Patterns of Recurrence in Stage I Endometrioid Endometrial Adenocarcinoma With Lymphovascular Space Invasion

Objective: The objective of this study was to determine the patterns of recurrence of stage IB-IIA endometrioid endometrial adenocarcinoma (EMCA) with lymphovascular invasion (LVSI). Methods: A multicenter retrospective study of 1988 International Federation of Gynecology and Obstetrics stage IB-IITA EMCA patients with LVSI treated with surgery with or without radiation was conducted. Those with papillary serous or clear cell histologies and women treated with chemotherapy were excluded. Data regarding surgical-pathologic factors, treatment, and outcome were collected. Data were analyzed using chi(2) test, Kaplan-Meier estimates, and Cox multivariate proportional hazards models. Results: From 1997 to 2008, we identified 131 patients with LVSI who met entry criteria among 5 institutions. Median age was 67 years (25%-75%: 60-75 years), and median follow-up was 4.25 years (25%-75%: 3-10 years). Following surgery, 45 patients were observed (Obs), and 86 patients received adjuvant radiation. We observed 30 total relapses 30/131 (23%): 11/45 (24%) in the Obs group and 19/86 (22%) in the adjuvant radiation group. Recurrence rates were similar between staged and unstaged patients: 24% (20/84) and 21% (10/47), respectively. Among Obs patients, 82% of relapses were local, whereas in patients treated with adjuvant radiation, 84% were distant. Relapses were significantly associated with invasion of the lower uterine segment (LUS) (P = 0.035). Both cancer-related survival and overall survival (OS) were not significantly impacted by adjuvant radiation, because of distant failure rates. Adjuvant radiation significantly improved pelvic control (P = 0.007). In a multivariate analysis, OS correlated with LUS invasion (P = 0.008) and was borderline-associated with stage (P = 0.06), whereas age (P = 0.12), grade (P = 0.31), myometrial invasion (P = 0.99), and radiation treatment (P = 0.23) were not. Conclusions: Overall recurrence rates for stage IB-IIA EMCA patients with LVSI are high (23%). Although adjuvant radiation therapy improved pelvic control, it did not impact recurrence rates, cancer-related survival, and OS, likely secondary to distant failures. The role of systemic therapy with or without radiotherapy for early-stage EMCA with LVSI should be evaluated, particularly in patients with high-grade tumors or involvement of the LUS.