Antonio Simone Laganà

The Role of Tumor Biomarkers in Tailoring the Approach to Advanced Ovarian Cancer

Growing evidence has demonstrated the role of mutations of tumor biomarkers in diagnosing and treating epithelial ovarian cancer. This review aims to analyze recent literature on the correlation between tumor biomarkers and chemotherapy in nonmucinous ovarian cancer, providing suggestions for personalized treatment approaches. An extensive literature search was conducted to identify relevant studies and trials. BRCA1/2 mutations are central in homologous recombination repair deficiency (HRD) in ovarian cancer, but several other genetic mutations also contribute to varying cancer risks. While the role of MMR testing in ovarian cancer is debated, it is more commonly linked to non-serous ovarian cancer, often associated with Lynch syndrome. A significant proportion of ovarian cancer patients have HRD, affecting treatment decisions in both first-line (especially in advanced stages) and second-line therapy due to HRD’s connection with platinum-based therapy and PARP inhibitors’ response. However, validated genetic tests to identify HRD have not yet been universally implemented. There is no definitive therapeutic algorithm for advanced ovarian cancer, despite ongoing efforts and multiple proposed tools. Future research should focus on expanding the utility of biomarkers, reducing resistance, and increasing the actionable biomarker pool.

Chemoembolization, Radioembolization, and Percutaneous Ablation: New Opportunities for Treating Ovarian Cancer Liver Metastasis

Parenchymal liver metastases from ovarian cancer, occurring in 2-12.5% of cases, significantly worsen prognosis. While surgery and systemic treatments remain primary options, unresectable or chemotherapy-resistant multiple liver metastases pose a significant challenge. Recent advances in liver-directed therapies, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization (TACE), and radioembolization, offer potential treatment alternatives. However, the efficacy of these techniques is limited by factors such as tumor size, number, and location. The ideal candidate for tumor ablation is a patient with paucifocal disease, a single tumor up to 5 cm or up to 3 tumors smaller than 3 cm and tumors 1 cm away from major bile ducts and high-flow vessels. Transarterial chemoembolization could be performed in patients with less than 70% tumor load. Differently, radioembolization is available with less limitation on the sites or number of liver cancers. Radioembolization techniques are also able to downsize liver metastases. However, there are limited data regarding the outcomes of loco-regional therapy in patients with hepatic metastases from ovarian cancer. Advancing liver-directed therapies through interventional oncology, combined with robust data on the oncological efficacy of these local treatments, will validate their potential as effective locoregional therapies for liver metastases. This could offer a promising treatment option for patients with ovarian cancer and unresectable hepatic metastases.

The Female Reproductive Tract Microbiota and Endometrial Cancer: A Systematic Review

This systematic review aimed to summarize the available evidence on the associations between the female reproductive tract microbiota and endometrial cancer (EC). While gut microbiota has been studied extensively, microbial communities within the endometrium, cervix, and vagina remain relatively understudied. A systematic literature search was conducted in PubMed, Scopus, Web of Science, EMBASE, and the Cochrane Library for studies published up to January 2025. Predefined PECO-based criteria included studies on women or human cell models assessing genital tract microbiota in EC versus non-EC controls, focusing on composition, diversity, or function; reviews and non-microbiota studies were excluded. A total of 21 studies were included. Overall, there was a consistent depletion of protective Lactobacillus species and enrichment of anaerobic, pro-inflammatory bacteria like Prevotella, Atopobium, and Porphyromonas in EC tissues. Beta-diversity was significantly different between EC and controls across studies, indicating distinct microbial profiles. Some studies also identified fungal and viral taxa associated with EC, and functional assays demonstrated that certain species could modulate host immune responses or promote tumor growth. Despite methodological heterogeneity and the lack of evidence supporting causality due to the observational design, the findings support an association between altered genital tract microbiota and EC.

Lymphadenectomy in endometrial cancer – achieving more with less?

The lymph node status of patients with endometrial cancer is known to be a crucial determinant for the prognosis of the disease. It also provides the indication for further adjuvant treatment. The staging of endometrial cancer by surgery has been a controversial issue for more than 30 years. The significant complication rate after lymphadenectomy and the development of minimally invasive surgery have led to the use of sentinel lymph node (SLN) mapping. In the present review, we present the development of surgical staging procedures in patients with endometrial cancer and summarize the recently expanding body of published literature on the subject. SLN mapping is a safe and accurate technique, especially when indocyanine green is used as a tracer. SLN mapping appears to reduce complication rates as well as costs without affecting the oncologic outcome. Large prospective studies are needed to establish the effects of SLN mapping on the outcome of disease, especially in high-risk patients with endometrial cancer. Furthermore, the need for additional systematic lymphadenectomy prior to adjuvant radio-chemotherapy in patients diagnosed with isolated lymph node metastasis during SLN biopsy must be investigated further. This might pave the way for a new surgical approach in patients with endometrial cancer.

Reproductive and Oncologic Outcomes in Young Women with Stage IA and Grade 2 Endometrial Carcinoma Undergoing Fertility-Sparing Treatment: A Systematic Review

Background: Endometrial cancer (EC) is the most common gynecological malignancy in both Europe and the USA. Approximately 3–5% of cases occur in women of reproductive age. Fertility-sparing treatment (FST) options are available, but very limited evidence regarding grade 2 (G2) ECs exists in the current literature. This systematic review aimed to comprehensively evaluate reproductive and oncologic outcomes among young women diagnosed with stage IA or G2EC disease who underwent FST. Methods: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies that reported the oncologic and reproductive outcomes of patients with stage IA and G2EC tumors who underwent FST were considered eligible for inclusion in this systematic review (CRD42023484892). Studies describing only the FST for endometrial hyperplasia or G1 EC were excluded. Results: Twenty-two papers that met the abovementioned inclusion criteria were included in the present systematic review. Preliminary analysis suggested encouraging oncologic and reproductive outcomes after FST. Conclusions: The FST approach may represent a feasible and safe option for women of childbearing age diagnosed with G2EC. Despite these promising findings, cautious interpretation is warranted due to inherent limitations, including heterogeneity in study designs and potential biases. Further research with standardized methodologies and larger sample sizes is imperative for obtaining more robust conclusions.

Beyond Sentinel Lymph Node: Outcomes of Indocyanine Green-Guided Pelvic Lymphadenectomy in Endometrial and Cervical Cancer

Background: The aim of our study was to compare the number of lymph nodes removed during indocyanine green (ICG)-guided laparoscopic/robotic pelvic lymphadenectomy with standard systematic lymphadenectomy in endometrial cancer (EC) and cervical cancer (CC). Methods: This is a multicenter retrospective comparative study (Clinical Trial ID: NCT04246580; updated on 31 January 2023). Women affected by EC and CC who underwent laparoscopic/robotic systematic pelvic lymphadenectomy, with (cases) or without (controls) the use of ICG tracer injection within the uterine cervix, were included in the study. Results: The two groups were homogeneous for age (p = 0.08), Body Mass Index, International Federation of Gynaecology and Obstetrics (FIGO) stages (p = 0.41 for EC; p = 0.17 for CC), median estimated blood loss (p = 0.76), median operative time (p = 0.59), and perioperative complications (p = 0.66). Nevertheless, the number of lymph nodes retrieved during surgery was significantly higher (p = 0.005) in the ICG group (n = 18) compared with controls (n = 16). Conclusions: The accurate and precise dissection achieved with the use of the ICG-guided procedure was associated with a higher number of lymph nodes removed in the case of systematic pelvic lymphadenectomy for EC and CC.

Fertility-Sparing Strategies for Early-Stage Endometrial Cancer: Stepping towards Precision Medicine Based on the Molecular Fingerprint

Endometrial cancer represents the fifth most common cancer in women, and the most common gynecological malignancy in developed countries [...]

Progression Free Survival, Overall Survival, and Relapse Rate in Endometrioid Ovarian Cancer and Synchronous Endometrial-Ovarian Endometrioid Cancer (SEO-EC): Results from a Large Retrospective Analysis

Background and Objectives: We aimed to evaluate Progression Free Survival (PFS), Overall Survival (OS), and relapse rate in women affected by endometrioid ovarian cancer and synchronous endometrial-ovarian endometrioid cancer (SEO-EC). As secondary outcome, we assessed whether systematic pelvic and para-aortic lymphadenectomy could be considered a determinant of relapse rate in this population. Materials and Methods: We performed a retrospective analysis of women with diagnosis of endometrioid ovarian cancer or SEO-EC between January 2010 to September 2020, and calculated PFS, OS and relapse rate. Results: In almost all the patients (97.6%) who underwent systematic pelvic and para-aortic lymphadenectomy, there were no lymph node metastases confirmed by histology. We did not find a significant difference (p = 0.6570) for the rate of relapse in the group of women who underwent systematic pelvic and para-aortic lymphadenectomy (4/42; 9.5%) compared with the group of women who did not undergo the same procedure (1/21; 4.8%). During a median follow-up was 23 months, both PFS and OS were excellent. Conclusions: Women affected by early-stage low-grade endometrioid cancer and SEO-EC without apparent lymph node involvement at pre-operative imaging showed a very low rate of lymph node metastasis and similar relapse rate with or without lymphadenectomy.

Role of laparoscopic hysterectomy in cervical and endometrial cancer: a narrative review

Endometrial cancer is the most common carcinoma of the female genital organs and cervical cancer is the leading cause of cancer death in women worldwide. The aim of this review is to evaluate the role of laparoscopic hysterectomy in patients with endometrial and cervical cancer in this period, and analyze the outcome of hysterectomy in terms of survival. Moreover, we present the historical background, new techniques, the anatomical features, and surgical steps of radical hysterectomy. According to new evidence, minimally invasive surgery in patients with cervical cancer is associated with higher rates of recurrence and mortality compared to the open approach. Despite the numerous explanations offered for this phenomenon, the reasons for these results are unclear. Additional large trials have been launched to reevaluate the above-mentioned data. On contrary, the laparoscopic approach provides surgical outcomes and similar survival rates as open surgery in patients with early endometrial carcinoma. Furthermore, the radicality of hysterectomy does not influence local recurrence rates or overall survival in cases with complete surgical removal of the tumor. A laparoscopic radical hysterectomy is no longer an option in patients with cervical cancer. When minimally invasive surgery is offered, the patients must be counseled in detail about the current debate.

Fertility-Sparing Approach in Women Affected by Stage I and Low-Grade Endometrial Carcinoma: An Updated Overview

Endometrial cancer (EC) is a deleterious condition which strongly affects a woman’s quality of life. Although aggressive interventions should be considered to treat high-grade EC, a conservative approach should be taken into consideration for women wishing to conceive. In this scenario, we present an overview about the EC fertility-sparing approach state of art. Type I EC at low stage is the only histological type which can be addressed with a fertility-sparing approach. Moreover, no myometrium and/or adnexal invasion should be seen, and lymph-vascular space should not be involved. Regarding the pharmaceutical target, progestins, in particular medroxyprogesterone acetate (MPA) or megestrol acetate (MA), are the most employed agent in conservative treatment of early-stage EC. The metformin usage and hysteroscopic assessment is still under debate, despite promising results. Particularly strict and imperious attention should be given to the follow-up and psychological wellbeing of women, especially because of the double detrimental impairment: both EC and EC-related infertility consequences.

Molecular Basis of Endometriosis and Endometrial Cancer: Current Knowledge and Future Perspectives

The human endometrium is a unique tissue undergoing important changes through the menstrual cycle. Under the exposure of different risk factors in a woman’s lifetime, normal endometrial tissue can give rise to multiple pathologic conditions, including endometriosis and endometrial cancer. Etiology and pathophysiologic changes behind such conditions remain largely unclear. This review summarizes the current knowledge of the pathophysiology of endometriosis and its potential role in the development of endometrial cancer from a molecular perspective. A better understanding of the molecular basis of endometriosis and its role in the development of endometrial pathology will improve the approach to clinical management.

PET-CT scan in the preoperative workup of early stage intermediate- and high-risk endometrial cancer

Hydatidiform Mole with Coexisting Normal Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis

Background and Objectives: This study aimed to evaluate obstetric, neonatal, and oncologic outcomes of pregnancies complicated by a hydatidiform mole coexisting with a live fetus (HMCF) carried beyond viability, and to assess the impact of delivery mode on outcomes. Materials and Methods: A systematic review and individual participant data meta-analysis included HMCF cases progressing beyond 23 weeks. Obstetric and neonatal outcomes, delivery patterns, and oncologic risks were analyzed. Results: Among 118 pregnancies complicated by HMFC (124 newborns), most were complete moles (87%). Median delivery occurred at 31.6 weeks, with over half before 32 weeks. Common complications included vaginal bleeding (59%), preeclampsia (30%), and hyperthyroidism (18%). Cesarean delivery was performed in 79% of cases, often for mole-related factors, but was not associated with reduced maternal or oncologic risk. Neonatal deaths occurred exclusively in infants delivered ≤32 weeks, highlighting extreme prematurity as the key determinant of survival. Severe preeclampsia was strongly linked to earlier delivery. Conclusions: With close monitoring, continuation of HMCF pregnancies is possible. Neonatal mortality is mainly driven by prematurity, which appears to be an indirect consequence of HMFC through the development of mola-associated complications. Cesarean section does not appear to improve maternal and oncologic outcomes. Vaginal delivery can be considered when no standard contraindications exist.

Reproductive Outcomes in Young Women with Early-Stage Cervical Cancer Greater than 2 cm Undergoing Fertility-Sparing Treatment: A Systematic Review

Background and Objectives: Despite advancements in detection and treatment, cervical cancer remains a significant health concern, particularly among young women of reproductive age. Limited data exists in the literature regarding fertility-sparing treatment (FST) of cervical cancers with tumor sizes greater than 2 cm. The objective of this systematic review was to evaluate the reproductive outcomes of women diagnosed with cervical cancer greater than 2 cm who underwent FST. Materials and Methods: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies (retrospective or prospective) that reported reproductive outcomes of patients with cervical cancer >2 cm were considered eligible for inclusion in this systematic review (CRD42024521964). Studies describing only the oncologic outcomes, involving FST for cervical cancers less than 2 cm in size, and case reports were excluded. Results: Seventeen papers that met the abovementioned inclusion criteria were included in the present systematic review. In total, 443 patients with a cervical cancer larger than 2 cm were included in this systematic review. Eighty pregnancies occurred, with 24 miscarriages and 54 live births. Conclusions: FST appears to be a viable option for women of childbearing age diagnosed with cervical cancer larger than 2 cm. However, careful consideration is advised in interpreting these encouraging results, as they are subject to limitations, such as variability in study designs and potential biases. In addition, reproductive outcomes should be further cross-referenced with oncologic outcomes to clarify the potential risk–benefit ratio. It is critical to conduct further research using standardized approaches and larger participant groups to strengthen the validity of the conclusions drawn.

Surgical treatment of large adnexal masses: a retrospective analysis of 330 consecutive cases

Role of V-Y flap reconstruction in vulvar cancer patients: multicenter retrospective study

To assess if the use of a V-Y reconstructive flap after excisional radical surgery positively influences the surgical outcomes in patients with vulvar cancer. This was a multicenter, retrospective, controlled study. Surgical outcomes and complication rates of women with invasive vulvar cancer who underwent radical surgery and vulvar reconstruction and those who underwent radical surgery without the reconstruction step were compared. Only patients who underwent bilateral or unilateral V-Y advancement fascio-cutaneous flaps were included in the reconstruction group. Univariate and multivariate logistic regression models were used to analyze predicting variables for their association with complication rates. Overall, 361 patients were included: 190 (52%) underwent the reconstructive step after the excisional radical procedure and were compared with 171 (47.4%) who did not undergo the reconstructive step. At multivariate analysis, body mass index >30 kg/m The adoption of V-Y flaps in vulvar surgery was correlated with reduced surgical related complications, particularly in vulnerable patients involving large surgical defects following excisional radical procedures.

Vaginal Stenosis After Cervical Cancer Treatments: Challenges for Reconstructive Surgery

Evaluation of Surgical Outcomes of Abdominal Radical Hysterectomy and Total Laparoscopic Radical Hysterectomy for Cervical Cancer: A Retrospective Analysis of Data Collected before the LACC Trial

Although a surgical approach is one of the key treatments for stages IA1-IIA2, results of the Laparoscopic Approach to Cervical Cancer (LACC) published in 2018 radically changed the field, since minimally invasive surgery was associated with a four-fold higher rate of recurrence and a six-fold higher rate of all-cause death compared to an open approach. We aimed to evaluate surgical outcomes of abdominal radical hysterectomy (ARH) and total laparoscopic radical hysterectomy (TLRH) for cervical cancer, including data collected before the LACC trial. In our retrospective analysis, operative time was significantly longer in TLRH compared to ARH (p < 0.0001), although this disadvantage could be considered balanced by lower intra-operative estimated blood loss in TLRH compared with ARH (p < 0.0001). In addition, we did not find significant differences for intra-operative (p = 0.0874) and post-operative complication rates (p = 0.0727) between ARH and TLRH. This was not likely to be influenced by age and Body Mass Index, since they were comparable in the two groups (p = 0.0798 and p = 0.4825, respectively). Finally, mean number of pelvic lymph nodes retrieved (p = 0.153) and nodal metastases (p = 0.774), as well as death rate (p = 0.5514) and recurrence rate (p = 0.1582) were comparable between the two groups. Future studies should be aimed at assessing whether different histology/grades of cervical cancer, as well as particular subpopulations, may have significantly different outcomes using minimally invasive surgery or laparotomy, with or without neoadjuvant chemotherapy.

New Advances in Cervical Cancer: From Bench to Bedside

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) has emerged as the mainstay in the surgical management of early-stage cervical cancer, bringing advantages such as a lower operative morbidity and shorter hospital stay compared to open surgery, while maintaining comparable oncologic outcomes in numerous retrospective studies. Considering oncological patients, it is mandatory to assess the oncological outcomes and safety of this type of surgery. Moreover, there are different future outlooks on cervical cancer therapy, based on immunotherapy, target therapy, and poly-ADP-ribose polymerases (PARP) inhibitors in combination with each other, and in combination with standard chemotherapy and radiotherapy. The goal is to find an approach that is as personalized as possible.

Minimally Invasive Surgery for Cervical Cancer: Should We Look beyond Squamous Cell Carcinoma?

Incidence of pre-neoplastic and neoplastic lesions of the cervix before and after the COVID-19 pandemic

The COVID-19 pandemic had significant effects on healthcare systems worldwide, including the disruption of routine screening programs for cervical cancer. This study aimed to compare the incidence of cervical intra-epithelial neoplasia (CIN)2 and CIN3 lesions, adenocarcinoma, and squamous carcinoma of the cervix before and after the COVID-19 pandemic. A retrospective analysis was performed using archive data from the Policlinico di Bari, Unit of Gynecology and Obstetrics. The study included patients who tested positive for high-risk human papillomavirus (HPV) at the level I screening test (HPV test) and were subsequently referred to level II screening, which involves the Papanicolaou (Pap) test and colposcopic examination. We excluded individuals who did not comply with the recommended follow-up, patients with low-risk HPV infection, those with autoimmune diseases, oncologic diseases, or those undergoing immunosuppressive therapies. The time period spanned from January 2020 to December 2022. The incidence of CIN2/CIN3 lesions, adenocarcinoma, and squamous carcinoma of the cervix was compared between the pre-screening period (2017-2019) and the post-screening period (2020-2022). The study comprised a cohort of 1558 consecutive European sexually active women with a median age of 34 years (range 25-65) who underwent colposcopic evaluation of the uterine cervix as a level II screening program. The comparison between the pre-screening and post-screening periods showed an increase in the incidence of CIN2/CIN3 lesions, rising from 23.9 to 63.3 per 100 000 (HR 2.62, 95% CI 1.64 to 4.20; p<0.001). Additionally, although there was an absolute increase in the incidence of cervical carcinoma and adenocarcinoma, the comparison did not reach statistical significance (squamous carcinoma: 2017-2019, 2.5 per 100 000; 2020-2022 3.4 per 100 000, p=0.72; adenocarcinoma: 2017-2019, 3.5 per 100 000; 2020-2022 7.6 per 100 000, p=0.24). This study showed a significant increase in the incidence rate of CIN2/CIN3 lesions after the COVID-19 pandemic. Our findings may be attributed to the temporary suspension of follow-up programs during the pandemic, although the study does not rule out direct effects of SARS-CoV-2 on the risk of pre-neoplastic and neoplastic conditions of the cervix.

Surgical outcomes and morbidity in open and videoendoscopic inguinal lymphadenectomy in vulvar cancer: A systematic review and metanalysis”

Surgical evaluation of inguinal lymph nodes is essential to correctly guide the adjuvant treatment of vulvar cancer patients. Open inguinal lymphadenectomy (OIL) approach is the preferred route, while the videoendoscopic inguinal lymphadenectomy (VEIL) seems to be associated with better results. This meta-analysis aimed to compare the surgical outcomes of OIL vs VEIL in vulvar cancer. The meta-analysis was conducted according to the PRISMA guideline. The search string included the following keywords: "(vulvar cancer) AND ((inguinal) OR (femoral)) AND ((lymph node dissection) OR (lymphadenectomy))". Three double-blind researchers independently extracted data. Seventeen studies were considered eligible for the analysis. Seven studies were included in the OIL group and ten studies in the VEIL group. A total of 372 groins were included in OIL group and 197 groins in VEIL group. 153 groins (41.1 %) in the OIL group and 25 groins (12.6 %) in the VEIL group developed major complications. The analysis of all lymphatic and wound complications showed that VEIL had a lower rate of lymphatic and wound complications. Estimated blood loss (p = 0.4), hospital stay (p = 0.18), time of drainage (p = 0.74), number of lymph node excised (p = 0.74) did not show significant difference between the two approaches. VEIL route may be a valid alternative to OIL route with no differences in terms of surgical outcomes, except for operative time that is shorter for OIL. Future analysis of randomized controlled trials in this specific patient population are warranted to confirm these results.

Evaluation of Indocyanine Green-guided Systematic Pelvic Lymphadenectomy in Endometrial and Cervical Cancer

The lymph nodes involvement is one of the most important prognostic factors in endometrial (EC) and cervical cancer (CC). Indeed, the lymph node involvement in cancer patients modifies the International Federation of Gynecology and Obstetrics (FIGO) stage and plays a pivotal role in the choice of the adjuvant therapy. Since the modern imaging techniques are not yet able to accurately detect lymph nodes metastasis, pelvic systematic lymphadenectomy has still an important role and it still represents the gold standard in EC and CC. The sentinel lymph node (SLN) biopsy, which is a standard practice in breast cancer and melanoma, is often used in some early stage gynaecological cancers such as EC and CC. Indocyanine green (ICG) is the most used tracer for the detection of SLN in gynaecological cancer, especially in laparoendoscopic setting. ICG allows a complete visualization of the lymphatic drainage and, for this reason, it may be used even in systematic pelvic lymphadenectomy to guide the surgeon during the procedure. Several studies have demonstrated an advantage of the ICG-guided lymphadenectomy in other types of cancers, showing a higher number of lymph nodes removed with this technique when compared to standard lymphadenectomy (without ICG). To date, there is no published study about ICG-guided systematic pelvic lymphadenectomy in EC and CC. In this scenario, the aim of this study will be to compare systematic ICG-guided pelvic lymphadenectomy and standard lymphadenectomy in EC and CC.