J. Alejandro Rauh-Hain

Platinum resistance after neoadjuvant chemotherapy compared to primary surgery in patients with advanced epithelial ovarian carcinoma.

OBJECTIVE Primary debulking surgery (PDS) has historically been the standard treatment for advanced ovarian cancer. Recent data appear to support a paradigm shift toward neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) for a subset of women with advanced ovarian cancer. It remains unresolved whether NACT-IDS increases the risk of platinum resistance. We compared response to chemotherapy in patients that received NACT-IDS vs. PDS. METHODS From our Cancer Registry database we identified patients with stages IIIC and IV epithelial ovarian cancer who underwent treatment from January, 2005 to December, 2010. Standard univariate analyses were performed, as were multivariable analysis with logistic regression. The Kaplan-Meier method was used to generate survival data. RESULTS The study population consisted of 425 patients, 95 (22.3%) underwent NACT-IDS and 330 (77.6%) PDS. After the initial platinum-based chemotherapy, 42 (44.2%) women in the NACT-IDS group were considered to have platinum resistant disease, compared to 103 (31.2%) in the PDS group (P=0.01). When multivariate logistic regression was used to control for factors independently associated with platinum resistance, NACT-IDS was no longer associated with an initial increased risk. However, in women that had a recurrence and were retreated with platinum-based chemotherapy, 32 (88.8%) in the NACT-IDS group had developed a recurrence within six months and were considered platinum resistant, compared to 62 (55.3%) in the PDS (P<0.001). CONCLUSION In women with EOC that have a recurrence and are treated again with platinum-based chemotherapy, NACT-IDS appears to increase the risk of platinum resistance.

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.

Carcinosarcoma of the ovary: A case-control study

INTRODUCTION Carcinosarcoma of the ovary is a rare tumor with a grim prognosis. Chemotherapy for these tumors is chosen according to guidelines established for epithelial ovarian cancer (EOC). The purpose of this study is to compare response to chemotherapy and survival in patients with advanced stage carcinosarcoma of the ovary. METHODS We identified women with advanced carcinosarcoma of the ovary who underwent first-line platinum and taxane-based chemotherapy. Each case was matched to two women with serous EOC. Cases and controls were matched by age, stage, and year of diagnosis. The Kaplan-Meier method was used to generate overall survival (OS) data. Factors predictive of outcome were compared using the log-rank test and Cox proportional hazards model. RESULTS Fifty women treated with first line platinum and taxane-based chemotherapy had advanced carcinosarcoma of the ovary and were selected as cases. The response rates to chemotherapy for cases and controls were 62% and 83% (P=0.03), respectively. Median progression-free survival was 11 months (95% CI, 8 to 14 months) versus 16 months (95% CI, 12 to 21 months; P=0.02) and median overall survival was 24 months (95% CI, 18 to 29 months) versus 41 months (95% CI, 33 to 49 months; P=0.002) for cases and controls, respectively. CONCLUSION Patients with advanced carcinosarcoma of the ovary have a poorer response to platinum and taxane-based first-line chemotherapy and worse survival, compared to patients with serous EOC. Aggressive surgical treatment may play an important role. However, other alternative systemic therapeutic approaches should be sought for patients with carcinosarcoma of the ovary.

Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy.

OBJECTIVE To evaluate the predictive power of serum CA-125 changes in the management of patients undergoing neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis of epithelial ovarian carcinoma (EOC). METHODS Using the Cancer Registry databases from our institutions, a retrospective review of patients with FIGO stage IIIC and IV EOC who were treated with platinum-based NACT-IDS between January 2006 and December 2009 was conducted. Demographic data, CA-125 levels, radiographic data, chemotherapy, and surgical-pathologic information were obtained. Continuous variables were evaluated by Students t test or Wilcoxon-Mann-Whitney test. RESULTS One hundred-three patients with stage IIIC or IV EOC met study criteria. Median number of neoadjuvant cycles was 3. Ninety-nine patients (96.1%) were optimally cytoreduced. Forty-seven patients (47.5%) had resection to no residual disease (NRD). The median CA-125 at diagnosis and before interval debulking was 1749U/mL and 161U/mL, respectively. Comparing patients with NRD v. optimal macroscopic disease (OMD), there was no statistical difference in the mean CA-125 at diagnosis (1566U/mL v. 2077U/mL, p=0.1). There was a significant difference in the mean CA-125 prior to interval debulking, 92 v. 233U/mL (p=0.001). In the NRD group, 38 patients (80%) had preoperative CA-125≤100U/mL compared to 33 patients (63.4%) in the OMD group (p=0.04). CONCLUSIONS Patients who undergo NACT-IDS achieve a high rate of optimal cytoreduction. In our series, after treatment with taxane and platinum-based chemotherapy, patients with a preoperative CA-125 of ≤100U/mL were highly likely to be cytoreduced to no residual disease.

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).

Treatment for advanced and recurrent endometrial carcinoma: combined modalities.

Women with recurrent or advanced endometrial cancer constitute a heterogeneous group of patients. Depending on previous treatment, women with recurrent endometrial cancer may be appropriate candidates for surgery, radiation therapy, hormonal therapy, or chemotherapy. Women with advanced stage disease at presentation may also be appropriate candidates for systemic and local therapies. We review the treatment options available to treat recurrent and locally advanced endometrial cancer. Treatment choice depends largely on the localization of disease, the patients performance status and previous treatment history, as well the tumors hormonal receptor status. Radiation therapy is appropriate for isolated vaginal recurrences in patients with no previous history of radiation therapy. Patients with recurrent low-grade tumors overexpressing estrogen and progesterone receptors may be treated with progestin therapy. Systemic therapy is appropriate for patients with disseminate recurrences or advanced stage disease at presentation, or for those with receptor-negative tumors. We review all these different treatment strategies available to patients with advanced or recurrent endometrial cancer.

Prognostic determinants in patients with stage IIIC and IV uterine papillary serous carcinoma

OBJECTIVE The aim of this study was to evaluate the survival impact of cytoreductive surgery and other prognostic determinants in patients with stage IIIC and IV uterine papillary serous carcinoma (UPSC). METHODS All patients with FIGO stage IIIC and IV UPSC who underwent surgical staging at the two participating institutions, between January 1, 1995 and December 31, 2007, were identified from the tumor registry database. The Kaplan-Meier method was used to generate overall survival (OS) data. Factors predictive of outcome were compared using the log-rank test and Cox regression analysis. RESULTS Analysis of 79 patients with stage IIIC-IV disease was performed. Optimal cytoreduction was associated with a median survival of 36 months, compared with 12 months for patients who underwent a suboptimal surgical effort (p=0.001), and a disease-free survival (DFS) of 21 months vs. 10 months (p=0.001), respectively. Regression analysis identified stage (HR=2.4, p=0.03), absence of visible residual disease (HR=0.5, p=0.03), and chemotherapy (HR=0.1, p<0.001) as independent predictors of OS. CONCLUSIONS Cytoreduction to no gross residual disease and the use of platinum therapy are associated with a significant survival benefit for patients with stage IIIC-IV UPSC. Recommended management for this group of patients should consist of maximal surgical cytoreduction followed by platinum-based chemotherapy, preferably in combination with paclitaxel. Adjuvant radiation therapy should also be considered.

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.