• John Nikitas, Parsa Jamshidian, Alison C Tree, Emma Hall, David Dearnaley, Jeff M Michalski, W Robert Lee, Paul L Nguyen, Howard M Sandler, Charles N Catton, Himanshu R Lukka, Luca Incrocci, Wilma Heemsbergen, Floris J Pos, Soumyajit Roy, Shawn Malone, Eric Horwitz, Jessica Karen Wong, Stefano Arcangeli, Giuseppe Sanguineti, Tahmineh Romero, Yilun Sun, Michael L Steinberg, Luca F Valle, Joanne B Weidhaas, Daniel Spratt, Donatello Telesca, and Amar U Kishan.
• Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA.
• Lancet Oncol. 2025 Jan 30.

BackgroundThe association between acute and late toxicity following prostate radiotherapy has not been well studied using data from multiple randomised clinical trials and fractionation schedules. We aimed to characterise the relationship between acute and late genitourinary and gastrointestinal toxicity among patients receiving conventionally fractionated or moderately hypofractionated prostate radiotherapy.MethodsThis was an individual patient data meta-analysis that identified randomised phase 3 trials of conventionally fractionated or moderately hypofractionated prostate radiotherapy in the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium that had individual-level acute and late toxicity data available and were available before Dec 1, 2023. Trials without individual patient data were excluded. Data were provided to MARCAP by study investigators. The associations between acute (≤3 months after radiotherapy) and late (>3 months after radiotherapy) grade 2 or greater genitourinary and gastrointestinal toxicities were assessed using adjusted generalised linear mixed models (adjusted for age, androgen deprivation therapy status, type of radiotherapy, radiation dose, and radiation schedule). In the subset of trials that collected Expanded Prostate Cancer Index Composite quality of life (QOL) evaluations, the association between acute genitourinary and gastrointestinal toxicity and decrements at least twice the minimal clinically important difference (MCID) for urinary and bowel QOL were also evaluated.FindingsSix of 26 available trials met all the eligibility criteria. 6593 patients were included (conventionally fractionated: n=4248; moderately hypofractionated: n=2345). Median follow-up was 72 months (IQR 61-94). Acute grade 2 or greater genitourinary toxicity was associated with both late grade 2 or greater genitourinary toxicity (odds ratio 2·20 [95% CI 1·88-2·57], p<0·0001) and decrement at least twice the MCID in urinary QOL (1·41 [1·17-1·68], p=0·0002). Acute grade 2 or greater gastrointestinal toxicity was associated with both late grade 2 or greater gastrointestinal toxicity (2·53 [2·07-3·08], p<0·0001) and decrement at least twice the MCID in bowel QOL (1·52 [1·26-1·83], p<0·0001).InterpretationAcute toxicity following prostate radiotherapy was statistically significantly associated with late toxicity and with decrement in patient-reported QOL metrics. These data support efforts to evaluate whether interventions that reduce acute toxicity ultimately reduce the risk of late toxicity.FundingNational Institutes of Health and US Department of Defense.Copyright © 2025 Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

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