Role of Brachytherapy in Adjuvant Radiation Practices for FIGO Stage II Endometrial Cancer

Abstract

FIGO stage II endometrial adenocarcinoma (EAC) involves the cervical stroma but is otherwise confined to the uterus. Management involves total hysterectomy and bilateral salpingo-oophorectomy (TH/BSO) followed by risk-adapted adjuvant therapy which may include radiation and chemotherapy (CHT). We sought to investigate whether patients with FIGO II EAC undergoing adjuvant radiation benefit from addition of vaginal cuff brachytherapy (VCB). The National Cancer Database was queried to identify patients with FIGO II EAC diagnosed in 2010-2019 who received TH/BSO followed by adjuvant EBRT alone, VCB alone, or EBRT+VCB. Patients <18 years old or with <6 months follow-up were excluded. Clinical and demographic data were compared by treatment received using two-sided Z-tests and χ2 tests. Predictors of VCB were identified using multinomial logistic regression. Multivariate regression was used to identify predictors of death. Survival was evaluated with Kaplan-Meier estimators and Cox proportional hazards modeling. A total of 6152 women with FIGO II EAC met inclusion criteria. After TH/BSO, 1792 (29%) patients received EBRT alone, 2428 (40%) received VCB alone, and 1923 (31%) received EBRT+VCB. Lymphovascular space invasion (LVSI) was present in 2224 (36%) patients, of which 751 (34%) received EBRT alone, 698 (31%) received VCB alone, and 775 (35%) received EBRT+ VCB. CHT was given to 548 (31%) treated with EBRT alone, 248 (16%) with VCB alone, and 414 (21%) with EBRT+VCB. Positive surgical margins (+SM) were present in 211 patients (3%), of which 92 (44%) were treated EBRT alone and 70 (33%) with EBRT+VCB. Compared to EBRT alone, relevant relative risk ratios (RRR) of receiving VCB alone include grade 2 (RRR -0.25, p = 0.020) or 3 (RRR -0.41, p = 0.004) disease, single agent CHT (RRR -0.83, p = 0.001), and LVSI (RRR -0.56, p<0.001). RRR of receiving EBRT+VCB include age>70 (RRR -0.37, p = 0.022), grade 3 disease (RRR 0.30, p = 0.024), and single (RRR -0.42, p = .046) or multi- (RRR -0.24, p = 0.026) agent CHT. Predictors of death in the study cohort include age 50-69 (OR 1.8, p<0.001) and >70 (OR 4.1, p<0.001), Charlson-Deyo Comorbidity Index ≥1 (OR 1.4, p<0.001), grade 2 (OR 1.8, p<0.001) or 3 (OR 3.0, p<0.001) disease, cervical stromal invasion (OR 1.4, p = 0.001), and LVSI (OR 1.5, p<0.001). Compared to EBRT alone, both VCB alone (OR 0.81, p = 0.023) and EBRT+VCB (OR 0.70, p<0.001) were associated with decreased risk of death. Five-year overall survival in patients receiving EBRT alone was 77.9% (95% CI 75.8-79.8%), whereas VCB alone and EBRT+VCB were 84.8% (83.2-86.2%, log rank p<0.001) and 82.9% (81.0-84.6%, log rank p<0.001) respectively. Survival differences remained significant when isolating patients with LVSI, grade 3, and +SM. VCB as monotherapy or in combination with EBRT in patients with FIGO II EAC was associated with improved survival. Inclusion of adjuvant VCB maintains an important role in treating patients with FIGO II EAC.