Defining optimal adjuvant treatment for high-risk early-stage endometrial cancer

Abstract

<h3>Objectives:</h3> There is a paucity of data to determine the optimal adjuvant treatment of early-stage, high-risk endometrial histologies. While many retrospective series focus on uterine serous cancer, the optimal treament for other high risk subtypes, including G3 endometrioid cancer, clear cell carcinoma or carcinosarcoma is not yet clear. We sought to determine patterns and outcomes of adjuvant treatment for early-stage high-risk endometrial cancers of multiple histologic subtypes. <h3>Methods:</h3> After Institutional Review Board approval, a retrospective review of patients at Montefiore Medical Center diagnosed with early stage high-risk endometrial cancer between 2006 and 2018 was conducted. Inclusion criteria included: 1) Stage I-II disease 2) Grade 3 endometrioid, carcinosarcoma, clear cell, serous, or mixed histologies. Demographic and clinical information pertaining to cancer treatment was collected. The primary outcome was recurrence-free survival. Univariate and multivariate analyses were performed and a Kaplan-Meier progression free survival curve was created using STATA 14.2. P-value <0.05 was considered statistically significant. <h3>Results:</h3> A total of 1208 patients with endometrial cancer were identified, 249 of which met inclusion criteria. Sixty-percent (149) of patients had serous, clear cell, or mixed histologies, 17% (43) had carcinosarcoma, 23% (57) had Grade 3 endometrioid histology. Most patients received adjuvant combination chemoradiotherapy (52%, N=131) whereas 20% (49) received radiation alone (brachytherapy or external beam), 7% (18) received chemotherapy alone, and 20% (50) received no adjuvant treatment. Of the 48 (19%) disease recurrences, 25 (45%) were distant metastases at the time of recurrence. Combined chemoradiotherapy was associated with increased recurrence-free survival compared with chemotherapy alone (p=0.026) or radiation alone (p=0.004). Compared to G3 endometrioid histology, the hazard ratios for recurrence were: 3.70 (CI 1.31-10.41, p=0.01) for serous histology, 1.37 (CI 0.15-12.21, p=0.78) for clear cell, 9.70 (CI 3.22-29.16, p<0.01) for carcinosarcoma, and 4.59 (CI 1.28-16.46, p=0.02) for mixed histology. Charlson Cormorbidity Index was also associated with cancer recurrence (HR 1.53, CI 1.28-1.82, p<0.01), as was age (HR 0.95, CI 0.92-0.99, p=0.01). <h3>Conclusions:</h3> Multimodal treatment with chemotherapy and radiation therapy is associated with increased recurrence free survival in patients with high-risk early-stage endometrial cancers, in comparison to radiation or chemotherapy alone after surgical staging. Histologic subtype, comorbid conditions, and age all significantly impact survival. Notably, recurrence in clear cell tumors were not significantly impacted by adjuvant treatment with chemotherapy and radiation therapy. Randomized trials are needed to determine the optimal treatment of high-risk histologic subtypes.