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Men with diabetes may appear to be at lower risk for prostate cancer because they are less likely to get a biopsy when they have elevated prostate-specific antigen (PSA), a large cohort study suggested.

The study, which included data on 564,666 men followed for 10 years, found that the likelihood of undergoing a biopsy after elevated PSA was lower among men receiving metformin (OR 0.87, 95% CI 0.80-0.96) and insulin (OR 0.83, 95% CI 0.74-0.93) compared with men without diabetes, reported Kerri Beckmann, PhD, of King's College London, and colleagues.

As shown in their study online in , there were no differences in prostate cancer detection at biopsy in men with diabetes, regardless of the PSA level that triggered the biopsy. "This study's findings do not support the hypothesis that the inverse association between diabetes and prostate cancer is mediated through antidiabetic medications lowering PSA levels to mask prostate cancer," the researchers said. "They do suggest potential detection bias due to fewer biopsies among men receiving antidiabetic medications, which may explain the lower prostate cancer risk in men with diabetes."

Previous studies have reported several potential links between diabetes and prostate cancer, including a lower incidence, a higher risk of aggressive cancer, and poorer prognosis in men with diabetes. The reasons for the apparent lower incidence are unclear, but one suggestion has been that antidiabetic medications may be protective. Metformin, for example, has been suggested to be protective in the early stages of prostate cancer due to its antineoplastic properties, the study authors noted.

To explore potential links, Beckmann's team analyzed data on the 564,666 initially prostate cancer-free men ages 40-79 from the Stockholm PSA and Biopsy Registry. Of these, 4,583 were prescribed metformin, 1,104 sulfonylureas, and 978 insulin.

The team then compared the men taking diabetes medications with age-matched controls to examine whether the drugs were associated with PSA levels, frequency of PSA testing, receipt of biopsy following elevated PSA results, or prostate cancer detection at biopsy. Data were collected from 2006 through 2015.

The lower biopsy rates in men with diabetes may be due to the fact that clinicians are less likely to recommend biopsy due to concerns about comorbidities commonly associated with diabetes, which may thus make a patient less suitable for prostate cancer treatment, Beckmann and colleagues suggested. In addition, some evidence has suggested that men with diabetes may be less compliant with biopsy recommendations.

Writing in an , Kyla Velaer, MD, and John Leppert, MD, of Stanford University Medical School in California, explained the clinical implications of the study: "Taken together, these data suggest that diabetes medications are not associated with the modification of PSA values or the likelihood of being diagnosed with prostate cancer. Clinicians can continue to use similar PSA thresholds when considering prostate biopsy in men with or without exposure to diabetes medications."

Previous reports suggesting a lower risk of prostate cancer in men on diabetes medications can be partially explained by detection bias rather than a protective effect of the drugs, Velaer and Leppert continued. "While the volume and grade of prostate cancer was not included in this report, future studies will help determine whether diabetes medications may be associated with the diagnosis of clinically significant (high-grade or high-volume) prostate cancer."

There are also other potential links between diabetes and prostate cancer left to explore, the editorialists noted. For example, Beckmann's team found that men with diabetes had lower median PSA levels before starting antidiabetic medications compared with controls (1.2 ng/mL, 95% CI 0.7-2.5 vs 1.6 ng/mL, 95% CI 0.8-3.2). However, PSA was not significantly different in men with diabetes after they started taking medication.

"It remains a clinical challenge to disentangle the role of diabetes medications from the presence of diabetes and other potential confounders like obesity and metabolic syndrome," Velaer and Leppert wrote. "Prospective clinical trials are currently enrolling patients to test whether metformin is associated with improved outcomes when combined with approved systemic treatments for patients with metastatic prostate cancer."

Study limitations, Beckmann and co-authors said, were a lack of data on lifestyle factors such as body weight and smoking, which could have affected the outcomes. In addition, the study did not adjust for medications such as antihypertensives or lipid-lowering drugs, commonly taken by men with diabetes, which could have affected PSA levels.

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