The impact of multi-modal therapy on survival for uterine carcinosarcomas.

OBJECTIVES: To investigate treatment outcomes of patients with carcinosarcoma of the uterus and to identify parameters predictive of survival. Secondary objectives included (a) the assessment of treatment failures as a function of histologic subtypes and (b) the impact of the new FIGO staging classification system. METHODS: This is a retrospective outcomes analysis of 121 patients diagnosed with primary carcinosarcoma of the uterus. Clinical, surgical and pathological data were reviewed and patients were classified according to the new 2009 FIGO staging system for endometrial carcinoma. Survivorship curves were evaluated with the log-rank test and associations between events and variables with Cox proportional hazards model. RESULTS: In the multivariate analyses for disease-specific survival (DSS) and disease-free survival (DFS), the only independent factors were FIGO stage, adjuvant chemotherapy after surgery and the presence of clear cell histology in the tumor. The 5-year DSS for stages I-II, III and IV was 59%, 22% and 9%, respectively. The administration of platin-based chemotherapy provided a significant benefit with regard to both DFS (OR=0.28; p=0.001) and DSS (OR=0.35; p=0.01). While radiotherapy (RT) appeared to control vaginal failures in all stages, pelvic RT did not impact DSS. Of importance, the epithelial component was the predominant histology in both the primary extrauterine metastases (94%) and the distant failure sites (82%). CONCLUSIONS: This highly aggressive uterine malignancy warrants comprehensive surgical staging to assess tumor dissemination followed by systemic therapy in patients with both early and advanced stage disease.

Rationale for folate receptor alpha targeted therapy in "high risk" endometrial carcinomas.

Advanced and recurrent endometrial cancers account for the majority of deaths from this disease with limited therapeutic options. High grade, and nonendometrioid histology, pathologically characterize the endometrial tumors associated with adverse outcome and are classified as "high risk". The identification of molecular prognostic factors that might be targeted for therapy among "high risk" endometrial cancers is an active area of investigation. We hypothesize that the FRalpha, highly expressed in endometrial cancer cells, is a potential target for this disease. Our objectives were to determine if FRalpha overexpression is associated with adverse prognostic factors and worse outcome. Three hundred and thirty-two endometrial cancer cores were arrayed onto a tissue microarray and stained using a FRalpha-specific monoclonal antibody. Staining was scored as absent or weak and moderate or strong. Forty-one percent of 310 evaluable cases stained moderate/strong. Moderate/strong FRalpha staining was significantly associated with other poor prognostic factors including: advanced stage, nonendometrioid histology and high grade. An association was observed between moderate/strong FRalpha staining and recurrence (p < 0.0014). These findings support further exploring a role for FRalpha targeted approaches for therapy and diagnostics in endometrial cancer.