"Pioglitazone: No Longer a Worry for Bladder Cancer?"

This epidemiological study aimed to assess the association of pioglitazone use and the risk of developing bladder cancer, as well as 10 additional cancers. These included prostate, female breast, lung, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectum and melanoma.

The study utilized cohort and nested case-control analyses in a population of patients with diabetes. The cohorts utilized in the analysis were drawn from the electronic records of Kaiser Permanente Northern California (KPNC), the source population being drawn from the KPNC diabetes registry. Patients with a pre-existing diagnosis of bladder cancer were excluded from the analysis. Degree of exposure to pioglitazone was evaluated as follows: ever use, duration of use, cumulative dose and time since initiation of pioglitazone. The bladder cancer cohort (BCC) consisted of 193,099 patients with diabetes who were 40 years of age or older between 1997-2002. They were followed until December 2012. Case control analysis was performed on 464 case patients with 464 matched controls for additional cofounders. A secondary cohort analysis of 236,507 patients over 40 was also examined for the 10 additional cancers. 18% (34,181) of patients in the BCC had received pioglitazone for a median duration of 2. 8 years (0. 2-13. 2 years). A new bladder tumor was diagnosed in 1261 (0. 65%) patients during the observation period. The resulting crude incidences of bladder cancer in pioglitazone users and nonusers were 89. 8 and 75. 9 per 100,000 person-years, respectively. Further analysis demonstrated that pioglitazone use was not associated with bladder cancer (adjusted hazard ratio [HR] 1. 06; 95% CI, 0. 89-1. 26). These results were confirmed in a case control analysis, in which pioglitazone use was observed in19. 6% of case patients and 17. 5% of controls (adjusted odds ratio, 1. 18; 95% CI 0. 78-1. 80). Analysis of the additional 10 cancers found no association for 8 of them. However, pioglitazone use was, in adjusted analyses, associated with an increased risk of prostate cancer (HR, 1. 13; 95% CI, 1. 02-1. 26), as well as an increased risk of pancreatic cancer (HR 1. 41; 95% CI, 1. 16-1. 71). Crude incidences of prostate and pancreatic cancer in pioglitazone users vs nonusers were 453. 3 vs 449. 3 and 81. 1 vs 48. 4 per 100 000 person-years, respectively. In this study no association was found between time since initiation, duration or dose of pioglitazone and risk of cancer. Furthermore no statistically significant increased risk of bladder cancer was demonstrated with pioglitazone use.

Urology. 2016 Feb 15 [Epub ahead of print]

Edmund Cp Chedgy, Peter C Black

Vancouver Prostate Centre, University of British Columbia. , Vancouver Prostate Centre, University of British Columbia.