Adjuvant Treatment in Early-stage Endometrial Cancer: Context-dependent Impact of Somatic Mutation on Recurrence-free Survival

Objective: The primary objective of this study was to determine whether women whose tumors harbor a somatic mutation have longer recurrence-free survival if they receive traditional adjuvant therapy strategies compared with those who do not.

Methods: A retrospective, stage I endometrial cancer cohort from MD Anderson Cancer Center was assessed. Clinical and pathological characteristics and type of adjuvant therapy (cuff brachytherapy, pelvic radiation, chemotherapy) were obtained by review of medical records. exon 3 sequencing was performed. Summary statistics were calculated, and recurrence-free survival was measured using the Kaplan-Meier product-limit estimator.

Results: The analysis included 253 patients, 245 with information regarding adjuvant therapy. Most patients had tumors of endometrioid histology (210/253, 83%) with superficial myometrial invasion (197/250, 79%) and no lymphatic/vascular space invasion (168/247, 68%). Tumor mutations were present in 45 (18%) patients. Patients receiving adjuvant therapy were more likely to have higher-grade tumors, non-endometrioid histology, deep myometrial invasion, and lymphatic/vascular invasion. For patients with low-risk features not receiving adjuvant therapy, the presence of mutation did not significantly impact recurrence-free survival (11.3 years wild-type vs 8.1 years mutant, p=0.65). The cohort was then limited to intermediate-risk tumors, defined as endometrioid histology of any grade with deep myometrial invasion and/or lymphatic/vascular space invasion. When recurrence-free survival was stratified by mutation status and adjuvant therapy, patients with mutations and no adjuvant therapy had the shortest recurrence-free survival at 1.6 years, followed by patients with mutations who received adjuvant therapy (4.0 years), and wild-type with and without adjuvant therapy (8.5 and 7.2 years, respectively) (comparison for all four groups, p=0.01).

Conclusion: In patients with intermediate-risk endometrioid endometrial cancers, the use of adjuvant therapy was associated with an improvement in recurrence-free survival for patients with tumor mutations in .