Background

The link between diabetes and prostate cancer progression is poorly understood and complicated by obesity. We investigated associations between diabetes and prostate cancer-specific mortality (PCSM), castrate-resistant prostate cancer (CRPC), and metastases in obese and nonobese men undergoing radical prostatectomy (RP).

Methods

We included 4688 men from the Shared Equal Access Regional Cancer Hospital cohort of men undergoing RP from 1988 to 2017. Diabetes prior to RP, anthropometric, and clinical data were abstracted from 6 Veterans Affairs Medical Centers electronic medical records. Primary and secondary outcomes were PCSM and metastases and CRPC, respectively. Multivariable-adjusted hazard ratios (adj-HRs) and 95% confidence intervals (CIs) were estimated for diabetes and PCSM, CRPC, and metastases. Adjusted hazard ratios were also estimated in analyses stratified by obesity (body mass index: nonobese <30 kg/m² ; obese ≥30 kg/m² ). All statistical tests were 2-sided.

Results

Diabetes was not associated with PCSM (adj-HR = 1.38, 95% CI = 0.86 to 2.24), CRPC (adj-HR = 1.05, 95% CI = 0.67 to 1.64), or metastases (adj-HR = 1.01, 95% CI = 0.70 to 1.46), among all men. Interaction terms for diabetes and obesity were statistically significant in multivariable models for PCSM, CRPC, and metastases (P  ≤ .04). In stratified analyses, in obese men, diabetes was associated with PCSM (adj-HR = 3.06, 95% CI = 1.40 to 6.69), CRPC (adj-HR = 2.14, 95% CI = 1.11 to 4.15), and metastases (adj-HR = 1.57, 95% CI = 0.88 to 2.78), though not statistically significant for metastases. In nonobese men, inverse associations were suggested for diabetes and prostate cancer outcomes without reaching statistical significance.

Conclusions

Diabetes was associated with increased risks of prostate cancer progression and mortality among obese men but not among nonobese men, highlighting the importance of aggressively curtailing the increasing prevalence of obesity in prostate cancer survivors.