Characteristics of early-stage endometrial cancer and factors that influence disease recurrence.
Authors: Chung Su Yun , Shen Janice , Kohn Nina , Hernandez Jennifer , Frimer Marina , Bloom Beatrice , Lee Jean Kyung , John Veena S. 
Published: June 2021

e17567

Background: Early-stage endometrial cancer (EEC) with FIGO stage I-II generally has a favorable prognosis and overall survival (OS). However, up to 10% of EEC patients (pts) relapse and risk factors for recurrence remain unclear. We evaluated clinical and histopathologic characteristics of EEC and correlated them with OS and recurrence free survival (RFS) through a single-center retrospective analysis. Methods: We conducted a retrospective chart review on 511 pts with EEC identified by our cancer registry from 1/1/2009 to 12/31/2019. The two main histologic groups were endometrioid adenocarcinomas (E) and other subtypes (O) including carcinosarcoma, undifferentiated, and clear cell carcinomas. Papillary serous histology was excluded. Histopathologic and clinical findings recorded included age, FIGO stage and grade, tumor size, presence of recurrence, adjuvant therapies received, percent of myometrial invasion (MI), and lymphovascular invasion (LVI). OS and RFS were estimated, and each predictor was compared using the log-rank test. The association between OS and each continuous characteristic was examined using the Cox proportional hazards model. Factors significantly associated with OS and RFS in the univariable analysis (p < 0.05) were included in a multivariable analysis to examine the joint effects of those factors on survival. Results: A total of 511 cases were reviewed. The analysis included 501 pts (E = 485, O = 16), of which 47 had recurrent disease (E = 45, O = 2) and 17 had died without recurring (E = 15, O = 2) as of their last follow-up. Overall median age was 63 years. Factors significantly associated with recurrence in the multivariable analysis were FIGO grade, (Hazard Ratios (HR): Grade 2 vs 1: 1.95, 95% CI: 1.06-3.58, p = 0.0320, Grade 3 vs 1: 2.88, 95% CI: 1.50-5.52, p = 0.0015), LVI (HR: 2.03, 95% CI: 1.10-3.75, p = 0.0244), and greater than 50% of MI (HR: 3.15, 95% CI: 1.35-7.36, p = 0.0080). The overall RFS was 92% and 86% at three and five years, respectively. On univariate analysis, among pts with a measurable tumor size (n = 446), larger tumors were not significantly associated with OS (p = 0.65) but was associated with increased recurrence (HR 1.22, 95% CI: 1.10-1.37, for a unit increase, p = 0.0003). On univariate analysis, pts who received adjuvant therapy were more likely to recur (p = 0.0002) with RFS of 86% and 76% at three and five years respectively, versus RFS of 94% and 90%, for those who did not. Conclusions: We confirmed the clinical and histopathologic characteristics that are currently considered to increase risk of recurrence in EEC. On multivariate analysis, risk of recurrence was associated with FIGO grades 2 and 3, presence of LVI, and > 50% MI. A limitation of this study is the lack of molecular analysis. Further molecular stratification may help us identify the subset of pts who are at high risk of recurrence, enabling customized adjuvant therapy in EEC.