Clinical impact of opioid use in patients with urothelial carcinoma treated with pembrolizumab: a single center retrospective study

Background Opioids may influence anti-programmed cell death-1/programmed death-ligand 1 antibody efficacy through effects on the gut microbiome and immune function. Although reduced efficacy has been suggested in non-small cell lung cancer, the impact of opioid use in urothelial carcinoma remains unclear. This study examined the impact of opioids on pembrolizumab efficacy in patients with urothelial carcinoma.Methods We conducted a retrospective cohort study of patients with metastatic or unresectable urothelial carcinoma treated with pembrolizumab at our hospital between January 2018 and December 2021. Opioid use was defined as administration of opioid analgesics for pain control within 30 days before or after pembrolizumab initiation. Stabilized inverse probability of treatment weighting (IPTW) using propensity scores was applied to adjust for baseline imbalances and evaluate outcomes.Results Of 76 recruited patients, 68 were eligible. In IPTW-weighted Cox regression analyses, opioid use was associated with shorter progression-free survival (median 6.7 vs. 4.1 months; hazard ratio [HR] 2.85, 95% confidence interval [CI] 1.67–4.88; p < 0.001) and overall survival (18.9 vs. 6.9 months; HR 4.06, 95% CI 1.73–9.55; p = 0.001).Conclusion Opioid use was associated with worse pembrolizumab outcomes in urothelial carcinoma, suggesting the need for careful, clinically appropriate opioid use during treatment.