Two-Year Outcomes of the XXX Trial: Longitudinal Analysis of Safety, PSA Kinetics, and Patient-Reported Outcomes.

PURPOSE: To assess the 2-year incidence and longitudinal trajectory of grade (G) ≥2 genitourinary (GU) and gastrointestinal (GI) adverse events (AEs) following single-dose ablative radiotherapy (SDRT) for organ-confined prostate cancer (PCa), alongside associated changes in patient-reported outcomes (PROs) and PSA kinetics.

METHODS

XXX (XXX) is a single-institution prospective study enrolling patients with unfavorable intermediate-risk or selected high-risk organ-confined PCa treated with SDRT delivering 24 Gy in one fraction to the prostate and seminal vesicles. Treatment incorporated urethra-sparing and intrafraction motion control and was delivered on a linear accelerator using a 10-MV flattening filter-free single partial arc in combination with androgen deprivation therapy (ADT). AEs were graded using CTCAE v5.0. PSA and testosterone were monitored longitudinally, and scheduled multiparametric MRI (mpMRI) were performed to assess radiological response. PROs were assessed using EORTC QLQ-C30, QLQ-PR25, IPSS, and IIEF questionnaires. Mixed-effects models evaluated longitudinal trajectories and associations with baseline and dosimetric factors.

RESULTS

Thirty patients were treated. At 2 years, no ≥G3 AEs were observed. Cumulative G2 GU and GI AEs were 23% and 7%, respectively. Two years point prevalent G2 GU and GI AEs were 10% and 3%, respectively. Longitudinal analysis showed an overall stable safety profile, with higher baseline IPSS and bladder trigone D1cc significantly associated with higher GU AEs. PRO analyses demonstrated statistically significant changes in urinary domains, although effect sizes remained below minimal important difference thresholds, indicating no clinically meaningful deterioration. Baseline symptom burden strongly predicted long-term PROs trajectories. Biochemical relapse-free survival was 100% at 2 years, with a consistent and significant PSA decline over time and local radiological control confirmed by mpMRI. Testosterone recovery occurred in 76% of patients receiving ADT.

CONCLUSIONS

Single-fraction 24 Gy SDRT combined with ADT was feasible and well tolerated, with low rates of ≥G2 AEs and largely maintained quality of life at 2 years in patients with unfavorable localized prostate cancer. Early oncologic outcomes are encouraging but require confirmation with longer follow-up and comparative validation.