Diabetes and prostate cancer outcomes in men with nonmetastatic castrate-resistant prostate cancer: Results from the SEARCH Cohort

Background: The prognosis of diabetic men with advanced prostate cancer (PC) is poorly understood and understudied. Hence, we studied associations between diabetes and progression to metastases, PC-specific mortality (PCSM) and all-cause mortality (ACM) in men with non metastatic castrate-resistant PC (nmCRPC). Methods: Data from men diagnosed with nmCRPC between 2000 and 2017 at 8 Veterans Affairs Health Care Centers were analyzed using Cox regression to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between diabetes and outcomes. Men with diabetes were classified according to (i) ICD-9/10 codes only, (ii) two HbA1c values > 6.4% (missing ICD-9/10 codes), and (iii) all diabetic men ((i) and (ii) combined). Results: Of 976 men (median age: 76 years), 304 (31%) had diabetes at nmCRPC diagnosis, of whom 51% had ICD-9/10 codes. During a median follow-up of 6.5 years, 613 men were diagnosed with metastases, and 482 PCSM and 741 ACM events occurred. In multivariable48 adjusted models, ICD-9/10 code-identified diabetes was inversely associated with PCSM (HR= 0.67; 95%CI: 0.48-0.92) while diabetes identified by high HbA1c values (no ICD-9/10 codes) was associated with an increase in ACM (HR=1.41; 95%CI: 1.16-1.72). Duration of diabetes, prior to CRPC diagnosis was inversely associated with PCSM among men identified by ICD- 9/10 codes and/or HbA1c values (HR=0.93; 95%CI: 0.88-0.98). Conclusion: In men with late-stage PC, ICD-9/10 code identified diabetes is associated with better overall survival than 'undiagnosed' diabetes identified by high HbA1c values only.