Patterns of Recurrence By Adjuvant Radiation Therapy Type for Stage II Endometrial Cancer: A Provincial Review

Abstract

Optimal adjuvant treatment of FIGO stage II endometrial cancer is controversial. As surgical practice evolves to include nodal resection, there may be a role for de-intensifying adjuvant therapy. In this province-wide retrospective review, patterns of recurrence were analyzed, alongside adjuvant radiotherapy (RT) practices including pelvic external beam (EB) RT, vaginal vault brachytherapy (BT), and small “minipelvis” (MP) EBRT fields, covering surgical bed, vaginal vault, and parametria, but not the classic elective nodal volumes. We identified patients diagnosed with stage II endometrial cancer between 2000-2014 who received adjuvant RT in Alberta, Canada. We collected demographics, disease characteristics, treatment details, and clinical outcomes. Recurrence-free survival (RFS) was calculated by Kaplan-Meier analysis and factors associated with recurrence were determined by univariate and multivariate analysis. A total of 264 patients (median age 62 [35-87]) met inclusion criteria. 83% had endometrioid adenocarcinoma, 25% grade 3 disease, 56% outer half myometrial invasion, and 44% lymphovascular invasion (LVI). Nodes were surgically assessed in half: 130 (49%) pelvic and 26 (10%) para-aortic. 34 patients (13%) had chemotherapy. RT was predominantly full pelvis (FP) EBRT+BT (114), but included BT alone (63), FP-EBRT alone (42), MP-EBRT+BT (34), and MP-EBRT alone (11). 5 year RFS for the entire cohort was 87%, with median follow-up 93.0 months [5.0-212.7]. 57 patients recurred (22%), including 25% of those treated with FP-EBRT+BT, 16% receiving BT alone, 14% receiving FP-EBRT alone, 21% receiving MP-EBRT+BT, and 55% receiving MP-EBRT alone. On multivariate analysis (reference: FP-EBRT+BT), no treatment group was significantly associated with recurrence. A trend was seen for MP-EBRT alone (hazard ratio [HR] 4.25, p=0.052). Mixed histology and presence of LVI were associated with recurrence (HR 3.73, p=0.008; and HR 3.38, p=0.001, respectively). Chemotherapy was protective (HR 0.20, p=0.012). Pathologic nodal assessment was not correlated with recurrence (p=0.90). Median time to recurrence was 19.9 months [2.9-92.3]. Recurrence was locoregional-only (not para-aortic nor distant) for a minority of patients (N=19/57, 33%), comparable for FP-EBRT+BT (N=8, 7.0%) and MP-EBRT+BT (N=3, 8.8%) groups. Among all patients, 62 (24%) had recorded late toxicity, most frequently gastrointestinal (N=40), including grade 3-4 (N=3) and grade 5 (N=2), with all grades 3-5 having received FP-EBRT+/-BT. No single best adjuvant treatment strategy exists for stage II endometrial cancer. Careful risk stratification is suggested in selecting optimal adjuvant treatment. MP-EBRT+BT is an option for local treatment of the surgical bed, vaginal vault, and parametria, with potential to decrease toxicity.