Nonsteroidal anti-inflammatory drug use and site-specific risk of urological cancers: a systematic review and meta-analysis

The role of nonsteroidal anti-inflammatory drugs (NSAIDs) in urological carcinogenesis remains controversial, with epidemiological studies reporting inconsistent findings across cancer sites and drug classes. We performed an updated systematic review and meta-analysis to evaluate the associations of overall NSAID use and specific NSAID classes with the risk of kidney, prostate, and bladder cancers. We systematically searched PubMed, Web of Science, EMBASE, and the Cochrane Library for epidemiological studies published up to May 1, 2025. Pooled relative effect estimates and 95% confidence intervals (CIs) were calculated using random-effects models. Primary meta-analyses were restricted to internally adjusted effect estimates (ORs, RRs, and HRs), whereas studies reporting standardized incidence ratios (SIRs) were evaluated separately in sensitivity analyses. Heterogeneity was assessed using the I² statistic, and prespecified subgroup and sensitivity analyses were conducted. Overall NSAID use was associated with a borderline higher pooled estimate for kidney cancer risk (1.16, 95% CI 1.00–1.34; I² = 56.2%). Aspirin use was not clearly associated with kidney cancer risk (1.11, 95% CI 0.98–1.26; I² = 76.4%) but was associated with a lower pooled estimate for prostate cancer risk (0.90, 95% CI 0.87–0.94; I² = 79.8%). Use of non-aspirin NSAIDs was associated with a higher pooled estimate for kidney cancer risk (1.28, 95% CI 1.05–1.55; I² = 48.6%), and ibuprofen use was associated with a lower pooled estimate for prostate cancer risk (0.90, 95% CI 0.85–0.97; I² = 45.6%). For bladder cancer, the use of non-aspirin NSAIDs was associated with a lower pooled estimate in the primary analysis (0.61, 95% CI 0.41–0.90; I² = 32.1%), but the evidence base was sparse and this finding should be interpreted cautiously. Several analyses showed substantial between-study heterogeneity. Associations between NSAID use and the risk of urological cancers appeared to vary by cancer site and drug class. Use of non-aspirin NSAIDs was associated with a higher pooled estimate for kidney cancer, whereas aspirin use and ibuprofen use were associated with lower pooled estimates for prostate cancer. For bladder cancer, the pooled analysis suggested a possible inverse association with use of non-aspirin NSAIDs, but the evidence was limited and sparse, and the finding should be considered exploratory rather than conclusive. However, substantial heterogeneity and the observational nature of the evidence preclude causal inference.