Making a Difference: Distinguishing Two Primaries From Metastasis in Synchronous Tumors of the Ovary and Uterus

For women with early-stage ovarian or endometrial cancers, prognosis is very good, with overall survival for both sites between 80% and 90%. This stands in stark contrast to metastatic disease (advanced stage), where the overall survival is less than 15%. We have long recognized that subtypes of disease also inform these statistics, with high-grade serous carcinomas conferring a far worse prognosis compared with others, including low-grade serous or endometrioid tumors. Yet even with our present understanding, a not uncommon finding is the diagnosis of women with carcinoma at both the ovary and the uterus (a situation that occurs in up to 10% of patients), raising the question of synchronous primaries or of metastatic disease. The implications of these clinical scenarios are very relevant: If a conclusion of synchronous primaries is made, then prognosis should be excellent and hence no further treatment beyond surgery is required for cure. However, the finding of metastatic disease (from the ovary to the uterus or vice versa) will substantially change the prognostic implications, with these patients having a higher risk of recurrence and death from metastatic disease. In addition, this differential diagnosis can change therapeutic recommendations, with metastatic disease requiring more aggressive adjuvant therapy. Thus, the issue is both a biologic and clinical one.