Diabetes, prostate cancer screening and risk of low- and high-grade prostate cancer: an 11 year historical population follow-up study of more than 1 million men.

An inverse association has consistently been shown between diabetes and prostate cancer incidence. We investigated whether lower prostate cancer incidence among men with diabetes is attributable to lower detection due to prostate cancer screening patterns.

We studied a population-based historical cohort of 1,034,074 Israeli men aged 21-90 years, without a previous history of cancer. The cohort was followed-up from 2002 to 2012, according to diabetes morbidity, for frequency of prostate-specific antigen (PSA) testing, mean PSA values and detection of prostate cancer, after adjustment for age, ethnic origin, socioeconomic status and PSA testing.

In January 2002, 74,756 men had prevalent diabetes. During the 11 year follow-up, 765,483 (74%) remained diabetes-free and 193,835 developed diabetes. Approximately 10% more PSA screening was performed in men with than without diabetes, but the rate of PSA positivity (>4 μg/l) was 20% lower in men with diabetes. PSA values were already significantly lower in men who developed diabetes than in those who did not, 3 years before diabetes diagnosis. Reduced prostate cancer risk was observed among men with incident diabetes only for low-moderate grade tumours (Gleason score 2-6: adjusted HR 0.83; 95% CI 0.77, 0.89). No association was observed for high-grade tumours (Gleason score 7-10: HR 0.99; 95% CI 0.88, 1.11).

Our findings suggest that diabetes comorbidity is a factor to be considered in prostate cancer screening strategies, and specifically in the interpretation of PSA levels. Furthermore, our demonstration of reduced incidence of low-moderate grade but not high-grade prostate cancer tumours among men with diabetes supports the possibility that low PSA levels, rather than lower tumour risk, explains the observed reduced incidence of prostate cancer in men with diabetes.

ClinicalTrials.gov NCT02072902.

Diabetologia. 2016 May 17 [Epub ahead of print]

Rachel Dankner, Paolo Boffetta, Lital Keinan-Boker, Ran D Balicer, Alla Berlin, Liraz Olmer, Havi Murad, Barbara Silverman, Moshe Hoshen, Laurence S Freedman

Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, 52621, Israel. ., Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Israel Center for Disease Control (ICDC), Israel Ministry of Health, Tel Hashomer, Israel., Clalit Research Institute, Clalit Health Services, Tel Aviv, Israel., Unit for Cardiovascular Epidemiology, The Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, 52621, Israel., Biostatistics Unit, Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel., Biostatistics Unit, Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel., Sackler Faculty of Medicine, School of Public Health, Department of Epidemiology and Preventive Medicine, Tel Aviv University, Tel Aviv, Israel., Clalit Research Institute, Clalit Health Services, Tel Aviv, Israel., Sackler Faculty of Medicine, School of Public Health, Department of Epidemiology and Preventive Medicine, Tel Aviv University, Tel Aviv, Israel.