Poorly controlled diabetes increases the risk of metastases and castration-resistant prostate cancer in men undergoing radical prostatectomy: Results from the SEARCH database.

Although diabetes is inversely related to prostate cancer (PC) risk, to the authors' knowledge the impact of glycemic control on PC progression is unknown. In the current study, the authors tested the association between hemoglobin A1c (HbA1c) and long-term PC outcomes among diabetic men undergoing radical prostatectomy (RP).

The authors retrospectively reviewed data regarding men undergoing RP from 2000 to 2017 at 8 Veterans Affairs hospitals. Diabetic patients were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes (250.x) or by an HbA1c value >6.5% at any time before RP. Cox models tested the association between HbA1c and biochemical disease recurrence (BCR), castration-resistant PC (CRPC), metastases, PC-specific mortality, and all-cause mortality. The model for BCR was adjusted for multiple variables. Due to limited events, models for long-term outcomes were adjusted for biopsy grade and prostate-specific antigen only.

A total of 1409 men comprised the study population. Of these, 699 patients (50%) had an HbA1c value <6.5%, 631 (45%) had an HbA1c value of 6.5% to 7.9%, and 79 (6%) had an HbA1c value ≥8.0%. Men with an HbA1c value ≥8.0% were younger (P < .001) and more likely to be black (P = .013). The median follow-up after RP was 6.8 years (interquartile range, 3.7-10.6 years). On multivariable analysis, HbA1c was not found to be associated with BCR. However, a higher HbA1c value was associated with metastasis (hazard ratio [HR], 1.21; 95% CI, 1.02-1.44 [P = .031]) and CRPC (HR, 1.27; 95% CI, 1.03-1.56 [P = .023]). Although not statistically significant, there were trends between higher HbA1c and risk of PC-specific mortality (HR, 1.24; 95% CI, 0.99-1.56 [P = .067]) and all-cause mortality (HR, 1.09; 95% CI, 0.99-1.19 [P = .058]).

Among diabetic men undergoing RP, a higher HbA1c value was associated with metastases and CRPC. If validated in larger studies with longer follow-up, future research should test whether better glycemic control improves long-term PC outcomes.

Cancer. 2019 Apr 29 [Epub ahead of print]

Farnoosh Nik-Ahd, Lauren E Howard, Adva T Eisenberg, William J Aronson, Martha K Terris, Matthew R Cooperberg, Christopher L Amling, Christopher J Kane, Stephen J Freedland

David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California., Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Duke University School of Medicine, Durham, North Carolina., Department of Endocrinology, Duke University School of Medicine, Durham, North Carolina., Department of Urology, University of California at Los Angeles School of Medicine, Los Angeles, California., Section of Urology, Veterans Affairs Medical Center, Augusta, Georgia., Department of Urology, University of California at San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California., Division of Urology, Department of Surgery, Oregon Health and Science University, Portland, Oregon., Department of Urology, University of California at San Diego Health System, San Diego, California., Division of Urology, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.