Oncological and reproductive outcomes following fertility-preserving treatment in mismatch repair-deficient endometrial cancer or atypical endometrial hyperplasia

OBJECTIVE: To investigate oncological and reproductive outcomes in patients with mismatch repair-deficient (MMRd) endometrial endometrioid carcinoma (EEC) or atypical endometrial hyperplasia (AEH) undergoing fertility-preserving treatment to inform clinical management of this molecular subtype. METHODS: Clinical and pathological data from 14 patients with MMRd EEC or AEH who received fertility-preserving treatment at Peking Union Medical College Hospital from January 2020 to December 2023 were retrospectively analyzed. RESULTS: The mean age at diagnosis of the patients was 33.6 ± 4.2 years. Loss of MLH1/PMS2 expression was the most common immunohistochemical abnormality, followed by loss of MSH6, MSH2/MSH6, and PMS2 expression. Among the 12 patients who underwent germline genetic testing, pathogenic/likely pathogenic germline variants in MMR genes were identified in three patients. During the follow-up period (median 34.5 months, range 26-117 months), seven patients achieved complete remission (CR), with a median time to CR of 8 months. The recurrence rate among these patients was 57.1%, and the median time to recurrence was 11 months. Nine patients underwent surgery after treatment failure or recurrence, with postoperative pathology revealing histologic upgrading and/or metastasis in eight patients. Two patients successfully conceived through assisted reproductive technology and achieved live births. CONCLUSION: Patients with MMRd EEC or AEH undergoing fertility-preserving treatment demonstrated relatively low remission rates, high recurrence rates, and suboptimal reproductive outcomes. Careful risk assessment and close surveillance for recurrence are warranted for patients desiring fertility.