# Urologic malignancy risk with chronic tumor necrosis factor-alpha inhibitor (TNF-I) exposure: a multicenter, retrospective cohort study

## TL;DR

Long-term use of TNF inhibitors is linked to lower prostate cancer risk but higher-grade tumors and worse features in bladder and kidney cancers.

## Contribution

First multicenter study showing modified urologic cancer risks with chronic TNF inhibitor use.

## Key findings

- TNF-I exposure was associated with lower prostate cancer risk but higher Gleason grade group.
- Bladder cancer patients on TNF-I had increased multifocal and high-grade tumors.
- Kidney cancer patients on TNF-I had higher clinical stage tumors.

## Abstract

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).

Retrospective non-matched cohort study of patients with chronic inflammatory conditions from 1996 to 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.

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).

TNF-I exposure was associated with lower risk of PCa but higher-grade group PCa. TNF-I exposure was associated with 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.

In this report, we looked at exposure to TNF inhibitor medications and their risk of prostate, bladder, and kidney cancer. We found that, compared to patients who did not take these medications, there was a lower risk of prostate cancer but with higher grade disease. There was no change in the overall risk of bladder or kidney cancer diagnosis, but they did have worse features. Further studies of patients on TNF inhibitors should be performed to confirm these findings.

The online version contains supplementary material available at 10.1007/s00345-026-06309-0.