Current Oncology Reports

Advances in the Management of Recurrent Cervical Cancer: State of the Art and Future Perspectives

Abstract Purpose of Review This review aims to give an insight into the currently available options for recurrent/metastatic (R/M) cervical cancer (CC), along with the main future, potentially practice-changing perspectives in this field. Recent Findings Improvements in terms of tumor responses were observed with the use of immune checkpoints inhibitors (ICIs) in the previously treated CC population, followed by emerging striking data in terms of both antitumor activity and survival rates with the addition of the ICIs to platinum-based chemotherapy with or without bevacizumab in the first-line setting. Furthermore, the CC treatment landscape took another step forward in 2021 with the introduction of antibody–drug conjugates (ADCs) in the second-line setting, a highly targeted therapeutic strategy, which demonstrated to be a valid alternative option in the recurrent setting. Summary R/M CC is a hard-to-treat disease. However, after several years of limited systemic therapeutic options for the recurrent setting, the year 2018 marked a turning point for R/M CC patients, with the introduction of immunotherapy in the treatment paradigm, which completely reshaped the therapeutic armamentarium of the disease. Besides, another valuable treatment option represented by ADCs demonstrated its efficacy in the recurrent setting, thus further widening the treatment landscape for those patients. Yet, the introduction of immunotherapy in the upfront setting brought along new issues to be addressed such as the emerging ICIs resistance and the following need for alternative options in the post-ICIs setting. Several innovative therapeutic strategies are under investigation in ongoing clinical trials, with the aim of overcoming ICIs resistance with the addition of immunomodulatory agents or bypassing the ICIs resistance with novel alternative drugs.

Surgery for Recurrent Epithelial Ovarian Cancer

Abstract Purpose of Review To review evidence around the value and challenges of surgery for recurrent epithelial ovarian cancer (ROC). Both cytoreductive and palliative aspects will be addressed Recent Findings Prospective and retrospective evidence demonstrates a significantly longer remission derived from the combination of surgical and systemic modalities as opposed to systemic treatment alone in carefully selected ROC-patients who have relapsed more than 6 months from the end of their 1st line platinum-based chemotherapy. Nevertheless, this benefit appears to be limited when total macroscopic tumor clearance is not achieved. Selection algorithms to identify optimal surgical candidates are of paramount importance to prevent surgical morbidity without the equivalent oncological benefit. In the palliative setting, the risks and benefits of salvage surgery need to be counterbalanced with the advances of conservative techniques for optimal care. Summary Well-defined selection algorithms to identify those who will benefit from surgery in the relapsed setting appear to be the key to oncologic and surgical success.

PARP Inhibitors in Gynecologic Cancers: What Is the Next Big Development?

Conventional and novel applications of Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi) are reviewed in the context of recently published clinical trials and preclinical data supporting rapidly expanding uses of this class of chemotherapy. PARPi block a pathway of DNA repair and target defects in homologous recombination repair (HRR), a pathway responsible for high-fidelity repair of double-strand breaks in DNA. BRCA1/2 proteins are essential to this pathway. Approximately 15-30% of women with ovarian cancer will have a germline or somatic BRCA mutation, and PARPi have shown promise in this population in a variety of settings. With growing understanding of the HRR pathway and its role in gynecologic malignancies, the potential applications of PARPi continue to expand. While the role of PARPi in gynecologic malignancies is most established in ovarian cancer, there are also promising applications in uterine and cervical cancer. We review current indications for PARPi use and promising applications of these medications in gynecologic malignancies.

Lymphadenectomy in Ovarian Cancer: Is It Still Justified?

The aim of this review is to determine, in the light of recent evidences, the role of lymphadenectomy in ovarian cancer. The lymphadenectomy in ovarian neoplasms (LION) trial reports no better outcomes and higher complication and mortality rates associated with lymphadenectomy. Even if performed by expert hands, lymphadenectomy has a cost in terms of longer operative time, blood loss, higher rates of transfusions, and intensive unit care. If on the one hand retroperitoneal staging is not correlated to survival benefits both in early and advanced ovarian cancer, on the other hand it is associated with an increased surgery-related morbidity. Surgical treatment of isolated nodal recurrences seems to be feasible and associated with survival benefits.

Low-grade Serous Tumors: Are We Making Progress?

This review provides an overview of the current clinical standard in low-grade serous ovarian cancer (LGSOC). The available evidence for surgery and standard treatments is elaborated. In addition, we discuss recent findings and novel treatments for LGSOC. Two large multicenter trials studying MEK inhibitors in LGSOC have been presented in the last year. Binimetinib demonstrated an activity in LGSOC, especially in KRAS-mutated disease. Trametinib was associated with an improved progression-free survival in relapsed LGSOC. Based on the current results, MEK inhibitors could be an alternative treatment for LGSOC. Surgery is an important step in the treatment of LGSOC. Hormonal therapy and bevacizumab can be beneficial, next to chemotherapy. Targeted treatments, such as the MEK-inhibitor trametinib, seem to be efficient and should be introduced into clinical practice.

Prevention of Ovarian Cancer: Where are We Now and Where are We Going?

To describe current and future strategies to reduce the burden of ovarian cancer through prevention. Current strategies in genetic testing are missing a substantial number of individuals at risk, representing a missed opportunity for ovarian cancer prevention. Past efforts at screening and early detection have thus far failed to improve ovarian cancer mortality, and novel techniques are needed. Surgical prevention is highly effective, but surgical menopause from oophorectomy has significant side effects. Novel surgical strategies aimed at reducing risk while minimizing these harms are currently being studied. To maximize ovarian cancer prevention, a multi-pronged approach is needed. We propose that more inclusive and accurate genetic testing to identify more individuals at risk, novel molecular screening and early detection, surgical prevention that maximizes quality of life while reducing risk, and broader adoption of targeted and opportunistic salpingectomy will together reduce the burden of ovarian cancer.

Treatment Perspectives for Ovarian Cancer in Europe and the United States: Initial Therapy and Platinum-Sensitive Recurrence after PARP Inhibitors or Bevacizumab Therapy

Although the survival rate of patients with ovarian cancer (OC) has significantly improved, OC is still one of the most common causes of gynecologic cancer death in women worldwide. The current advances in primary treatment are based on recent regulatory approvals and recurrency of such treatments, challenging the development of a unified approach to care. Herein, we examine how integration of these new approaches is applied to patient's treatment. We and others have recently reported clinical trials using bevacizumab and/or inhibitors of Poly (ADP-ribose) polymerase (PARP), which have greatly affected the change in first-line treatments for OC. As first-line therapy has evolved, therapeutic agents once designated for recurrent disease are increasingly being incorporated, changing our standard of care following previously indexed trials. Here, we provide an overview of the current treatment for OC patients, and we highlight practice patterns in Europe and in the USA with corresponding opinions on current and future treatments for platinum-sensitive recurrent OC.

Resistance to Poly (ADP-Ribose) Polymerase Inhibitors (PARPi): Mechanisms and Potential to Reverse

This review will focus on the most common mechanisms for poly (ADP-ribose) polymerase inhibitors' (PARPi) resistance and the main strategies for overcoming acquired or de novo PARPi resistance. Initial approvals for PARPi as part of treatment for advanced epithelial ovarian cancer (EOC) started in 2014 with patient with recurrent cancer characterized by BRCA mutations in the 3rd and 4th line and now have approvals for front-line maintenance in both the BRCA mutated and BRCAwt populations. As with all therapies, patients will eventually develop resistance to treatment. The most common mechanisms for PARPi resistance include reversion mutations, methylation events, and restoration of homologous recombination deficiency (HRD) through combinations and targeting replication stress. As more and more patients receive initial treatment (and potential retreatment with PARPi), we need to better understand the mechanisms in which tumors acquire PARPi resistance.

Primary or Interval Debulking Surgery in Advanced Ovarian Cancer: a Personalized Decision—a Literature Review

Summarize the writings published in the last 5 years on the management of surgery in the first line of treatment for advanced ovarian cancer. For patients with a significant tumor burden, the neoadjuvant chemotherapy therapy (NACT) with interval debulking surgery (IDS) strategy shows comparable efficacy than primary debulking surgery (PDS) in terms of survival in randomized studies with less morbidity. Advanced epithelial ovarian cancer generates more than half cases a recurrence. First-line treatment is based on a chemotherapy regimen combining a platinum-based and a taxane-based, associated with surgery. This review considers papers of last 5 years of timing, thinking tools, and innovation in the management. The choice of strategy, PDS or IDS, would be a personalized recommendation. The challenge is to adapt the timing of the surgery to the patient's characteristics and that of her disease.

Advancements in Low-Grade Serous Carcinoma of the Ovary and Peritoneum

Low-grade serous ovarian cancer (LGSOC) is a rare form of epithelial ovarian cancer that generally exhibits a protracted course and is less sensitive to chemotherapy than high-grade serous ovarian cancer. Over the past decade, it has become clear that patients with LGSOC have a clinically distinct course and are molecularly and histologically unique from patients with high-grade serous ovarian cancer. Endocrine therapy is frequently used for the treatment of patients with recurrent LGSOC and is now also part of the standard upfront treatment of this disease, with an ongoing phase III clinical trial seeking to determine if chemotherapy can be eliminated altogether from the initial treatment of LGSOC. Tumors are frequently found to exhibit alterations affecting the mitogen-activated protein kinase (MAPK) pathway, recently leading to developments in the use of targeted treatments for those patients with recurrent disease. LGSOC is a clinically, histologically, and molecularly unique form of epithelial ovarian cancer. Recent advances in the understanding of endocrine and molecular drivers of this disease have led to changes in both the treatment of newly diagnosed and recurrent disease, with ongoing studies focused on refining upfront therapy and seeking novel targeted combinations for those patients with recurrent disease.

Small Cell and Other Rare Histologic Types of Cervical Cancer

The goal of this paper was to summarize the recent evidence on rare subtypes of cervical cancer including small-cell carcinoma of the cervix (SCCC), gastric-type adenocarcinoma, and carcinosarcoma. All three cervical cancer subtypes are aggressive with poor treatment response and high recurrence rates. Molecular studies have identified various actionable mutations in both SCCC (PIK3CA, MYC, TP53, PTEN, ARID1A, KRAS, BRCA2) and gastric-type adenocarcinoma (KRAS, ARID1A, PTEN). While there are a limited number of case reports demonstrating a favorable response for recurrent SCCC to immune checkpoint inhibitors, a larger case series failed to show benefit. The checkpoint inhibitors role in gastric-type adenocarcinoma and carcinosarcoma is yet to be determined. Ninety-one percent of SCCC cases show PARP expression, suggesting a possible role for PARP inhibitors; however, this has yet to be examined in future clinical trials. More studies are needed, with a focus on targeted therapies. The role of PARP inhibitors in SCCC is potentially promising, but significant collaboration between centers/groups will be required to achieve this.

Breast cancer Treatment and Fertility Preservation: A Narrative Review of Impacts, Strategies and Ethical Considerations

Balancing Fertility Preservation and Treatment Efficacy in (Neo)adjuvant Therapy for Adolescent and Young Adult Breast Cancer Patients: a Narrative Review

Changing the Perspective on Fertility Preservation for Women with Metastatic or Advanced Stage Cancer

Liquid Biopsy in Uterine Leiomyosarcoma: Current Biomarkers, Emerging Technologies, and Future Perspectives

Uterine leiomyosarcoma (uLMS) is a rare but aggressive malignant mesenchymal tumor, accounting for 2-5% of uterine malignancies. Because its symptoms and imaging features often resemble those of benign uterine leiomyoma (LM), accurate preoperative diagnosis remain difficult. This review summarizes recent advances in liquid biopsy for uLMS and explores its potential for early detection, molecular characterization, and treatment monitoring. Liquid biopsy enables minimally invasive detection of tumor-derived components such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), non-coding RNAs, and extracellular vesicles (EVs). Recurrent mutations in TP53, RB1, and ATRX have been identified through ctDNA analysis, while CTCs, ncRNAs, and EVs provide complementary information for monitoring tumor dynamics and therapeutic response. Emerging technologies including CRISPR-Cas systems, nanotechnology, electrochemical biosensors, and multi-omics integration enhance detection sensitivity and specificity. Liquid biopsy holds promise for improving uLMS diagnosis and management. However, standardization and biomarker validation remain essential to achieve reliable clinical translation and enable earlier, more precise treatment strategies.

Targeting the PI3K Pathway in Gynecologic Malignancies

This review explores the PI3K pathway aberrations common in gynecologic malignancies, the relevant therapeutic targets that have been explored to date particularly given their success in endometrial cancers, and predictive biomarkers of response to therapy. Landmark trials have been noted involving this pathway, particularly in endometrial cancers. One phase II trial of the potent orally bioavailable mTOR inhibitor, everolimus, in combination with letrozole demonstrated an unprecedented clinical benefit rate (CBR) of 40% and high objective response rate (RR) of 32% in hormone agnostic endometrial cancers. This was followed by GOG 3007 that compared everolimus and letrozole to hormonal therapy yielding similar response rates but double progression-free survival rates. The phosphoinositide 3-kinase (PI3K) signaling pathway is implicated in tumorigenesis given its regulation over cell growth, cellular trafficking, and angiogenesis. In gynecologic malignancies, alterations in PI3K signaling are common. Therefore, developing modulators of the PI3K pathway and identifying molecular markers to predict response are of great interest for these cancer types.

Circulating Transcripts and Biomarkers in Uterine Tumors: Is There a Predictive Role?

Uterine cancer comprises endometrial carcinoma and the uterine sarcoma. Endometrial carcinomas are the most frequent variant and have early symptoms and a solid diagnostic work up, resulting in a rather fair prognosis. However, in case of advanced stage disease and relapse, treatment options are limited and prognosis is impaired. Uterine sarcomas are rare, often lacking symptoms and no diagnostic tool for correct pre-operative diagnosis are available. Prognosis is poor. Circulating biomarkers as a liquid biopsy could be beneficial as a diagnostic tool in uterine sarcomas. For both carcinomas and sarcomas, circulating biomarkers could be of use in predicting early disease recurrence. This review in endometrial carcinoma and uterine sarcoma focus on circulating biomarkers; such as proteins; circulating tumor cells; circulating tumor DNA; microRNA; and immune cells.

First-Line Management of Advanced High-Grade Serous Ovarian Cancer

Abstract Purpose of Review Epithelial ovarian cancer is a disease that encompasses a number of histologically and molecularly distinct entities; the most prevalent subtype being high-grade serous (HGS) carcinoma. Standard first-line treatment of advanced HGS carcinoma includes cytoreductive surgery plus intravenous paclitaxel/platinum-based chemotherapy. Despite excellent responses to initial treatment, the majority of patients develop recurrent disease within 3 years. The introduction of the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, and poly(ADP-ribose) polymerase (PARP) inhibitors into first-line management has changed the outlook for this lethal disease. In this review, we summarise the most recent clinical trials that determine current primary therapy of advanced HGS carcinoma and the ongoing trials that aim to change management in the future. Recent Findings Recent phase III clinical trials have shown that delayed primary surgery after completing neo-adjuvant chemotherapy is non-inferior to immediate primary surgery, but could provide a survival benefit in FIGO (International Federation of Gynecology and Obstetrics) stage IV disease. The use of weekly intravenous chemotherapy regimens has not been proven to be more effective than standard 3-weekly regimens in Western patient populations, and the use of intraperitoneal chemotherapy remains controversial in the first-line setting. In contrast, newer systemic anti-cancer therapies targeting angiogenesis and/or HR-deficient tumours have been successfully incorporated into front-line therapeutic regimens to treat HGS carcinoma. Recent results from randomised trials investigating the use of PARP inhibitors as monotherapy and in combination with the anti-angiogenic agent, bevacizumab, have demonstrated highly impressive efficacy when combined with traditional first-line multi-modality therapy. Summary Management of HGS carcinoma is evolving, but further work is still required to optimise and integrate tumour and plasma biomarkers to exploit the potential of these highly efficacious targeted agents.

Lys-ing the Resistance: Targeting Lysosomes to Overcome Chemoresistance in Ovarian Cancer

Abstract Purpose of Review For decades, ovarian cancer (OC) therapy has mainly relied on a regimen of tumor resection followed by treatment with cisplatin and paclitaxel. While this treatment is usually effective initially, resistance to this regimen in OC is widespread and is often the cause of death in OC patients. In the attempt to find new molecular targets for the treatment of chemoresistant OC, understanding the precise mechanisms of chemoresistance remains a paramount task. This review examines the critical roles of the lysosome in the instigation of chemoresistance in OC and explores possible clinical applications for overcoming chemoresistance. Recent Findings Lysosomes contribute to chemoresistance through various mechanisms, including increased lysosomal biogenesis, resulting from the enhanced activity of transcription factor EB, a master regulator of the autophagy-lysosome pathway, which enhances cellular capacity for drug sequestration. Lysosomal exocytosis allows the cell to secrete chemotherapeutic agents from OC cells. Lysosomal autophagy pathways enable OC cells to selectively recycle cell components during chemotherapeutic stress. Finally, lysosomal signaling pathways disrupt various cell death mechanisms such as apoptosis, necroptosis, and ferroptosis, which allow cancer cells to evade death under chemotherapeutic stress. Summary Targeting lysosomal biogenesis, stage-specific autophagy modulation, and lysosome-dependent metabolic vulnerabilities are promising avenues for sensitization of chemoresistant OC cells.

Integrative Medicine for Ovarian Cancer

Integrative oncology (IO) services provide a wide range of complementary medicine therapies, many of which can augment the beneficial effects of conventional supportive and palliative care for patients with ovarian cancer. This study aims to assess the current state of integrative oncology research in ovarian cancer care. We review the clinical research both supporting the effectiveness of leading IO modalities in ovarian cancer care as well as addressing potential safety-related concerns. There is growing amount of clinical research supporting the use of IO and implementation of integrative gynecological oncology models of care within the conventional supportive cancer care setting. Additional research is still needed in order to create clinical guidelines for IO interventions for the treatment of female patients with ovarian cancer. These guidelines need to address both effectiveness and safety-related issues, providing oncology healthcare professionals with indications for which these patients can be referred to the IO treatment program.

PARP Inhibitors in Breast Cancer: a Short Communication

Abstract Purpose of Review In the last decade, poly (ADP-ribose) polymerase (PARP) inhibitors have been approved in the treatment of several cancers, such as breast and ovarian cancer. This article aims to discuss the current uses, limitations, and future directions for PARP inhibitors (PARPis) in the treatment of breast cancer. Recent Findings Following the results of the OlympiAD and EMBRACA trials, PARPis were approved in HER2-negative breast cancer with a germline BRCA mutation. We reviewed this class of drugs’ mechanism of action, efficacy, and limitations, as well as further studies that discussed resistance, impaired homologous recombination repair (HRR), and the combination of PARPis with other drugs. Summary Improving understanding of HRR, increasing the ability to target resistance, and combining PARPis with other novel agents are continuing to increase the clinical utility of PARPis.

PARP Inhibitors in the Neoadjuvant Setting; A Comprehensive Overview of the Rationale for their Use, Past and Ongoing Clinical Trials

Abstract Purposeof Review Poly (ADP-ribose) polymerases (PARPs) are enzymes essential for detecting and repairing DNA damage through poly-ADP-ribosylation. In cancer, cells with deficiencies in homologous recombination repair mechanisms often become more dependent on PARP-mediated repair mechanisms to effectively repair dsDNA breaks. As such, PARP inhibitors (PARPis) were introduced into clinical practice, serving as a key targeted therapy option through synthetic lethality in the treatment of cancers with homologous recombination repair deficiency (HRD). Though PARPis are currently approved in the adjuvant setting for several cancer types such as ovarian, breast, prostate and pancreatic cancer, their potential role in the neoadjuvant setting remains under investigation. This review outlines the rationale for using PARPi in the neoadjuvant setting and evaluates findings from early and ongoing clinical trials. Recent Findings Our analysis indicates that numerous studies have explored PARPi as a neoadjuvant treatment for HRD-related cancers. The majority of neoadjuvant PARPi trials have been performed in breast and ovarian cancer, while phase II/III evidence supporting efficacy in prostate and pancreatic cancers remains limited. Summary Studies are investigating PARPi in the neoadjuvant setting of HRD-related cancers. Future research should prioritize combination strategies with immune checkpoint inhibitors and expand outcome measures to include patient satisfaction and quality-of-life metrics.

Frontline Maintenance Treatment for Ovarian Cancer

Abstract Purpose of Review Advanced epithelial ovarian cancer remains the most lethal gynaecological cancer. Most patients with advanced disease will relapse within 3 years after primary treatment with surgery and chemotherapy. Recurrences become increasing difficult to treat due to the emergence of drug resistance and 5-year survival has changed little over the last decade. Maintenance treatment, here defined as treatment given beyond primary chemotherapy, can both consolidate the response and prolong the control of disease which is an approach to improve survival. Recent Findings Here we review maintenance strategies such as targeting angiogenesis, interference of DNA repair through inhibition of PARP, combinations of targeting agents, and immunotherapy and hormonal therapy. Summary Much has been learnt from the success and challenges of these treatments that have in the last few years which led to significant reduction in disease recurrence, changed the guidelines for treatment, and established a new paradigm for the treatment of ovarian cancer.

Integrating Precision Medicine into the Contemporary Management of Gynecologic Cancers

The treatment of patients with advanced gynecologic malignancies remains challenging. Advancements in genomics have led to recognition and development of individualized therapeutic targets. This article reviews the current trends in precision medicine for treatment of gynecologic cancers. With the identification of the molecular aberrations inherent to gynecologic malignancies, we have discovered targetable mutations. Specific to ovarian, endometrial and cervical cancers, potential therapeutic targets that have been identified and shown to have benefit include: hormonal therapies, anti-angiogenic agents, poly-ADP-ribose polymerase inhibitors (PARPi), and immunotherapy. The adoption of targeted therapeutics for the treatment of gynecologic cancers has been gradual, but we have started to see the rapid employment of novel targeted agents into clinical trial development, leading to new treatment approvals. However, there are challenges to the universal precision medicine implementation, and future studies need to identify, discover, and validate robust biomarkers with strong prognostic/predictive capabilities.

Surgical Management of Early Cervical Cancer: When Is Laparoscopic Appropriate?

This paper reviews the recent literature data on minimally invasive surgical approach to early cervical cancer compared to abdominal approach, with the aim of evaluate the oncological outcomes and the appropriateness of current indications. A recent multicenter randomized controlled trial and a concurrent large epidemiological study, contrary to the previous retrospective data, showed that minimally invasive surgery is associated with significantly poorer survival than the open approach. Open surgery is to be considered the standard of care for early cervical cancer as implemented in the current guidelines, and the patients must be carefully counseled if minimally invasive surgery is offered. Minimally invasive surgery can be considered safe only for sentinel lymph node mapping in a fertility-sparing setting and could be considered after preoperative conization and for small tumors, adopting preventive surgical maneuvers and in reference centers. However, prospective evidences about the suggested indications are not yet available.

Management of Stage IIB Cervical Cancer: an Overview of the Current Evidence

To review and discuss the present evidence of surgery- and radiation-based treatment strategies for stage IIB cervical cancer. Recently, two randomized controlled trials compared the efficacy of neoadjuvant chemotherapy followed by radical hysterectomy (NACT + RH) with that of concurrent chemoradiotherapy (CCRT) for stage IB3-IIB cervical cancer. When these studies were combined (N = 1259), NACT + RH was associated with a shorter disease-free survival [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.13-1.64], but with a similar overall survival (HR 1.11, 95% CI 0.90-1.36) when compared with the findings for CCRT. Stage-specific analysis for stage IIB cervical cancer demonstrated that disease-free survival was significantly worse with NACT + RH than with CCRT (HR 1.90, 95% CI 1.25-2.89); however, no significant difference was observed for stage IB3-IIA cervical cancer. Based on the results of recent level I evidence, the standard treatment for stage IIB cervical cancer remains CCRT.

Immunotherapy in Cervical Cancer

This review aims to summarize the current immunotherapy studies and the potential targeted therapies showing promise in the treatment of cervical cancer. There are promising ongoing monotherapy and combination therapy trials using different immune checkpoint inhibitors, poly adenosine diphosphate ribose polymerase inhibitors, tumor angiogenesis inhibitors (i.e., bevacizumab), antibody-drug conjugates, therapeutic vaccines, and tumor-infiltrating T lymphocytes (adoptive immunotherapy). Some of these novel modalities are also being evaluated in combination with standard platinum-based chemotherapy regimen. At this time, pembrolizumab is approved for the treatment of relapsed or metastatic programmed death ligand 1 (PD-L1) positive cervical cancer after frontline chemotherapy treatment. Multiple novel therapeutic modalities are emerging as safe and effective for the treatment of cervical cancer patients. Development and participation in investigative treatments can provide benefit and improve outcomes in cervical cancer.

The Dairy and Cancer Controversy: Milking the Evidence

Fertility-Sparing and Less Radical Surgery for Cervical Cancer

AbstractPurpose of ReviewPatients with early-stage cervical cancer who desire future fertility may be candidates for less radical surgery. We review the literature supporting this approach in early-stage disease.Recent FindingsRetrospective data have shown that in carefully selected patients, the risk of parametrial involvement is less than 1%. This has led to interest in moving away from radical surgery towards more conservative approaches. Data from the newly published ConCerv trial, a prospective study evaluating the feasibility of conservative surgery in women with early-stage, low-risk cervical carcinoma, suggest that conservative surgery is feasible and safe in this patient population. Furthermore, neoadjuvant chemotherapy is being assessed as an option to extend fertility-sparing treatment to a larger group of women.SummaryLess radical surgery may be appropriate for carefully selected women with early-stage, low-risk cervical cancer, including those desiring future fertility.

Weight Management for Fertility-Preservation Therapy in Endometrial Cancer: Opportunities and Challenges

Obesity is increasingly recognized as a significant factor impacting the outcomes of fertility-preserving therapies for endometrial cancer (EC). This review explores the effects of glycolipid metabolism on EC and its relationship with body weight. We will examine how excess body weight influences the effectiveness of fertility-preserving treatments and discuss potential mechanisms for effective weight management. Additionally, the review highlights the importance of comprehensive weight management as an adjunct strategy to enhance the efficacy of fertility-preserving interventions, providing insights into how to integrate metabolic health into clinical treatment protocols. Weight management can modify the tumor microenvironment by depriving the tumor of nutrients, whereas exercise can enhance immunity, potentially leading to tumor cell death. In addition, progesterone therapy may impede the proliferation of EC cells. Comprehensive weight management can serve as an essential adjuvant treatment for patients undergoing fertility-preserving therapies for EC. In this review, we highlight that comprehensive weight management can serve as a crucial adjuvant treatment for patients undergoing fertility-preserving therapies for endometrial cancer. Targeting glycolipid metabolism and addressing adiposity can improve hormonal balance, reduce inflammation, and enhance fertility outcomes. Further research is necessary to establish specific protocols and evaluate the effectiveness of these strategies in clinical practice.

Uterine-Conserving Treatment Options for Atypical Endometrial Hyperplasia and Early Endometrial Cancer

This review aims to synthesize available literature on uterine-conserving treatment options for atypical endometrial hyperplasia and grade 1 endometrial carcinoma while highlighting remaining unanswered questions. The need for uterine-conserving treatment options for atypical endometrial hyperplasia and grade 1 endometrial carcinoma is growing with the increasing number of cases in younger patients or those who cannot undergo surgery. We reviewed the oncological and reproductive outcomes associated with endocrine therapies used for atypical endometrial hyperplasia and grade 1 endometrial carcinoma. The rising prevalence of delayed childbearing, obesity, and diabetes in reproductive-age individuals and of medical comorbidities associated with high surgical risk continues to amplify the demand for uterine-conserving therapies. Appropriate patient selection for such therapies is imperative to maximize likelihood of treatment response. The ideal candidates are patients with atypical endometrial hyperplasia or early-stage, low-grade endometrial cancer with no evidence of myometrial invasion or extrauterine disease. The most accepted conservative therapeutic approach is hormonal therapy with close surveillance, with or without eventual hysterectomy following childbearing or failure of treatment. Further prospective and randomized trials are needed to address optimal patient and treatment selection, as well as the use of molecular profiling for treatment individualization and prognostication.

Lymphatic Mapping and Sentinel Node Biopsy in High-Grade Uterine Cancers

Sentinel lymph node (SLN) mapping has been adopted as an acceptable method of lymph node evaluation in the surgical staging for low-grade endometrial cancer. In this review, we analyze the literature on the utility of SLN mapping in high-grade endometrial cancer. SLN mapping in high-grade endometrial cancer demonstrates similar high detection rates and diagnostic accuracy as seen in low-grade endometrial cancers. However, obtaining sufficient operator experience (at least 30 cases) and following SLN mapping algorithm continues to be essential to preserving diagnostic accuracy. Although limited in retrospective study design and short-term follow-up, current studies have not demonstrated inferior survival outcomes of SLN mapping compared to traditional lymphadenectomy. SLN mapping is an acceptable and accurate method of lymph node evaluation in high-grade endometrial cancer. Future prospective studies are needed to evaluate long-term oncologic outcomes between SLN mapping and systematic lymphadenectomy in this patient population.

Integrative Oncology for Biochemical Recurrence of Epithelial Ovarian Cancer

Impact of Molecular Classification on Treatment Paradigms in Uterine Cancers

This article will discuss the recent data on the prognostic significance of molecular classification of endometrial carcinoma, as well as its impact on directing treatment decisions. Molecular classification has emerged as a complement to the current paradigm of endometrial cancer (EC) risk stratification. POLE mutations appear to portend favorable prognoses, but data are insufficient to indicate withholding treatment based on this signature. Copy number high (CNH) EC carries a worse prognosis and may benefit from more aggressive therapy. MMRd tumors are likely to have other prognostic features that indicate adjuvant treatment and many recurrences respond favorably to pembrolizumab. Progression of molecular profiling may allow further discrimination of the no specific molecular profile (NSMP) group. Treatment for this group remains largely based on conventional risk factors. For both the NSMP and the CNH groups, treatment with lenvatinib and pembrolizumab is an attractive contemporary option for recurrence management. Molecular classification is a useful adjunct to conventional risk stratification paradigms for both prognostic counseling and treatment selection. Clinical trials incorporating molecular signatures in assigning treatment strategies may further elucidate the value of this classification system.