Short-Course Vaginal Cuff Brachytherapy Noninferior to Standard Regimens in Endometrial Cancer

In a phase 3 randomized, multicenter trial examining the optimal dose and schedule for vaginal cuff brachytherapy (VCB), researchers found short-course VCB had noninferior short-term patient-reported outcomes and acceptable acute toxicity when compared with standard regimens.

Endometrial cancer is the most diagnosed gynecologic cancer in the United States. While most cases are diagnosed at an early stage, adjuvant therapy, including VCB, is often used to reduce recurrence risk. However, the optimal dose and fractionation schedule for high-dose-rate VCB remain uncertain.

Given this, the objective of the SAVE trial (Short-Course Adjuvant Vaginal Cuff Brachytherapy in Early Endometrial Cancer Compared with Standard of Care) was to determine whether a shorter treatment course could maintain QoL and treatment efficacy while minimizing toxicity.

“SAVE is the first US-based, multi-institutional, prospective randomized trial examining optimal dose fractionation for VCB,” the authors wrote.

For their study, Suneja and colleagues enrolled 108 patients across five U.S. centers, randomly assigning them to short-course VCB arm of higher doses with two sessions (11 Gy × 2 at the surface) or a control arm, one of three standard regimens, three to five session with loser doses (7 Gy × 3 at 0.5 cm depth, 5-5.5 Gy × 4 at 0.5 cm depth, or 6 Gy × 5 at the surface).

The primary endpoint was Global Health Status on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Module (QLQ-C30), with a prespecified noninferiority margin of 15 points. Secondary endpoints included patient-reported symptom burden, toxicities, and recurrence rates.

Both treatment arms demonstrated stable quality of life (QoL) scores over time. The short-course regimen was noninferior to standard treatment at 1, 6, and 12 months (P = .01, P = .003, and P = .02, respectively).

Patient-reported symptoms assessed by the EORTC Endometrial Cancer Module (QLQ-EN24) showed no significant differences in vaginal, sexual, urologic, or gastrointestinal symptom scores between treatment arms. Short-term adverse events occurred in 37% of the short-course VCB arm versus 57% of the standard arm (P = .053), with significantly fewer urinary toxicities in the experimental group (P = .0004). At a median follow-up of 28 months, the vaginal control rate was 96% in both groups, and the isolated vaginal control rate in the experimental arm was 100%.

The study's limitations include a relatively small sample size and a follow-up duration that may not fully capture long-term toxicity or late recurrences. Additionally, sexual health outcomes beyond the first year were not explored, warranting further investigation.

"Short-course VCB has noninferior short-term quality of life compared with standard regimens with acceptable short-term acute toxicity and cancer control outcomes," the authors concluded.

Reference
Suneja G, Huang YJ, Boucher KM, et al. Short-course adjuvant vaginal cuff brachytherapy in early endometrial cancer compared with standard of care (save): a randomized clinical trial. JCO Onc Adv. 2024;1:1. DOI: 10.1200/OA.24.00014.