Surgery is considered a cornerstone in the treatment of advanced ovarian cancer. The absence of macroscopic residual tumor at the end of surgery is associated with a better outcome in primary debulking surgery and secondary cytoreduction for patients with a first relapse. Despite the absence of randomized clinical trials in the front-line setting, nobody questions the value of surgery in the initial management of primary advanced ovarian cancer due to extensive data showing a clear benefit in overall survival of complete cytoreduction after primary debulking surgery and interval debulking surgery. In the first relapse, three randomized clinical trials have produced apparently contradictory results. It is important to mention (for the best understanding of the question that we are dealing with), that only the studies including clearly defined selection criteria for cytoreduction, AGO-OVAR DESKTOP-III and SOC1, have produced a positive result in terms of progression-free survival. In addition, the AGO-OVAR study has also shown a benefit in overall survival.

Concomitant chemo-radiation followed by brachytherapy, for the treatment of locally advanced cancer, is considered as the standard of care in many countries. The place of “adjuvant” hysterectomy to remove potential residual disease after the end of radiation therapy fuels a lot of debates during the three last decades. But using modern technics of external radiation therapy and brachytherapy (3D image-guided adaptive procedure) the rate of patients with residual disease is low (<10%) and the morbidity of hysterectomy in this previously irradiated area consistent. As randomized trial failed to demonstrate a survival improvement of such hysterectomy, many teams considered this procedure as useless and obsolete. Such surgery could be nevertheless considered in patients having “really” a residual disease at the end of treatment but such cases should be highly selected to ensure the absence of extra-cervical disease in these patients having chemo-radio-resistant disease with a higher risk of extra-pelvic occult spread.

The radical trachelectomy procedure is now recognized as a “standard of care” option for young women with early-stage cervical cancer who wish to preserve fertility. However, the oncologic safety of this approach has mostly been validated for small lesions measuring <2 cm. The optimal management for patients with larger lesions who wish to preserve fertility remains unsettled and there is currently no standard of care. There are essentially two alternatives: either to proceed with upfront radical trachelectomy or neo-adjuvant chemotherapy (NACT) followed by fertility-sparing surgery (FSS). The balance between oncologic outcomes and surgical morbidity versus fertility and obstetrical outcomes need to be carefully balanced and addressed. We wish to present to the readers with arguments for and against both options in the hopes that it will help clinicians decide which is the best option for their individual patients.

The introduction of molecular profiling into the management of endometrial cancer would be premature, unjust, and frankly unnecessary. Prospective randomized control trials proving the utility of molecular profiling are an absolute necessity before the wide implementation of this prognostic stratification. As yet these do not exist. Endometrial cancer occurs throughout the world and across all socioeconomic classes. As such, any approach to the management of endometrial cancer should be accessible to all. Molecular profiling is an expensive, highly specialized technique. Any introduction of this technology into the management of endometrial cancer would lead to significant inequity across the globe. Finally, the vast majority of endometrial cancers are adequately classified using histopathology and immunohistochemistry both of which are available worldwide in a cost-effective and reproducible manner. Until prospective randomized controlled trials show that the implementation of molecular profiling into the management of endometrial cancer improves survival and reduces treatment-related morbidity we should temper our enthusiasm.

Despite the success in various other cancer types, there are no approved immune therapies for ovarian cancer, as response of ovarian cancer to immunotherapies thus far have been modest. Early studies of single agent anti-PD-1 antibodies in patients with platinum-resistant or recurrent ovarian cancer demonstrated response rates of between 8–15%. Combination strategies combining PD-1 or PD-L1 antibodies with anti-CTLA-4 antibodies have demonstrated slightly higher response rates of over 30%. Additional studies including chemotherapy in combination with immune checkpoint inhibitors (ICI) have shown no additional benefit of addition of ICI to traditional chemotherapy regimens. We argue that outside of a clinical trial, there is no evidence to support routine usage of ICIs in EOC, even in a heavily pretreated platinum-resistant setting, although we are hopeful that biomarkers that may predict response to ICIs in ovarian cancer may be identified in the future. Lastly, we anticipate that emerging approaches in ovarian cancer immunotherapy such as novel ICI combinations, antibody-drug conjugates, bispecific antibodies, cytokines, and adoptive cell therapies will prove to be successful and look forward to the results of these studies.

Vulvar/vaginal melanomas are uncommon malignancies. Due to the relative infrequency of vulvo-vaginal melanomas, many treatments are used after initial surgical resection. Pelvic radiation may be used in patients who are initially unresectable, have positive lymph nodes or have close margins. Pelvic exenteration after pelvic recurrence of vulvo-vaginal melanomas in a radiated field may be necessary and appropriate in select patients.

The radical trachelectomy procedure is now recognized as a “standard of care” option for young women with early-stage cervical cancer who wish to preserve fertility. However, the oncologic safety of this approach has mostly been validated for small lesions measuring <2 cm. The optimal management for patients with larger lesions who wish to preserve fertility remains unsettled and there is currently no standard of care. There are essentially two alternatives: either to proceed with upfront radical trachelectomy or neo-adjuvant chemotherapy (NACT) followed by fertility-sparing surgery (FSS). The balance between oncologic outcomes and surgical morbidity versus fertility and obstetrical outcomes need to be carefully balanced and addressed. We wish to present to the readers with arguments for and against both options in the hopes that it will help clinicians decide which is the best option for their individual patients.

A malignant bowel obstruction (MBO) from recurrent or progressive gynecologic cancer is a terminal diagnosis that is associated with symptoms of pain and nausea, emotional distress, and significant cost to the healthcare system. Prioritizing patient needs in the form of emotional support and symptom control, rather than detracting from these needs with aggressive surgery, can optimize multiple outcomes at the time of an MBO diagnosis. In this context, gastrostomy tubes are the best option to help control nausea and vomiting and potentially allow patients to receive more chemotherapy, with less risk of side effects or complications. Gastrostomy tubes are also associated with lower cost than surgical interventions for MBO and less intensive care at the end of life, setting the stage for appropriate focus on quality of life.

During the last few decades, radical hysterectomy (RH) for early-stage cervical cancer has been performed either by laparotomy or a minimally invasive (MIS) approach, which were both considered acceptable and safe. However, the results of the phase III multicentric randomized LACC trial showed that MIS radical hysterectomy was associated with worse disease-free survival and overall survival.

A recently published Swedish nationwide population-based cohort study showed that the recurrence pattern was similar after open and robotic RH for women with early-stage cervical cancer. Based on these results, the authors designed the Robot-assisted Approach to Cervical Cancer (RACC) study, a randomized non-inferiority trial of robot-assisted laparoscopic surgery versus laparotomy. A European observational study comparing MIS versus open surgery showed that MIS increased the risk of relapse and death compared with open surgery. However, by avoiding use of the uterine manipulator and utilizing maneuvers to prevent tumor spread at the time of colpotomy, MIS was associated with similar outcomes to open surgery.

Whilst hormonal therapy may be the preferred front-line systemic therapy for selected patients with low-grade endometrial carcinoma without rapidly progressive disease, the efficacy in advanced/recurrent endometrial cancer (EC) post chemotherapy is limited. We have entered an era where PD-1/L1 inhibitors have transformed the treatment of EC and immunotherapy should now be considered as a priority option for patients in clinical practice.

The integrated genomic analysis of high-grade serous ovarian cancer carried out by The Cancer Genome Atlas Research Network (TCGA) identified two large subgroups of patients, those harboring homologous recombination (HR) deficiency (50%), characterized by genetic and epigenetic alterations of HR genes, most commonly the BRCA1 and BRCA2 genes, and those with an intact HR pathway, enriched in Cyclin E1 (CCNE1) amplifications. These HR-proficient tumors are associated with inferior survival outcomes and poorer response to PARP inhibitors (PARPi), in comparison with HR-deficient tumors [1,2].

Currently, two of the most used commercially available assays to test HR-deficiency status, Myriad myChoice CDx and the Foundation Medicine’s FoundationFocus CDx, are challenged by the reliable identification of HR-proficient tumors.

Uterine leiomyosarcomas are rare diseases but represent the commonest subtype of uterine sarcomas. For patients with early-stage localized disease, it is well-known that surgery is the most important part of treatment. However, approximately 40% of patients will present recurrent disease with distant metastasis, and for these patients the question arises as to whether they should have secondary cytoreductive surgery or systemic therapy alone. Decision making needs to take various factors into consideration, as only carefully selected patients will benefit from surgery. Patients for whom surgery is most likely to be beneficial are those with small-volume metastatic disease and late recurrences. In contrast, patients with rapidly progressive disease, or those for whom surgery will not achieve complete macroscopic removal, are unlikely to benefit from surgery, which should be avoided.

Complete cytoreduction is the cornerstone of advanced ovarian cancer treatment. The positive impact of no residual disease has been demonstrated even in patients with stage IV disease. Involvement of cardiophrenic nodes (CPLNs), that qualifies as stage FIGO IVB, is common in advanced ovarian cancer. Surgical removal of CPLNs is considered a safe and feasible procedure, requiring a minimal surgical effort associated with a low morbidity. However, data about the impact of CPLN removal on oncologic outcomes are still scarce.

Immune checkpoint blockade (ICB) therapy has emerged as a valuable treatment modality for previously treated advanced or metastatic endometrial cancer (EC) that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H), with impressive and durable response rates seen in a significant proportion of patients. Conversely, a substantial proportion of patients with dMMR/MSI-H EC will not derive benefit from these therapies. It is vitally important to understand the mechanisms behind these disparate responses, as a one-size-fits-all approach, even within the dMMR/MSI-H EC subgroup, cannot be employed. Responses to ICB therapy in mismatch repair proficient (pMMR) or microsatellite stable (MSS) EC have been disappointing, and ICB monotherapy in this setting has not shown efficacy. Additional disadvantages of ICB therapy for the management of EC include the following: a lack of more definitive biomarkers predictive of response; the potential for long-term toxicity, which can necessitate the need for lifelong hormone replacement; a risk of serious sequalae (e.g., colitis, insulin-dependent diabetes mellitus); and extensive financial cost. Caution is warranted when considering this class of therapeutics for patients with EC, as there are still unanswered questions regarding their optimal use.

Treatment of platinum-resistant ovarian cancer poses a challenge to oncologists, as this type of cancers is incurable, and no optimal or standard treatment exists. The available cytotoxic drugs show similar progression-free survival and overall survival rates; therefore, oncologists should consider each case individually and assess not only efficacy but also the possible impact on patient’s quality of life and risks of toxicity. This chapter explores the different treatment options for platinum-resistant ovarian cancer.

In the era of targeted medicine, the use of poly (ADP-ribose) polymerase (PARP) inhibitors in homologous recombination deficient (HRD) tumors has represented the first clinically actionable mutation in gynecologic malignancies. The dramatic results seen across multiple clinical trials completely changed the landscape of epithelial ovarian cancer (EOC) treatments in both primary and recurrent settings. For many, it has spawned hope that additional biomarkers would soon be discovered that could find similarly spectacular results in different patient populations. However, molecular profiling’s efficacy in selecting targeted therapies and its economic practicality are difficult to justify.

Mucinous ovarian carcinomas (MOCs) are a rare subtype of epithelial ovarian cancer accounting for less than 10% of all epithelial ovarian cancers. Improvements in diagnosis have suggested that the incidence has been overestimated and the true incidence is less than 5% [1]. Adjuvant chemotherapy studies have included mucinous tumors and other less common types of epithelial ovarian cancers together with high-grade serous tumors, the most common subtype.

Sixty-five to eighty percent of mucinous ovarian cancers are diagnosed at an early stage and have an excellent prognosis compared to early-stage serous cancers. The standard treatment approach for stage I MOC is surgery and based upon the surgical and pathological staging, further adjuvant treatment may be needed.

The notion that BEP is the optimal chemotherapy regimen for all ovarian germ cell tumors (OGCT) is flawed as there are a number of equally effective and potentially less toxic treatment regimens. OGCTs are highly curable and the focus over recent years has been on minimizing toxicity of treatment and in particular late effects. There has been much effort in de-escalating treatment particularly in patients with advanced stage dysgerminomas with excellent outcomes achieved with carboplatin either alone or in combination. Treatment options for patients with good prognosis, advanced non-dysgerminomatous germ cell tumors include four cycles of etoposide and cisplatin instead of three cycles of BEP. An effective alternative is to substitute ifosfamide for bleomycin and to use three cycles only. In the minority of patients with advanced OGCTs who have adverse prognostic factors, relapse is still high with BEP alone and they should be treated in expert centers with access to clinical trials.