Shortened brachytherapy course proves its worth in endometrial cancer

Short-course vaginal cuff brachytherapy (VCB) is just as efficacious as standard regimens for adjuvant treatment of endometrial cancer, yielding noninferior patient-reported outcomes without compromising disease control while having acceptable toxicity, according to the phase III, unblinded, multicentre SAVE trial.

Results for the primary outcome of the QLQ-C30 Global Health Status showed relatively stable scores over months 1, 6, and 12. But the scores were slightly higher among patients who received short-course VCB (74.4, 77.0, and 77.7, respectively) than among those who received standard-of-care VCB (69.6, 75.8, and 74.3, respectively). This established the noninferiority of the short-dose VCB protocol to standard of care for all time points (1 month: p=0.01; 6 months: p=0.003; 12 months; p=0.02). [JCO Oncol Adv 2024;10.1200/OA.24.0001]

Meanwhile, changes in symptom scores (assessed using the EORTC Quality of Life Questionnaire - Endometrial Cancer Module) for patient-reported vaginal/sexual, urologic, and gastrointestinal (GI) symptoms from baseline to 1 and 12 months did not significantly differ between the short-course and standard-of-care arms.

Short-term adverse events (AEs) occurred in 20 patients (37 percent) in the short-course arm and in 31 (57 percent) in the standard-of-care arm (p=0.053). Urinary AEs such as incontinence, urinary tract infection, and urgency were less common in the short-course arm than in the standard-of-care arm (1 vs 14; p=0.0004). GI AEs including diarrhoea and abdominal pain occurred in six and 13 patients, while vaginal toxicity such as dryness, pain, and discharge were documented in 10 and 18 patients in the respective arms. All treatment-related AEs were grade 1-2, except for two grade 3-4 AEs, namely peripheral neuropathy and urinary tract infection, which both occurred in the standard-of-care arm.

At a median follow up of 28 months, the vaginal control rate was 96 percent in both arms, with the isolated vaginal control rate being 100 percent in the short-course arm.

“These findings underscore the potential for a more streamlined and patient-centric approach to the delivery of adjuvant VCB in the management of endometrial cancer,” the investigators said.

They explained that a shorter treatment course with fewer radiotherapy fractions delivered may help overcome some barriers to radiotherapy access, including the limited availability of specialized treatment centres, particularly in rural or underserved areas, and the need for trained personnel to be present during each treatment session, among others.

Additionally, “reducing the number of administered treatments may alleviate stress and discomfort associated with adjuvant radiotherapy treatment, thereby improving the patient experience,” they continued.

SAVE included 108 patients with histologically confirmed endometrial carcinoma, specifically endometrioid, serous, and clear cell carcinomas and carcinosarcomas, and for whom VCB was indicated. These patients were randomly assigned to receive short-course (n=54, median age 65.3 years, 41 percent White) or standard-of-care VCB (n=54, median age 63.7 years, 45 percent White). The short-course arm received higher doses of radiation in just two sessions (11 Gy × two fractions at the surface), while the standard-of-care arm received lower treatment doses over three to five sessions (7 Gy × three fractions at 0.5 cm depth, 6 Gy × five fractions at the vaginal surface, or 5–5.5 Gy × four fractions at 0.5 cm depth).

Patient characteristics were balanced between the two treatment arms, except for lymphovascular space invasion, which was less common in the short-course arm (13 percent vs 31 percent). Most patients had endometrioid adenocarcinoma (70 percent) and FIGO stage IA (56 percent). Grade was distributed as FIGO grade 1 (23 percent), grade 2 (33 percent), and grade 3 (43 percent).