Stage IIIC endometrial cancer review: Current controversies in adjuvant therapy

Stage IIIC is the most common stage of locally advanced sub-stage of endometrial cancer, nevertheless, the optimal management for these patients remains controversial. Adjuvant chemotherapy alone more effectively suppressed distant metastases but resulted in a higher rate of pelvic failure, while adjuvant radiation more effectively controlled pelvic recurrences but was associated with more frequent distant metastases. Two recent randomized trials, PORTEC3 and GOG 258, each have attempted to integrate multimodal therapy. However, heterogeneous cohorts analyzed together, including high risk stage I, stage III and stage IV, limit our ability to make conclusions specific to stage IIIC disease. Here, we review clinical evidence pertaining to management and outcomes with stage IIIC uterine carcinoma with brief discussion on evolving approaches. The studies reviewed demonstrate for stage IIIC disease radiation improves local control but does not confer an overall survival benefit and chemotherapy can improve overall survival. The data seem to suggest that aside from the possibility of defining subgroups that may confer an overall survival benefit from combined modality therapy, the future to improving survival lies in the exploration of better therapeutic regimens that will result from tailored biomarker-based therapy.