NCCN Guidelines® Insights: Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer, Version 3.2024.

The NCCN Guidelines for Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer provide multidisciplinary diagnostic workup, staging, and treatment recommendations for this disease. These NCCN Guidelines Insights detail how the evolution of the use of PARP inhibitors as maintenance and single-agent regimens for the treatment of ovarian cancer informed panel recommendations in the guidelines.

Results of a randomized phase II trial of paclitaxel and carboplatin versus bleomycin, etoposide and cisplatin for newly diagnosed and recurrent Chemonaive stromal ovarian tumors: An NRG oncology/gynecologic oncology group study14.

OBJECTIVES: To assess the efficacy and toxicity of paclitaxel and carboplatin (PC) compared to bleomycin, etoposide, and cisplatin (BEP) for treatment of newly diagnosed Stage IIA-IV or recurrent chemotherapy-naive ovarian sex cord-stromal tumors (SCST). METHODS: This phase II noninferiority trial randomly assigned patients to receive PC (6 cycles P 175 mg/m2 and C AUC = 6 IV every 3 weeks), or BEP (4 cycles B 20 units/m2 IV push day 1, E 75 mg/m2 IV days 1-5, and cisplatin 20 mg/m2 IV days 1-5 every 3 weeks). The primary endpoint was progression- free survival (PFS). This trial is registered with ClinicalTrials.gov, NCT01042522. RESULTS: At the interim analysis, 63 patients (31 PC and 32 B.P. had accrued between Feb 8, 2010 and Apr 30, 2020. Median age was 48 years. 87% had granulosa cell tumors. 37% had measurable disease. The DSMB closed accrual early for futility of PC arm. The futility analysis was supported by an estimated HR = 1.11 [95% CI: 0.57 to 2.13] which exceeded the pre-determined threshold for non-inferiority (1.10). Median PFS was 27.7 months [11.2 to 41.0] for PC and 19.7 months for BEP [95% CI: 10.4-52.7]. PC patients had fewer grade 3 or higher adverse events (PC 77% vs BEP 90%). CONCLUSIONS: The study met its pre-specified criterion for stopping early for futility and so failed to demonstrate non-inferiority of PC versus BEP in ovarian SCSTs, in a non-inferiority test with a hazard ratio margin of 1.1. Both PC and BEP may be considered in patients with advanced/recurrent SCST.

Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024.

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.

Minimally invasive interval debulking surgery for advanced ovarian cancer after neoadjuvant chemotherapy.

OBJECTIVE: Assess outcomes of interval debulking surgery (IDS) after neoadjuvant chemotherapy via minimally invasive surgery (MIS) compared with laparotomy in patients with advanced epithelial ovarian cancer. METHODS: Patients diagnosed with stage IIIC or IV epithelial ovarian cancer between 2013 and 2018 who received neoadjuvant chemotherapy and IDS were identified in the National Cancer Database. Primary outcome was overall survival. Secondary outcomes were 5-year survival, 30- and 90-day postoperative mortality, extent of surgery, residual disease, hospitalization duration, surgical conversions, and unplanned readmissions. Propensity score matching was used to compare MIS and laparotomy for IDS. Association of treatment approach with overall survival was assessed using Kaplan-Meier method and Cox regression. Sensitivity analysis was conducted for effect of unmeasured confounders. RESULTS: A total of 7897 patients met inclusion criteria; 2021 (25.6%) underwent MIS. Percentage undergoing MIS increased from 20.3%-29.0% over the study period. After propensity score matching, median overall survival was 46.7 months in the MIS group versus 41.0 months in the laparotomy group [hazard ratio (HR) 0.86 (95%CI 0.79-0.94)]. Five-year survival probability was higher in MIS versus laparotomy (38.3% vs 34.8%, p < 0.01). There was lower 30- and 90-day mortality (0.3% vs 0.7% [p = 0.04] and 1.4% vs 2.5% [p = 0.01], respectively), shorter length of stay (median 3 vs 5 days, p < 0.01), lower residual disease (23.9% vs 26.7%, p < 0.01), and lower additional cytoreductive procedures (59.3% vs 70.8%, p < 0.01) in MIS compared to laparotomy, with similar rates of unplanned readmission (2.7% vs 3.1%, p = 0.39). CONCLUSIONS: Patients who undergo IDS by MIS have similar overall survival and decreased morbidity compared with laparotomy.

Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.

NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.

Minimally Invasive Surgery in Morbidly Obese Women.

Minimally invasive gynecologic surgery provides a number of clinical advantages compared with open laparotomy. Over the past 25 years, important modifications and innovations have further expanded the utility of these techniques. Complications such as surgical site infection, venous thromboembolism, and wound cellulitis or dehiscence rise in concert with escalating obesity, so it stands to reason that these patients would derive the most benefit from minimally invasive surgery. Yet, surgical complexity also rises proportionally, requiring fastidious technique and allowing little margin for error. As nonsurgical interventions become more commonplace and the rate of morbid obesity continues to increase, those women actually requiring a gynecologic operation through an abdominal approach will be ever more likely to present a number of challenges to safe completion of minimally invasive surgery. This article frames the topic and offers some tips across the range of care to enhance the likelihood of achieving success in this patient population most in need of surgical expertise.

Laparoscopic diverting loop ileostomy for spontaneous colon perforation in advanced ovarian cancer.

OBJECTIVE: Neoadjuvant chemotherapy for advanced ovarian cancer is associated with reduced morbidity in the elderly (Meyer et al., 2018). Spontaneous colonic perforation often leads to multisystem organ failure and death (Carter and Durfee, 2007; Rose and Piver, 1995). METHODS: A 76-year old woman with stage IIIC disease initiated carboplatin AUC 5 and paclitaxel 175 mg/m2 with unanticipated development of profound neutropenia. She clinically deteriorated by day nine and CT scan revealed a large volume of free air. Emergent surgery was performed. RESULTS: Diagnostic laparoscopy confirmed the presence of intra-abdominal stool and extensive inflammatory exudate (Video). The likelihood of identifying the site of perforation appeared remote, but pelvic tumor encasement was highly suggestive of a sigmoid origin. The stool was evacuated, the exudate gently debrided and the terminal ileum partially mobilized. Copious irrigation was performed with drain placement and the pneumoperitoneum was decompressed. The right lower abdominal wall trocar incision was extended so that the ileal segment could be brought out and matured. She was discharged to rehab on postoperative day 2 to continue a two week course of broad spectrum antibiotics. Single-agent carboplatin was resumed within a month. Uncomplicated ileostomy takedown with parastomal hernia repair was performed between cycles five and six. The patient is currently in remission. CONCLUSION: Bowel perforation in the elderly, presenting with cachexia and treatment-induced pancytopenia for advanced ovarian cancer, is often a harbinger of early death. Selected patients may benefit from a minimally invasive approach by an experienced gynecologic oncologist instead of vertical laparotomy, abdominal washout, diversion and the potential sequelae of an open abdomen.

Stage IV Gestational Choriocarcinoma Diagnosed in the Third Trimester.

BACKGROUND: Gestational trophoblastic neoplasia rarely occurs in term pregnancies. Stage IV choriocarcinoma treated with conventional chemotherapy can result in death as a result of hemorrhagic sequelae at tumor sites. CASE: A 30-year-old woman at 34 weeks of gestation presented with a persistent cough, worsening dyspnea, and vaginal bleeding. Chest radiograph demonstrated innumerable lung nodules, and quantitative ß-hcg concentration exceeded 1.3 million milli-international units/mL. Cesarean delivery was performed for presumed abruption. Placental pathology demonstrated choriocarcinoma, and imaging confirmed stage IV disease with a World Health Organization score of 14. Remission was achieved after two courses of low-dose induction chemotherapy followed by 10 cycles of combination chemotherapy. CONCLUSION: Gestational trophoblastic neoplasia should be considered in a pregnant or postpartum woman presenting with atypical vaginal bleeding. Coexistent pulmonary or neurologic findings may suggest advanced disease.

Trends in Place of Death Among Patients With Gynecologic Cancer in the United States.

OBJECTIVE: To describe the change over time in place of death (hospital, home, hospice) among all women in the United States who died of gynecologic malignancies and compare them with other leading causes of female cancer deaths. METHODS: This is a retrospective cross-sectional study using national death certificate data from the Mortality Multiple Cause-of-Death Public Use Record Data. All women who died from gynecologic, breast, lung, and colorectal cancers were identified according to International Classification of Diseases, 10 Revision, cause of death from 2003 to 2015. Regression analyses with ordinary least-squares linear probability modeling were used to test for differences in location of death over time, and differences in trends by cancer type, while controlling for age, race, ethnicity, marital status, and education status. RESULTS: From 2003 to 2015, 2,133,056 women died from gynecologic, lung, breast, and colorectal malignancies in the United States. A total of 359,340 died from gynecologic malignancies, including ovarian cancer (n=188,366 [52.4%]), uterine cancer (n=106,454 [29.6%]), cervical cancer (n=52,320 [14.6%]), and vulvar cancer (n=12,200 [3.4%]). Overall, 49.2% (n=176,657) of gynecologic cancer deaths occurred at home or in hospice. The relative increase from 2003 to 2015 in the rate of deaths at home or in hospice was 47.2% for gynecologic cancer deaths (40.5% in 2003 to 59.5% in 2015). In adjusted analyses, the trend in the percentage of deaths at home or in hospice increased at a rate of 1.6 percentage points per year for gynecologic cancer deaths (95% CI 1.5-1.6) vs 1.5 (95% CI 1.4-1.5, P<.001), 1.4 (95% CI 1.4-1.5, P<.001), and 1.5 (95% CI 1.4-1.5, P=.09) percentage points per year for lung, breast, and colorectal cancer deaths, respectively. CONCLUSION: Between 2003 and 2015, there was a 47.2% increase (40.5-59.5%) in the rates of gynecologic cancer deaths occurring at home or in hospice. This trend may represent an increase in advance care planning and value-based treatment decisions.

Racial and ethnic disparities over time in the treatment and mortality of women with gynecological malignancies.

OBJECTIVE: To examine temporal trends in treatment and survival among black, Asian, Hispanic, and white women diagnosed with endometrial, ovarian, cervical, and vulvar cancer. METHODS: Using the National Cancer Database (2004-2014), we identified women diagnosed with endometrial, ovarian, cervical, and vulvar cancer. For each disease site, we analyzed race/ethnicity-specific trends in receipt of evidence-based practices. Professional societies' recommendations were used to define these practices. Using data from the Surveillance, Epidemiology, and End Results Program (2000-2009) we analyzed trends in 5-year survival. RESULTS: Throughout the study period black (64.8%) and Hispanic (68.3%) women were less likely to undergo lymphadenectomy for stage I ovarian cancer compared to Asian (79.5%) and white patients (74.6%). Black women were the least likely group to undergo lymphadenectomy in all periods. Among patients with stage II-IV ovarian cancer, 76.6% of white and Asian women received both surgery and chemotherapy, compared to 70.8% of black and 73.9% Hispanic women. Hispanic women with deeply invasive or high-grade stage I endometrial cancer underwent lymphadenectomy less frequently (74.5%) than all other groups (80.7%). Black women were less likely to have chemo-radiotherapy for stage IIB-IVA cervical cancer (75.6% versus 80.4% of all others). Black women were also less likely to have a surgical lymph node evaluation for vulvar cancer (58.8% versus 63.5% of all others). Among women diagnosed with ovarian, endometrial, and cervical cancer, black women had lower five-year survival than other groups. CONCLUSION: Significant racial disparities persist in the delivery of evidence-based care. Black women with ovarian, endometrial, and cervical cancer continue to experience higher cancer-specific mortality than other groups.

Meigs to modern times: The evolution of debulking surgery in advanced ovarian cancer.

Joe V. Meigs was a visionary clinician and an early adopter of radical techniques in the surgical treatment of ovarian cancer. His 1934 textbook "Tumors of the Female Pelvic Organs", consolidated his approach to this "hopeless" disease, with pearls on diagnosis, outcomes, and even speculations about the benefits of minimally invasive surgery. Decades before adjuvant chemotherapy would prove of value, and in an era when sophisticated statistics were unheard of, he nonetheless tried to eke out what benefits he could using the methods available in his time. We transition his original findings and observations through the advent of platinum-based chemotherapy, retrospective cohort studies supporting the benefits of primary debulking, and finally the long-awaited randomized controlled trial. We aim to provide historical context for the underpinnings of how cytoreductive surgery has evolved into its current role in the treatment of advanced ovarian cancer.

Modeling treatment outcomes for patients with advanced ovarian cancer: Projected benefits of a test to optimize treatment selection.

OBJECTIVE: For patients with advanced stage epithelial ovarian cancer (EOC), substantial emphasis has been placed on diagnostic tests that can discern which of two treatment options - primary cytoreductive surgery (PCS) or neoadjuvant chemotherapy followed by interval cytoreductive surgery (NACT+ICS) - optimizes patient-level outcomes. Our goal was to project potential life expectancy (LE) gains that could be achieved by use of such a test. METHODS: We developed a microsimulation model to project LE for patients with stage IIIC EOC. We compared: a "standard-of-care" strategy, in which patients were triaged to PCS vs. NACT+ICS based on current clinical practice; and a "test" strategy, in which patients were triaged based on results of a hypothetical test. We identified those test performance characteristics for which the test strategy outperformed the standard-of-care strategy, from a LE standpoint. Effects of parameter uncertainty were evaluated in sensitivity analysis. RESULTS: Even with a perfect test, the LE gain was modest (LE with test vs. standard-of-care strategy=67.6 vs. 66.4months; LE gain=1.2months). In order to outperform the standard-of-care, the test had to have a high probability of correctly identifying "resectable" patients at PCS (i.e. those for whom complete or optimal cytoreduction would be possible); this test property was more important than correct triage of unresectable patients to NACT+ICS. Results were sensitive to the proportion of patients whose underlying disease was resectable at PCS. CONCLUSION: Diagnostic tests that are designed to triage patients with advanced stage EOC will likely have only a modest effect on LE.

Society of Gynecologic Oncology Clinical Outcomes Registry: From small beginnings come great things.

OBJECTIVE: Clinical registries within medical societies have demonstrated the capacity to promote quality improvement. Opportunities for well-designed data repositories could yield reliable national standards for informing reimbursement, determining adherence to care guidelines, maintaining board certification, and developing bundled payment models. Looking to the future, we set out to develop a gynecologic cancer registry serving the members of the Society of Gynecologic Oncology (SGO). METHODS: The SGO Clinical Outcomes Registry (COR) initiated a web-based data entry platform as a foray into developing a functional registry, compiling data elements specific to gynecologic oncology. Endometrial and ovarian cancer patients began enrollment in early 2014. Within one year, 19 sites were participating with the addition of cervical cancer patients in January 2015. RESULTS: To date, >6500 patients are currently entered from 29 sites, and the COR is being queried to address topics of quality improvement, disparities, and cancer outcomes. CONCLUSIONS: The SGO COR has proven the feasibility of developing a functional gynecologic cancer registry, with high uptake, rapid accrual, and ability to investigate topics of quality and outcome using the COR.