Evaluation of Survival, Recurrence Patterns and Adjuvant Therapy in Surgically Staged High-Grade Endometrial Cancer with Retroperitoneal Metastases

SIMPLE SUMMARY: High-grade endometrial carcinomas present a clinical challenge due to their propensity to metastasize beyond the pelvis. Stage IIIC disease represents a unique entity relative to all other stages, as the retroperitoneal lymph nodes are involved. Prior randomized controlled trials have suggested that chemotherapy alone is sufficient to treat stage III and IV endometrial carcinoma. However, no prospective trial has specifically evaluated adjuvant therapy strategies in stage IIIC disease; therefore, it is difficult to generalize the results of trials including all advanced stage patients to this unique group. In the present study, we observed improved progression-free and overall survival in those patients with stage IIIC disease receiving a combination of both chemotherapy and radiation, suggesting that radiation plays a key role in the management of retroperitoneal metastasis and should be considered in addition to chemotherapy. ABSTRACT: Background: We seek to evaluate the difference in recurrence patterns and survival among stage IIIC high-grade endometrial cancer treated with surgery followed by adjuvant chemotherapy alone, radiation therapy alone, or both (chemoradiation). Methods: A multicenter retrospective analysis of surgically staged IIIC HGEC receiving adjuvant therapy was conducted. HGEC was defined as grade 3 endometrioid adenocarcinoma, serous, clear cell and carcinosarcoma. Differences in the frequency of recurrence sites and treatment delays were identified using Pearson’s χ(2) test. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier estimates. Results: A total of 155 patients were evaluable: 41.9% carcinosarcoma, 36.8% serous, 17.4% grade 3 and 3.9% clear cell. Of these, 67.1% received chemoradiation, 25.8% received chemotherapy and 7.1% received radiation therapy. There was no difference in the frequency of treatment delays between regimens (p = 0.571). There was a trend towards greater retroperitoneal recurrence with chemotherapy (25.9%) versus chemoradiation (8.4%) and radiation therapy (7.7%) (p = 0.252). Grade 3 tumors had improved progression-free and overall survival (26 and 42 months, respectively) versus serous (17 and 30 months, respectively), carcinosarcoma (14 and 24 months, respectively) and clear cell (24 and 30 months respectively) (p = 0.002, p < 0.001). Overall, chemoradiation was superior to chemotherapy and radiation therapy in PFS (p < 0.001) and OS (p < 0.001). Upon multivariate analysis, only histology and receipt of chemoradiation were independent predictors of survival. Conclusion: The majority of stage IIIC high-grade endometrial carcinomas recurred. Chemoradiation was associated with improved survival and less retroperitoneal recurrence. Grade 3 tumors demonstrated improved survival versus other histologies regardless of adjuvant treatment modality.