Survival Outcomes of Stage IIIC Endometrioid and Non-Endometrioid Endometrial Cancer Treated with Combined Modality Adjuvant Therapy

Abstract

The optimal adjuvant treatment for stage IIIC endometrial cancer remains controversial with the recent report of GOG 258 and PORTEC-3 leading to potentially conflicting conclusions about the benefit of combined modality treatment. These randomized trials included endometrioid and non-endometrioid subsets although they are known to have different patterns of recurrence. We aimed to identify the adjuvant treatment regimen associated with the best survival outcomes for histologic subsets. Patients with clinical or pathological stage IIIC who underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and lymph node sampling between 2/1985 – 9/2015 were identified. Median follow-up time from the time of surgery for these 282 patients was 56 months (range, 2-325 months). The Kaplan-Meier method was used to calculate overall survival (OS), disease specific survival (DSS), and pelvic disease control from the time of surgery. Comparisons between patient and treatment characteristics were assessed using log-rank tests. Univariate and multivariable analyses were calculated using Cox proportional hazards modeling. Among patients with endometrioid histology (n=177), 87% received external beam radiation therapy (EBRT); the most common regimen was concurrent chemoradiation followed by adjuvant chemotherapy (34%). The majority of patients with non-endometrioid (serous, clear cell, carcinosarcoma, adenosquamous; n=105) and grade 3 (n=143) histologies received chemotherapy with or without EBRT at rates of 84% and 80%, respectively; adjuvant chemotherapy alone was utilized in 44% and 37% of patients, respectively. OS, DSS, and pelvic disease control for all patients at 5 years was 63%, 65%, and 77%. Among the grade 1/2 endometrioid subset, 5-year DSS was 80% for EBRT alone and 84% for chemoradiation (p=0.8); grade 3 endometrioid patients had rates of 58% and 66%, respectively (p=0.6). For non-endometrioid patients, 5-year DSS improved with chemoradiation (72%) as compared to chemotherapy alone (42%; p<0.02). Age >60 (HR 2.39 [95% CI 1.57-3.63], p<0.001), non-endometrioid histology (HR 2.27 [95% CI 1.22-4.23], p=0.01), grade 3 (HR 2.62 [95% CI 1.65-4.14], p<0.001), adnexal involvement (HR 1.65 [95% CI 1.08-2.50], p=0.02), and >50% myometrial invasion (HR 2.47 [95% CI 1.55-3.91], p<0.001) were independently associated with lower DSS. Pelvic failure was associated with death (HR 1.68 [95% CI 1.08-2.60], p=0.02). Patients with gross disease who received EBRT with a boost experienced a similar high rate of pelvic disease control as patients without gross disease treated with EBRT without a boost (92% vs. 90%, p=0.8). Patients with endometrioid cancer had similar outcomes if treated with EBRT with or without chemotherapy. Combined modality treatment resulted in higher rates of DSS and pelvic disease control in patients with non-endometrioid high-risk histology as compared to patients who received chemotherapy alone.