 3D-IGABT group compared to the 2D-BT group (OR 0.22[0.10–0.52]), late gastrointestinal (OR 0.31[0.10–0.93]), genitourinary (OR 0.31[0.09–1.01]) and vaginal toxicities (0% vs. 29.6%). Grade ≥ 3 toxicity was low in both groups (2D-BT: 8.2% acute, 13.3% late vs. 3D-IGABT: 6.3% acute, 4.4% late, NS). The five-year LRC, DC, FFS, CSS and OS for 3D-IGABT were 92.0%, 63.4%, 61.7%, 75.4% and 73.6%, compared to 87.3%, 71.8%, 63.7%, 76.3% and 70.8% for 2D-BT (NS). Conclusions: 3D-IGABT for the treatment of LACC is associated with a decrease in overall late gastrointestinal, genitourinary and vaginal toxicities. The disease control or survival outcomes were comparable to contemporary 3D-IGABT studies.

The Effect of Contemporary Brachytherapy Practices on Prognosis in Women with Locally Advanced Cervical Cancer

(1) Background: Over the past two decades use of new imaging modalities and the adaptation of applicators have allowed for advances in volumetric (3D) imaging-based brachytherapy practices for patients with locally advanced cervical cancer. The aim of this study was to compare the oncological outcome and toxicity for three consecutively introduced brachytherapy practices in a large single-center cohort; (2) Methods: Patients treated for cervical cancer with primary radiotherapy and curative intent were consecutively included in this retrospective, single-center cohort study from 2006 to 2019. This cohort was divided into three groups (CT, MRI, and MRI+needles) based on the timing of the introduction of a novel brachytherapy practice; 3D brachytherapy planning using CT- and MRI-guided adaptive brachytherapy and the use of parametrial interstitial needles, respectively. Actuarial estimates were compared between groups. Multivariable Cox regression analyses were performed to correct for other risk factors. Crude rates of severe (≥grade 3) late toxicity were reported; (3) Results: A total of 397 patients were included in this cohort. At a median follow-up of 40 months (interquartile range (IQR) 22–62), actuarial 3-year local control, pelvic control, disease-free survival, and overall survival for the entire cohort were 91% (95% (Confidence Interval (CI)) 88–94), 88% (95% CI 84–91), 69% (95% CI 64–74), and 75% (95% CI 70–79), respectively). Local control, disease-free survival, and overall survival were significantly improved in the MRI+needles group compared to the CT group (p = 0.040, p = 0.004, and p < 0.001, respectively). Independent risk factors for overall survival were treatment in either the CT or MRI group (vs. MRI+needles), older age at diagnosis, adeno (squamous) carcinoma, FIGO stage III/IV, and lymph node metastases. The crude rate of severe late toxicity was 27% in the CT, 26% in the MRI, and 20% in the MRI+needles group; (4) Conclusions: Prognosis in women with locally advanced cervical cancer treated with state-of-the-art MRI-guided adaptive brachytherapy combined with parametrial interstitial needles compares favorably to patients treated with more traditional CT only based brachytherapy.

Therapeutic Prospects of Abemaciclib for Patients with Endometrial Cancer

Endometrial cancer (EC) is a common gynecologic malignancy with a rising incidence due to obesity, comorbid conditions, and related lifestyle factors. The standard of care for primary disease consists of surgical resection with/without chemotherapy ± radiotherapy for select patients. Recurrence is common in patients with advanced-stage disease and/or high-risk features, who primarily are treated with systemic therapy. The identification of novel targets in malignant EC has led to the development of wide-range inhibitors. Abemaciclib is an orally active unique cyclin-dependent kinase (CDK) inhibitor, selective for the CDK4 and CDK6 cell cycle pathways. This agent has potential anti-neoplastic activity and is indicated in combination with various therapies such as endocrine therapy, aromatase inhibitors, and hormone therapies, primarily in breast cancer (BC). Herein, we sought to summarize the biochemical/pharmacological properties of abemaciclib and its therapeutic potential in EC. While the therapeutic role(s) of abemaciclib was fairly established in a subset of patients with advanced/metastatic BC through the pivotal MONARCH trials, its attributes and clinical utility in EC are limited. Thus, based on some promising pre-clinical/translational insights and a recent phase II study, we highlight abemaciclib’s properties and potential clinical usefulness in patients with EC, particularly in recurrent estrogen-receptor-positive cases.

Tumor-Bowel Fistula as a Rare Form of Recurrent Ovarian Cancer—Imaging and Treatment: Preliminary Report

Background. The aim of this pilot study was to evaluate the value of imaging techniques, including computed tomography (CT) and magnetic resonance imaging (MRI), in the diagnosis of a tumor-bowel fistula as a rare form of epithelial ovarian cancer (EOC) relapse. We also performed an initial assessment of the effectiveness of the treatment of this form of relapse. Methods. The study group consisted of eight patients with suspected platinum-sensitive recurrence in the form of a tumor/bowel fistula. All patients finished their first line of chemotherapy and subsequently showed complete remission for 6 months or more. To qualify patients for further treatment, CT and MRI were performed, which suggested the presence of a fistula between the recurrent tumor and intestine. DESKTOP study criteria were used to qualify patients for secondary cytoreduction. Second-line chemotherapy was given after secondary debulking. Results. In all patients, fistulas formed between the tumor and large bowel. On CT, the fistulas were indirectly visible. In all cases, the fistula was visible on MR images, which showed hypointensity on the T2 and T1 post-contrast sequences but did not show restricted diffusion on the diffusion-weighted imaging (DWI) sequence. Patients who were qualified for the study underwent secondary debulking with bowel resection. In all eight cases, the fistula between the tumor and surrounding organs was confirmed. During surgery, seven intestinal anastomoses and one colostomy were performed. No residual macroscopic tumor remained in seven cases (resection R0-87.5%). The progression-free survival (PFS) was 8.4–22.6 months (median 13.4). In the group with cytoreduction R0, the median PFS was 15.5 months (12–22). Conclusion. In patients with suspected EOC recurrence with clinically suspected fistula, CT scan is not sufficient. In CT, the presence of a fistula is suspected based on indirect symptoms. MRI, as a method with much greater tissue resolution, confirms the diagnosis. In addition, MRI can identify the point of the tumor/bowel junction. This is especially true with a large infiltration covering several intestinal parts. Bowel resection with simultaneous anastomosis is a good and safe solution for these patients. However, appropriate qualification for the procedure is necessary, which will allow for surgery without residual macroscopic disease (R0 surgery). Due to the small number of cases, our results cannot be generalized. We treat them as a hypothesis that can be verified in a larger study.

Survival in Advanced Epithelial Ovarian Cancer Associated with Cardiovascular Comorbidities and Type 2 Diabetes Mellitus

Background: Ovarian carcinoma (OC) is usually diagnosed at an advanced stage, necessitating a multimodal approach that includes surgery and systemic therapy. The incidence of OC is approximately five times higher in women over 65 years of age. Cardiovascular comorbidities and type 2 diabetes mellitus, both prevalent at this age, can influence therapeutic strategy and have an adverse effect on survival. Objectives: Our study aimed to determine the impact of cardiovascular diseases and diabetes mellitus on survival in advanced ovarian cancer. Materials and methods: From 2004 to 2012, we retrospectively studied 104 patients with advanced epithelial ovarian cancer (FIGO stage II–IV) who underwent surgical treatment at the Gynecology Clinic, St. Anna University Hospital, Varna, Bulgaria. Patients were followed for an average of 90 (52–129) months. We divided the study population into two groups: those with concurrent cardiovascular diseases and type 2 diabetes mellitus (CVD) and those without these comorbidities (No-CVD group). Overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were compared between groups using Kaplan–Meier survival analysis. Cardiovascular comorbidities and diabetes mellitus were evaluated for their prognostic value for survival using multivariate Cox proportional regression analysis adjusted for age, stage of OC, grade and histological type of the tumor, ascites presence, residual tumor size (RT), performance status, and type of hysterectomy. Results: The Kaplan–Meier analysis showed reduced OS and DSS in the CVD group compared to the No-CVD group. The median OS was 24.5 months (95% CI 18.38 months) and 38 months (95% CI 26, not reached), respectively (Log-rank p = 0.045). The median DSS was 25.5 months (95% CI 19.39 months) and 48 months (95% CI 28, not reached), respectively (Log-rank p = 0.033). The Cox regression multivariate analysis established a lower (by 68%) overall survival rate for the CVD patient group than the No-CVD group, approaching statistical significance (HR 1.68, 95% CI 0.99, 2.86, p = 0.055). Cardiovascular diseases and diabetes were associated with a 79% reduction in DSS (HR 1.79, 95% CI 1.02, 3.13, p = 0.041) and a twofold increase in the risk of disease progression (HR 2.05, 95% CI 1.25, 3.37, p = 0.005). Conclusions: According to our study, cardiovascular comorbidities and diabetes may adversely affect OC survival. Optimal control of cardiovascular diseases, diabetes mellitus, and their risk factors may be beneficial for patients with advanced OC. Further research involving a larger patient population is necessary to establish these comorbidities as independent prognostic factors.

An Investigation of the Effect of Attachment on Distress among Partners of Patients with Ovarian Cancer and Their Relationship with the Cancer Care Providers

Caregivers of patients with ovarian cancer experience distress related to caregiving difficulties within cancer care. Attachment insecurity is a well-known protector of distress, particularly as it relates to support from others. Using multivariate analyses, this study sought to determine the contribution of attachment insecurity and experiences with cancer care on symptoms of depression and anxiety, and investigated whether attachment insecurity moderated the relationship between caregiving experiences and distress. Multiple hierarchical regression analyses were conducted as part of a larger cross-sectional questionnaire study of distress among partners of patients with ovarian cancer. Participants (n = 82) were predominantly male, white, had household incomes over $100,000 and postsecondary education. Caregiving experiences explained 56% of the variance in depression, and 28% of the variance in anxiety. Specifically, lack of time for social relations as a result of caregiving significantly predicted depression and anxiety. Attachment anxiety correlated with both depression and anxiety, but attachment avoidance did not. Neither attachment anxiety nor attachment avoidance significantly contributed to distress variance, and neither moderated any of the relationships between caregiving experiences and distress outcomes. This study highlights the importance for cancer care to recognize the effect of caregiving responsibilities upon caregivers’ mental health, regardless of vulnerability to distress.

A Case of Stevens–Johnson Syndrome in Recurrent Late-Stage Ovarian Cancer Patient after Management of Chronic Pain with Elastomeric Pump

(1) Background. Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, characterized by extensive necrosis and detachment of the epidermis. (2) Case presentation. We present a case of a 46-year-old patient with late-stage high-grade serous ovarian cancer who was primarily treated with neoadjuvant chemotherapy and interval debulking, which was followed by adjuvant chemotherapy. At first recurrence, she was again treated with chemotherapy, and due to severe abdominal pain, an elastomeric pump containing analgesics, anti-inflammatories, and ondansetron was administered. In the same month, she was admitted to the hospital due to severe dysphagia, and in the following days she developed haemorrhagic vesiculobullous lesions on the facial skin and trunk. Stevens–Johnson syndrome was confirmed and ondansetron as a plausible leading cause was discontinued. Despite multimodal treatment, her condition deteriorated, and she died. (3) Discussion and conclusion. Although gynaecologists rarely encounter Stevens–Johnson syndrome, high mortality of the disease should ensure a low threshold for diagnosing and treating this disease.

Physicians’ Controversies Towards Fertility Preservation in Young Patients with Gynecological Cancer: An MITO Survey

Guidelines on fertility preservation (FP) have been developed to help young women preserve their fertility, which may have been impaired due to cancer. Nevertheless, the correct management of oncological patients of childbearing age remains controversial, especially regarding gynecological malignancies. For this reason, we explored the current knowledge, attitudes, and clinical practices of physicians towards the challenges of FP in this population. A specially developed questionnaire on fertility-related issues in patients with gynecological cancer was administered via email to 167 people, representing 167 centers of the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) group. A total of 56 physicians, who represented 56 out of these 167 centers, responded to our survey (response rate: 33.5%). Approximately half of these physicians stated that they had adequate knowledge about the use of gonadotropin-releasing analog (GnRHa) injections (n = 30; 53.6%), the cryopreservation of oocytes (n = 25; 44.6%), and the cryopreservation of ovarian tissue (n = 27; 48.2%) in patients with gynecological tumors. Meanwhile, regarding (borderline) ovarian tumors, endometrial or cervical cancer, and genetic mutation carriers, attitudes varied substantially. In conclusion, the results of our survey highlight the different perspectives on controversial topics among physicians directly involved in the treatment of these tumors. These findings also demonstrate the lack of evidence on these issues to adequately counsel this specific patient population.

Linking Intermediate to Final “Real-World” Outcomes: Is Financial Toxicity a Reliable Predictor of Poorer Outcomes in Cancer?

Traditionally, economic evaluations are based on clinical trials with well-defined patient populations that exclude many patient types. By contrast, studies that incorporate general patient populations end up including those in lower income categories, some of whom have significant financial burdens (often described as financial toxicity) related to their care. Consideration of these patient burdens when examining the incremental cost-effectiveness of newer treatments from a clinical trial perspective can result in differing conclusions regarding cost-effectiveness. The challenge is to reliably assess the link between financial toxicity, quality of life and potential decisions to forego or delay care. It is also well-documented that these financial effects are not evenly distributed across populations, with those with low income and of black or Latino decent being most affected. There is a paucity of literature in this space, but some of the early work has suggested that for lung, breast, colorectal and ovarian cancers there are poorer quality-of-life scores and/or shorter overall survival for those experiencing financial toxicity. Hence, we may see both a lower quality of life and a shorter duration of life for these populations. If this is the case, additional considerations include: are the benefits of newer, more-expensive treatment strategies muted by the lack of adherence to these newer treatments due to financial concerns, and, if true, can these effects be effectively quantified as “real-world” outcomes? This rapid review examines these possibilities and the steps that may be required to examine this reliably.

Advocacy in Action: Leveraging the Power of Patient Voices to Impact Ovarian Cancer Outcomes in Canada

Prior to 1997, ovarian cancer (OC) was a ‘poor target’ for patient advocacy. At that time, there were only three OC researchers in Canada, little information available for women diagnosed, and no community of survivors existed. The Corinne Boyer Fund to advance OC was founded in 1997 (later renamed the National Ovarian Cancer Association (NOCA) and subsequently Ovarian Cancer Canada (OCC)), and a Blueprint for Action was established. NOCA developed training programs for public education, partnered with clinicians and scientists, established a Tissue Banking Network across Canada In 2015, the Ladyballs awareness campaign was launched nationally, giving the community a presence and voice. Strategic planning by the organization put advocacy for research funding as a top priority and, working with patients and researchers across the country, petitioned the government for C$10 million in research funding. In 2019, OCC received the funding. In 2020, the OvCAN project was launched with the aim to improve the outcomes of women diagnosed with OC. In the first three years of OvCAN, a pan-Canadian team of 25 Patient Partners was established, and 41 projects to date on research models, pre-clinical and clinical trials covering a wide spectrum of OC types have been funded.

Perceived Quality-of-Life Importance Among Saudi Gynecologic Cancer Survivors: Latent Class Analysis

Quality-of-life (QoL) needs among gynecologic cancer survivors are multifaceted and culturally mediated, yet limited research has examined how survivors in the Middle East prioritize key domains such as sexual function, emotional well-being, and relational quality. This study aimed to identify subgroups of survivors based on the perceived importance of these domains and to explore demographic and clinical predictors of subgroups within the Saudi Arabian context. We conducted a cross-sectional, survey-based study among 129 women with a history of breast or cervical cancer attending a tertiary oncology center in Jeddah, Saudi Arabia. Participants rated the importance of sexual, emotional, and relational QoL domains using a 4-point Likert scale. Latent class analysis (LCA) was used to segment survivors based on their perceived domain importance. Differences in demographic and clinical characteristics across classes were assessed using chi-square tests. A decision tree classifier was employed. Three latent classes emerged: Class 0 (48.8%) prioritized all domains highly; Class 1 (17.8%) reported low importance across domains; and Class 2 (33.3%) emphasized emotional and relational domains while downplaying sexual function. Class group was significantly associated with age (p = 0.001), education (p = 0.04), nationality (p = 0.03), and number of children (p < 0.001). Decision tree analysis identified number of children, age, and marital status as the strongest predictors of high-importance class group. Gynecologic cancer survivors in Saudi Arabia hold diverse priorities regarding QoL domains, primarily shaped by sociocultural context than clinical variables. Tailored survivorship interventions that reflect survivors’ lived values, particularly in relation to age, family structure, and cultural norms, are critical for person-centered oncology care in the region.

Updated Guidelines for the Diagnosis and Treatment of Endometrial Carcinoma: The Polish Society of Gynecological Oncology (2025v)

In 2023, the Polish Society of Gynecologic Oncology (PSGO) published clinical recommendations for the diagnosis, treatment, and care of women with endometrial cancer (EC), developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. A 2025 update was initiated in response to new evidence, particularly regarding systemic therapies for metastatic, advanced, or recurrent EC, and the introduction of an updated FIGO classification. A targeted literature review identified relevant phase III clinical trials and systematic reviews, including RUBY, GY-018, AtTend, and DUO-E. These trials were critically assessed by an Expert Panel in accordance with the AGREE II methodology. Updated recommendations were formulated based on this evidence, with a comparative analysis of the old and new FIGO staging systems and visual updates to treatment pathways. Key changes include the addition of immunotherapy (I/O) plus chemotherapy (CHTH) as first-line treatment for all molecular subtypes of high-grade endometrioid and non-endometrioid carcinomas, replacing chemotherapy alone. For MMRp-positive cases, the 2025 version introduces the use of Olaparib alongside Durvalumab and CHTH. HER2-positive MMRp serous carcinoma remains eligible for trastuzumab in combination with CHTH. Second-line treatment guidance remains unchanged for patients who did not receive I/O plus CHTH initially. However, options for those previously treated with this combination are still under evaluation. This update ensures alignment with the latest international standards and reinforces evidence-based, personalized care for EC patients.

Evaluating the Feasibility and Acceptability of a Community-Based, Co-Created Yoga Program for Women with Gynecologic Cancer: A Series N-of-1 Feasibility Study

Purpose: Current yoga programs for cancer survivors do not meet participants’ needs and are rarely implemented in community-based settings, despite reported benefits. The aim of the current study was to implement a co-created 12-week bi-modal Hatha-based yoga program for adults diagnosed with gynecologic cancer in the community and assess the feasibility and acceptability of the program and study methods. Methods: Using a mixed methods series N-of-1 A1BA2 research design, participants were recruited from The Ottawa Hospital. Participants self-selected a morning or evening program, completed surveys 9 to 11 times and were interviewed post-program. The yoga instructor was interviewed post-program about her experience delivering the program. Quantitative feasibility outcomes were tracked throughout the study. Qualitative acceptability outcomes were explored during post-program semi-structured interviews. Audio and video recordings of the yoga classes and data from the instructor interview were used to assess fidelity outcomes to determine whether the protocol could be adhered to consistently. Results: Forty-one individuals were screened for eligibility and 20 consented (48.7%). Seventeen participants (85.0%) completed the final survey. Participants attended 83.1% (19.9/24) of classes with varied engagement with optional features. The instructor was 61.3% adherent to the prescribed protocol, using recommended behaviors 44.6% of the time. Participants shared barriers and facilitators that influenced the success of the trial methods and program. Conclusions: The program was well-received and trial methods were moderately successful, but refinements are warranted before a large-scale trial. Community-based yoga programs could be feasible and acceptable for women with gynecologic cancer.

The PREPARE Study: Acceptability and Feasibility of a Telehealth Trimodal Prehabilitation Program for Women with Endometrial Neoplasia

Patients with endometrial neoplasia (EN) often have multiple comorbidities and a higher surgical risk. Prehabilitation programs (PPs) combine various interventions to improve preoperative conditions and reduce impairment due to surgical stress. We conducted a pragmatic pilot study to evaluate the acceptability and feasibility of a trimodal telehealth PP (exercise, nutrition, and psychological support) for EN patients. The participants could select their exercise group: (1) a supervised PP (SPP), group sessions 3×/week; (2) a semi-supervised PP (SSPP), group session 1×/week, training alone 2×/week; or (3) a physical activity counseling session (PACS). Out of the 150 EN patients awaiting surgery screened during the 18 months of the study recruitment, 66% (99/150) were eligible, and 40% consented to participate (SPP, n = 13; SSPP, n = 17; PACS, n = 9). The overall dropout was low (13%; 5/39), with no significant differences across groups. No serious adverse events occurred. We observed a positive impact on different outcomes across the different groups, such as in the Functional Assessment of Cancer Therapy quality of life score (SPP; delta = 6.1 [CI: 0.9; 12.6]) and functional capacity measured using the 30″ sit-to-stand test (PACS delta = 2.4 [CI: 1.2; 3.6]). The same-day hospital leave was high in the SSPP group (54.5%). Our pilot telehealth PP seems to be safe, feasible, and well accepted and may procure clinical and patient-centered gains that need to be confirmed in a larger trial.

Multimodal Prehabilitation for Gynecologic Cancer Surgery

Surgical treatment is commonly employed to treat patients with gynecologic cancer, although surgery itself may function as a stressor, reducing the patients’ functional capacity and recovery. Prehabilitation programs attempt to improve patients’ overall health and baseline function prior to surgery, thereby enhancing recovery and lowering morbidity. In recent years, prehabilitation has come to primarily refer to multimodal programs that combine physical activity, nutritional support, psychological well-being, and other medical interventions. However, the specific methods of implementing prehabilitation and measuring its effectiveness are heterogeneous. Moreover, high-level evidence regarding prehabilitation in gynecologic cancer surgery is limited. This review provides a summary of multimodal prehabilitation studies in gynecologic oncologic surgery. Enhanced postoperative recovery, lower postoperative complications, lower rate of blood transfusions, and faster gastrointestinal functional recovery have been reported after multimodal prehabilitation interventions. Patients and healthcare professionals should recognize the importance of prehabilitation in the field of gynecologic oncologic treatment, based on the emerging evidence. In addition, there is a need to establish an appropriate target group and construct a well-designed and tailored prehabilitation program.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Is Associated with Cervical Stromal Involvement in Endometrial Cancer Patients: A Cross-Sectional Study in South China

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant health issue closely associated with multiple extrahepatic cancers. The association between MAFLD and clinical outcomes of endometrial cancer (EC) remains unknown. Methods: We retrospectively included 725 EC patients between January 2012 and December 2020. The odds ratios (ORs) were calculated using logistic regression analyses. Kaplan–Meier survival curves were used for survival analysis. Results: Among EC patients, the prevalence of MAFLD was 27.7% (201/725, 95% confidence interval (Cl) = 0.245–0.311). MAFLD was significantly associated with cervical stromal involvement (CSI) (OR = 1.974, 95% confidence interval (Cl) = 1.065–3.659, p = 0.031). There was a significant correlation between overall survival (OS) and CSI (HR = 0.31; 95%CI: 0.12–0.83; p = 0.020), while patients with MAFLD had a similar OS to those without MAFLD (p = 0.952). Moreover, MAFLD was significantly associated with CSI in the type I EC subgroup (OR = 2.092, 95% confidence interval (Cl) = 1.060–4.129, p = 0.033), but not in the type II EC subgroup (p = 0.838). Further logistic regression analysis suggested that the hepatic steatosis index (HSI) was significantly associated with CSI among type I EC patients without type 2 diabetes mellitus (T2DM) (OR = 1.079, 95% confidence interval (Cl) = 1.020–1.139, p = 0.012). Conclusions: About one-quarter of our cohort had MAFLD. MAFLD was associated with the risk of CSI in EC patients, and this association existed in type I EC patients but not in type II EC patients. Furthermore, the HSI can help predict CSI in type I EC patients without T2DM.

Predicting High-Grade Acute Urinary Toxicity and Lower Gastrointestinal Toxicity After Postoperative Volumetric Modulated Arc Therapy for Cervical and Endometrial Cancer Using a Normal Tissue Complication Probability Model

(1) Background: Volumetric modulated arc therapy (VMAT) can deliver more accurate dose distribution and reduce radiotherapy-induced toxicities for postoperative cervical and endometrial cancer. This study aims to retrospectively analyze the relationship between dosimetric parameters of organs at risk (OARs) and acute toxicities and provide suggestions for the dose constraints. (2) Methods: A total of 164 postoperative cervical and endometrial cancer patients were retrospectively analyzed, and the endpoints were grade ≥ 2 acute urinary toxicity (AUT) and acute lower gastrointestinal toxicity (ALGIT). The normal tissue complication probability (NTCP) model was established using the logistic regression model. Restricted cubic spline (RCS) curves were used to explore the association between dosimetric parameters and toxicities. The receiver operating characteristic (ROC) curve, calibration curve, Akaike’s corrected information criterion (AICc), decision curve analysis (DCA), and clinical impact curve (CIC) were analyzed to evaluate the performance of NTCP models. (3) Results: Bladder V40Gy was identified to develop the NTCP model of AUT, and the mean AUC was 0.69 (CI: 0.58–0.80). Three candidate predictors, namely the small intestine V30Gy, colon D45%, and rectum D55%, were identified to develop the NTCP model of ALGIT, and the mean AUC was 0.71 (CI: 0.61–0.80). Both models were considered to have relatively good discriminative accuracy and could provide a high net benefit in clinical applications. (4) Conclusions: We developed NTCP models to predict the probability for grade ≥ 2 AUT and ALGIT. We recommend that bladder V40Gy, the small intestine V30Gy, colon D45%, and rectum D55% be controlled below 42%, 20.4%, 16.9 Gy, and 32.0 Gy, respectively.

Fertility Preservation in Cervical Cancer—Treatment Strategies and Indications

Cervical cancer is frequently diagnosed in women during their reproductive years, and fertility preservation is an essential part of their cancer treatment. In highly selected patients with early stage, low-risk cervical cancer and a tumor size ≤ 2 cm, several treatment strategies can be offered for patients wishing to preserve fertility, including radical/simple trachelectomy or conization with pelvic lymph node assessment. Trachelectomy can be performed through a vaginal, abdominal, or minimally invasive approach and has been shown to have an equivalent oncologic outcome compared to radical hysterectomy. All surgical approaches for radical trachelectomy seem to have excellent survival with comparable oncologic outcomes. Nevertheless, patients undergoing vaginal trachelectomy have better obstetric outcomes compared to the other routes. In patients with larger tumors (2–4 cm), neoadjuvant chemotherapy followed by fertility-sparing surgery is an alternative option. Several chemotherapy regimens have been used for this indication, with a pathologic complete response rate of 17–73%. For locally advanced diseases that require radical hysterectomy or primary chemoradiation, fertility preservation can be performed using oocyte, embryo, or ovarian tissue cryopreservation, as well as ovarian transposition. For these patients, future pregnancy is possible through surrogacy. In addition to fertility preservation, ovarian transposition, where the ovaries are repositioned outside of the radiation field, is performed to maintain ovarian hormonal function and prevent premature ovarian failure. In summary, fertility-preservation treatment strategies for patients with early stage cervical cancer are continuously evolving, and less radical surgeries are becoming more acceptable. Additional and ongoing evidence is helping determine the impact of conservative procedures on oncologic and obstetric outcomes in these patients.

Combination of Osimertinib and Olaparib Therapy to Treat Non-Small Cell Lung Cancer and High-Grade Serous Ovarian Carcinoma: A Case Report

We present the case of a 75-year-old female with simultaneous EGFR-mutated stage IV lung cancer and advanced BRCA2-mutated ovarian cancer, treated with a unique regimen. In this case report, the patient was treated with alternating months of osimertinib and olaparib to control her lung and ovarian cancers, respectively. When both diseases showed progression, the patient underwent a trial of concurrent therapy with both drugs, yet this was discontinued due to patient-reported adverse side effects. Combination targeted drug therapy may be required to treat complex diagnoses such as dual malignancies. However, combination drug therapy consisting of osimertinib and olaparib has not previously been explored. This case report represents the first to demonstrate osimertinib and olaparib combination therapy as a unique treatment regimen for concurrent lung and ovarian cancers. These two drugs can either be given in an alternating way or given together, short-term, with a higher but tolerable toxicity profile.

Mark3 a Prognostic Marker for the Endometrial Cancer

Introduction: Endometrial cancer (EC) is one of the most common gynecologic cancers, with an increasing incidence due to variables such as aging and lifestyle changes. Current biomarkers exhibit limited prognostic value, despite advancements in understanding their molecular basis, underscoring the necessity for new molecular markers. Microtubule affinity-regulating kinase 3 (MARK3) has been identified as a potential candidate owing to its established prognostic significance in various cancers; however, its function in endometrial cancer (EC) is not yet well understood. Methods: This study investigates the function of MARK3 in endometrial cancer through the analysis of Ishikawa and HEC-1B cell lines. A series of assays were conducted, including colony formation, CCK-8 viability, EDU proliferation assays, scratch wound healing tests, and Transwell migration assays, to investigate the effects of MARK3 overexpression. We conducted RT-qPCR, Western blot, and immunofluorescence assays to evaluate the molecular mechanisms influencing cell proliferation and migration. Bioinformatics analysis utilized publicly available datasets to examine the gene enrichment and co-expression networks. Results: The overexpression of MARK3 markedly reduced colony formation in both Ishikawa (p = 0.0039) and HEC-1B (p = 0.0014) cell lines. Furthermore, the overexpression of MARK3 led to decreased cell viability, as demonstrated by the EDU assay results (Ishikawa-OE p = 0.0302; HEC-OE p = 0.0037). The molecular analysis supported these findings, indicating an increase in phosphorylated AKT (pAKT), thereby suggesting MARK3’s role in regulating cell survival pathways. Gene enrichment analysis revealed pathways associated with cell cycle regulation and apoptosis, whereas co-expression analysis pinpointed critical interacting genes that may play a role in EC progression. Conclusions: MARK3 is essential in the regulation of cell proliferation and migration in endometrial cancer, positioning it as a potential prognostic biomarker and therapeutic target. This study represents the inaugural investigation into the functional role of MARK3 in endothelial cell progression, thereby enhancing our comprehension of its mechanistic influence on cancer biology and its implications for personalized therapy. Bioinformatics analysis reinforces the relevance of MARK3 in endometrial cancer, offering new insights into its clinical significance.

Endometrial Cancer: Transitioning from Histology to Genomics

Endometrial carcinoma (EC) is traditionally treated with surgery and adjuvant treatment depending on clinicopathological risk factors. The genomic analysis of EC in 2013 and subsequent studies using immunohistochemistry have led to the current EC molecular classification into: polymerase epsilon mutated (POLEmut), p53 abnormal (p53abn), mismatch repair deficient (MMRd), and no specific molecular profile (NSMP). The four groups have prognostic value and represent a promising tool for clinical decision-making regarding adjuvant treatment. Molecular classification was integrated into the recent European Society of Gynecologic Oncology (ESGO) management guidelines. POLEmut EC has favorable outcomes and retrospective studies found that omitting adjuvant treatment is safe in this group; two prospective clinical trials, PORTEC-4 and TAPER, are ongoing to assess this. p53 abn is associated with increased recurrence, decreased survival, and benefitted from chemotherapy in the PORTEC-3 subgroup molecular analysis. The clinical trials PORTEC-4a and CANSTAMP will prospectively assess this. MMRd and NSMP groups have intermediate prognosis and will likely continue to rely closely on clinicopathological features for adjuvant treatment decisions. In addition, the molecular classification has led to exploring novel treatments such as checkpoint inhibitors. Overall, the molecular perspective on EC and associated clinical trials will likely refine EC risk stratification to optimize care and avoid overtreatment.

Risk Factors for Venous Thromboembolism in Endometrial Cancer

Background: Venous thromboembolism (VTE) in malignancy is associated with poor outcomes. We conducted a retrospective review of VTE in patients with endometrial cancer to characterize the VTE incidence, identify factors that contribute to VTE risk, and compare survival outcomes in patients with and without VTE. Methods: A retrospective chart review identified 422 eligible patients who underwent surgery for endometrial cancer (1 January 2014 to 31 July 2016). The primary outcome was VTE. Binary logistic regression identified risk factors for VTE; significant risk factors were included in a multivariate analysis. Kaplan–Meier estimates are reported, and log rank tests were used to compare the Kaplan–Meier curves. Risk-adjusted estimates for overall survival based on VTE were determined using a multivariate Cox proportional hazards model. Results: The incidence of VTE was 6.16% overall and 0.7% within 60 days postoperatively. Non-endometrioid histology, stages 3 and 4 disease, laparotomy, and age (p < 0.1) were identified as factors associated with VTE and were included in a multivariate analysis. The overall death rate in patients with VTE was 42% (9% without VTE): hazard ratio, 5.63; 95% confidence interval, 2.86 to 11.08; p < 0.0001. Adjusting for age, stage of disease, and histology, risk of death remained significant for patients with a VTE: hazard ratio, 2.20; 95% confidence interval, 1.09 to 4.42; p = 0.0271. Conclusions: A method to identify patients with endometrial cancer who are at high risk for VTE is important, given the implications of VTE for patient outcomes and the frequency of endometrial cancer diagnoses. Factors identified in our study might assist in the recognition of such patients.

Advances in Screening, Immunotherapy, Targeted Agents, and Precision Surgery in Cervical Cancer: A Comprehensive Clinical Review (2018–2025)

Cervical cancer remains a significant global health burden, disproportionately affecting women in low- and middle-income countries despite being preventable. Since 2018, rapid advances in molecular profiling, immunotherapy, refinement of minimally invasive surgery, and targeted therapeutics have transformed diagnostic and therapeutic paradigms. This narrative review synthesizes clinical and translational progress across the continuum of care from 2018 to 2025. We summarize the evolving landscape of precision screening—including HPV genotyping, DNA methylation assays, liquid biopsy, and AI-assisted cytology—and discuss their implications for global elimination goals. Surgical management has shifted toward evidence-based de-escalation with data from SHAPE, ConCerv, and ongoing RACC informing fertility preservation and minimally invasive approaches. For locally advanced disease, KEYNOTE-A18 establishes pembrolizumab plus chemoradiation as a new curative standard, while INTERLACE underscores the benefit of induction chemotherapy. In the metastatic setting, survival outcomes have improved with the integration of checkpoint inhibitors (KEYNOTE-826, BEATcc, EMPOWER-Cervical 1), vascular-targeted therapies, and antibody–drug conjugates, including tisotumab vedotin and emerging HER2 and TROP-2–directed agents. We further highlight emerging biomarkers—PD-L1, TMB, MSI status, HPV integration patterns, APOBEC signatures, methylation classifiers, ctHPV-DNA—and their evolving role in treatment selection and surveillance. Future directions include neoadjuvant checkpoint inhibition, PARP-IO combinations, HER3-directed ADCs, DDR-targeted radiosensitizers, HPV-specific cellular therapies, and AI-integrated precision medicine. Collectively, these advances are reshaping cervical cancer care toward biologically individualized, globally implementable strategies capable of accelerating WHO elimination targets.

Prognostic Significance of Complete Blood Count-Derived Inflammatory Biomarkers in Patients with Small Cell Neuroendocrine Carcinoma of the Cervix

Background: Small cell neuroendocrine carcinoma of the cervix (SCNEC) is a rare and highly aggressive malignancy with limited prognostic biomarkers available for clinical use. Inflammatory markers derived from complete blood count (CBC) have been shown to reflect the systemic immune response and tumor progression in various cancers, but their prognostic value in SCNEC remains unclear. Methods: We retrospectively analyzed clinical data from patients diagnosed with SCNEC between 2004 and 2024 across two centers. Internal validation was performed by dividing patients into training and test cohorts. Cox regression analyses and Kaplan–Meier survival analyses were used to evaluate prognostic factors and treatment outcomes. Inverse probability of treatment weighting (IPTW) was applied to reduce baseline imbalances. Patients were randomly divided into training and test cohorts. A nomogram was constructed to predict 3-year and 5-year progression-free survival (PFS) with performance evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Results: 196 participants were included in the study. Age, FIGO 2018 stage, surgery, neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR) were independently associated with PFS. High MLR (>0.19) was significantly linked to shorter PFS. After IPTW adjustment, the protective effect of low MLR on PFS remained significant (p = 0.029). The constructed nomogram demonstrated excellent predictive performance, with area under the curve (AUC) values of 0.799 and 0.787 for 3-year and 5-year PFS in the training cohort, and 0.802 for endpoints in the test cohort. Conclusions: MLR was identified as an independent prognostic biomarker for PFS in SCNEC, with potential value in risk stratification and personalized treatment strategies. Additionally, we developed a reliable nomogram that accurately predicts 3-year and 5-year PFS, serving as a practical tool for individualized prognosis and clinical decision-making.

Self-Screening for Cervical Cancer Offered through a Digital Platform in a Region of British Columbia with Lower Screening Rates

Cervical cancer is highly preventable through vaccination, early detection, and treatment, yet is the fourth most common cancer globally. HPV testing is superior to cytology for the detection of cervical pre-cancer, and jurisdictions around the world are implementing HPV primary screening, which offers the opportunity for self-screening, an important self-care intervention. Digital health solutions are also increasingly important components of self-care. In this study, we assessed the acceptability and completion of self-screening for cervical cancer offered through a digital platform within a low screening uptake region of British Columbia. The primary objective of this study was to evaluate the acceptability of self-screening for cervical cancer offered through a digital platform as measured by return rates of self-screening kits. Patients due or overdue for cervix screening were invited to participate. Eligible participants registered online to receive a self-screening kit, which included a device for vaginal self-screening, instructions, and a return envelope, sent to their home. After self-screening using the vaginal device, HPV testing was conducted. HPV-negative participants were returned to routine screening, and HPV-positive participants were recommended for cytology or colposcopy. Attendance rates at follow-up were evaluated. Participants were invited to complete an acceptability survey. From April 2019 to December 2023, 283 participants were sent kits, with 207 kits returned for a completion rate of 73%. Of valid samples (n = 202), 15 were HPV positive, and 93% attended follow-up care. Most respondents found the CervixCheck website easy to use, informative, and secure and were satisfied with receiving their results online. CervixCheck had a high completion rate among participants who were sent a self-screening kit. High compliance with recommended follow-up and high acceptability of self-screening for cervical cancer was observed. Most participants indicated they would self-screen again in the future. Innovative approaches to cervical screening, including self-screening and the use of digital health interventions, are ways to enhance equity and improve uptake of cervical screening.

Time Trends Analysis of Cervical Cancer Incidence in Cluj County, Romania, Using Data from a Population-Based Cancer Registry

(1) Background: Romania has one of the highest cervical cancer incidence rates in Europe. In Cluj County, the first screening program was initiated in 1998. We aimed to investigate the time trends of cervical cancer incidence in women from Cluj County and to evaluate the data quality at the Cancer Registry. (2) Methods: We calculated time trends of standardized incidence rates in the period 1998–2014 and the Annual Percent Change (APC%). To assess data quality, we used the indicators: mortality/incidence ratio (M/I), percentage of cases declared only at death (DOD%), and percentage of cases with pathological confirmation (PC%). (3) Results: The standardized incidence rate increased steadily, from 23.74 cases/100,000 in 1998, to 32/100,000 in 2014, with an APC% of 2.49% (p < 0.05). The rise in incidence affected both squamous cell carcinoma (APC% 2.49%) (p < 0.05) and cervical adenocarcinoma (APC% 10.54%) (p < 0.05). The M/I ratio was 0.29, DOD% 2.66%, and MC% 94.8%. The last two parameters are within the silver standard concerning data quality. (4) Conclusions. Our study revealed an ascending trend of cervical cancer incidence, more consistent for adenocarcinoma, in the context of a newly introduced screening program and partially due to the improvement of the quality of case reporting at the Cancer Registry from Cluj.

A Phase Ib Study of Indirect Immunization with Oregovomab and Toll-like-Receptor-3 Stimulation with Hiltonol® in Patients with Recurrent Platinum-Resistant Ovarian Cancer

Objectives: This phase Ib study assessed the safety and compatibility of indirect oregovomab immunization and Toll-like-receptor-3 (TLR3) stimulation with immune adjuvant Hiltonol® (poly-ICLC) and induced clinically relevant CA125-specific anti-tumor immunity in heavily pretreated patients with progressive platinum-resistant ovarian cancer (PROC). Methods: Patients with elevated serum CA125 level >50 U/mL received four intravenous infusions with 2 mg oregovomab followed by 2 mg Hiltonol® intramuscular 30 min and 48 h post-oregovomab at weeks 0, 3, 6, and 9. At week 12, imaging was performed, and salvage chemotherapy was allowed post-progression per the investigator’s discretion. The Fifth/final oregovomab with Hiltonol® infusion was given at week 16. Results: Fifteen enrolled patients were analyzed for safety and efficacy. Thirteen (87%) patients completed at least three Hiltonol® infusions with oregovomab, specifically, two cycles (n = 2), three cycles (n = 2), four cycles (n = 3), and five cycles (n = 8). Adverse events included mild fatigue, flu-like symptoms, chills, axillary pain, and injection site discomfort in 13 (87%) patients. Serious adverse events were reported in seven (47%) patients, including Grade 3 hypertension (n = 2), thrombocytopenia (n = 1), and Grade 3 events attributed to underlying disease (n = 4). Ten (67%) patients had disease progression, three (20%) had stable disease, and two were unevaluable. Early humoral response by week 6 was observed in seven of nine (77%) patients, median progression-free survival was 2.7 months (95% confidence interval [CI]: 2.2, 3.3), and median overall survival was 15.0 months (95% CI: 8.2–23.9). Conclusions: The safety and compatibility of combining oregovomab with Hiltonol® have been demonstrated in this study. The potential to enhance activity of chemotherapy using oregovomab indirect immunization and Hiltonol® stimulation is proposed.

The -124C>T Mutation of the TERT Promoter Indicates Favorable Prognosis in Ovarian Clear Cell Carcinoma: A Single Institutional Study in China

Background: Ovarian clear cell carcinoma (OCCC) is characterized by chemoresistance and poor prognosis in advanced or recurrent cases. This study aimed to find specific prognostic markers for OCCC. Methods: We analyzed 169 OCCC patients for clinicopathological features. TERT promoter and PIK3CA mutations were assessed by Sanger sequencing, and immunohistochemistry for ARID1A, HDAC6, Cyclin E1, and p53 was performed on tissue microarrays. Survival analysis was conducted using Kaplan–Meier and Cox regression models. Results: The -124C>T TERT promoter mutation was associated with longer OS and PFS and was an independent predictor of favorable OS. This mutation correlated with lower CA125 levels and higher SNP frequency. p53 mutations indicated advanced disease, bilateral tumors, reduced Cyclin E1, and poor prognosis. Low HDAC6 expression was linked to worse PFS. Mutual exclusivity was observed between PIK3CA exon 20 mutations and SNPs. Conclusions: The -124C>T TERT promoter mutation may serve as a favorable prognostic marker in OCCC, while p53 mutations and reduced HDAC6 expression are associated with poor outcomes.

Incidence and Predictors of Acute Kidney Injury Following Advanced Ovarian Cancer Cytoreduction at a Tertiary UK Centre: An Exploratory Analysis and Insights from Explainable Artificial Intelligence

Background/Objectives: The incidence of acute kidney injury (AKI) following advanced epithelial ovarian cancer (EOC) surgery has not been extensively studied. This study aimed to investigate the incidence of AKI and identify preoperative and intraoperative predictors in patients undergoing advanced EOC cytoreduction using both traditional statistics and Artificial Intelligence (AI) modelling. Methods: Retrospective data were collected for 134 patients with a suspected or confirmed diagnosis of advanced EOC (FIGO Stage III–IV) who underwent surgical cytoreduction between January 2021 and December 2022 at a UK tertiary referral centre. AKI was diagnosed according to the KDIGO criteria. Data on 22 patient variables were extracted, including age, Charlson Comorbidity Index (CCI), procedure length, surgical complexity, and length of hospital stay. Logistic regression analysis was used for feature selection to identify AKI predictors, and an extreme gradient boost (XGBoost) model was applied to all variables related to AKI events. Results: The incidence of postoperative AKI was 6.72% (n=9). Predictive factors for AKI included younger age (OR = 0.942, p=0.037), lower CCI (OR = 0.415, p=0.015), longer procedure duration (OR = 1.006, p=0.019), and greater surgical effort (OR = 1.427, p=0.007). Patients with perioperative AKI experienced a doubling in the length of hospital stay (p=0.008). Mortality rates were similar between patients with and without AKI. AI-driven algorithms highlighted the complexity of AKI prediction and provided individual risk profiles, enabling future stratification and prompting different frequencies of AKI monitoring following cytoreduction. Conclusions: Predicting AKI is a complex task. This study found a lower-than-expected incidence of AKI following advanced EOC cytoreductive surgery. AKI is linked to heightened surgical risk-taking, underscoring the need for improved guidelines focusing on postoperative monitoring for targeted patients. Artificial Intelligence offers the potential for personalized AKI prediction.

Does an Autoimmune Disorder Following Ovarian Cancer Diagnosis Affect Prognosis?

We investigated whether developing an autoimmune disorder (AID) following a high-grade epithelial ovarian cancer diagnosis improves overall survival. This retrospective study included data from women treated for high-grade serous, endometrioid, or transitional cell ovarian, fallopian tube, or peritoneal cancer FIGO stage III or IV at a Swiss cantonal gynecological cancer center (2008–2023). We used Kaplan–Meier estimates and the Cox proportional hazards model using time-varying covariates for the survival function estimation. In all, 9 of 128 patients developed an AID following a cancer diagnosis. The median time from cancer diagnosis to AID was 2 years (IQR 2–5). These women survived for a median of 3031 days (IQR 1765–3963) versus 972 days (IQR 568–1819) for those who did not develop an AID (p = 0.001). The median overall survival of nine women with a pre-existing AID was 1093 days (IQR 716–1705), similar to those who never had an AID. The multivariate analyses showed older age (p = 0.003, HR 1.04, 95% CI 1.013–1.064) was associated with a poorer prognosis, and developing an AID after a cancer diagnosis was associated with longer survival (p = 0.033, HR 0.113, 95% CI 0.015–0.837). Clinical manifestations of autoimmune disorders following ovarian cancer diagnoses were associated with better overall survival (8 versus 2.7 years), indicating an overactive immune response may improve cancer control.

Neuroendocrine Carcinomas of the Uterine Cervix, Endometrium, and Ovary Show Higher Tendencies for Bone, Brain, and Liver Organotrophic Metastases

Neuroendocrine carcinoma (NEC) of the female genital tract is a rare and aggressive subtype of cancer that is still poorly understood. Several recent studies reported that pulmonary and gastroenteropancreatic neuroendocrine neoplasms show significantly different patterns of metastasis compared to non-NECs of the same primary sites. The aim of this study was to evaluate the metastatic patterns of gynecologic NECs and to compare the metastatic patterns of NECs and non-NECs of the same primary sites. We retrieved and analyzed cervical, endometrial, and ovarian NEC cases from the Surveillance, Epidemiology, and End Results (SEER) database. To validate the results, we also retrieved and analyzed cervical NEC cases from an institutional database. Uterine cervical NEC was the most common NEC. The overall metastatic rate was significantly higher in the NEC group than in the non-NEC group for all three primary sites. All cervical, endometrial, and ovarian NECs showed a higher tendency for bone, brain, and liver organotrophic metastasis than non-NECs of the same primary sites. We demonstrated that gynecologic NECs show significantly different metastatic patterns compared to non-NECs of the same primary sites. These findings might help clinicians to better manage patients with gynecologic NECs.

Prediction of Postoperative Pathologic Risk Factors in Cervical Cancer Patients Treated with Radical Hysterectomy by Machine Learning

Pretherapeutic serological parameters play a predictive role in pathologic risk factors (PRF), which correlate with treatment and prognosis in cervical cancer (CC). However, the method of pre-operative prediction to PRF is limited and the clinical availability of machine learning methods remains unknown in CC. Overall, 1260 early-stage CC patients treated with radical hysterectomy (RH) were randomly split into training and test cohorts. Six machine learning classifiers, including Gradient Boosting Machine, Support Vector Machine with Gaussian kernel, Random Forest, Conditional Random Forest, Naive Bayes, and Elastic Net, were used to derive diagnostic information from nine clinical factors and 75 parameters readily available from pretreatment peripheral blood tests. The best results were obtained by RF in deep stromal infiltration prediction with an accuracy of 70.8% and AUC of 0.767. The highest accuracy and AUC for predicting lymphatic metastasis with Cforest were 64.3% and 0.620, respectively. The highest accuracy of prediction for lymphavascular space invasion with EN was 59.7% and the AUC was 0.628. Blood markers, including D-dimer and uric acid, were associated with PRF. Machine learning methods can provide critical diagnostic prediction on PRF in CC before surgical intervention. The use of predictive algorithms may facilitate individualized treatment options through diagnostic stratification.

Risk Factors for Recurrence in Serous Borderline Ovarian Tumors and Early-Stage Low-Grade Serous Ovarian Carcinoma

Background: Tumor recurrence significantly impacts the quality of life and fertility of patients with serous borderline ovarian tumors (SBOT) and early-stage low-grade serous ovarian carcinoma (LGSOC). This study aims to characterize recurrence patterns, identify independent risk factors for recurrence, and develop a nomogram to predict recurrence-free survival (RFS). Methods: We conducted a retrospective case-control study to investigate recurrence in patients undergoing fertility-sparing surgery (FSS) and radical surgery (RS). Logistic regression and Cox regression were used to identify risk factors. Kaplan–Meier analysis was applied to evaluate RFS. A nomogram was developed based on identified variables to predict RFS. Results: Tumor capsule disruption and micropapillary were associated with higher recurrence risk in the FSS group. Non-invasive implants were associated with higher recurrence risk in the RS group. The nomogram prediction model was developed based on identified risk factors. The area under the curve (AUC) for RFS predictions was 0.74 (95% CI: 0.62–0.85) at 3 years and 0.78 (95% CI: 0.67–0.89) at 5 years for the FSS group and 0.87 (95% CI: 0.76–0.98) at 3 years and 0.81 (95% CI: 0.65–0.97) at 5 years for the RS group. Conclusions: We identified the risk factors for recurrence of SBOT and early-stage LGSOC following FSS and RS procedures and developed a predictive model for forecasting RFS. This model provides valuable guidance for patients and clinicians in predicting recurrence risk for patients.

Antibody–Drug Conjugates: A Start of a New Era in Gynecological Cancers

Antibody–drug conjugates (ADCs) are a new class of therapeutic agents designed to target specific antigens on tumor cells, combining the specificity of monoclonal antibodies with the cytotoxicity of chemotherapy agents. ADCs have been available for over a decade, but in gynecological cancers, these agents are relatively new with great promise ahead. More than 80% of ongoing trials in gynecological cancers are evaluating ADCs’ safety and efficacy, of which 40% are early-phase trials. Around twenty ADCs are currently under investigation, either alone or in combination with chemotherapies or immune checkpoint inhibitors. Among them, mirvetuximab soravtansine has been recently approved by the Food and Drug Administration (FDA) in platinum-resistant ovarian cancer with high folate-α receptor expression, as a single agent or in combination. Tisotumab vedotin and trastuzumab deruxtecan are also now approved by the FDA in patients with pre-treated cervical and uterine cancers and further investigation is ongoing. Overall, the toxicity profiles of ADCs are acceptable. Ocular toxicity is one of the specific side effects of some ADCs, but most of the cases are manageable with the use of prophylactic steroids and dose adjustments. This review aims to provide an overview of the fundamental and operational features of ADCs and examine the latest and most promising data, with a particular focus on the Canadian viewpoint.

Impacts of Self-Esteem and Self-Perceived Burden on Health-Related Quality of Life Among Patients with Ovarian Cancer: Does Age Matter?

Background: Ovarian cancer, the most lethal gynecologic malignancy, is characterized by a poor health-related quality of life (HRQoL). The present study examined the mediating role of self-perceived burden (SPB) in the impact of self-esteem on HRQoL and whether age moderated the associations among ovarian cancer patients. Methods: 203 patients effectively completed the Functional Assessment of Cancer Therapy-General (FACT-G), Rosenberg Self-Esteem Scale, and SPB scale, respectively. For the FACT-G, physical (PWB), social/family (SFWB), emotional (EWB), and functional well-being (FWB) were scored separately. Results: Significant mediation of SPB in the impacts of self-esteem on PWB (a × b = 0.074, 95% CI: 0.018, 0.153), EWB (a × b = 0.048, 95% CI: 0.001, 0.125), and FWB (a × b = 0.056, 95% CI: 0.009, 0.114) were revealed. Age positively moderated the impact of self-esteem on SPB (β = 0.159, p < 0.05), and the associations of SPB with PWB (β = 0.173, p < 0.05) and EWB (β = 0.240, p < 0.01), indicating a moderated mediation. Conclusions: Ovarian cancer patients’ self-esteem could improve the PWB, EWB, and FWB domains of HRQoL by reducing SPB. Age could attenuate SPB’s mediation in the impacts of self-esteem on PWB and EWB, indicating stronger impacts in younger patients. Clinical programs integrating components that strengthen self-esteem and reduce SPB may be particularly beneficial for younger women with ovarian cancer.

Magnesium Depletion Score as a Prognostic Indicator in Endometrial Cancer: A Retrospective Cohort Study

Magnesium is essential for cellular metabolism, and its deficiency has been associated with adverse outcomes in various cancers. The MDS, which considers factors such as diuretic and proton pump inhibitor use, alcohol consumption, and kidney function, is a practical indicator of Mg deficiency. This retrospective cohort study assessed 200 patients with EC treated between 2010 and 2024 to explore the prognostic value of MDS. Patients were divided into low (0–1), intermediate (2), and high (≥3) MDS risk categories. Higher MDSs were significantly associated with older age, comorbid conditions, hypertension, diabetes, and reduced serum magnesium and vitamin D levels (all p < 0.001). Kaplan–Meier analysis revealed that patients with high MDSs experienced notably shorter overall and progression-free survival than those with lower scores. Multivariate Cox regression analysis identified age, tumor grade, lymphovascular invasion, and stage as independent prognostic factors, excluding those for MDS. These results indicate that although MDS is associated with comorbidities, biochemical deficiencies, and poorer unadjusted survival, it does not independently predict the prognosis of EC. The MDS could be a straightforward and cost-effective tool for identifying metabolically vulnerable patients, especially among the elderly, and merits further validation in prospective studies.

Current Limitations of Sentinel Node Biopsy in Vulvar Cancer

Background: Vulvar cancer is a rare gynecologic malignancy with increasing incidence. Lymph node status is the most critical prognostic factor, traditionally assessed through inguinofemoral lymphadenectomy, a procedure associated with significant morbidity. Sentinel lymph node biopsy (SLNB), in selected cases, has emerged as a less invasive alternative with favorable oncologic outcomes. Objective: This review summarizes current evidence on the indications, technique, safety, and oncologic outcomes of SLNB in vulvar cancer, with a focus on controversial scenarios such as recurrent and larger tumors. Methods: A narrative review of PubMed-indexed studies published in English over the last 35 years was conducted. Eligible studies included original research, systematic reviews, meta-analyses, randomized controlled trials, and case-control studies. Results: SLNB is recommended for unifocal vulvar tumors < 4 cm with stromal invasion > 1 mm and clinically negative nodes. Landmark trials, including GROINSS-V-I and GOG-173, confirmed its accuracy and lower morbidity compared to lymphadenectomy. SLNB utilization has increased since its inclusion in guidelines, with a concurrent decline in lymphadenectomy rates. Combined detection techniques are mandatory, while indocyanine green (ICG) is an emerging option. Future studies should focus on refining patient selection criteria, improving detection techniques, and clarifying the implications of low-volume nodal disease to further optimize outcomes for patients with vulvar cancer. Conclusion: SLNB is a validated, minimally invasive staging approach in early-stage vulvar cancer. Further research is needed to refine its role in high-risk cases and optimize detection methods.

Dysregulation of Cholesterol Homeostasis in Ovarian Cancer

Cholesterol plays an essential role in maintaining the rigidity of cell membranes and signal transduction. Various investigations confirmed empirically that the dysregulation of cholesterol homeostasis positively correlates with tumor progression. More specifically, recent studies suggested the distinct role of cholesterol in ovarian cancer cell proliferation, metastasis and chemoresistance. In this review, we summarize the current findings that suggest the contribution of cholesterol homeostasis dysregulation to ovarian cancer progression and resistance to anti-cancer agents. We also discuss the therapeutic implications of cholesterol-lowering drugs in ovarian cancer.

Bevacizumab Treatment for Low-Grade Serous Ovarian Cancer: A Systematic Review

Serous epithelial ovarian cancer, classified as either high-grade (90%) or low-grade (10%), varies in molecular, histological, and clinicopathological presentation. Low-grade serous ovarian cancer (LGSOC) is a rare histologic subtype that lacks disease-specific evidence-based treatment regimens. However, LGSOC is relatively chemo-resistant and has a poor response to traditional treatments. Alternative treatments, including biologic therapies such as bevacizumab, have shown some activity in LGSOC. Thus, the objective of this systematic review is to determine the effect and safety of bevacizumab in the treatment of LGSOC. Following PRISMA guidelines, Medline ALL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase all from the OvidSP platform, ClinicalTrials.gov, International Clinical Trials Registry Platform, International Standard Randomised Controlled Trial Number Registry were searched from inception to February 2022. Articles describing bevacizumab use in patients with LGSOC were included. Article screening, data extraction, and critical appraisal of included studies were completed by two independent reviewers. The effect of bevacizumab on the overall response rate, progression-free survival, overall survival, and adverse effects were summarized. The literature search identified 3064 articles, 6 of which were included in this study. A total of 153 patients were analyzed; the majority had stage IIIC cancer (56.2%). The overall median response rate reported in the studies was 47.5%. Overall, bevacizumab is a promising treatment for LGSOC, with response rates higher than traditional treatment modalities such as conventional chemotherapy, and is often overlooked as a treatment tool. A prospective clinical trial evaluating the use of bevacizumab in LGSOC is necessary to provide greater evidence and support these findings.

Vulvar Metastasis in Renal Cell Carcinoma: A Case Report Highlighting the Aggressive Nature of Clear Cell Renal Cell Carcinoma

Vulvar cancer is one of the rarest gynecological malignancies. The development of this condition can be associated with either dysplasia linked to human papillomavirus (HPV), primarily affecting younger women, or vulvar dermatoses such as lichen sclerosus, which predominantly affect older women. Over the last decade, the incidence of vulvar cancer has risen by 0.6% annually, while the relative survival rate has declined. Although metastasis to the vulva is uncommon, it can occur, particularly from cancers in nearby organs such as the cervix, bladder, rectum, or anus. More rarely, metastases from breast cancer and renal cell carcinoma have been reported in the vulva. Vaginal metastases from clear cell renal carcinoma are especially rare. In this article, we present the case of a 56-year-old patient diagnosed with clear cell renal carcinoma, who came to our clinic with a lesion on the right labia, which was identified as a metastasis originating from the kidney. Given the rarity of genital metastases in renal cancer, such cases should be examined and discussed to encourage further research and studies.

HPV Self-Sampling for Cervical Cancer Screening in Under-Screened Saskatchewan Populations: A Pilot Study

Of all cancers in female Canadians, the most rapidly increasing incidence is that of cervical cancer. The objective of this pilot study was to assess how HPV self-sampling might improve cervical cancer screening participation in both urban and rural settings in Saskatchewan, one of the most sparsely populated provinces in Canada. Study groups consisted of n = 250 participants to whom self-swabbing kits were mailed with instructions and n = 250 participants to whom kits were handed out in 6 urban and rural clinics. The inclusion criteria selected subjects aged 30–69 years who were Saskatchewan residents for at least 5 years with valid health coverage, had a cervix, and had no record of cervical cancer screening in 4 years. The returned samples were analyzed for specific HPV strains using the Roche Molecular Diagnostics Cobas 4800® System. The overall response rate was ~16%, with the response to the handout distribution being roughly double that of the mailout. While HPV positivity did not differ across the distribution groups, participants at a specific inner-city clinic reported significantly higher positivity to at least one HPV strain as compared to any other clinic and all mailouts combined. For this high-risk population, in-person handout of self-sampling kits may be the most effective means of improving screening.

The Consistency and Quality of ChatGPT Responses Compared to Clinical Guidelines for Ovarian Cancer: A Delphi Approach

Introduction: In recent years, generative Artificial Intelligence models, such as ChatGPT, have increasingly been utilized in healthcare. Despite acknowledging the high potential of AI models in terms of quick access to sources and formulating responses to a clinical question, the results obtained using these models still require validation through comparison with established clinical guidelines. This study compares the responses of the AI model to eight clinical questions with the Italian Association of Medical Oncology (AIOM) guidelines for ovarian cancer. Materials and Methods: The authors used the Delphi method to evaluate responses from ChatGPT and the AIOM guidelines. An expert panel of healthcare professionals assessed responses based on clarity, consistency, comprehensiveness, usability, and quality using a five-point Likert scale. The GRADE methodology assessed the evidence quality and the recommendations’ strength. Results: A survey involving 14 physicians revealed that the AIOM guidelines consistently scored higher averages compared to the AI models, with a statistically significant difference. Post hoc tests showed that AIOM guidelines significantly differed from all AI models, with no significant difference among the AI models. Conclusions: While AI models can provide rapid responses, they must match established clinical guidelines regarding clarity, consistency, comprehensiveness, usability, and quality. These findings underscore the importance of relying on expert-developed guidelines in clinical decision-making and highlight potential areas for AI model improvement.

An Overview of Endometrial Cancer with Novel Therapeutic Strategies

Endometrial cancer (EC) stands as the most prevalent gynecologic malignancy. In the past, it was classified based on its hormone sensitivity. However, The Cancer Genome Atlas has categorized EC into four groups, which offers a more objective and reproducible classification and has been shown to have prognostic and therapeutic implications. Hormonally driven EC arises from a precursor lesion known as endometrial hyperplasia, resulting from unopposed estrogen. EC is usually diagnosed through biopsy, followed by surgical staging unless advanced disease is expected. The typical staging consists of a hysterectomy with bilateral salpingo-oophorectomy and sentinel lymph node biopsies, with a preference placed on a minimally invasive approach. The stage of the disease is the most significant prognostic marker. However, factors such as age, histology, grade, myometrial invasion, lymphovascular space invasion, tumor size, peritoneal cytology, hormone receptor status, ploidy and markers, body mass index, and the therapy received all contribute to the prognosis. Treatment is tailored based on the stage and the risk of recurrence. Radiotherapy is primarily used in the early stages, and chemotherapy can be added if high-grade histology or advanced-stage disease is present. The risk of EC recurrence increases with advances in stage. Among the recurrences, vaginal cases exhibit the most favorable response to treatment, typically for radiotherapy. Conversely, the treatment of widespread recurrence is currently palliative and is best managed with chemotherapy or hormonal agents. Most recently, immunotherapy has emerged as a promising treatment for advanced and recurrent EC.

BRCA1/2 Mutation Types Do Not Affect Prognosis in Ovarian Cancer Patients

Background: High grade serous ovarian carcinoma (HGSOC) is the most lethal type of epithelial ovarian cancer, with a prevalence of germline BRCA1/2 mutations as high as 20%. Our objective is to determine whether the location of mutations in the different domains of the BRCA1/2 genes affects the clinical outcome of HGSOC patients. Methods: A total of 51 women with BRCA1 or BRCA2 mutated ovarian cancer were identified. Progression-free survival (PFS) and overall survival (OS) were analyzed. Results: In our study cohort, 35 patients were carriers of germline mutations in BRCA1 and 16 in BRCA2. The median PFS time following completion of the primary therapy was 23.8 months (95% CI 20.1–27.5) and the median OS was 92.9 months (95% CI 69.8–116.1) in all BRCA carriers. After multivariate analysis, no significant association among the location or type of BRCA1/2 mutation with PFS or OS was identified. Notably, significant differences in PFS between carriers of identical mutations in the same BRCA gene were detected. Conclusions: Among HGSOC patients, BRCA1/2 carriers with mutations in different locations of the genes show no significant difference in survival outcomes, in terms of PFS and OS, suggesting the potential effect of other genetic abnormalities and co-contributing risk factors.

Omental Macrophagic “Crown-like Structures” Are Associated with Poor Prognosis in Advanced-Stage Serous Ovarian Cancer

The tumor microenvironment is a well-recognized framework in which immune cells present in the tumor microenvironment promote or inhibit cancer formation and development. A crown-like structure (CLS) has been reported as a dying or dead adipocyte surrounded by a ‘crown’ of macrophages within adipose tissue, which is a histologic hallmark of the inflammatory process in this tissue. CLSs have also been found to be related to formation, progression and prognosis of some types of cancer. However, the presence of CLSs in the omentum of advanced-stage high-grade serous ovarian carcinoma (HGSOC) has not been thoroughly investigated. By using CD68, a pan-macrophage marker, and CD163, an M2-like polarization macrophage marker, immunohistochemistry (IHC) was performed to identify tumor-associated macrophages (TAMs) and CLSs. This retrospective study analyzed 116 patients with advanced-stage HGSOC who received complete treatment and had available clinical data from July 2008 through December 2016 at National Cheng Kung University Hospital (NCKUH) (Tainan, Taiwan). Based on multivariate Cox regression analysis, patients with omental CD68+ CLSs had poor OS (median survival: 24 vs. 38 months, p = 0.001, hazard ratio (HR): 2.26, 95% confidence interval (CI): 1.41–3.61); patients with omental CD163+ CLSs also had poor OS (median survival: 22 vs. 36 months, HR: 2.14, 95%CI: 1.33–3.44, p = 0.002). Additionally, patients with omental CD68+ or CD163+ CLSs showed poor PFS (median survival: 11 vs. 15 months, HR: 2.28, 95%CI: 1.43–3.64, p = 0.001; median survival: 11 vs. 15 months, HR: 2.17, 95%CI: 1.35–3.47, respectively, p = 0.001). Conversely, the density of CD68+ or CD163+ TAMs in ovarian tumors was not associated with patient prognosis in advanced-stage HGSOC in our cohort. In conclusion, we, for the first time, demonstrate that the presence of omental CLSs is associated with poor prognosis in advanced-stage HGSOC.

Management of the Elderly Patients with High-Grade Serous Ovarian Cancer in the REAL-WORLD Setting

Treatment of elderly patients with neoplasia is challenging. Age is a known prognostic factor in ovarian cancer but the optimal treatment of elderly patients has not been determined. We undertook a retrospective analysis to determine clinical practice in advanced-stage ovarian cancer patients older than 70 years of age. Methods: Medical records of women with high-grade serous ovarian cancer, stage III and IV were retrospectively analyzed. Results: A total of 735 patients were identified with a median age of 61.5 years. 22.4% among them were older than 70 years of age at diagnosis. First-line Progression-Free Survival (PFS) and Overall Survival (OS) were significantly worse in elderly patients in comparison to the younger ones [mPFS 11.3 months vs. 14.8 months, (p < 0.001) and mOS 30.2 months vs. 45.6 months (p < 0.001)]. However, elderly patients were characterized by worse ECOG-Performance Status and they were more frequently treated with Neoadjuvant Chemotherapy followed by Interval Debulking Surgery, while often they were more frequently denied debulking surgery compared to patients under 70 years of age. Moreover, elderly patients received more frequently monotherapy with platinum as frontline treatment. In contrast, there was no significant difference in the outcome of the debulking surgery in comparison to the younger patients or the frequency that gBRCA test was performed. Age over 70 years did not retain its significance for either Progression-Free Survival or Overall Survival when adjusted for all other reported prognostic factors. Conclusions: Elderly ovarian cancer patients have a worse prognosis. Comprehensive geriatric assessment should be performed for the optimal treatment of these patients.

Stratification of Length of Stay Prediction following Surgical Cytoreduction in Advanced High-Grade Serous Ovarian Cancer Patients Using Artificial Intelligence; the Leeds L-AI-OS Score

(1) Background: Length of stay (LOS) has been suggested as a marker of the effectiveness of short-term care. Artificial Intelligence (AI) technologies could help monitor hospital stays. We developed an AI-based novel predictive LOS score for advanced-stage high-grade serous ovarian cancer (HGSOC) patients following cytoreductive surgery and refined factors significantly affecting LOS. (2) Methods: Machine learning and deep learning methods using artificial neural networks (ANN) were used together with conventional logistic regression to predict continuous and binary LOS outcomes for HGSOC patients. The models were evaluated in a post-hoc internal validation set and a Graphical User Interface (GUI) was developed to demonstrate the clinical feasibility of sophisticated LOS predictions. (3) Results: For binary LOS predictions at differential time points, the accuracy ranged between 70–98%. Feature selection identified surgical complexity, pre-surgery albumin, blood loss, operative time, bowel resection with stoma formation, and severe postoperative complications (CD3–5) as independent LOS predictors. For the GUI numerical LOS score, the ANN model was a good estimator for the standard deviation of the LOS distribution by ± two days. (4) Conclusions: We demonstrated the development and application of both quantitative and qualitative AI models to predict LOS in advanced-stage EOC patients following their cytoreduction. Accurate identification of potentially modifiable factors delaying hospital discharge can further inform services performing root cause analysis of LOS.

Surgical Management for Transposed Ovarian Recurrence of Cervical Cancer: A Systematic Review with Our Experience

In early-stage cervical cancer, ovarian metastasis is relatively rare, and ovarian transposition is often performed during surgery. Although rare, the diagnosis and surgical approach for recurrence at transposed ovaries are challenging. This study focused on the diagnosis and surgical management of transposed ovarian recurrence in cervical cancer patients. A 45-year-old premenopausal woman underwent radical hysterectomy, bilateral salpingectomy, and pelvic lymphadenectomy following postoperative concurrent chemoradiotherapy for stage IB1 cervical cancer. During the initial surgery, the ovary was transposed to the paracolic gutter, and no postoperative complications were observed. Ovarian recurrence was diagnosed using positron emission tomography–computed tomography, and a laparoscopic bilateral oophorectomy was performed. A systematic review identified nine women with transposed ovarian recurrence with no other metastases of cervical cancer, and no studies have discussed the optimal surveillance of transposed ovaries. Of those (n = 9), four women had died of the disease within 2 years of the second surgery, and the prognosis of transposed ovarian cervical cancer seemed poor. Nevertheless, three women underwent laparoscopic oophorectomies, none of whom experienced recurrence after the second surgery. Few studies have examined the surgical management of transposed ovarian recurrence. The optimal surgical approach for transposed ovarian recurrence of cervical cancer requires further investigation.

Referral, Genetic Counselling, and BRCA Testing in the Manitoba High-Grade Serous Ovarian Cancer Population, 2004–2019

(1) Background: The primary objective of this study was to examine the rate of genetic referral, BRCA testing, and BRCA positivity amongst all patients with high-grade serous ovarian cancers (HGSOC) from 2004–2019. The secondary objective was to analyze secondary factors that may affect the rates of referral and testing. (2) Methods: This population-based cohort study included all women diagnosed with HGSOC using the Manitoba Cancer Registry, CervixCheck registry, Medical Claims database at Manitoba Health, the Hospital Discharge abstract, the Population Registry, and Winnipeg Regional Health Authority genetics data. Data were examined for three different time cohorts (2004–2013, 2014–2016; 2017–2019) correlating to practice pattern changes. (3) Results: A total of 944 patients were diagnosed with HGSOC. The rate of genetic referrals changed over the three timeframes (20.0% → 56.7% → 36.6%) and rate of genetic testing increased over the entire timeframe. Factors found to increase rates of referral and testing included age, histology, history of oral contraceptive use, and family history of ovarian cancer. Prior health care utilization indicators did not affect genetic referral or testing. (4) Conclusion: The rate of genetic referral (2004–2016) and BRCA1/2 testing (2004–2019) for patients with a diagnosis of HGSOC increased over time. A minority of patients received a consultation for genetics counselling, and even fewer received testing for a BRCA1/2. Without a genetic result, it is difficult for clinicians to inform treatment decisions. Additional efforts are needed to increase genetics consultation and testing for Manitoban patients with HGSOC. Effects of routine tumour testing on rates of genetic referral will have to be examined in future studies.

New Targeted Therapies and Combinations of Treatments for Cervical, Endometrial, and Ovarian Cancers: A Year in Review

This review of the meaningful data from 2021 on cervical, endometrial, and ovarian cancers aims to provide an update of the most clinically relevant studies presented at important oncologic congresses during the year (the American Society of Clinical Oncology (ASCO) Annual Meeting, the European Society for Medical Oncology (ESMO) Congress and the Society of Gynecologic Oncology (SGO) Annual Meeting). Despite the underlying existence of the COVID-19 pandemic, the last year has been notable in terms of research, with significant and promising advances in gynecological malignancies. Several major studies reporting the effects of innovative therapies for patients with cervical, endometrial, and ovarian cancers might change the medical practice in the future.

Risk-Reducing Options for High-Grade Serous Gynecologic Malignancy in BRCA1/2

Ovarian cancer (OC) is the leading cause of death among women with gynecologic malignancy. Breast Cancer Susceptibility Gene 1 (BRCA 1) and Breast Cancer Susceptibility Gene 2 (BRCA 2) germline mutations confer an estimated 20 to 40 times increased risk of OC when compared to the general population. The majority of BRCA-associated OC is identified in the late stage, and no effective screening method has been proven to reduce mortality. Several pharmacologic and surgical options exist for risk-reduction of gynecologic malignancy in BRCA 1/2 mutation carriers. This review summarizes up-to-date research on pharmacologic risk-reducing interventions, including the oral contraceptive pill, acetylsalicylic acid/nonsteroidal anti inflammatory drugs (ASA/NSAID) therapy, and denosumab, and surgical risk-reducing interventions, including risk-reducing bilateral salpingo-oophorectomy, salpingectomy with delayed oophorectomy, and hysterectomy at the time of risk-reducing bilateral salpingo-oophorectomy.

Growing Teratoma Syndrome with Synchronous Gliomatosis Peritonei during Chemotherapy in Ovarian Immature Teratoma: A Case Report and Literature Review

Coexistent growing teratoma syndrome (GTS) and gliomatosis peritonei (GP) arising during chemotherapy of ovarian immature teratoma (IMT) is extremely rare and can be misdiagnosed as recurrent or progressive disease. We present a 33-year-old woman diagnosed with GTS with synchronous GP during chemotherapy of IMT. She underwent ovarian cystectomy due to ovarian immature teratoma and chemotherapy were administered. The α-fetoprotein (AFP) concentration decreased from 28.7 ng/mL to normal after the second cycle. Four days after the third cycle of chemotherapy, ultrasound and CT revealed an 8-cm mass with negative tumor markers in the pouch of Douglas. An exploratory laparotomy was conducted, and a smooth round cystic-solid 8-cm mass was noted in the pouch of Douglas. Extensive peritoneal seeding glial nodules were also observed on the surface of the uterus, peritoneum, and omentum. The patient underwent a partial omentectomy, intact resection of the tumor, and resection of most of the glial nodules. Postoperative pathology demonstrated a pure mature cystic teratoma component in the mass, as well as diffuse GP involving the uterine serosa, peritoneum, and omentum; this diagnosis of GTS with synchorous GP should be considered in IMT patients with mass newly identified during chemotherapy while tumor markers are normal after treatment.

Patterns of First-Line Systemic Therapy Delivery and Outcomes in Advanced Epithelial Ovarian Cancer in Ontario

Background: First-line treatment of epithelial ovarian cancer (EOC) consists of a combination of cytoreductive surgery and platinum-based chemotherapy. Recently, targeted therapies such as bevacizumab have been shown to improve oncologic outcomes in a subset of a high-risk population. The objective of this study is to evaluate the patterns of practice and outcomes of first-line systemic treatment of advanced EOC, focusing on the adoption of bevacizumab. Methods: A population cohort study was conducted using administrative data in Ontario, Canada. Patients diagnosed with advanced stage non-mucinous EOC between 2014 and 2018 were identified. Datasets were linked to obtaining information on first-line treatment including surgery, systemic therapy, providers of care, systemic therapy facilities, and acute care utilization (emergency department (ED) visits and hospitalizations) during systemic treatment. Multivariate logistic regression was used to determine factors associated with systemic therapy utilization. Results: Among 3726 patients with advanced EOC, 2838 (76%) received chemotherapy: 1316 (47%) received neoadjuvant chemotherapy, 1060 (37%) underwent primary cytoreductive surgery followed by chemotherapy, and 462 (16%) received chemotherapy only. The median age was 67 (range: 20–100). Most chemotherapies were prescribed by gynecologic oncologists (60%) and in level 1 academic cancer centres (58%). Only 54 patients (3.1%) received bevacizumab in the first-line setting after its approval in Ontario in 2016. Bevacizumab was more likely to be administered by medical oncologists compared to gynecologic oncologists (OR 3.95, 95% CI 2.11–7.14). In total, 1561 (55%) and 1594 (56%) patients had at least one ED visit and/or hospitalization during systemic treatment, respectively. The most common reasons for ED visits were fever and bowel obstruction. Conclusion: Patterns of care for EOC in Ontario differed between care providers. The uptake of bevacizumab for first-line treatment of EOC was low. Acute care utilization related to EOC was high.

Is There a Survival Benefit of Adjuvant Chemotherapy in Stage IC1 Epithelial Ovarian Cancer Patients? A Meta-Analysis

The purpose of the present systematic review is to clarify whether adjuvant chemotherapy improves survival rates in women with stage IC1 ovarian cancer. We searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar. We considered comparative observational studies and randomized trials that investigated survival outcomes (progression-free (PFS) and overall survival (OS)) among women with intraoperative rupture of early-stage epithelial ovarian cancer who received adjuvant chemotherapy and those that did not. Eleven studies, which recruited 7556 patients, were included. The risk of bias was defined as moderate after assessment with the Risk of Bias in non-Randomized Trials tool. Meta-analysis was performed with RStudio. Seven studies investigated the impact of adjuvant chemotherapy on recurrence-free survival of patients experiencing intraoperative cyst rupture for otherwise stage I ovarian cancer. The outcome was not affected by the use of adjuvant chemotherapy as the effect estimate was not significant (HR 1.24, 95% CI 0.74, 2.04). The analysis of data from 5 studies similarly revealed that overall survival rates were comparable among the two groups (HR 0.75, 95% CI 0.54, 1.05). This meta-analysis did not detect any benefit from adjuvant chemotherapy for stage IC ovarian cancer patients with cyst rupture. However, conclusions from this investigation are limited by a study population which included multiple histologic subtypes, high and low grade tumors and incompletely staged patients.

Promising Therapeutic Impact of a Selective Estrogen Receptor Downregulator, Fulvestrant, as Demonstrated In Vitro upon Low-Grade Serous Ovarian Carcinoma Cell Lines

Few studies have reported hormonal agent use in the treatment of low-grade serous ovarian carcinomas (LGSOCs), which are chemoresistant. Considering the need for novel effective therapies, we investigated the hormone receptor expression and hormonal inhibition efficacy in LGSOCs. Using immunohistochemistry, we assessed the estrogen receptor (ER) expression status in 33 cases of histologically confirmed serous ovarian tumors, including 10, 11, and 12 cases of LGSOCs, serous borderline tumors (SBTs), and serous cystadenomas (SCAs), respectively. The genetic background reported in our previous study was used in the current study. MPSC1 cells, which were established from LGSOCs, were used in cell proliferation assays. We observed a higher ER expression in LGSOCs and SBTs than in SCAs (70%, 81%, and 50%, respectively). Thus, LGSOCs and SBTs exhibit higher ER expression than SCAs. Moreover, the PIK3CA mutation positively correlated with ER expression in LGSOCs (p = 0.0113). MPSC1 cells showed low ER expression on Western blotting. MPSC1 cell proliferation was significantly inhibited by fulvestrant (a selective ER downregulator). The activation of ER and PI3K/AKT signaling pathways may play an important role in LGSOC carcinogenesis. ER downregulation with fulvestrant or combination therapy with PI3K inhibitors is a possible novel treatment for patients with LGSOCs.

A Pan-Canadian Consensus Statement on First-Line PARP Inhibitor Maintenance for Advanced, High-Grade Serous and Endometrioid Tubal, Ovarian, and Primary Peritoneal Cancers

The majority of patients with advanced, high-grade epithelial-tubo ovarian cancer (EOC) respond well to initial treatment with platinum-based chemotherapy; however, up to 80% of patients will experience a recurrence. Poly(ADP-ribose) Polymerase (PARP) inhibitors have been established as a standard of care maintenance therapy to prolong remission and prevent relapse following a response to first-line platinum-chemotherapy. Olaparib and niraparib are the PARP inhibitors currently approved for use in the first-line maintenance setting in Canada. Selection of maintenance therapy requires consideration of patient and tumour factors, presence of germline and somatic mutations, expected drug toxicity profile, and treatment access. This paper discusses the current clinical evidence for first-line PARP inhibitor maintenance therapy in patients with advanced, high-grade EOC and presents consensus statements and a treatment algorithm to aid Canadian oncologists on the selection and use of PARP inhibitors within the Canadian EOC treatment landscape.

Mutation Profiles of Ovarian Seromucinous Borderline Tumors in Japanese Patients

Ovarian seromucinous tumors (SMBTs) are relatively rare, and their carcinogenesis is largely unknown. In this study, the molecular features of SMBTs in Japan are assessed. DNA was extracted from microdissected paraffin-embedded sections from 23 SMBT cases. Genetic mutations (KRAS, BRAF, PIK3CA, and ERBB2) were evaluated using Sanger sequencing. Immunohistochemistry for p53, ARID1A, and PTEN was also performed as a surrogate for the loss of functional mutations in these tumor suppressor genes. The prevalence of KRAS, BRAF, PIK3CA, and ERBB2 mutations was 4.3% (1/23), 8.6% (2/23), 8.6% (2/23), and 17.3% (4/23), respectively. Overexpression or loss of p53 expression occurred in 26% (6/23), loss of ARID1A expression in 4.3% (1/23), and none of the cases showed expression of PTEN loss. These findings suggest that KRAS/BRAF/PIK3CA and PTEN mutations are rare carcinogenic events in SMBTs. The high frequency of positive p53 staining and a low frequency of loss of ARID1A staining suggests that SMBT carcinogenesis may be related to the alteration of p53 rather than that of ARID1A. ERBB2 oncogenic mutations may play an important role in the tumorigenesis of Japanese SMBTs.

Patient Experience with a Gynecologic Oncology-Initiated Genetic Testing Model for Women with Tubo-Ovarian Cancer

Background: Up to 20% of women diagnosed with tubo-ovarian carcinoma carry a germline pathogenic variant in a cancer-predisposing gene (e.g., BRCA1/BRCA2). Identifying these variants can help to inform eligibility for therapies, guide surveillance and prevention of new primary cancers, and assess risk to family members. The Gynecologic Oncology-Initiated Genetic Testing Model (GOIGT) was initiated at the McGill University Health Centre (MUHC) to streamline universal germline genetic testing for this population, while addressing the limited resources in the public healthcare system. This study aimed to evaluate the patient experience of participating in this model. Methods: Study participants were patients diagnosed with high-grade non-mucinous epithelial tubo-ovarian cancer who underwent genetic testing through the GOIGT model between 1 January 2017 and 31 December 2020. Eligible participants completed the retrospective questionnaires at least one month after result disclosure. Results: A total of 126 patients were tested through the GOIGT model during the study period, of which 56 were invited to participate. Thirty-four participants returned the study questionnaire. Overall, participants did not report decision regret following the genetic testing and were satisfied with the GOIGT model. Participants reported low levels of uncertainty and distress related to the implications of their test results for themselves and their family members. Conclusions: The results of this study support the continued implementation of mainstreamed genetic testing models for women with high-grade non-mucinous tubo-ovarian cancer. Further studies are required to compare experiences for patients with different genetic test results.

Serology-Based Model for Personalized Epithelial Ovarian Cancer Risk Evaluation

This study aimed to establish a prognosis-prediction model based on serological indicators in patients with epithelial ovarian cancer (EOC). Patients initially diagnosed as ovarian cancer and surgically treated in Fudan University Shanghai Cancer Center from 2014 to 2018 were consecutively enrolled. Serological indicators preoperatively were collected. A risk model score (RMS) was constructed based on the levels of serological indicators determined by receiver operating characteristic curves. We correlated this RMS with EOC patients’ overall survival (OS). Finally, 635 patients were identified. Pearson’s χ2 results showed that RMS was significantly related to clinical parameters. Kaplan–Meier analysis demonstrated that an RMS less than 3 correlated with a longer OS (p < 0.0001). Specifically, significant differences were perceived in the survival curves of different subgroups. Multivariate Cox analysis revealed that age (p = 0.015), FIGO stage (p = 0.006), ascites (p = 0.015) and RMS (p = 0.005) were independent risk factors for OS. Moreover, RMS combined with age, FIGO and ascites could better evaluate for patients’ prognosis in DCA analyses. Our novel RMS-guided classification preoperatively identified the prognostic subgroups of patients with EOC and showed higher accuracy than the conventional method, meaning that it could be a useful and economical tool for tailored monitoring and/or therapy.

What Should Be the Topics of a Prospective Study on Ovarian Masses in Children?—Results of a Multicenter Retrospective Study and a Scoping Literature Review

Purpose: to determine management problems of ovarian masses in girls in order to form a baseline for prospective randomized studies of the established topics and quality improvement of our management. Materials and Methods: We performed a national analysis of clinical aspects of ovarian masses in girls operated on in Poland, analyzed retrospectively medical files of all consecutive patients aged 0–18 who underwent surgeries for ovarian lesions between 2012 and 2017 at 17 pediatric surgical departments and complemented the analysis with a scoping review of a recent primary research related to ovarian masses in children. Results: The study group comprised 595 patients. Forty-four (7.39%) girls were diagnosed with malignant tumors. The overall preservation rate was 64.54%. The analysis revealed that positive tumor markers (OR = 10.3), lesions larger than 6 cm (OR = 4.17) and solid mass on ultrasound examination (OR = 5.34) are interdependent variables differentiating malignant tumors from non-malignant lesions (X42 = 79.1; p = 0.00000). Our scoping review revealed 10 major branches of research within the topic of ovarian masses in pediatric population. Conclusions: We have developed an overview of the field with the emphasis on the local environment. Our next step is a multi-institutional prospective study of a quality improvement project implementation based on the obtained knowledge.

Case Report of Small Cell Carcinoma of the Ovary, Hypercalcemic Type (Ovarian Rhabdoid Tumor) with SMARCB1 Mutation: A Literature Review of a Rare and Aggressive Condition

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive condition that is associated with the SMARCA4 mutation and has a dismal prognosis. It is generally diagnosed in young women. Here, we report a case of a young woman with SCCOHT harboring a rare molecular finding with a highly aggressive biological behavior. The patient had a somatic SMARCB1 mutation instead of an expected SMARCA4 alteration. Even though the patient was treated with high-dose chemotherapy followed by stem cell transplantation, she evolved with disease progression and died 11 months after her first symptoms appeared. We present a literature review of this rare disease and discuss the findings in the present patient in comparison to expected molecular alterations and options for SCCOHT treatment.

Safety Profile of Niraparib as Maintenance Therapy for Ovarian Cancer: A Systematic Review and Meta-Analysis

Background: Patients with epithelial ovarian cancer (EOC), treated with niraparib maintenance, present with haematological and gastrointestinal toxicities. Limited data exist on niraparib safety assessment. Objective: To evaluate niraparib safety profile, as maintenance therapy, in women with platinum-sensitive EOC. Methods: PubMed and Cochrane searches were carried out up to April 2021 for randomised controlled trials (RCTs) evaluating niraparib versus placebo in EOC patients with a response to platinum-based chemotherapy. Regarding the meta-analysis, for dichotomous data, the pooled risk ratio (RR) was calculated. Results: A total of 1539 patients from three RCTs revealed that niraparib-treated patients are associated with a significantly higher risk of any grade of nausea (RR, 2.15; 95% CI, 1.86 to 2.48), fatigue (RR, 1.26; 95% CI, 1.05 to 1.52, p < 0.00001), anemia (RR, 6.86; 95% CI, 2.54 to 18.52, p = 0.0001), thrombocytopenia (RR, 7.02; 95% CI, 1.68 to 29.38, p < 0.00001), vomiting (RR, 2.51; 95% CI, 1.50 to 4.19, p = 0.0005), neutropenia (RR, 2.96; 95% CI, 1.13 to 7.73, p < 0.00001), headache (RR, 2.08; 95% CI, 1.57 to 2.74, p < 0.00001), constipation (RR, 2.10; 95% CI, 1.72 to 2.57, p < 0.00001) and insomnia (RR, 2.48; 95% CI, 1.52 to 2.89, p = 0.0003) when compared with placebo. For grade 3 or 4 adverse effects, significantly higher risk was only noted for fatigue (RR,6.25; 95% CI, 1.70 to 23.05, p = 0.006), anemia (RR, 16.23; 95% CI, 4.86 to 54.17, p < 0.00001), thrombocytopenia (RR, 35.12; 95% CI, 12.23 to 100.82, p < 0.00001) and neutropenia episodes (RR, 6.35; 95% CI, 2.08 to 19.39, p = 0.001) for those taking niraparib. Notably, incidents of adverse effects and discontinuation rates were substantially lower among patients treated with an individualised niraparib dose than those treated with the standard one. Efficacy was not reduced, and no treatment-related deaths occurred during the included trials. Conclusion: Niraparib is considered an effective and well-tolerated choice, with an improved safety profile, for the maintenance treatment of EOC patients.

Cancer Screening Interventions in Indigenous Populations: A Rapid Review

Cancer screening is an important component of a cancer control strategy. Indigenous people in Canada have higher incidence rates for many types of cancer, including those that can be detected early or prevented through organized screening programs. Increased participation and retention in cancer screening is critical to improved population health outcomes amongst Indigenous people. This rapid review evaluates cancer screening interventions published in the last six years. Included studies demonstrated increased participation in breast, colorectal, or cervical cancer screening programs in Indigenous populations or showed promise of increased participation based on the factors that influence people’s screening practices, such as knowledge, attitude, or intent to screen. The Preferred Reporting Items for Systematic Reviews guided the search strategy. The review identified 85 articles with 12 meeting the specified criteria: seven studies reported an increase in cancer screening participation and five studies reported improved knowledge, attitude, or intent to screen. The use of multiple culturally appropriate strategies in co-designed studies were the most effective. This review will be used to inform First Nations (FN) populations and Screening Programs in Alberta of potential strategies to address disparities identified through a recent data analysis comparing cancer screening and outcomes between FN and non-FN people.

Role of Age, Comorbidity, and Frailty in the Prediction of Postoperative Complications After Surgery for Vulvar Cancer: A Retrospective Cohort Study with the Development of a Nomogram

Surgery is the cornerstone of vulvar cancer treatment, but it is associated with a significant risk of complications that may impact prognosis, particularly in older patients with multiple comorbidities. The objective of this study was to evaluate the role of age, comorbidities, and frailty in predicting postoperative complications after vulvar cancer surgery and to develop a predictive nomogram. A retrospective cohort study was conducted, including patients who underwent surgery for vulvar cancer at two Italian institutions from January 2018 to December 2023. A logistic regression model for the rate of Clavien-Dindo 2+ 30-days complications was run, considering the age-adjusted Charlson Comorbidity Index (AACCI), body mass index (BMI), and frailty as exposures. Lesion characteristics and surgical procedures were considered as confounders. Among the 225 included patients, 50 (22.2%) had a grade 2+ complication. The predictive score of the nomogram ranged from 44 to 140. The AACCI (0–64 points) and BMI (0–100 points) were independently associated with a risk of complications. A nomogram including the AACCI and BMI predicts the risk of complications for patients undergoing surgery for vulvar cancer. The preoperative determination of the risk of complications enables surgical planning and allows a tailored peri- and postoperative management plan.

Extramammary Paget’s Disease of the Vulva and Concomitant Premalignant/Malignant Vulvar Lesions: A Potential Challenge in Diagnosis and Treatment

The aim of the present study was to evaluate the incidence of concomitant vulvar cancers or premalignant lesions in women surgically treated for extramammary Paget’s disease of the vulva (EMPDV) through a multicenter case series. The medical records of all women diagnosed with and treated for EMPDV from January 2010 to December 2020 were retrospectively analyzed. Women with EMPDV and synchronous vulvar cancer, vulvar intraepithelial neoplasia (VIN) and/or lichen sclerosus (LS) at the histology report were included in the study. A total of 69 women eligible for the present study were considered. Concomitant vulvar lesions occurred in 22 cases (31.9%). A total of 11 cases of synchronous VIN (50%) and 14 cases (63.6%) of concomitant LS were observed. One patient (4.5%) had synchronous vulvar SCC (FIGO stage 1B). Women with EMPDV and concomitant premalignant/malignant vulvar lesions had a significantly higher rate of invasive EMPDV and wider lesions with an extravulvar involvement. The specific meaning of the association between EMPDV, VIN, SCC and LS remains unclear. The potential overlapping features between different vulvar lesions highlight the importance of dedicated gynecologists and pathologists in referral centers.

Performance of Indocyanine Green Compared to 99mTc-Nanocolloids for Sentinel Lymph Node Detection in Early Vulvar Cancer

Study objective: The aim of this study was to evaluate the performance of indocyanine green (ICG) compared to that of the gold standard 99mtechnetium (99mTc-nanocolloids) in detecting sentinel lymph nodes (SLN) in early vulvar cancer. Material and Methods: A single-center retrospective cohort study comparing SLN detection by 99mTc-nanocolloids and ICG was performed in patients presenting early vulvar cancer (T1/2), with clinically negative nodes. All SLN showing a radioactive and/or fluorescent signal were resected. The primary endpoints were the sensitivity, positive predictive value (PPV) and false negative (FN) rate of ICG in detecting SLN compared to 99mTc-nanocolloids. Results: Thirty patients were included and 99 SLN were identified in 43 groins. Compared to 99mTc-nanocolloids, ICG had a sensitivity of 80.8% (95% CI [72.6; 88.6%]), a PPV of 96.2% (95% CI [91.8; 100%]) and a FN rate of 19.1% in detecting SLN. Seventeen (17.1%) infiltrated (positive) SLN were identified out of the 99 SLN detected. Compared to 99mTc-nanocolloids, ICG showed a sensitivity of 82.3% (95% CI [73.1; 91.5%]), a PPV of 100% and a FN rate of 17.6% (3/17) in detecting infiltrated SLN. Conclusion: Despite its many advantages, ICG cannot be used as the sole tracer for the detection of SLN in early vulvar cancer and should be employed in conjunction with 99mTc-nanocolloids.

PD-1 Inhibitor Maintenance Therapy Combined Iodine-125 Seed Implantation Successfully Salvage Recurrent Cervical Cancer after CCRT: A Case Report

Cervical cancer is the fourth most common cancer in females worldwide. Patients with stage III and IV cervical cancer based on the Federation of Gynecology and Obstetrics (FIGO) classification have higher recurrence rates. Because of organs at risk (OAR) protection and the low indication rate of salvage surgery, the choice of treatment is always challenging. Systemic chemotherapy is palliative and can be performed in conjunction with surgery or radiotherapy; however, it has no significant benefit to survival. Brachytherapy and stereotactic body radiotherapy (SBRT) are characterized by extremely high radiation doses applied to tumor cells while sparing the normal tissues. Several studies have investigated the efficacy of these technologies in recurrent cervical cancer and showed promising results. The immune checkpoint inhibitors approach was also investigated and showed promising results too. Herein, we report a case of a patient with cervical cancer that recurred five months after adjuvant chemotherapy and concurrent chemoradiotherapy. The disease prognosis after interstitial implantation brachytherapy (IIB) was determined. Then, the patient underwent radioactive 125I-seed implantation combined with PD-1 inhibitor treatment. The patient exhibited a partial response after seed implantation, and up to now, the duration of this partial response was 24 months.

Detection of Cervical Cancer Cells in Whole Slide Images Using Deformable and Global Context Aware Faster RCNN-FPN

Cervical cancer is a worldwide public health problem with a high rate of illness and mortality among women. In this study, we proposed a novel framework based on Faster RCNN-FPN architecture for the detection of abnormal cervical cells in cytology images from a cancer screening test. We extended the Faster RCNN-FPN model by infusing deformable convolution layers into the feature pyramid network (FPN) to improve scalability. Furthermore, we introduced a global contextual aware module alongside the Region Proposal Network (RPN) to enhance the spatial correlation between the background and the foreground. Extensive experimentations with the proposed deformable and global context aware (DGCA) RCNN were carried out using the cervical image dataset of “Digital Human Body” Vision Challenge from the Alibaba Cloud TianChi Company. Performance evaluation based on the mean average precision (mAP) and receiver operating characteristic (ROC) curve has demonstrated considerable advantages of the proposed framework. Particularly, when combined with tagging of the negative image samples using traditional computer-vision techniques, 6–9% increase in mAP has been achieved. The proposed DGCA-RCNN model has potential to become a clinically useful AI tool for automated detection of cervical cancer cells in whole slide images of Pap smear.

Cytochrome 4Z1 Expression Is Correlated with Poor Prognosis in Patients with Cervical Cancer

Background: cervical cancer is one of the most common malignancies in women worldwide and its management remains challenging and complex. As Cytochrome4Z1 (CYP4Z1) is overexpressed in many tumours, its expression in cervical cancer is unknown. Therefore, the present study aimed to evaluate CYP4Z1 expression in cervical cancers. Methods: CYP4Z1 expression was immunohistochemically assessed in 100 cases of cervical cancers along with ten normal cervix tissues, and the enzyme’s relationship to several clinicopathological features and survival was explored. Results: CYP4Z1 was strongly expressed in 55% of cervical cancer patients. Normal cervix samples were negative for CYP4Z1 expression. Importantly, this expression was significantly found in patients with the late stage of the disease, lymph node metastasis, and high tumour invasion (p < 0.05). Interestingly, CYP4Z1 expression was significantly correlated with shorter survival times of cervical cancer patients. Univariate analysis showed that CYP4Z1 expression, tumour stage, lymph node metastasis, and tumour invasion were significantly correlated with patient survival (p < 0.05). The multivariate analysis revealed that only CYP4Z1 expression and tumour stage were significantly correlated with patient survival (p < 0.05). Conclusions: CYP4Z1 expression is associated with cervical cancer patients’ survival and may serve as an independent predictor of poor prognosis in cervical cancer patients.

Designing Inclusive HPV Cancer Vaccines and Increasing Uptake among Native Americans—A Cultural Perspective Review

Despite a global and nationwide decrease, Native Americans continue to experience high rates of cancer morbidity and mortality. Vaccination is one approach to decrease cancer incidence such as the case of cervical cancer. However, the availability of vaccines does not guarantee uptake, as evident in the Coronavirus 2019 pandemic. Therefore, as we consider current and future cancer vaccines, there are certain considerations to be mindful of to increase uptake among Native Americans such as the incidence of disease, social determinants of health, vaccine hesitancy, and historical exclusion in clinical trials. This paper primarily focuses on human papillomavirus (HPV) and potential vaccines for Native Americans. However, we also aim to inform researchers on factors that influence Native American choices surrounding vaccination and interventions including cancer therapies. We begin by providing an overview of the historical distrust and trauma Native Americans experience, both past and present. In addition, we offer guidance and considerations when engaging with sovereign Tribal Nations in vaccine development and clinical trials in order to increase trust and encourage vaccine uptake.

Radiation-Induced Emesis (RIE) in Extended-Field Radiotherapy for Gynecological Malignancies: Dosimetric and Non-Dosimetric Factors

Radiation-induced emesis (RIE) is usually noted during abdominal-pelvic radiotherapy. In gynecological malignancies, it is usually noted in para-aortic but not whole-pelvic irradiation. Irradiated small bowel (SB) may be associated with RIE. The significance of SB dosimetry remains unclear. Dosimetric and non-dosimetric factors were evaluated and correlated with RIE in 45 patients with gynecological malignancies undergoing extended-field radiotherapy (EFRT) (median 45 Gy) from 2006 to 2021. Early-onset RIE (within 72 h after the first fraction of EFRT) was noted in 10 of 12 RIE patients. RIE was significantly associated with the SB mean dose. The RIE rates were 58.3% and 15.2% (p = 0.007) in patients with a low (<63%) and high (≥63%) SB mean dose. Logistic regression revealed that the SB mean dose remained the independent factor of overall RIE (p = 0.049) and early-onset RIE (p = 0.014). Therefore, constraint of the SB mean dose limited to less than 63% of the prescribed dose is suggested to decrease RIE.

3q26 Amplifications in Cervical Squamous Carcinomas

Background: Squamous carcinomas of the uterine cervix often carry mutations of the gene encoding for the catalytic sub-unit of kinase PI3K, PIK3CA. The locus of this gene at chromosome 3q26 and neighboring loci are also commonly amplified. The landscape of 3q26-amplified cases have not been previously characterized in detail in cervical cancer. Methods: Published genomic data and associated clinical data from TCGA cervical cancer cohort were analyzed at cBioportal for amplifications in genes at 3q26. The clinical and molecular characteristics of the group of patients with 3q26 amplifications was compared with the group without 3q26 amplifications. Comparative prevalence of amplification and expression of genes at 3q26 in amplified squamous cervical cancer cases were surveyed as well as 3q26 amplifications in cervical cancer cell line databases. Results: Amplification of 3q26 locus is a prevalent molecular lesion in cervical squamous cell carcinomas encountered in about 15% of cases in TCGA cohort of 247 patients. Cancer-related genes commonly amplified from 3q26 include PIK3CA, TBL1XR1, DCUN1D1, SOX2, MECOM, PRKCI, and TERC. Amplified cases do not completely overlap with PIK3CA mutant cases. Differences exist between 3q26-amplified and non-amplified carcinomas in the frequency of mutations and frequency of other amplifications. Most commonly over-expressed genes in 3q26 amplified cases include PIK3CA, TBL1XR1, DCUN1D1, and less commonly SOX2 and PRKCI. Conclusion: The subset of squamous cervical carcinomas with 3q26 amplifications is not overlapping with cancers carrying PIK3CA mutations and contains, besides PIK3CA, other cancer-associated genes that are over-expressed at the mRNA level, including TBL1XR1 and DCUN1D1. DCUN1D1, a regulator of SCF ubiquitin ligase activity, may be a relevant pathogenic player given the importance of ubiquitination and the proteasome in the disease. These observations could form the basis for therapeutic exploitation in this subset of squamous cervical carcinomas.

Evaluation of Surgical Approaches and Use of Adjuvant Radiotherapy with Respect to Oncologic Outcomes in the Management of Clinically Early-Stage Cervical Carcinoma

The standard of care for early-stage cervix cancer is radical hysterectomy with pelvic lymphadenectomy. Adjuvant radiotherapy (RT) or chemoradiotherapy may be administered to reduce the risk of recurrence in patients considered to be at elevated risk based on a combination of pathologic factors. We performed a retrospective review to determine oncologic outcomes in patients treated for early-stage cervix cancer and to determine if surgical approach impacted oncologic outcomes or the decision to use adjuvant therapy. In total, 174 women underwent radical hysterectomy and pelvic lymphadenectomy over the 15-year period. Most of these women (146) had open surgery and 28 had minimally invasive surgery (MIS). In total, 81 had adjuvant pelvic RT; 76 in the open surgery group (52%) and 5 in the MIS group (18%). Five-year PFS and OS, respectively, were 84% and 91%. Five-year PFS was significantly lower in patients who had MIS vs. open surgery, without a difference in 5-year OS, suggesting MIS should be avoided. Five-year PFS was the same with RT or with its omission, despite those treated with RT having higher risk disease. We have demonstrated excellent outcomes in patients with early-stage cervix cancer after primary surgery and selective use of RT, with few recurrences and excellent survival.

CircRNA-Based Cervical Cancer Prognosis Model, Immunological Validation and Drug Prediction

Background: Cervical cancer (CC) is a common cancer in female, which is associated with problems like poor prognosis. Circular RNA (circRNA) is a kind of competing endogenous RNA (ceRNA) that has an important role in regulating microRNA (miRNA) in many cancers. The regulatory mechanisms of CC immune microenvironment and the transcriptome level remain to be fully explored. Methods: In this study, we constructed the ceRNA network through the interaction data and expression matrix of circRNA, miRNA and mRNA. Meanwhile, based on the gene expression matrix, CIBERSORT algorithm was used to reveal contents of tumor-infiltrating immune cells (TIICs). Then, we screened prognostic markers based on ceRNA network and immune infiltration and constructed two nomograms. In order to find immunological differences between the high- and low-risk CC samples, we examined multiple immune checkpoints and predicted the effect of PD-L1 ICI immunotherapy. In addition, the sensitive therapeutics for high-risk patients were screened, and the potential agents with anti-CC activity were predicted by Connective Map (CMap). Results: We mapped a ceRNA network including 5 circRNAs, 17 miRNAs and 129 mRNAs. From the mRNA nodes of the network six genes and two kind of cells were identified as prognostic makers for CC. Among them, there was a significant positive correlation between CD8+ T cells and SNX10 gene. The results of TIDE and single sample GSEA (ssGSEA) showed that T cells CD8 do play a key role in inhibiting tumor progression. Further, our study screened 24 drugs that were more sensitive to high-risk CC patients and several potential therapeutic agents for reference. Conclusions: Our study identified several circRNA-miRNA-mRNA regulatory axes and six prognostic genes based on the ceRNA network. In addition, through TIIC, survival analysis and a series of immunological analyses, T cells were proved to be good prognostic markers, besides play an important role in the immune process. Finally, we screened 24 potentially more effective drugs and multiple potential drug compounds for high- and low-risk patients.

The Implementation of a Primary HPV Self-Testing Cervical Screening Program in Malaysia through Program ROSE—Lessons Learnt and Moving Forward

Program ROSE (removing obstacles to cervical screening) is a primary HPV-based cervical screening program that incorporates self-sampling and digital technology, ensuring that women are linked to care. It was developed based on the principles of design thinking in the context of Malaysia. The program illustrates the importance of collaborative partnerships and addressing the multi-faceted barriers from policy changes, and infrastructure readiness to the implementation of a radically new cervical screening program in communities. The paradigm shift in cervical cancer requires a monumental and concerted effort in educating both the healthcare providers and the general public. In this short review, we highlight how Pilot Project ROSE incorporated evidence-based tools that rapidly scaled up to Program ROSE. These ideas and solutions can be adapted and adopted by other countries. Notwithstanding the impact of COVID-19, it is incumbent on countries to pave the road towards the elimination of cervical cancer with pre-existing footpaths.

Factors Affecting the Cervical Cancer Screening Behaviors of Japanese Women in Their 20s and 30s Using a Health Belief Model: A Cross-Sectional Study

In recent years, the incidence and mortality rates of cervical cancer (CC) have increased among young women. Cervical cancer screening (CCS) is crucial to reducing the incidence and mortality of CC in a country such as Japan, where it is challenging to raise HPV vaccination rates. The purpose of this study was to identify psychological and personal characteristics relating to CCS participation among young people by using the Health Belief Model (HBM). For this cross-sectional study, an internet survey was conducted between February–March 2018. Based on HBM and personal characteristics, χ2 tests and logistic analyses were used to identify factors influencing CCS. Responses obtained from 816 women in their 20s and 30s were used in the analysis. For HBM-based psychological characteristics, the odds ratios were significantly higher for “cues to participation in screening” and “barriers to participation at the time of cancer screening”, while “barriers to participation before cancer screening” showed significantly lower odds ratios. On the other hand, it was found that the presence of children and having regular health checkups affected the attributes of screening that were significant for decision-making. Therefore, it is important to create proactive measures to encourage younger women to undergo medical examinations.

Neoadjuvant Chemotherapy in Pregnant Patients with Cervical Cancer: A Monocentric Retrospective Study

Background: To date, little and discordant data still exists on the management of cervical cancer (CC) during pregnancy. In this paper, we report our experience of the treatment of these patients analyzing the oncologic, obstetric, and neonatal outcomes. Methods: Between January 2010 and December 2021, 13 patients were diagnosed with CC during pregnancy. All patients underwent platinum-based neoadjuvant chemotherapy (NACT) and 11/13 patients underwent a cesarean radical hysterectomy (CRH). Results: All 13 patients were diagnosed with squamous-cell carcinoma, FIGO-2018 stage between IB2-IIIC1. The majority of patients had a partial (61.5%) or complete (15.4%) response to NACT. Most patients had a regular course of pregnancy and the obstetric complications observed were gestational diabetes mellitus in 23.1% and IUGR in 15.4% of cases. CRH was performed in the absence of major complications. Only 2 patients (15.4%) had disease recurrence and only 1 patient (7.7%) died of disease. All children are currently healthy. At birth, we observed mainly prematurity-related complications (38.5% respiratory distress syndrome and 7.7% neonatal jaundice) and only a case of congenital malformation (hypospadias). In our pediatric population, we reported a case of malignancy (acute myeloid leukemia). Conclusion: NACT seems to be safe and efficacious in controlling tumor burden during pregnancy. CRH following NACT appears to be feasible, avoiding repeated surgery and treatment delays. This approach is also reasonably safe from a maternal, obstetric, and neonatal point of view.

A Case for Offering HPV Self-Sampling to Well-Screened Women. Comment on Lesack et al. Willingness to Self-Collect a Sample for HPV-Based Cervical Cancer Screening in a Well-Screened Cohort: HPV FOCAL Survey Results. Curr. Oncol. 2022, 29, 3860–3869

Lesack et al. recently published a cross-sectional study that focused on human papillomavirus (HPV) self-sampling in the screened population, a population not conventionally thought of for HPV self-sampling. They found 52% of well-screened, highly educated women who participated in the Human Papillomavirus For Cervical Cancer (HPV FOCAL) screening trial in British Columbia, Canada, would be willing to self-collect an HPV sample. We published a similar study in 2021 on well-screened, highly educated women affiliated with a family medicine clinic in Edmonton, Alberta, Canada, and found that 60% of these women preferred to have the option of HPV self-sampling. Our findings reinforce Lesack et al.’s results and together provide evidence for offering HPV self-sampling as an option for the well-screened population.

Re-Irradiation for Recurrent Cervical Cancer: A State-of-the-Art Review

The recurrence rate of cervical cancer after primary treatment can reach 60%, and a poor prognosis is reported in most cases. Treatment options for the recurrence of cervical cancer mainly depend on the prior treatment regimen and the location of recurrent lesions. Re-irradiation is still considered as a clinical challenge, owing to a high incidence of toxicity, especially in in-field recurrence within a short period of time. Recent advances in radiotherapy have preliminarily revealed encouraging outcomes of re-irradiation. Several centers have concentrasted on stereotactic body radiation therapy (SBRT) for the treatment of well-selected cases. Meanwhile, as the image-guiding techniques become more precise, a better dose profile can also be achieved in brachytherapy, including high-dose-rate interstitial brachytherapy (HDR-ISBT) and permanent radioactive seed implantation (PRSI). These treatment modalities have shown promising efficacy with a tolerable toxicity, providing further treatment options for recurrent cervical cancer. However, it is highly unlikely to draw a definite conclusion from all of those studies due to the large heterogeneity among them and the lack of large-scale prospective studies. This study mainly reviews and summarizes the progress of re-irradiation for recurrent cervical cancer in recent years, in order to provide potential treatment regimens for the management of re-irradiation.

Is There a Place for Adjuvant Chemotherapy in the Treatment of Locally Advanced Cervical Cancer?

Findings on the efficacy of adjuvant chemotherapy (ACT) of locally advanced cervical cancer (LACC) after the concurrent chemoradiation (CCRT) therapy were inconsistent, and the OUTBACK trial was expected to shed some light regarding the topic. Its results on ACT in LACC were negative, with the conclusion of not to use it. The objective of this review was to present the inconsistencies of previous studies, along with the OUTBACK trial in more detail, and to rethink whether its results provide an unambiguous and definite answer to the optimal position of ACT in the treatment of LACC. To critically appraise the OUTBACK trial and understand the consequences of its results, we used only randomized controlled studies (RCTs) on ACT in LACC that have been included in high-quality systematic reviews and meta-analyses. We calculated the pooled prediction intervals using a random effects meta-analysis of all published randomized studies including the OUTBACK trial. After combining the OUTBACK trial with the results of four previous randomized trials, the pooled hazard ratio for overall survival benefit of CCRT + ACT was 0.95 (95% CI 0.75; 1.20). The pooled hazard ratio of the four previous trials was 1.00 (95% CI 0.69; 1.44). The OUTBACK trial improved the precision of the pooled estimate, but the clinical heterogeneity and the consequent prediction intervals are still very wide, and with 95% reliability, we can expect that if the new study, using a similar approach to the ACT, on a randomly selected patient population from the presented five trials is conducted, its hazard ratio for overall survival after ACT would be between 0.47 and 1.93. In conclusion, there is an absolute need for further research in order to optimally define the position of ACT in the treatment of LACC.

Significance of the Number and the Location of Metastatic Lymph Nodes in Locally Recurrent or Persistent Cervical Cancer Patients Treated with Salvage Hysterectomy plus Lymphadenectomy

We retrospectively investigated the significance of metastatic lymph nodes in patients with locally recurrent or persistent cervical cancer in a previously irradiated field and subsequently had salvage hysterectomy. Clinical data were obtained from a chart review, and the prognostic impact of the presence, number (1–2 versus ≥3), and location (pelvic versus pelvic plus para-aortic) of lymph node metastasis was investigated by comparing recurrence and survival. In total, 50 patients were included in this study, of which 21 (42.0%) showed pathological evidence of lymph node metastasis (node-positive group). Both the univariate and multivariate analyses showed that lymph node metastasis was an independent prognostic factor for postoperative recurrence (hazard ratio (HR) 5.36; 95% CI 1.41–6.66; p = 0.0020). The predominant sites of recurrence after salvage surgery were the visceral organs and lymph nodes in the node-negative and node-positive groups, respectively. Patients with ≥3 node metastases showed similar survival to those with 1–2 node metastases. Patients with pelvic node metastasis showed similar survival to those with pelvic and para-aortic node metastases. The presence, not number or location, of lymph node metastasis was an independent poor prognostic factor for post-operative recurrence in patients who developed locally recurrent or persistent cervical cancer treated with salvage hysterectomy plus lymphadenectomy.

Willingness to Self-Collect a Sample for HPV-Based Cervical Cancer Screening in a Well-Screened Cohort: HPV FOCAL Survey Results

Self-collection may provide an opportunity for innovation within population-based human papillomavirus (HPV) cervical cancer screening programs by providing an alternative form of engagement for all individuals. The primary objective was to determine willingness to self-collect a vaginal sample for primary HPV screening and factors that impact willingness in individuals who participated in the Human Papillomavirus For Cervical Cancer (HPV FOCAL) screening trial, a large randomized controlled cervical screening trial. A cross-sectional online survey was distributed between 2017 and 2018 to 13,176 eligible participants exiting the FOCAL trial. Bivariate and multivariable logistic regression assessed factors that influence willingness to self-collect on 4945 respondents. Overall, 52.1% of respondents indicated willingness to self-collect an HPV sample. In multivariable analysis, the odds of willingness to self-collect were significantly higher in participants who agreed that screening with an HPV test instead of a Pap test was acceptable to them (odds ratio (OR): 1.45 (95% confidence interval (CI): 1.15, 1.82), those who indicated that collecting their own HPV sample was acceptable to them (p < 0.001), and those with higher educational ascertainment (OR: 1.31, 95% CI: 1.12, 1.54). The findings offer insight into the intentions to self-collect in those already engaged in screening, and can inform cervical cancer screening programs interested in offering alternative approaches to HPV-based screening.

HPV Vaccination: An Underused Strategy for the Prevention of Cancer

Human papillomavirus (HPV) vaccination prevents cervical, head and neck, and anogenital cancers. However, global HPV vaccine coverage falls short of global targets and has seen unexpected and dramatic declines in some countries. This paper synthesizes the impact of HPV on the global burden of cancer and the potential benefit of HPV vaccination. Approximately 5% of the world’s cancers are specifically attributed to HPV. While the greatest global burden of HPV is cervical cancers in low- and middle-income countries, HPV-associated head and neck cancers are increasing in high-income countries and have surpassed cervical cancer as the primary HPV-associated cancer in some countries. Therefore, it is also critical to improve gender-neutral HPV vaccination. Understanding the modifiable drivers of vaccine acceptance and uptake is important for increasing HPV vaccination. The Behavioural and Social Drivers of Vaccination framework is broadly applied to identify key factors associated with HPV vaccination including domains concerning practical issues, motivation, social processes, and thinking and feeling. Among the behavioural strategies available to reduce the incidence and mortality of cancer, increasing HPV vaccination stands out as having unrealized potential to prevent disease, financial cost, and psychological distress. An understanding of the shifting burden of HPV and the factors associated with vaccination can be leveraged to regularly measure these factors, develop interventions to promote vaccine uptake, and improve global HPV vaccine coverage. Future research in diverse contexts is necessary to investigate the barriers and facilitators of global HPV vaccination.

The Effect of Surgeon Volume on the Outcome of Laser Vaporization: A Single-Center Retrospective Study

Although laser vaporization is a popular minimally invasive treatment for cervical intraepithelial neoplasia (CIN), factors influencing CIN recurrence are understudied. Moreover, the effect of surgeon volume on patients’ prognosis after laser vaporization for CIN is unknown. This single-center retrospective study evaluated the predictive value of surgeon volume and patient characteristics for laser vaporization outcomes in women with pathologically confirmed CIN2. Histologically confirmed CIN2 or higher grade after laser vaporization was defined as persistent or recurrent. Various patient characteristics were compared between women with and those without recurrence to examine the predictive factors for laser vaporization. There were 270 patients with a median age of 36 (18–60) years. The median follow-up period was 25 (6–75.5) months and the median period between treatment and persistence or recurrence was 17 (1.5–69) months. The median annual number of procedures for all seven surgeons was 7.8. There were 38 patients (14.1%) with persistent or recurrent lesions—24 had CIN2, 13 had CIN3, and one had adenocarcinoma in situ. Patient age, body mass index, surgeon volume, and history of prior CIN treatment or invasive cervical cancer were not significantly correlated with lesion persistence or recurrence. In conclusion, laser vaporization has comparable success rates and is a feasible treatment for both low- and high-volume surgeons.

Minimally Invasive Surgery for Cervical Cancer in Light of the LACC Trial: What Have We Learned?

Cervical cancer is the most common gynecologic malignancy and the fourth most common cancer in women worldwide. Over the last two decades, minimally invasive surgery (MIS) emerged as the mainstay in the surgical management of cervical cancer, bringing advantages such as lower operative morbidity and shorter hospital stay compared to open surgery while maintaining comparable oncologic outcomes in numerous retrospective studies. However, in 2018, a prospective phase III randomized controlled trial, “Laparoscopic Approach to Carcinoma of the Cervix (LACC)”, unexpectedly reported that MIS was associated with a statistically significant poorer overall survival and disease-free survival compared to open surgery in patients with early-stage cervical cancer. Various hypotheses have been raised by the authors to try to explain these results, but the LACC trial was not powered to answer those questions. In this study, through an exhaustive literature review, we wish to explore some of the potential causes that may explain the poorer oncologic outcomes associated with MIS, including the type of MIS surgery, the size of the lesion, the impact of CO2 pneumoperitoneum, prior conization, the use of uterine manipulator, the use of protective measures, and the effect of surgical expertise/learning curve.

The Path to Eliminating Cervical Cancer in Canada: Past, Present and Future Directions

Cervical cancer remains a common cancer affecting women in Canada. While cervical cancer incidence and mortality in Canada have declined for several decades due to the success of organized, provincial cervical cancer screening programs, further decreases will require enhancement of primary, secondary, and tertiary prevention efforts. The present commentary provides a historical overview of cervical cancer trends in Canada, presents current statistics on cervical cancer incidence, mortality and survival, and discusses future directions in relation to cervical cancer elimination.

Cervical Cancer Prevention and High-Risk HPV Self-Sampling Awareness and Acceptability among Women Living with HIV: A Qualitative Investigation from the Patients’ and Providers’ Perspectives

Routine cervical cancer screening is important for women living with HIV (WLH) due to the greater incidence and persistence of high-risk HPV (HR-HPV) infection. HR-HPV self-sampling has been proposed to overcome barriers to in-office cervical cancer screening in underserved populations. However, little is known about baseline knowledge of HR-HPV and the acceptability of HR-HPV self-sampling among WLH. This paper describes WLH’s experiences and needs regarding cervical cancer screening, specifically HR-HPV self-sampling, and seeks to reconcile their experiences with the views of their providers. In total, 10 providers and 39 WLH participated in semi-structured interviews and group discussions, respectively. Knowledge of cervical cancer and HR-HPV was generally limited among WLH; when present, it was often due to personal experience of or proximity to someone affected by cervical cancer. Most WLH were not familiar with HR-HPV self-sampling but, despite some of the providers’ skepticism, expressed their willingness to participate in a mail-based HR-HPV self-sampling intervention and highlighted convenience, ease of use, and affordability as facilitators to the uptake of HR-HPV self-sampling. The experiences identified can be used to guide patient-centered communication aimed at improving cervical cancer knowledge and to inform interventions, such as HR-HPV self-sampling, designed to increase cervical cancer screening among under-screened WLH.

microRNA Profile Associated with Positive Lymph Node Metastasis in Early-Stage Cervical Cancer

Lymph node metastasis (LNM) is an important prognostic factor in cervical cancer (CC). In early stages, the risk of LNM is approximately 3.7 to 21.7%, and the 5-year overall survival decreases from 80% to 53% when metastatic disease is identified in the lymph nodes. Few reports have analyzed the relationship between miRNA expression and the presence of LNM. The aim of this study was to identify a subset of miRNAs related to LNM in early-stage CC patients. Formalin-fixed paraffin-embedded tissue blocks were collected from patients with early-stage CC treated by radical hysterectomy with lymphadenectomy. We analyzed samples from two groups of patients—one group with LNM and the other without LNM. Global miRNA expression was identified by microarray analysis, and cluster analysis was used to determine a subset of miRNAs associated with LNM. Microarray expression profiling identified a subset of 36 differentially expressed miRNAs in the two groups (fold change (FC) ≥ 1.5 and p < 0.01). We validated the expression of seven miRNAs; miR-487b, miR-29b-2-5p, and miR-195 were underexpressed, and miR-92b-5p, miR-483-5p, miR-4534, and miR-548ac were overexpressed according to the microarray experiments. This signature exhibited prognostic value for identifying early-stage CC patients with LNM. These findings may help detect LNM that cannot be observed in imaging studies.

Mode of Minimally Invasive Surgery Associated with Venous Thromboembolism Incidence in Gynecologic Cancer Patients

Postoperative venous thromboembolism (VTE) after minimally invasive surgery (MIS) for gynecologic malignancy is uncommon. Our objective was to characterize the rates and identify risk factors of postoperative VTE. A retrospective cohort study of patients undergoing MIS for gynecologic malignancy at three Canadian institutions from 2014 to 2020 was performed. The primary outcome was incidence of VTE within 90 days post-operatively. Descriptive statistics were used for clinicopathologic factors, and univariate analysis compared differences between groups. Rate and 95% confidence interval for VTE per 1000 surgeries were calculated. A total of 1786 patients met inclusion criteria, 85.3% uterine, 11.5% cervical, and 2.3% had ovarian cancer. Modes of surgery included robotic (49.4%), laparoscopic (20.7%), or combined laparoscopic/vaginal (29.9%). There were 15 VTE events at 90 days post-operatively (0.84%). Rates of VTE were lowest in patients who underwent robotic surgery, followed by combined laparoscopic/vaginal, and highest in a laparoscopic approach (p = 0.047). Pelvic lymphadenectomy (p = 0.038) and adjuvant chemotherapy (p = 0.022) were the only significant factors associated with risk of VTE. The incidence of VTE after MIS for gynecologic malignancy is low. Robotic surgery was associated with a lower incidence, although event rates are low, and further research is warranted.

Shifting Survival Horizons in Advanced Ovarian Cancer: A Conditional Survival Perspective

Advanced-stage epithelial ovarian cancer (EOC) is defined by biological heterogeneity and poor outcomes, and traditional survival metrics fail to reflect the evolving nature of prognosis as patients survive longer. This study aimed to evaluate conditional survival (CS) in advanced EOC using both overall survival (OS) and progression-free survival (PFS) metrics to provide a dynamic understanding of long-term outcomes. We retrospectively analyzed 808 patients with FIGO stage III–IV EOC who underwent surgery at Baskent University Ankara Hospital between 2004 and 2024. CS estimates were calculated for additional 1- and 5-year intervals among patients who had already survived 6 months, 1, 3, or 5 years after surgery. Median OS and PFS were 4.37 and 1.70 years, respectively. Peritoneal dissemination and platinum resistance were independent predictors of poor survival. Approximately 11% of patients achieved survival beyond ten years. The 1-year CS-OS increased from 87% at 6 months to 95% at 5 years, while the 5-year CS-OS rose from 49% to 66%; corresponding CS-PFS values increased from 89% to 95% and from 44% to 62%. Conditional survival analysis underscores that prognosis in advanced ovarian cancer is not static but continually improves with time survived and sustained disease control. These insights redefine long-term outcomes and provide a modern foundation for individualized patient counseling and survivorship planning.

A Novel Approach to Reducing Chemoresistance in Advanced Ovarian Cancer: The Effect of Itraconazole—A Single-Institution Randomized Placebo-Controlled Trial

Background: The five-year survival rate of patients with ovarian cancer remains less than 50%, secondary to chemotherapy resistance. Purpose: This study aims to evaluate the effects of itraconazole as a supplementary treatment with paclitaxel and carboplatin on malignancy response and in preventing the initial development of chemoresistance in chemotherapy-naïve patients with advanced ovarian epithelial cancer. Method: This randomized placebo-controlled double-blind study involved 60 chemotherapy-naïve patients with advanced epithelial ovarian malignancy who were randomized into two arms; the placebo and itraconazole groups. The placebo group received six chemotherapy cycles and four inactive capsules, while the itraconazole group received six chemotherapy cycles and 400 mg oral itraconazole for five days per cycle. Results: Following completion of six chemotherapy cycles and when contrasted with the control arm, the itraconazole arm demonstrated statistically significant improvements in tumor response. The objective response rate was 80% in the itraconazole group compared with 47% in the placebo group (p = 0.015), while the disease control rate was 100% versus 80%, respectively (p = 0.023). The median progression-free survival (PFS), defined as the time point at which 50% of patients experienced disease progression or death, was 13.5 months for the overall study population. PFS was evaluated as a fixed-time endpoint at 18 months following completion of chemotherapy for the overall study population. Progression-free survival was significantly improved in the itraconazole group, with 70% of patients remaining progression-free compared with 26.7% in the placebo group (p = 0.001). Also, the itraconazole group produced significant declines in the serum levels of CA-125 (p = 0.005) and p-glycoprotein (p = 0.042) with significant elevation in VEGFR-2 (p = 0.006) as compared to the control group. Itraconazole was safe and its use was associated with a significant improvement in the quality of life (QOL). Conclusions: Itraconazole could represent a promising add-on therapy to enhance tumor response to chemotherapy in patients with ovarian cancer.

The Role of Cancer-Associated Fibroblasts and Tumor-Associated Macrophages in the Tumor Microenvironment and Their Impact on Ovarian Cancer Survival and Therapy

Ovarian cancer is the deadliest gynecologic cancer, mainly because it is often diagnosed late and resists standard treatments. The tumor microenvironment (TME) plays a major role in disease progression and therapy failure. Two key components of the TME, cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), create conditions that facilitate tumor growth and immune evasion. CAFs are highly diverse and originate from sources like fibroblasts and stem cells. They support cancer by remodeling the extracellular matrix, promoting angiogenesis, and releasing cytokines and growth factors that aid tumor survival. TAMs, which are usually in an M2 state, also promote metastasis and suppress immune responses by secreting immunosuppressive molecules. Together, CAFs and TAMs interact with cancer cells to activate pathways such as the TGF-β, IL-6, and PI3K/AKT pathways, which drive resistance to therapy. New treatments aim to block these interactions by targeting CAFs and TAMs through depletion, reprogramming, or pathway inhibition, often combined with immunotherapy. Advances such as single-cell sequencing and spatial transcriptomics now enable more precise identification of CAF and TAM subtypes, enabling more targeted therapies. This review summarizes their roles in epithelial ovarian cancer and explores how targeting these cells could improve outcomes.

Endometriosis in Carriers of a Pathogenic Variant in BRCA1 or BRCA2: A Descriptive Analysis of a Large Multicentral BRCA Carrier Cohort

Background: Endometriosis affects an estimated 10% of reproductive-aged women and is associated with increased ovarian cancer risk. While BRCA1/2 mutations are established risk factors for ovarian cancer, their association with endometriosis remains unclear. This study aimed to characterize the prevalence and clinical features of endometriosis within a large cohort of BRCA mutation carriers. Methods: A descriptive analysis was conducted using data from a multi-center longitudinal cohort of women with pathogenic BRCA variants. Reproductive history and related factors were collected through self-reported questionnaires and compared. Results: Among 16,950 BRCA carriers, the prevalence of endometriosis was 2.4%. Compared to BRCA carriers without endometriosis, those with endometriosis were more likely to carry a BRCA2 mutation, have post-secondary education, and experience earlier menarche. BRCA carriers with endometriosis had a lower ovarian cancer prevalence than those without (10% vs. 15%, p < 0.001). Conclusions: This is the first study of this scale to report the prevalence of endometriosis among BRCA mutation carriers, which was lower than previously reported in the general population. The association between endometriosis and ovarian cancer does not appear to be generalizable to this population. Further prospective studies are warranted to clarify this association among BRCA mutation carriers.