Association between dose to specific pelvic substructures and urinary and sexual dysfunction following Single-Dose ablative radiotherapy for prostate Cancer: A post hoc analysis from the ABRUPT trial

Abstract

Purpose

To investigate the association between radiation dose to pelvic functional substructures and the incidence of urinary and sexual side-effects following single-dose ablative radiotherapy (SDRT) for localized prostate cancer.

Methods and Materials

A post hoc analysis was conducted on the 30 patients from the prospective ABRUPT trial (NCT04831983). Functional substructures, including the bladder trigone, urogenital diaphragm, neurovascular bundles (NVB), penile bulb (PB), internal pudendal arteries (IPA), and crura, were contoured by an experienced radiation oncologist. Maximum and mean doses were extracted from planning dose-volume histograms. Adverse events (AEs) were assessed using CTCAE and patient-reported outcomes (PRO). Logistic regression, Wilcoxon-Mann-Whitney, and ROC analyses were used to explore dose-toxicity associations and predictive thresholds, with cross-validation for robustness.

Results

Late urinary dysfunction correlated with bladder trigone D1cc ≥ 20.3 Gy (cross-validated AUC = 0.80; PPV = 64.3%; NPV = 75.0%), consistent across physician- and patient-reported endpoints. Larger bladder volumes (>166.8 cc) were also associated with urinary PRO deterioration (p = 0.030). Among 22 patients (76% of 29) who recovered testosterone (median = 10 months post ADT completion), erectile dysfunction showed a suggestive association with NVB D0.035 cc ≥ 23.6 Gy (apparent AUC = 0.98), although based on a limited number of events. Trends toward higher IPA and crura doses were observed in patients with sexual dysfunction, while no relationship was observed for PB dose.

Conclusions

This exploratory analysis highlights the bladder trigone as potential predictor of urinary morbidity in SDRT. Incorporating substructure-sparing into treatment planning could improve functional preservation and reduce late toxicity, pending prospective validation in larger trials.