Urologic malignancy risk with chronic Tumor Necrosis Factor-Alpha Inhibitor (TNF-I) exposure: a multicenter, retrospective cohort study

Purpose : Chronic inflammation has been linked to oncogenesis, including in prostate cancer (PCa). Tumor Necrosis Factor (TNF) has been implicated in many of these chronic inflammatory pathways. We assessed urologic malignancy risk in patients with long-term exposure to TNF inhibitors (TNF-I). Methods : Retrospective non-matched cohort study of patients with chronic inflammatory conditions from 1996–2023. TNF-I exposure was identified using medications. The unmatched control cohort consisted of TNF-I-unexposed patients with the same chronic inflammatory conditions. Urologic malignancies identified using ICD-10 codes and manual chart review. Inverse Probability of Treatment Weighting was used to balance distributions across exposure groups. Hazard ratios (HR) were estimated using multivariable regression followed by logistic regression for relative risk (RR) on sub-analysis. Results : There were 13,377 patients with TNF-I exposure and 42,832 patients without TNF-I exposure. TNF-I exposure was negatively associated with PCa (HR 0.50, 95%CI 0.28–0.90, P  = 0.02), but with higher Gleason grade group (RR 1.11, 95%CI 1.01–1.22, P  = 0.04). TNF-I exposure was not associated with bladder cancer diagnosis (HR 0.71, 95%CI 0.26–1.95, P  = 0.51) but had increased risk of multifocal tumor development ( P  = 0.001) and high-grade tumor ( P  = 0.004). TNF-I exposure was not associated with kidney cancer risk (HR 1.47, 95%CI 0.85–2.54, P  = 0.17) but with increased risk of higher clinical stage (RR 2.01, 95%CI 1.21–3.33, P  = 0.01). Conclusion : Patients with TNF-I exposure had lower risk of PCa but higher-grade group PCa. Patients with TNF-I exposure had higher risk of multifocal and high-grade bladder cancer and of higher stage kidney cancer. TNF-I exposed patients may need modified urologic cancer screening.