Trends in the use of neoadjuvant chemotherapy for low-grade serous ovarian cancer in the United States.

OBJECTIVE: To describe trends in neoadjuvant chemotherapy (NACT) use for low-grade serous ovarian carcinoma (LGSOC) and to quantify associations between NACT and extent of cytoreductive surgery. METHODS: We identified women treated for stage III or IV serous ovarian cancer in a Commission on Cancer accredited program between January 2004-December 2020. Regression models were developed to evaluate trends in NACT use for LGSOC, to identify factors associated with receipt of NACT, and to quantify associations between NACT and bowel or urinary resection at the time of surgery. Demographic and clinical factors were used for confounder control. RESULTS: We observed 3350 patients who received treatment for LGSOC during the study period. The proportion of patients who received NACT increased from 9.5% in 2004 to 25.9% in 2020, corresponding to an annual percent change of 7.2% (95% CI 5.6-8.9). Increasing age (rate ratio (RR) 1.15; 95% CI 1.07-1.24), and stage IV disease (RR 2.66; 95% CI 2.31-3.07) were associated with a higher likelihood of receiving NACT. For patients with high-grade disease, NACT was associated with a decrease in likelihood of bowel or urinary surgery (35.3% versus 23.9%; RR 0.68, 95% CI 0.65-0.71). For LGSOC, NACT was associated with a higher likelihood of these procedures (26.6% versus 32.2%; RR 1.24, 95% CI 1.08-1.42). CONCLUSION: NACT use among patients with LGSOC has increased from 2004 to 2020. While NACT was associated with a lower rate of gastrointestinal and urinary surgery among patients with high-grade disease, patients with LGSOC receiving NACT were more likely to undergo these procedures.

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.

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.

Anal and Cervical High-Risk Human Papillomavirus Genotyping in Women With and Without Genital Neoplasia.

OBJECTIVE: The aim of the study was to compare the prevalence, genotypes, and rates of concomitant anal and cervical high-risk human papillomavirus (HR-HPV) in women with and without a history of HPV-related genital neoplasia. MATERIALS AND METHODS: This was a prospective cohort study conducted from December 2012 to February 2014. Women with a history of neoplasia were considered the high-risk group. Women without a history of neoplasia were considered the low-risk group. Cervical and anal cytology and HPV genotyping were performed. All women with abnormal anal cytology were referred for anoscopy. RESULTS: One hundred eighty-four women met inclusion criteria. High-risk HPV was detected in the anal canal of 17.4% of the high-risk group and 1.5% of the low-risk group (p = .003). High-risk HPV was detected in the cervix of 30.5% of the high-risk group and 7.6% of the low-risk group (p < .001). Concomitant anal and cervical high-risk HPV was detected in 4.4% of the high-risk group and was not detected in the low-risk group (p = .2). Among women with anal intraepithelial neoplasia 2 or greater (n = 5), 60% had HR-HPV detected in the anal canal while none had HR-HPV detected in the cervix. CONCLUSIONS: Women with a history of genital neoplasia are more likely to be positive for anal and cervical HR-HPV compared with women without a history of genital neoplasia. Although there was no significant difference in rates of concomitant HR-HPV between low- and high-risk groups, HR-HPV can be found concomitantly in the anus and the cervix and may be associated with anal intraepithelial neoplasia or carcinoma.

Minimally Invasive Staging Surgery in Women with Early-Stage Endometrial Cancer: Analysis of the National Cancer Data Base.

PURPOSE: The aim of this study was to determine factors associated with the adoption of minimally invasive surgery (MIS) compared with laparotomy in the treatment of endometrial cancer and to compare surgical outcomes and survival between these two surgical modalities. METHODS: We utilized the National Cancer Data Base (NCDB) to identify women diagnosed with presumed early-stage endometrial cancer between 2010 and 2012. We also identified factors associated with the performance of MIS and utilized propensity score matching to create a matched cohort of women who underwent minimally invasive staging surgery or laparotomy for surgical staging. RESULTS: Overall, 20,346 women were eligible for inclusion in the study; 12,604 (61.9%) had MIS, while 7742 (38.1%) had a laparotomy. African American race (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.49-0.60], Hispanic ethnicity (OR 0.70, 95% CI 0.61-0.80), Charlson score >2 (OR 0.79, 95% CI 0.69-0.91), high-grade histology (OR 0.63, 95% CI 0.59-0.68), presumed clinical stage II disease (OR 0.53, 95% CI 0.46-0.60), and surgery at a community cancer program (OR 0.46, 95% CI 0.39-0.55) or in the Midwest region (OR 0.70, 95% CI 0.64-0.76) were associated with a decreased likelihood of having MIS, while private insurance (OR 1.69, 95% CI 1.45-1.97) and highest quartile median household income (OR 1.13, 95% CI 1.03-1.24) were associated with an increased likelihood of having MIS. After propensity score matching, there was no association between minimally invasive staging surgery and 3-year overall survival (hazard ratio 1.03, 95% CI 0.92-1.16). CONCLUSION: There are notable racial, ethnic, socioeconomic, and geographic variations in the utilization of MIS for endometrial cancer staging in the US. After controlling for the aforementioned factors, MIS had a similar 3-year survival compared with laparotomy in women undergoing staging surgery for endometrial cancer.

Associations between residual disease and survival in epithelial ovarian cancer by histologic type.

OBJECTIVE: Surgical cytoreduction has been postulated to affect survival by increasing the efficacy of chemotherapy in ovarian cancer. We hypothesized that women with high-grade serous ovarian cancer, which usually responds to chemotherapy, would derive greater benefit from complete cytoreduction than those with histologic subtypes that are less responsive to chemotherapy, such as mucinous and clear cell carcinoma. METHODS: We conducted a retrospective cohort study of patients who underwent primary cytoreductive surgery and adjuvant chemotherapy for stage IIIC or IV epithelial ovarian cancer from 2011 to 2013 using data from the National Cancer Database. We constructed multivariable models to quantify the magnitude of associations between residual disease status (no residual disease, ≤1cm, or >1cm) and all-cause mortality by histologic type among women with clear cell, mucinous, and high-grade serous ovarian cancer. Because 26% of the sample had unknown residual disease status, we used multiple imputations in the primary analysis. RESULTS: We identified 6,013 women with stage IIIC and IV high-grade serous, 307 with clear cell, and 140 with mucinous histology. The association between residual disease status and mortality hazard did not differ significantly among histologic subtypes of ovarian cancer (p for interaction=0.32). In covariate adjusted models, compared to suboptimal cytoreduction, cytoreduction to no gross disease was associated with a hazard reduction of 42% in high-grade serous carcinoma (hazard ratio [HR]=0.58, 95% confidence interval [CI]=0.49-0.68), 61% in clear cell carcinoma (HR=0.39, 95% CI=0.22-0.69), and 54% in mucinous carcinoma (HR=0.46, 95% CI=0.22-0.99). CONCLUSIONS: We found no evidence that surgical cytoreduction was of greater prognostic importance in high-grade serous carcinomas than in histologies that are less responsive to chemotherapy.

Disparities in receipt of care for high-grade endometrial cancer: A National Cancer Data Base analysis.

PURPOSE: To examine patterns of care and survival for Hispanic women compared to white and African American women with high-grade endometrial cancer. METHODS: We utilized the National Cancer Data Base (NCDB) to identify women diagnosed with uterine grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear cell carcinoma and papillary serous carcinoma between 2003 and 2011. The effect of treatment on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. RESULTS: 43,950 women were eligible. African American and Hispanic women had higher rates of stage III and IV disease compared to white women (36.5% vs. 36% vs. 33.5%, p<0.001). African American women were less likely to undergo surgical treatment for their cancer (85.2% vs. 89.8% vs. 87.5%, p<0.001) and were more likely to receive chemotherapy (36.8% vs. 32.4% vs. 32%, p<0.001) compared to white and Hispanic women. Over the entire study period, after adjusting for age, time period of diagnosis, region of the country, urban or rural setting, treating facility type, socioeconomic status, education, insurance, comorbidity index, pathologic stage, histology, lymphadenectomy and adjuvant treatment, African American women had lower overall survival compared to white women (Hazard Ratio 1.21, 95% CI 1.16-1.26). Conversely, Hispanic women had improved overall survival compared to white women after controlling for the aforementioned factors (HR 0.87, 95% CI 0.80-0.93). CONCLUSIONS: Among women with high-grade endometrial cancer, African American women have lower all-cause survival while Hispanic women have higher all-cause survival compared to white women after controlling for treatment, sociodemographic, comorbidity and histopathologic variables.

Laparoscopic staging for apparent stage I epithelial ovarian cancer.

BACKGROUND: Whereas advances in minimally invasive surgery have made laparoscopic staging technically feasible in stage I epithelial ovarian cancer, the practice remains controversial because of an absence of randomized trials and lack of high-quality observational studies demonstrating equivalent outcomes. OBJECTIVE: This study seeks to evaluate the association of laparoscopic staging with survival among women with clinical stage I epithelial ovarian cancer. STUDY DESIGN: We used the National Cancer Data Base to identify all women who underwent surgical staging for clinical stage I epithelial ovarian cancer diagnosed from 2010 through 2012. The exposure of interest was planned surgical approach (laparoscopy vs laparotomy), and the primary outcome was overall survival. The primary analysis was based on an intention to treat: all women whose procedures were initiated laparoscopically were categorized as having had a planned laparoscopic procedure, regardless of subsequent conversion to laparotomy. We used propensity methods to match patients who underwent planned laparoscopic staging with similar patients who underwent planned laparotomy based on observed characteristics. We compared survival among the matched cohorts using the Kaplan-Meier method and Cox regression. We compared the extent of lymphadenectomy using the Wilcoxon rank-sum test. RESULTS: Among 4798 eligible patients, 1112 (23.2%) underwent procedures that were initiated laparoscopically, of which 190 (17%) were converted to laparotomy. Women who underwent planned laparoscopy were more frequently white, privately insured, from wealthier ZIP codes, received care in community cancer centers, and had smaller tumors that were more frequently of serous and less often of mucinous histology than those who underwent staging via planned laparotomy. After propensity score matching, time to death did not differ between patients undergoing planned laparoscopic vs open staging (hazard ratio, 0.77, 95% confidence interval, 0.54-1.09; P = .13). Planned laparoscopic staging was associated with a slightly higher median lymph node count (14 vs 12, P = .005). Planned laparoscopic staging was not associated with time to death after adjustment for receipt of adjuvant chemotherapy, histological type and grade, and pathological stage (hazard ratio, 0.82, 95% confidence interval, 0.57-1.16). CONCLUSION: Surgical staging via planned laparoscopy vs laparotomy was not associated with worse survival in women with apparent stage I epithelial ovarian cancer.

Emerging strategies for targeting PI3K in gynecologic cancer.

Ovarian, endometrial and cervical cancers are the most prevalent gynecologic cancers in the United States and account for significant mortality. Translational research into these cancers has highlighted the distinctive molecular and genomic profiles of these cancers finding that, even within a disease site, the landscapes and drivers of neoplasia are distinctive. Despite this molecular diversity, activation of the phosphatidylinositol-3-kinase (PI3K) pathway appears to be conserved in subsets of these tumors, suggesting that strategies that antagonize mediators in this signaling cascade could offer anti-tumor efficacy. Extensive pre-clinical and clinical data have demonstrated that single agent targeted therapies lead to modest single agent activity of generally limited duration, even in the setting of innate PI3K pathway activation via mutation or amplification. These findings in the laboratory and clinic have prompted investigations into resistance pathways following PI3K pathway inhibition in order to understand escape pathways and restore tumor cell sensitivity. A next generation of clinical trial investigations will focus on novel combinations in order to define how these important therapeutics can be used in the clinic. This review will present preclinical data that supports the role of the PI3K pathway in ovarian, endometrial and cervical cancers, in addition to discussing the reported clinical trial experience with PI3K pathway inhibition. A specific focus will be on the rationale behind ongoing clinical trials utilizing novel agents in concert with PI3K pathway inhibitors to reverse resistance in populations with and without gain of function alterations in this oncogenic signaling cascade.

Patterns of care, predictors and outcomes of chemotherapy for ovarian carcinosarcoma: A National Cancer Database analysis.

OBJECTIVE: The aim of this study is to determine if outcomes of patients with ovarian carcinosarcoma (OCS) differ from those of women with high-grade papillary serous ovarian carcinoma (HG-PSOC) when compared by stage and treatment modalities. METHODS: The National Cancer Database was queried to identify patients with OCS and HG-PSOC diagnosed between 2003 and 2011. Demographic and clinical data were compared, and the impact of tumor histology on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. RESULTS: The final study group consisted of 45,153 women. 2886 (6.39%) had OCS and 42,267 (93.61%) had HG-PSOC. The mean age at diagnosis was 65.43 (±12.21) years for women with OCS and 61.52 (±12.6) years for HG-PSOC (P<0.001). African-American women had higher rate of OCS relative to white non-hispanic women (7.84% vs. 6.37%; P=0.002). Overall, women with OCS had a worse five-year survival rate, 26.63% [95% Confidence Interval (CI)=24.86%-28.53%] vs. 43.61% (95% CI=43.07%-44.17%). This difference persisted for each FIGO disease stage I-IV, with five-year survival consistently worse for women with OCS compared to those with HG-PSOC. Over the entire study period and after adjusting for histology, age, period of diagnosis, SEER registry, marital status, stage, surgery, radiotherapy, and lymph node dissection, carcinosarcoma histology was associated with decreased survival. CONCLUSION: OCS is associated with a poor prognosis compared to HG-PSOC. This difference was noted across all FIGO stages.

Trends in the use of neoadjuvant chemotherapy for advanced ovarian cancer in the United States.

OBJECTIVE: Neoadjuvant chemotherapy and interval debulking surgery for the treatment of advanced ovarian cancer has remained controversial, despite the publication of two randomized trials comparing this modality with primary cytoreductive surgery. This study describes temporal trends in the utilization of neoadjuvant chemotherapy and interval debulking surgery in clinical practice in the United States. METHODS: We completed a time trend analysis of the National Cancer Data Base. We identified women with stage IIIC and IV epithelial ovarian cancer diagnosed between 2004 and 2013. We categorized subjects as having undergone one of four treatment modalities: primary cytoreductive surgery followed by adjuvant chemotherapy, neoadjuvant chemotherapy followed by interval debulking surgery, surgery only, and chemotherapy only. Temporal trends in the frequency of treatment modalities were evaluated using Joinpoint regression, and χ2 tests. RESULTS: We identified 40,694 women meeting inclusion criteria, of whom 27,032 (66.4%) underwent primary cytoreductive surgery and adjuvant chemotherapy, 5429 (13.3%) received neoadjuvant chemotherapy and interval surgery, 5844 (15.4%) had surgery only, and 2389 (5.9%) received chemotherapy only. The proportion of women receiving neoadjuvant chemotherapy and surgery increased from 8.6% to 22.6% between 2004 and 2013 (p<0.001), and adoption of this treatment modality occurred primarily after 2007 (95%CI 2006-2009; p=0.001). During this period, the proportion of women who received primary cytoreductive surgery and chemotherapy declined from 68.1% to 60.8% (p<0.001), and the proportion who underwent surgery only declined from 17.8% to 9.9% (p<0.001). CONCLUSION: Between 2004 and 2013 the frequency of neoadjuvant chemotherapy and interval surgery increased significantly in the United States.

Ready for the robot? A cross-sectional survey of OB/GYN fellowship directors' experience and expectations of their incoming fellow's robotic surgical skills.

To describe OB/GYN fellowship directors' (FDs) observations, expectations, and preferences of incoming fellow's robotic surgery preparedness. Cross-sectional study. OB/GYN FDs in gynecologic oncology, minimally invasive gynecologic surgery, female pelvic medicine and reconstructive surgery, and reproductive endocrinology and infertility in the United States. 60 FDs answered the questionnaire. Participants completed an online questionnaire about their preferences and expectations of robotic surgery experience for incoming fellows. FDs observed that many incoming first-year fellows had a baseline understanding of robotic technology (60%) and robotic bedside assist experience (53%). However, few could perform more advanced robotic tasks; with FDs indicating fellows could infrequently robotically suture (18%), or perform the entire hysterectomy (15%). FDs reported higher composite observation than expectation scores (34.3 versus 22.2, p < 0.0001), and higher preference than expectation scores (34.0 versus 22.2, p < 0.0001). The composite expectation score of high-volume divisions was greater than of low-volume divisions (23.7 versus 14.0, p = 0.04). Among the domains identified, FDs most strongly preferred their fellows be able to bedside assist, have a basic understanding of robotic technology, and have basic robotic operative skills. While incoming fellows have more robotic skill than their FDs expect, few are deemed competent to independently operate the robot. Higher volume robotic surgery divisions have higher expectations of the robotic skills of their incoming fellows compared to low-volume divisions; however, FDs neither expected nor preferred their incoming fellows to be fully competent in all aspects of robotic surgery.

Outcomes of Women With High-Grade and Low-Grade Advanced-Stage Serous Epithelial Ovarian Cancer.

OBJECTIVE: To compare outcomes of women with advanced-stage low-grade serous ovarian cancer and high-grade serous ovarian cancer and identify factors associated with survival among patients with advanced-stage low-grade serous ovarian cancer. METHODS: A retrospective study of patients diagnosed with grade 1 or 3, advanced-stage (stage IIIC and IV) serous ovarian cancer between 2003 and 2011 was undertaken using the National Cancer Database, a large administrative database. The effect of grade on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. Among women with low-grade serous ovarian cancer, propensity score matching was used to compare all-cause mortality among similar women who underwent chemotherapy and lymph node dissection and those who did not. RESULTS: A total of 16,854 (95.7%) patients with high-grade serous ovarian cancer and 755 (4.3%) patients with low-grade serous ovarian cancer were identified. Median overall survival was 40.7 months among high-grade patients and 90.8 months among women with low-grade tumors (P<.001). Among patients with low-grade serous ovarian cancer in the propensity score-matched cohort, the median overall survival was 88.2 months among the 140 patients who received chemotherapy and 95.9 months among the 140 who did not receive chemotherapy (P=.7). Conversely, in the lymph node dissection propensity-matched cohort, median overall survival was 106.5 months among the 202 patients who underwent lymph node dissection and 58 months among the 202 who did not (P<.001). CONCLUSION: When compared with high-grade serous ovarian cancer, low-grade serous ovarian cancer is associated with improved survival. In patients with advanced-stage low-grade serous ovarian cancer, lymphadenectomy but not adjuvant chemotherapy was associated with improved survival.

All-Cause Mortality After Fertility-Sparing Surgery for Stage I Epithelial Ovarian Cancer.

OBJECTIVE: To compare all-cause mortality between women who underwent fertility-sparing surgery with those who underwent conventional surgery for stage I ovarian cancer. METHODS: In a cohort study using the National Cancer Database, we identified women younger than 40 years diagnosed with stage IA and unilateral IC epithelial ovarian cancer between 2004 and 2012. Fertility-sparing surgery was defined as conservation of one ovary and the uterus. The primary outcome was time from diagnosis to death. We used propensity score methods to assemble a cohort of women who underwent fertility-sparing or conventional surgery but were otherwise similar on observed covariates and conducted survival analyses using the Kaplan-Meier method and Cox proportional hazard models. RESULTS: We identified 1,726 women with stage IA and unilateral IC epithelial ovarian cancer of whom 825 (47.8%) underwent fertility-sparing surgery. Fertility-sparing surgery was associated with younger age, residence in the northeastern and western United States, and serous or mucinous histology (P<.05 for all). Propensity score matching yielded a cohort of 904 women who were balanced on observed covariates. We observed 30 deaths among women who underwent fertility-sparing surgery and 37 deaths among propensity-matched women who underwent conventional surgery after a median follow-up of 63 months. Fertility-sparing surgery was not associated with hazard of death (hazard ratio 0.80, 95% confidence interval [CI] 0.49-1.29, P=.36). The probability of survival 10 years after diagnosis was 88.5% (95% CI 82.4-92.6) in the fertility-sparing group and 88.9% (95% CI 84.9-92.0) in the conventional surgery group. In patients with high-risk features such as clear cell histology, grade 3, or stage IC, 10-year survival was 80.5% (95% CI 68.5-88.3) among women who underwent fertility-sparing surgery and 83.4% (95% 76.0-88.7) among those who had conventional surgery (hazard ratio 0.86, 95% CI 0.49-1.53, P=.61). CONCLUSION: Compared with conventional surgery, fertility-sparing surgery was not associated with increased risk of death in young women with stage I epithelial ovarian cancer.