J.T. Clemmer

Tumor size, depth of invasion, and histologic grade as prognostic factors of lymph node involvement in endometrial cancer: A SEER analysis

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.

Racial disparities in treatment of high-grade endometrial cancer in the Medicare population.

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. LEVEL OF EVIDENCE: III

Racial disparities in cervical cancer survival over time

The purpose of this study is to examine changes over time in survival for African American (AA) and white women diagnosed with cervical cancer (CC).

Overall Survival Following Neoadjuvant Chemotherapy vs Primary Cytoreductive Surgery in Women With Epithelial Ovarian Cancer: Analysis of the National Cancer Database

Importance Uncertainty remains about the relative benefits of primary cytoreductive surgery (PCS) vs neoadjuvant chemotherapy (NACT) for advanced-stage epithelial ovarian cancer (EOC). Objective To compare overall survival of PCS vs NACT in a large national population of women with advanced-stage EOC. Design, Setting, and Participants Retrospective cohort study of women with stage IIIC and IV EOC diagnosed between 2003 and 2011 treated at hospitals across the United States reporting to the National Cancer Data Base. We focused on patients 70 years or younger with a Charlson comorbidity index of 0 who were likely candidates for either treatment. Exposures Initial treatment approach of PCS vs NACT, examined using an intent-to-treat analysis. Main Outcomes and Measures Overall survival, defined as months from cancer diagnosis to death or date of the last contact. We used propensity score matching to compare similar women who underwent PCS and NACT. The association of treatment approach with overall survival was assessed using the Kaplan-Meier method and the log-rank test. We assessed whether the findings were influenced by differences in the prevalence of an unobserved confounder, such as limited performance status (Eastern Cooperative Oncology Group 1-2), preoperative disease burden, and BRCA status. Results Among 22 962 patients (mean [SD] age, 56.12 [9.38] years), 19 836 (86.4%) received PCS and 3126 (13.6%) underwent NACT. We matched 2935 patients treated with NACT with similar patients who received PCS. The median follow-up was 56.5 (95% CI, 54.5-59.2) months in the PCS group and 56.3 (95% CI, 54.5-59.8) months in the NACT group in the propensity-matched cohort. Among propensity score–matched groups, the median overall survival was 37.3 (95% CI, 35.2-38.7) months in the PCS group and 32.1 (95% CI, 30.8-34.1) months in the NACT group (P < .001). However, if the NACT group had a higher proportion of women with performance statuses of 1 to 2 compared with those who underwent PCS (60% vs 50%), the association of PCS and improved survival would not be statistically significant. Conclusions and Relevance Primary cytoreductive surgery was associated with improved survival compared with NACT in otherwise healthy women with advanced-stage epithelial ovarian cancer aged 70 years or younger. The lower survival in women who received NACT could be explained by a higher prevalence of limited performance status in women undergoing NACT.

Carcinosarcoma of the ovary compared to papillary serous ovarian carcinoma: A SEER analysis

OBJECTIVE The aims of this study are to determine if outcomes of patients with ovarian carcinosarcoma (OCS) differ from women with high grade papillary serous ovarian carcinoma when compared by stage as well as to identify any associated clinico-pathologic factors. METHODS The Surveillance, Epidemiology, and End Results (SEER) Program data for all 18 registries from 1998 to 2009 was reviewed to identify women with OCS and high grade papillary serous carcinoma of the ovary. 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 hazard model. RESULTS The final study group consisted of 14,753 women. 1334 (9.04%) had OCS and 13,419 (90.96%) had high grade papillary serous carcinoma of the ovary. Overall, women with OCS had a worse five-year, disease specific survival rate, 28.2% vs. 38.4% (P<0.001). This difference persisted for each FIGO disease stages I-IV, with five year survival consistently worse for women with OCS compared with papillary serous carcinoma. Over the entire study period, after adjusting for histology, age, period of diagnosis, SEER registry, marital status, stage, surgery, radiotherapy, lymph node dissection, and history of secondary malignancy after the diagnosis of ovarian cancer, carcinosarcoma histology was associated with decreased cancer-specific survival. CONCLUSIONS OCS is associated with a poor prognosis compared to high grade papillary serous carcinoma of the ovary. This difference was noted across all FIGO stages.

Management for Elderly Women With Advanced-Stage, High-Grade Endometrial Cancer.

OBJECTIVE: To examine the treatment and survival of elderly women diagnosed with advanced-stage, high-grade endometrial cancer. METHODS: We performed a retrospective cohort study of women diagnosed between 2003 and 2011 with advanced-stage, high-grade endometrial cancers (grade 3 adenocarcinoma, carcinosarcoma, clear-cell carcinoma, and uterine serous carcinoma) using the National Cancer Database. Women were stratified by age: younger than 55, 55–64, 65–74, 75–84, and 85 years old or older. Multivariate logistic regression models and Cox proportional hazards survival methods for all-cause mortality were used for analyses. RESULTS: Twenty thousand four hundred sixty-eight patients were included, 14.9% younger than 55 years, 30.9% 55–64 years, 31.1% 65–74 years, 18.8% 75–84 years, and 4.3% 85 years old or older. Patients younger than 55 years had surgery more frequently compared with patients 75–84 years (97.2% compared with 95.8%; P<.001) and 85 years or older (97.2% compared with 94.8%; P<.001) and a higher rate of lymph node dissection (78.7% compared with 70.5%; P<.001 and 78.7% compared with 59.5%; P<.001, respectively). Women younger than 55 years old were more likely to receive chemotherapy compared with those 75–84 years (63.9% compared with 42.2%; P<.001) and 85 years old or older (63.9% compared with 22%; P<.001). After adjusting for prognostic factors, women ages 75–84 and 85 years or older were less likely to have received chemotherapy compared with women younger than 55 years (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.29–0.38 and OR 0.12, 95% CI 0.10–0.14). The same was true with surgery (OR 0.63, 95% CI 0.45–0.88 and OR 0.46, 95% CI 0.30–0.70) and radiotherapy (OR 0.61, 95% CI 0.53–0.70 and OR 0.45, 95% CI 0.37–0.56). The Cox regression model showed that in women with stage III disease, women 75–84 years had a twofold higher risk of death (hazard ratio [HR] 2.38, 95% CI 2.14–2.65) and those 85 years or older had a threefold higher risk (HR 3.16, 95% CI 2.76–3.61) compared with patients younger than 55 years. Patients with stage IV and age 75–84 years had a 24% increased risk of death (HR 1.24, 95% CI 1.11–1.40) and those 85 years or older had a 52% increased risk (HR 1.52, 95% CI 1.29–1.79). CONCLUSION: Elderly women with high-grade endometrial cancer are less likely to be treated with surgery, chemotherapy, or radiation. LEVEL OF EVIDENCE: II

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.

Prognostic determinants in patients with uterine and ovarian clear cell carcinoma: A SEER analysis

INTRODUCTION The purpose of this study is to analyze and compare the demographics, treatment, and survival rates in patients with uterine clear cell carcinoma (UCCC) and ovarian clear cell carcinoma (OCCC). METHODS The Surveillance, Epidemiology and End Results (SEER) program data for all 18 registries from 1988 to 2010 was reviewed to identify women with OCCC and UCCC. Demographic and clinical data were compared, and the impact of tumor site 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 5421 women with clear cell histopathology. 3631 (67%) had OCCC and 1790 (33%) had UCCC. The mean age at diagnosis was 56 (± 12) years for women with OCCC and 67.7 (± 12.0) years for UCCC (P<0.001). Patients with OCCC had a higher rate of late stage disease (38.9% vs. 21.2%; P<0.001). Over the entire study period, after adjusting for known variables, there was no significant difference in cancer specific mortality between UCCC and OCCC, HR 1.05 (0.92-1.19). In the subset analysis by staging, in women with localized disease there was an improved survival in UCCC compared to OCCC. In contrast, in women with distant disease there was an increased mortality in women with UCCC. CONCLUSION In the entire population, there was no significant difference in cancer related mortality between the groups. However, in women with localized disease, UCCC had improved survival, but increased mortality in distant disease compared to OCCC.

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

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.

Mucinous Adenocarcinoma of the Endometrium Compared With Endometrioid Endometrial Cancer: A SEER Analysis.

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.