Excellent local control and minimal toxicity with salvage intensity-modulated radiotherapy and high-dose-rate brachytherapy for vaginal recurrence of endometrial cancer: A 10-year retrospective analysis

Purpose
Salvage external beam radiation therapy (EBRT) followed by vaginal brachytherapy is commonly used to treat patients with vaginal recurrence of endometrial cancer, but limited data are available in the era of modern radiotherapy with intensity-modulated radiotherapy (IMRT) and high-dose-rate brachytherapy (HDR-BT). Our study aimed to assess survival outcomes and late toxicities associated with the combined treatment modality.

Material and methods
A retrospective review of 26 patients with biopsy-proven vaginal recurrence after surgically treated endometrial cancer, for whom salvage EBRT followed by HDR-BT were performed between February 2013 and September 2022. Median EBRT dose was 50 Gy (range, 45-59.4 Gy), and median HDR-BT was 16 Gy (range, 12-24 Gy). Recurrence-free intervals and overall survival (OS) rates were evaluated. Complications were assessed in terms of late RTOG toxicity (grade 3 or higher) of gastrointestinal tract, genitourinary tract, and vagina. Kaplan-Meier and Cox proportional hazards modeling were used to estimate survival. Severe (grade 3 or higher) radiation-related toxicities defined according to RTOG were recorded. Endpoints were measured from the date of diagnosis of vaginal recurrence.

Results
The median follow-up was 36.8 months (range, 4.2-97.8 months). The median age at recurrence was 65.5 years (range, 41-91 years), and the median time to recurrence from primary diagnosis was 20.6 months (range, 2.8-148.1 months). The most common symptom was per vaginal bleeding (30.8%) and vaginal spotting (23.1%). Twenty-four patients (92.3%) had central recurrence (18 vaginal apex, six distal vagina), and two patients (7.7%) had pelvic nodal recurrence with central recurrence. The median tumor size at recurrence was 1.5 cm (range, 0.4-5.0 cm). Eight patients developed a distant recurrence and five of them died due to the disease, with 5-year local control, disease-specific survival, and distant metastatic-free survival rates of 100%, 80.8%, and 69.2%, respectively. The median OS was 91.1 months (range, 15.7-1,503.6 months), and the median distant recurrence-free survival was 46.1 months (range, 7.7-133.8 months). Primary tumor high-grade and stage III were prognostics for poor OS (7.7% and 0%) and distant metastases-free survival (11.5% and 3.8%), respectively. No severe grade 3 or higher late toxicities were observed.

Conclusions
Recurrent vaginal endometrial cancer is amenable to salvage therapy using HDR-BT and EBRT. This combined treatment modality demonstrates excellent loco-regional control and minimal morbidity for vaginal recurrence of endometrial cancer. Early radiotherapy, including brachytherapy, should be considered for women with vaginal recurrence of endometrial cancer.