(UroToday.com) The 2024 ASTRO annual meeting included a session on novel prognostic tools in prostate cancer, featuring a presentation by Dr. John Nikitas discussing the interplay between acute and late toxicity among patients receiving prostate radiotherapy. Dose escalated external beam radiation therapy is the standard of care for localized prostate cancer, with excellent biochemical control rates. Unfortunately, both acute and late toxicity after prostate radiotherapy arises from normal tissue irradiation at the time of treatment.
Acute toxicity occurs following the death of rapidly proliferating cells and is generally considered reversible, whereas late toxicity occurs due to fibrosis and chronic inflammation and is more detrimental to the patient's quality of life. However, the association between acute toxicity and late toxicity remains poorly understood. Dr. Nikitas and colleagues sought to characterize the relationship between acute and late genitourinary and gastrointestinal toxicity, both as scored by physicians and as reported by patients, among patients receiving radiotherapy for prostate cancer.
Individual patient data for trials that included conventionally fractionated or moderately hypofractionated radiotherapy and had acute and late genitourinary and gastrointestinal toxicity data were extracted from the MARCAP consortium. Physician-reported acute (<=3 months from treatment) and late (>3 months from treatment) genitourinary and gastrointestinal toxicity were graded using RTOG criteria or CTCAE. Urinary and bowel patient-reported quality-of-life data from Expanded Prostate Cancer Index Composite (EPIC) questionnaires were used to identify late quality-of-life decrements greater than twice the minimal clinically important difference at any time beyond 3 months post-treatment. Minimal clinically important difference was defined as half of the standard deviation at baseline. Generalized linear mixed models were used to examine the relationship between acute grade 2+ genitourinary and gastrointestinal toxicity, and both late grade 2+ genitourinary and gastrointestinal toxicity and late decrement twice the minimal clinically important difference in urinary and bowel quality of life. These were adjusted for age, performance status, receipt of ADT, use of intensity-modulated radiotherapy (IMRT), and use of moderate hypofractionation. There were 7,555 patients from 8 trials (CHHiP, FCCC, HYPRO, Ottawa 0101, PROFIT, Regina Elena, RTOG 0126, and RTOG 0415) included in this analysis. All trials had toxicity data available and three trials (CHHiP, PROFIT, and RTOG 0415; n = 3,548) had longitudinal quality of life data available. The median follow-up was 72 months (IQR 62-98 months). Overall, 76% received IMRT, 44% received ADT, and 38% received moderate hypofractionation:
For physician-scored toxicity, rates of acute grade 2+ genitourinary and gastrointestinal toxicity were 29.8% and 14.7%, respectively. Rates of late-grade 2+ genitourinary and gastrointestinal toxicity were 17.0% and 14.6%, respectively. Reported quality of life, and rates of urinary and bowel quality decreased decrement twice the minimal clinically important differences were 19.5% and 31.3%, respectively.
Acute grade 2+ genitourinary toxicity was associated with late grade 2+ genitourinary toxicity (OR 2.20, 95% CI 1.88 – 2.57), and acute grade 2+ gastrointestinal toxicity was associated with late grade 2+ gastrointestinal toxicity (OR 2.53, 95% CI 2.07-3.08). Similarly, acute grade 2+ genitourinary toxicity was associated with late urinary quality of life decrement twice the minimal clinically important difference (OR 1.41, 95% 1.17-1.68), and acute grade 2+ gastrointestinal toxicity was associated with late bowel quality of life decrement twice the minimal clinically important difference (OR 1.97, 95% CI 1.50-2.60).
Dr. Nikitas noted several limitations of this analysis:
- These are posthoc analyses of 8 different randomized controlled trials, and there may be unmeasured confounders influencing the observations
- Trial toxicity data relied on physician or investigator reporting, which may not capture all events
- Five of the trials did not collect longitudinal EPIC data for the quality of life analysis, which may have introduced a source of bias in the data
Dr. Nikitas concluded his presentation discussing the interplay between acute and late toxicity among patients receiving prostate radiotherapy with the following take-home points:
- There was a significant association between acute and late toxicity following conventional fractionated or moderately hypofractionated prostate radiotherapy
- These associations were confirmed using both physician scoring and patient-reported quality-of-life metrics
- Further prospective studies are needed to evaluate whether strategies that mitigate the risk of acute toxicity translate into reduced rates of late toxicity and whether early interventions to treat acute toxicity impact rates of late toxicity.
Presented by: John Nikitas, MD, UCLA Radiation Oncology, Los Angeles, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting, Washington, DC, Sun, Sept 29 – Wed, Oct 2, 2024.