2538 - GLP-1 Receptor Agonists and Radiation Toxicity in Prostate Cancer: A Propensity-Matched Cohort Analysis
Presenter(s)
H. Markus1, D. Liu1, and V. Takiar2; 1Penn State College of Medicine, Hershey, PA, 2Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH
Purpose/Objective(s): GLP-1 receptor agonists (GLP-1RAs) have demonstrated anti-inflammatory properties, reduced cancer incidence, and vascular protective effects through enhanced nitric oxide production and reduced oxidative stress. With 4.1% of cancer patients now receiving GLP-1RAs (mean user age 58.7 years), understanding their effects during treatment is increasingly relevant. We investigated whether GLP-1RA use decreases radiation toxicity in prostate cancer patients.
Materials/Methods: Using the TriNetX electronic health record database, we identified patients with prostate cancer who received radiation treatment after 2021. Patients were excluded if they had undergone prostatectomy, had type 2 diabetes, lacked 1 year of EHR data prior to radiation treatment, or had less than 1 year of follow-up after radiation. The index date was defined as the date of radiation treatment initiation. Cases were defined as patients who received GLP-1RA therapy within 1 year of radiation treatment; controls received no GLP-1RA therapy. Propensity score matching (1:10) was performed using 13 noncancer Charlson Comorbidity Index (including congestive heart failure, peripheral vascular disease, rheumatologic disease, and renal disease), androgen deprivation therapy use, age, smoking history, alcohol use history, and radiation treatment modality. Outcomes included erectile dysfunction (ED), radiation proctitis, radiation cystitis, urinary incontinence, and urinary stricture. One-sided Fisher's exact test was used to assess whether GLP-1RA use decreased toxicity outcomes.
Results: After matching, 470 controls and 47 cases were included with well-balanced characteristics (standard mean difference = 0.15). Median follow-up was 2.38 years. ED showed a significant protective association with GLP-1RA use (odds ratio [OR] 0, 95% CI 0-0.94, p=0.042). No statistically significant associations were observed for radiation proctitis (OR 0.44, 95% CI 0-2.38, p=0.36), radiation cystitis (OR 1.44, 95% CI 0-5.53, p=0.82), urinary incontinence (OR 1.99, 95% CI 0-4.60, p=0.95), or urethral stricture (OR 0.0, 95% CI 0-8.31, p=0.61).
Conclusion: While GLP-1RAs have been shown to reduce prostate cancer incidence, this analysis found no significant associations with most radiation toxicities in patients undergoing radiotherapy. The observed protective association with erectile dysfunction may warrant further investigation given the known vascular and endothelial protective effects of GLP-1RAs. Limitations include the retrospective design, limited sample size, and relatively short follow-up duration. Further prospective studies are needed to determine whether GLP-1RAs have potential protective effects against specific radiation-induced toxicities.