Pathologic features associated with resolution of complex atypical hyperplasia and grade 1 endometrial adenocarcinoma after progestin therapy

Objective To determine the response of complex atypical hyperplasia (CAH) and well differentiated endometrioid adenocarcinoma of the uterus (WDC) to progestin therapy and whether pre-treatment estrogen and progesterone receptor status predicts outcome. Methods We performed a retrospective review encompassing women treated with progestin therapy for CAH or WDC at two institutions. Clinicopathologic, treatment, and recurrence data were recorded. Pre/post-treatment pathologic evaluation was performed. SAS 9.2 was used for statistical analyses. Results Forty-six patients were included. The median age was 35, and median BMI was 36.9. Thirty-seven percent were diagnosed with CAH and 63% had WDC. Megestrol acetate was the most commonly used agent (89%); 24% received multiple progestin therapies. Median treatment length was 6 months (range, 1-84); 36% of the patients underwent eventual hysterectomy, and 17.4% had carcinoma in their uterine specimens (8 primary endometrial, 1 primary ovarian). After a median follow-up of 35 months (range, 2-162), 65% experienced a complete response (CR), 28% had persistent or progressive disease, and 23% had a CR followed by recurrence. On univariate analysis, decreased post-treatment glandular cellularity (p = 0.0006), absence of post-treatment mitotic figures (p = 0.0008), and use of multiple progestin agents (p = 0.025) were associated with CR; however, only decreased glandular cellularity was significant on multivariate analysis (p = 0.007). Estrogen and progesterone receptor expression was not associated with treatment response. Conclusion In women with CAH or WDC, the overall response rate to progestin therapy was 65%; pre-treatment estrogen/progesterone receptor status did not predict response to treatment.