Early-stage Uterine Pure and Mixed Clear Cell Carcinoma: Outcomes and Recurrence With and Without Adjuvant Therapy

Objective: Clear cell carcinoma (CCC) of the uterus is a rare but aggressive histology for which the role of adjuvant therapy for stage I-II disease is unclear. Our study investigated outcomes and patterns of failure in these patients. Methods: We found 64 cases of CCC, including 26 of pure CCC, 22 mixed with endometrioid adenocarcinoma, and 16 mixed with uterine papillary serous carcinoma. Adjuvant treatment was given to 55%. Results: Median follow-up was 51.9 months. By Kaplan-Meier estimate, 5-year vaginal recurrence-free survival (RFS) was 91.3%, pelvic RFS was 92.6%, distant metastasis RFS was 81.6%, disease-free survival was 79.6%, and overall survival was 79.7%. Median time to recurrence was 20.7 months (range, 2 to 40.5 mo). Patients treated adjuvantly had higher proportion of stage II disease (40% vs. 6.9% observed, P=0.0031) and 20% (7/35) recurred. There were no significant differences in outcomes by histologic subtypes but numerically more recurrences with uterine papillary serous involvement. By univariate analysis, higher stage, presence of lymphovascular invasion, and lack of lymph node dissection were predictive of worse overall survival. Age 65 years and above was predictive of worse cancer-specific survival. Of 12 who progressed, only 1 was salvaged and 11 died of disease. Of progressors, 10 had documented distant metastasis. Median time from recurrence to death was 4.5 months (range, 0.2 to 21.2 mo). Conclusions: Given aggressive and often unsalvageable nature of recurrence, consideration of adjuvant treatment (including chemotherapy and radiation) is warranted for early-stage CCC, particularly for stage II or those with poor prognostic factors.

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