Efficacy and tolerability of hypofractionated and dose-boosted radiotherapy for localised prostate cancer: a systematic review and meta-analysis
Year: 2026
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: In this systematic review and meta-analysis (PROSPERO: CRD42024601045), we evaluated the efficacy and safety of hypofractionated and dose-boosted radiotherapy fractionation schedules in patients with clinically localised prostate cancer. We searched MEDLINE, Embase, Web of Science, CENTRAL, and Google Scholar on 2025-06-15 for randomised controlled trials (RCT) using equivalent doses in 2 Gy fractions (EQD2) ≥ 70 Gy in both arms, with outcomes including biochemical recurrence-free survival (BRFS), metastasis-free survival (MFS), overall survival (OS), and rates of grade ≥ 2/≥3 adverse events (AEs). Data were pooled using random-effects meta-analyses and presented in forest plots. Risk-of-bias (RoB) was assessed using the Cochrane RoB 2 tool. We identified 25 RCTs involving 12,479 patients. Combining external beam radiotherapy with brachytherapy or with focal boost was associated with significant MFS improvement (n = 1468, hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.6-0.95, p = 0.016) compared to standard radiotherapy. A sensitivity analysis including two studies with extended follow-up suggested possible OS benefit (n = 897, HR: 0.75, 95% CI: 0.6-0.95, p = 0.016). BRFS was evaluated in 15 trials testing hypofractionation (n = 10220). We found a small numerical improvement (HR 0.88, 95% CI 0.76-1, p = 0.058), though not well explained by the EQD2 model, and no significant differences in MFS or OS. Acute grade ≥ 2 gastrointestinal AEs were modestly increased with moderate hypofractionation, and acute grade ≥ 3 genitourinary AEs were increased with ultra-hypofractionation, without significant differences in late AEs. Primary limitations included concerns regarding RoB associated with patient allocation in dose-boost analysis, and impact of open-label study designs on AE reporting. These findings support the use of dose-boosting as a means to improve survival in high-risk patients, and hypofractionation as a method to reduce treatment time associated with a potential improvement in disease control.
Source: Radiotherapy and Oncology
Authors: Marcin Miszczyk, Nishan Sohoni, Shayan Smani, Matthias Moll, Ahmed R. Alfarhan, Navid Roessler, Keiichiro Miyajima, Shota Inoue, Giulia Marvaso, Federico Mastroleo, Constantinos Zamboglou, Timo F.W. Soeterik, Thomas Zilli, Mario Terlizzi, Pierre Blanchard, Paweł Rajwa, Tamás Fazekas, Guillaume Ploussard, Yi An, Michael S. Leapman, Oliver Blanck, Barbara A Jereczek-Fossa, Shahrokh F. Shariat
Institutions: Comprehensive Cancer Center Vienna, WSB University, Medical University of Vienna, Yale University, MedAustron, University Medical Center Hamburg-Eppendorf, Jikei University School of Medicine, Okayama University, University of Milan, European Institute of Oncology, University Medical Center Utrecht, St. Antonius Ziekenhuis, University of Geneva, Ente Ospedaliero Cantonale, Istituto Oncologico della Svizzera Italiana, Università della Svizzera italiana, Inserm, Université Paris-Saclay, Institut Gustave Roussy, University College London Hospitals NHS Foundation Trust, University College London, Semmelweis University, University Hospital Schleswig-Holstein, University of Jordan, Tabriz University of Medical Sciences, Charles University, Weill Cornell Medicine, The University of Texas Southwestern Medical Center
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,770
Funder: European Association of Urology
OpenAlex ID: W7129248913