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Purpose: To identify clinical and non-clinical factors associated with utilization of primary cytoreductive surgery (PCS) or neoadjuvant chemotherapy (NACT) in women with advanced stage epithelial ovarian cancer (EOC)., Methods: Using the National Cancer Database, we identified women with stage IIIC and IV EOC diagnosed from 2012 to 2014. The primary outcome was receipt of NACT, defined in the primary analysis as utilization of chemotherapy as the first cancer-directed therapy, irrespective of whether interval surgery was performed. Univariable and multivariable associations between clinical and non-clinical factors and receipt of NACT were investigated using mixed-effect logistic regression models. A secondary analysis excluded women who received primary chemotherapy but did not receive interval cytoreductive surgery., Results: Among 17,302 eligible women, 10,948 (63.3%) underwent PCS and 6354 (36.7%) received NACT. Older age, stage IV disease, high-grade, and serous histology were associated with receipt of NACT in univariate (p<0.001) and multivariable analyses (p<0.001). Analysis of non-clinical factors revealed that residency in the Northeast region and receipt of treatment closer to home were associated with NACT in univariate (p<0.05) but not multivariable analysis (p>0.05). In multivariable analysis, African-American race/ethnicity (p=0.04), low-income level (p=0.02), treatment in high-volume centers (p<0.01), and insurance by Medicare or other government insurance (p<0.001) were associated with receipt of NACT. When women who received no surgery were excluded, all factors that were independent predictors of NACT in the main analysis remained significant, except for race/ethnicity., Conclusions: Non-clinical factors were associated with the use of NACT at a magnitude similar to that of clinically relevant factors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: The aim of the study was to examine the patterns of care and the impact of chemotherapy and radiation on survival in women diagnosed with uterine clear cell carcinoma (UCCC). The primary outcomes of this analysis were receipt of treatment within 6 months of diagnosis and overall survival., Methods and Materials: Women diagnosed with UCCC from 2003 to 2011 were identified through the National Cancer Data Base. Standard univariate and multivariable analyses with logistic regression were performed. Kaplan-Meier survival analysis was used to generate overall survival data. Factors predictive of outcome were evaluated using the log-rank test and Cox proportional hazards model., Results: A total of 3212 patients were identified. Chemotherapy, radiation, and combination chemotherapy and radiation were administered in 23.3%, 19.7%, and 11.1% of women, respectively. After adjusting for age, race, socioeconomic status, facility type, stage, surgery, lymph node dissection, comorbidity index, period of diagnosis, and registry location, there was an association between combined chemotherapy and radiation (hazard ratio, 0.74; 95% confidence interval, 0.61-0.90) with improved survival. Adjuvant therapy was not associated with improved survival among patients with early-stage disease (stages I and II). Both chemotherapy and combined chemotherapy and radiation were associated with significantly improved survival among patients with advanced-stage disease (stages III and IV)., Conclusions: In patients with early-stage UCCC, adjuvant therapy was not associated with significantly improved survival. Chemotherapy and combination of chemotherapy and radiation were associated with improved survival in patients with advanced-stage UCCC.

Objective: Mucinous endometrial cancer (MEC) is a rare histologic subtype of endometrial cancers. The purpose of this study is to compare the outcomes of patients with MEC with patients with endometrioid endometrial cancers (EEC), and to determine whether there are significant clinicopathologic differences between these tumors., Methods: Surveillance, Epidemiology, and End Results (SEER) Program data for 1988 to 2009 was reviewed. Demographic and clinical data were compared. The impact of histology on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model., Results: The study group consisted of 104,659 women, 103,097 (98.5%) had EEC and 1562 (1.5%) MEC. The mean age at diagnosis for EEC and MEC was 62 and 63.4, respectively (P<0.001). MEC tumors were more frequently classified as grade 1 (51.3% vs. 44%; P<0.001). In patients with MEC, a higher rate of pelvic lymph node metastasis (16.3% vs. 10.4%; P<0.001) was noted, but not para-aortic lymph node metastasis (5.1% vs. 4%; P=0.1). After adjusting for race, period of diagnosis, SEER registry, marital status, stage, age, surgery, radiotherapy, grade, histology, and lymph node dissection, there was no difference in survival between MEC and EEC (hazard ratio 0.90; 95% confidence interval, 0.78-1.05)., Conclusions: Mucinous histology does not significantly affect survival when compared with endometrioid histology in endometrial cancer. Patients with MEC were more likely to have positive pelvic lymph nodes at the time of surgery.

Objective: Evaluate rates of chemotherapy and radiotherapy delivery in the treatment of uterine serous carcinoma, and compare clinical outcomes of treated and untreated patients., Methods: The National Cancer Database was queried to identify patients diagnosed with uterine serous carcinoma between 2003 and 2011. The impact of chemotherapy on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model., Results: A total of 13,752 patients met the study eligibility criteria. Stage I, II, III, and IV disease accounted for 4355 (31.7%), 1023 (7.4%), 3484 (25.3%), and 2451 (17.8%) of the study population, respectively. 2439 (17.7%) women had unknown stage. Chemotherapy was administered in 4290 (35.4%) patients, radiotherapy to 1673 (12.2%), adjuvant chemo-radiation to 2915 (21.2%), and 4874 (35.4%) of women did not receive adjuvant therapy during the study period. Utilization of chemotherapy became more frequent over time. Over the entire study period, after adjusting for age, period of diagnosis, race, facility location, facility type, insurance provider, socioeconomic status, comorbidity index, lymph node dissection, treatment modality, and stage, there was an association between treatment modality and survival, with the lowest hazard ratio in patients that received chemo-radiation. After adjusting for the same factors in women with stages I and II, chemo-radiation was associated with improved survival compared to patients that received no treatment. Radiotherapy or chemotherapy alone was not associated with improved survival., Conclusion: Utilization of chemotherapy is increased in this population over the study period from 2003-2012 and more importantly that survival, particularly in advanced stage patients, is improving., (Copyright © 2015. Published by Elsevier Inc.)

Objective: Evaluate rates of chemotherapy and radiotherapy delivery in the treatment of uterine carcinosarcoma, and compare clinical outcomes of treated and untreated patients., Methods: The National Cancer Database was queried to identify patients diagnosed with uterine carcinosarcoma between 2003 and 2011. The impact of chemotherapy on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model., Results: A total of 10,609 patients met study eligibility criteria. Stages I, II, III, and IV disease accounted for 2997 (28.2%), 642 (6.1%), 2037 (19.2%), and 1316 (12.4%) of the study population, respectively. Most patients (91.0%) underwent definitive surgery, and lymphadenectomy was performed in 68.7% of the patients. Chemotherapy was administered in 2378 (22.4%) patients, radiotherapy to 2196 (20.7%), adjuvant chemo-radiation to 1804 (17.0%), and 4231 (39.9%) of women did not received adjuvant therapy. Utilization of chemotherapy became more frequent over time. Over the entire study period, after adjusting for race, period of diagnosis, facility location, facility type, insurance provider, stage, age, treatment modality, lymph node dissection, socioeconomic status, and comorbidity index, there was an association between treatment modality and survival. The lowest hazard ratio observed was in patients that received chemo-radiation. The strongest quantitative predictor of death was stage at the time of diagnosis. In addition, surgical treatment, lymph node dissection, most recent time-periods, lower comorbidity index, and higher socioeconomic status were associated with improved survival., Conclusion: The overall rates of chemotherapy use have increased over time. Adjuvant chemotherapy and chemo-radiation were associated with improved survival., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To describe the incidence of thromboembolic events (venous thromboembolism) before and after the diagnosis of epithelial endometrial cancer and to evaluate the effects of these events on survival., Methods: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results cancer registries linked to Medicare claim files to identify patients with epithelial endometrial cancer diagnosed between 1992 and 2009. To identify venous thromboembolism events 3 months before diagnosis and up to 24 months after diagnosis, we used International Classification of Diseases, 9th Revision, and Healthcare Common Procedure Coding System codes., Results: A total of 23,122 patients were included; of them 1,873 (8.1%) developed a venous thromboembolism. Patients with low-grade (grades 1 and 2) endometrioid adenocarcinoma had a significantly lower rate of venous thromboembolism 3 months before and 6 months after the diagnosis of cancer (3.6%; 95% confidence interval [CI] 3.3-3.9%) compared with carcinosarcoma (9.2%; 95% CI 7.8-10.8%), clear cell (6.9%; 95% CI 4.8-9.7%), uterine serous cancer (8.1%; 95% CI 7.01-9.3%), and grade 3 endometrioid adenocarcinoma (6.1%; 95% CI 5.4-6.9%) (P<.001). On multivariate analysis during the same time period, most recent time periods of diagnosis, carcinosarcoma histology compared with lower grade endometrial cancer, higher stage, African American race, marital status, chemotherapy delivery, and lymph node dissection were associated with increased risk of venous thromboembolism. The median overall survival for women who experienced a venous thromboembolism 3 months before the diagnosis of endometrial cancer was 31 months (95% CI 20-48 months); in women diagnosed with venous thromboembolism 6 months after the cancer diagnosis was 37 months (95% CI 31-44), and in women who did not experienced a venous thromboembolism was 111 months (95% CI 109-114). After adjusting for prognostic factors, there was an association between venous thromboembolism diagnosed 3 months before endometrial cancer (hazard ratio 1.69, 95% CI 1.34-2.13) or 6 months after the diagnosis (hazard ratio 1.57, 95% CI 1.44-1.71) and lower survival., Conclusion: Patients with uterine serous cancer, carcinosarcoma, clear cell carcinoma, and grade 3 endometrioid adenocarcinoma had a higher rate of venous thromboembolism than patients with low-grade endometrioid adenocarcinoma. A diagnosis of venous thromboembolism was associated with decreased survival in elderly patients with endometrial cancer., Level of Evidence: II.

Objective: To examine the patterns of care and survival for African American and white women with high-grade endometrial cancer., Methods: The linked Surveillance, Epidemiology, and End Results and Medicare databases were queried to identify patients diagnosed with grade 3 endometrioid endometrial adenocarcinoma, uterine carcinosarcoma, uterine clear cell carcinoma, and uterine serous carcinoma between 1992 and 2009. The effect of treatment modality on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model., Results: A total of 9,042 patients met study eligibility criteria. African Americans had definitive surgery (76.8% compared with 88.7%; P<.001) less frequently. There was no difference in the rate of adjuvant treatment between the groups. In the crude models for both all-cause mortality and cancer-specific mortality, African American women had an increased overall and disease-specific hazard of death compared with white women. The overall hazard ratio for African American women was 1.6 (95% confidence interval [CI] 1.5-1.7), and the disease-specific hazard ratio was 1.5 (95% CI 1.3-1.6). Over the entire study period, after adjusting for stage, age, period of diagnosis, registry region, urban compared with rural setting, marital status, treatment, surgery, socioeconomic status, and comorbidities, there was no association between race and lower disease-specific survival (hazard ratio 1.1, 95% CI 1-1.2; P=.06)., Conclusion: African American women had lower cancer-specific and all-cause survival compared with white women. Controlling for treatment, sociodemographics, comorbidities, and histopathologic variables eliminated the difference between African American and white women in the disease-specific analysis.

Objective: Uterine leiomyosarcoma (LMS) is a relatively rare malignancy that is associated with a poor prognosis. The rarity of LMS has led to a lack of consensus regarding appropriate treatment. The goal of this study was to identify the role that chemotherapy and radiotherapy have played in the treatment of uterine LMS in the United States as well as the effectiveness of adjuvant treatment., Materials/methods: We used the SEER (Surveillance, Epidemiology, and End Results)-Medicare database to gather information on uterine LMS patients older than the age of 66 years diagnosed between 1992 and 2009. Basic demographic and clinical characteristics were collected. A logistic regression model analysis was performed to determine predictors of treatment. Cox proportional hazards models were used to identify clinical parameters and treatment strategies associated with survival differences., Results: Our final study group included 230 patients. We found that the rate of use of chemotherapy and radiotherapy in the treatment of patients with uterine LMS increased over the period investigated. However, we identified no significant survival advantage associated with either mode of therapy. The strongest predictor of survival was stage at diagnosis. The logistic regression model analysis revealed that age at diagnosis, treatment year, stage, and underlying health status were all independent predictors of chemotherapy. Age at diagnosis was also a predictor of radiation therapy., Conclusions: The increasing rates of chemotherapy and radiotherapy use in this population seem to be unfounded given the lack of survival benefit. Further investigation into alternative treatment regimens is merited. The prognostic significance of stage at diagnosis indicates the importance of improving early detection of uterine LMS.

Objectives: The objective of this investigation was to evaluate the risk of nodal metastasis in patients with endometrial cancer, using the Mayo criteria, in a population-based analysis., Materials and Methods: Data from the SEER registry was reviewed for endometrial cancer cases diagnosed between 1988 and 2010. Patients were considered at low-risk for nodal metastasis if their tumors were histologic grade 1 or 2, myometrial invasion was less than 50%, and tumor size equal to or less than 2 cm. Patients not meeting these criteria were considered at high-risk for nodal involvement., Results: The final study group consisted of 19,329 women with surgically staged endometrial cancer. Of these, 1035 (5.3%) had lymph node involvement. Based on Mayo criteria, 4095 (21.1%) patients were found to be at low-risk and 15,234 (78.9%) at high-risk for nodal metastasis. Low-risk features were associated with a 1.4% risk for lymph node metastasis, compared to 6.4% in patients with high-risk features (p<0.001). When myometrial invasion was removed from the analysis, low-risk pathologic features were associated with a 2.4% risk of lymph node metastasis, compared to 10.4% in patients with high-risk features (p<0.001)., Conclusions: In a population-based analysis, women with low-risk endometrial cancer, as defined by the Mayo criteria, have a low rate of lymph node metastasis., (Copyright © 2014 Elsevier Inc. All rights reserved.)