In an individual patient data meta-analysis reported in The Lancet Oncology, Nikitas et al found that early toxicity associated with radiotherapy for prostate cancer was associated with increased risk for late toxicity.
Study Details
The study included patient-level data from six randomized phase III trials of conventionally fractionated or moderately hypofractionated prostate radiotherapy in the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium available prior to December 2023. The associations between acute (≤ 3 months after radiotherapy) and late (> 3 months after radiotherapy) grade ≥ 2 genitourinary and gastrointestinal toxicities were assessed using models adjusted for age, androgen-deprivation therapy status, type of radiotherapy, radiation dose, and radiation schedule. In trials that collected Expanded Prostate Cancer Index Composite quality of life (QOL) evaluations, the association between acute genitourinary and gastrointestinal toxicity and decrements of at least twice the minimal clinically important difference (MCID) for urinary and bowel QOL were evaluated.
Key Findings
Median follow-up was 72 months.
Acute grade ≥ 2 genitourinary toxicity was associated with an increased risk of late grade ≥ 2 genitourinary toxicity (odds ratio [OR] = 2.20, 95% confidence interval [CI] = 1.88–2.57, P < .0001) and a decrement of at least twice MCID in urinary QOL (OR = 1.41, 95% CI = 1.17–1.68, P = .0002).
Acute grade ≥ 2 gastrointestinal toxicity was associated with an increased risk of late grade ≥ 2 gastrointestinal toxicity (OR = 2.53, 95% CI = 2.07–3.08, P < .0001) and a decrement of at least twice the MCID in bowel QOL (OR = 1.52, 95% CI = 1.26–1.83, P < .0001).
At 5 years, the cumulative rates of late grade ≥ 2 toxicity among patients with acute grade ≥ 2 toxicity vs those without acute grade ≥ 2 toxicity were 12.5% vs 7.5% for genitourinary toxicity and 21.5% vs 12.5% for gastrointestinal toxicity, respectively.
The investigators concluded, “Acute 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.”
Amar U. Kishan, MD, of the Department of Radiation Oncology, University of California, Los Angeles, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the National Institutes of Health and U.S. Department of Defense. For full disclosures of the study authors, visit thelancet.com.
