Adjuvant chemoradiation associated with improved outcomes in patients with microsatellite instability-high advanced endometrial carcinoma

Abstract

Evidence suggests that patients with microsatellite instability (MSI)-high endometrial carcinoma derive greater benefit from radiation therapy than their microsatellite-stable counterparts. We sought to evaluate the outcomes of patients with MSI-high advanced endometrial cancer treated with a combination of chemotherapy and radiation (chemoradiation) versus chemotherapy-alone to determine if there is a survival benefit associated with a particular adjuvant therapy regimen. METHODS A multicenter retrospective analysis of patients with stage III/IV, MSI-high endometrial carcinoma was conducted from January 2000 to December 2018. Inclusion criteria were primary surgical management, defined as hysterectomy with/without salpingoophorectomy, comprehensive surgical staging and/or tumor debulking, followed by adjuvant chemotherapy or chemoradiation. MSI status was determined by immunohistochemistry and/or next-generation sequencing. Differences in the frequencies of histology, stage, cytoreduction status, treatment delays, and sites of disease recurrence were identified using Pearson’s chi-square test. Progression-free and overall survival were calculated using Kaplan–Meier estimates. RESULTS Final analysis included 37 patients; 20 (54%) received chemoradiation and 17 (46%) received chemotherapy-alone. The mean age was 62 (range 51–81) years. Histology included 48.6% (n=18) endometrioid, 40.5% (n=15) serous, and 10.7% (n=4) clear cell tumors. There was no difference in the frequency of histologic subtypes (p=0.83), stage (p=0.12), cytoreduction status (p=0.45), treatment delays (p=0.63), or location of recurrence (p=0.89) between cohorts. There was a trend towards greater pelvic recurrence in the chemotherapy-alone cohort (36% vs 29%; p=0.16). The most frequent location of disease recurrence was the abdomen. The median progression-free survival favored chemoradiation (24 months) versus chemotherapy-alone (17 months) (p=0.04). There was a trend towards improved overall survival in patients receiving chemoradiation (35 months) versus chemotherapy-alone (22 months) (p=0.09). Chemoradiation demonstrated superiority over chemotherapy-alone in terms of 2-year progression-free (40.0% vs 29.5%, respectively; p=0.04) and 2-year overall survival (73.7% vs 52.9%, respectively; p=0.09).