Intensity-modulated radiotherapy reduces acute and delayed G2+GI toxicities versus 3D-CRT in high-risk prostate cancer

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Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Published June 1, 2026 Medically reviewed June 1, 2026 Study authors: Martínez Constanza, Tisseverasinghe Steven, Karim Muneeb U, Ka Kanta, Nabid Abdenour, Kaldany Edmond… PubMed ↗ DOI ↗ By Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic

Key Takeaway

Consider IMRT for high-risk PCa to reduce GI toxicity, noting increased acute G1 GU events.

This post hoc analysis of a Phase III randomized controlled trial included 296 patients with high-risk prostate cancer who received androgen suppression. The study compared intensity-modulated radiotherapy (IMRT) with three-dimensional conformal radiotherapy (3D-CRT). The primary outcome was not reported, but secondary outcomes focused on toxicity profiles and survival metrics.

Regarding gastrointestinal and genitourinary toxicities, IMRT significantly reduced the odds of acute G2+GI toxicities compared to 3D-CRT (OR 0.50; 95% CI, 0.29-0.91; p = 0.023). Similarly, delayed G2+GI toxicities were less frequent with IMRT (OR 0.36; 95% CI, 0.16-0.82; p = 0.015). Conversely, the odds of acute G1+GU toxicities were higher with IMRT (OR 1.77; 95% CI, 1.07-2.95; p = 0.03). No significant differences were found for biochemical failure-free survival, distant metastasis-free survival, or overall survival between the two techniques.

Safety data indicated that both acute and delayed genitourinary and gastrointestinal toxicities occurred. The study did not report serious adverse events, discontinuations, or overall tolerability. A key limitation is that this was a non-randomized comparison within a larger trial, and the study was a post hoc analysis. Consequently, causality cannot be definitively established, and these results represent associations rather than proven causal effects.

Study Details

Study typeRct

Sample sizen = 329

EvidenceLevel 2

PublishedJun 2026

PMID41905637

View Original Abstract ↓

PURPOSE: Prostate Cancer Study 5 (PCS-5) is a phase III, randomized controlled trial comparing conventionally fractionated radiotherapy (CFRT) vs. hypofractionated radiotherapy (HFRT) exclusively in patients with high-risk prostate cancer (PCa). This post hoc analysis evaluates differences in efficacy outcomes as well as genitourinary (GU) and gastrointestinal (GI) toxicities between intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). MATERIALS AND METHODS: PCS-5 randomized patients in a 1:1 ratio to CFRT (76 Gy in 38 fractions) or HFRT (68 Gy in 25 fractions). All patients received long-term androgen suppression (median duration: 24 months) and pelvic radiation therapy (RT). Acute toxicities were defined as ≤ 180 days post-RT, and delayed toxicities > 180 days using CTCAE v4. Multivariable logistic regression analyses were performed for acute and delayed toxicities, adjusting for clinical factors. Efficacy analyses utilized Cox proportional hazards regression models. RESULTS: Among 329 patients, 296 were included in this study. IMRT reduced acute G2 + GI toxicities (OR 0.50; 95% CI, 0.29-0.91; p = 0.023), delayed G2 + GI toxicities (OR 0.36; 95% CI, 0.16-0.82; p = 0.015), and increased acute G1 + GU toxicities (OR 1.77; 95% CI, 1.07-2.95; p = 0.03) compared to 3D-CRT. Biochemical failure-free survival, distant metastasis-free survival, and overall survival did not significantly differ between techniques. CONCLUSION: In PCS-5, HFRT is a standard treatment for high-risk PCa receiving external beam RT. In this post hoc analysis, IMRT was associated with lower acute and delayed G2 + GI toxicity than 3D-CRT, with a modest increase in acute G1 + GU toxicity and no differences in efficacy. Within the limitations of this non-randomized comparison, IMRT appears to be the preferred technique.