Endometriosis-Associated Ovarian Carcinoma (EAOC): An Entity Distinct from Other Ovarian Carcinomas as Suggested by a Nested Case-Control Study

Abstract

Objectives Endometriosis-associated ovarian carcinoma (EAOC) has recently received increasing attention due to its suggested biological behavior, distinctive from those of usual epithelial ovarian cancer. To elucidate some of the controversies on this intriguing entity, a series of patients with EAOC were compared to ovarian carcinoma cases without concomitant endometriosis.Methods To control the confounding effect of age, a nested case-control study was designed, where all 58 EAOC patients (mean age 54.5 +/- 11.5 years) were nested with four perfectly age-matched non-EAOC patients (n = 232; mean age 54.7 +/- 11.7 years) selected among 425 women representing all FIGO stages of ovarian carcinomas without endometriosis. Pertinent clinical data and results of analysis of the tumors were subjected to statistical analyses using life-table, univariate (Kaplan-Meier), and multivariate (Cox) survival techniques to disclose dissimilarities in the key biological characteristics of these two groups as well as the independent prognostic predictors of disease outcome.Results When compared in a case-control design with four perfectly age-matched non-EAOC patients nested to each EAOC case, the patients with EAOC proved to: (1) have a lower stage disease (both FIGO and TNM) (P = 0.000), (2) show a completely different distribution of histological subtypes (significant overpresentation of endometrioid and clear cell carcinomas) (P = 0.0001), (3) have predominantly lower grade lesions (P = 0.029), (4) be devoid of any primary residual tumor (P = 0.0001), and, most importantly (5) have demonstrated a significantly better overall survival (47/58 versus 126/232; OR 2.89, 95% CI 1.56-5.34, P = 0.0001). This better survival was evident (a) in all age groups and (b) for all histological subtypes, but (c) not explained by a better stage-specific survival in any FIGO stage. The two series also differed in their significant prognostic predictors in Kaplan-Meier and Cox analyses. In the EAOC group, the most significant (P = 0.0001) predictors of OS in univariate analysis were age, histological type, observation time for endometriosis, and distribution of endometriosis. In the non-EAOC group, such significant predictors were age, residual tumor, and type of therapy. In the multivariate (Cox) model, age and FIGO stage were the only two significant independent prognostic factors shared by these two series. In addition, histological type and type of therapy proved to be significant independent predictors in the non-EAOC series.Conclusions These data suggest that EAOC deviates from the non-EAOC in many of its key biological characteristics. The implications of these data in the diagnosis, treatment policy, and prognostication still require confirmation by further studies, however.