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).
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.
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.
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.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 2026 Mar 27 [Epub ahead of print]
Constanza Martínez, Steven Tisseverasinghe, Muneeb U Karim, Kanta Ka, Abdenour Nabid, Edmond Kaldany, Redouane Bettahar, Linda Vincent, Andre-Guy Martin, Marjory Jolicoeur, Michael Yassa, Maroie Barkati, Boris Bahoric, Robert Archambault, Hugo Villeneuve, Mohammed Mohiuddin, Tamim Niazi
McGill University Health Centre, Division of Radiation Oncology. Montreal, Quebec, Canada; Department of Oncology, Division of Radiation Oncology, Jewish General Hospital, Room G-002, 3755 Côte Ste. Catherine Road, Montreal, Quebec H3T 1E2, Canada., Department of Radiation Oncology, Gatineau Hospital, McGill University. Gatineau, Quebec, Canada., Department of Oncology, Division of Radiation Oncology, Jewish General Hospital, Room G-002, 3755 Côte Ste. Catherine Road, Montreal, Quebec H3T 1E2, Canada., Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Quebec, Canada., CSSS Rimouski-Neigette. Rimouski, Quebec, Canada., Pavillon Ste-Marie Centre hospitalier régional de Trois-Rivières (CHRTR). Trois-Rivieres, Quebec, Canada., Department of Radiation Oncology, CHU de Québec-Université Laval, Quebec, Canada., Charles LeMoyne Hospital. Longueuil, Quebec, Canada., CIUSSS de L'Est-de-I'lle-de Montreal Hopital Maisonneuve-Rosemont. Montreal, Quebec, Canada., Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, Quebec, Canada., McGill University Health Centre, Division of Radiation Oncology. Montreal, Quebec, Canada., CSSS de Chicoutimi, Chicoutimi, Quebec, Canada., Saint John Regional Hospital and Dalhousie University. Saint John, New Brunswick, Canada., Department of Oncology, Division of Radiation Oncology, Jewish General Hospital, Room G-002, 3755 Côte Ste. Catherine Road, Montreal, Quebec H3T 1E2, Canada. Electronic address: .