Does the Time to Adjuvant Radiotherapy Impact Outcomes in Women With Stage III Uterine Cancer?

Abstract

Adjuvant radiotherapy (ART) combined with chemotherapy (CT) is an effective adjuvant therapy in women with stage III uterine carcinoma (UC). However, there exists a sparse evidence for the optimal time to start ART. We evaluated the impact of time interval to ART initiation on survival endpoints for surgically staged patients with stage III EC receiving adjuvant multimodality therapy. We queried our prospectively- maintained database for women with FIGO stage III UC who underwent surgical staging at our institution between 12/1990 and 12/2019. All patients in the study received ART and CT with various sequences. CT consisted of 4-6 cycles of paclitaxel-carboplatin combined with ART (external beam RT (EBRT) ± vaginal brachytherapy (VB) boost). Time to RT initiation (TRTI) elapsing between surgical staging and 1st fraction of ART was calculated in weeks for each patient. We studied the influence of TRTI on relapse- free (RFS), disease- specific (DSS) and overall (OS) survival using log-rank test (continuous) and Kaplan-Meier curves to compare outcomes at weekly increments (8-12 weeks). Clinico-pathological and treatment characteristics were dichotomized at the 8 weeks' time-point and compared. Cox regression multivariate analyses (MVA) were performed to determine independent predictors for survival endpoints. 137 patients were identified. Median age was 64 years (range, 38-85), 45% of patients had non-endometrioid histology. Median number of lymph nodes (LN) examined was 23 (range, 1-55) and median number of positive LN was 2 (range, 0-18). Stage IIIC constituted 78% of the study cohort followed by stage IIIA (20%). 51% of the patients received EBRT alone, while 49% received an additional VB boost. 72 cases (52.5%) received ART ≤8 weeks after hysterectomy, and 47.5% (n = 65) received ART > 8 weeks. After a median follow up of 58 months (CI: 42-66), longer TRTI > 8 weeks was associated with worse 5-year RFS (49% (CI:36-62) vs. 71% (CI:55-83); p = 0.01), which persisted at latter time points (9-12 weeks), p<0.05 for all; with a trend when assessed as a continuous variable (p = 0.053). TRTI was neither correlated with 5-year OS or DSS. On MVA for RFS, TRTI (> vs. ≤ 8 weeks) (HR 2.9 (CI:1.4-6.03); p = 0.004), lymphovascular space invasion (HR 4.05; p = 0.009) and advanced stage (HR 3.63; p = 0.04) were all independent prognostic factors. African American race was the only independently predictive for shorter OS (HR 2.44; p = 0.002) and DSS (HR 3.26; p = 0.006). Within the context of multimodality therapy, our study suggests that earlier start of ART within 8 weeks was independently associated with improved recurrence- free survival in women with advanced stage endometrial cancer. Multi-institutional research collaboration is needed to validate our results.