Association between short-term radiation-induced toxicity and oncological outcomes in high-risk prostate cancer: a retrospective single-centre cohort study.

BACKGROUND AND PURPOSE: This retrospective cohort study aimed to explore the association between short-term genitourinary (GU) and gastrointestinal (GI) toxicity and oncological outcomes in high-risk prostate cancer patients treated with external beam radiotherapy (EBRT) alone or with high-dose-rate brachytherapy (HDR-BT). Patient/material and methods: High-risk prostate cancer patients treated at Örebro University Hospital (2008-2021) were divided into two cohorts based on treatment modality: EBRT-only (66 Gy/22 fractions), EBRT-BT (42 Gy/14 fractions + 14.5 Gy HDR-BT-boost). Maximum 6-month toxicity grade was categorised as: GU-low (grade 0-1), GU-high (grade ≥ 2), GI-low (grade 0) and GI-high (grade ≥ 1), respectively. Freedom from biochemical failure (FFBF), metastasis-free survival (MFS) and overall survival were compared between the low- and high- toxicity groups, using Kaplan-Meier and Cox proportional hazards regression. Prostate cancer-specific mortality was compared between the groups using the Aalen-Johansen method and Fine-Gray regression.

RESULTS

The EBRT-only cohort encompassed 114 and 162 patients for GU- and GI-analyses. The EBRT-BT cohort comprised 306 patients for GU- and 344 patients for GI-analyses. High GU-toxicity was associated with inferior FFBF (adjusted hazard ratio (aHR) = 2.57, 95% Confidence Interval [CI] = 1.32-5.00) and MFS (aHR = 2.22, 95% CI = 1.21-4.07) in the EBRT-only but not in the EBRT-BT cohort. No statistically significant associations were found between GI-toxicity and oncological outcomes.

INTERPRETATION: Early grade ≥ 2 GU-toxicity was linked to worse FFBR and MFS after EBRT alone, whereas no such association was seen after EBRT-BT. GI toxicity showed no prognostic impact. These exploratory findings warrant validation in larger studies addressing interactions between patient-, tumour- and treatment-related factors.