Recent studies have produced conflicting findings related to the effect of metformin use and prostate cancer (PCa) outcomes.
In one study, David Margel, MD, PhD, of the University of Toronto, and colleagues found that increased cumulative duration of metformin use by diabetic men after a PCa diagnosis is associated with improved all-cause and PCa-specific survival. In another study, Dharam Kaushik, MBBS, and others at Mayo Clinic in Rochester, Minn., demonstrated no beneficial effect of metformin on PCa outcomes among men who underwent radical prostatectomy.
The study by Dr. Margel’s group included 3,837 diabetic men diagnosed with PCa. The men had a median age of 75 years at diagnosis. During a median follow-up of 4.6 years, 1,343 (35%) died, 291 (7.6%) from PCa. Each additional six months of metformin use was associated with a significant 24% decreased risk for PCa-specific mortality after adjusting for potential confounders. The association with all-cause mortality also was significant, but declined over time from a 24% decreased risk in the first six months to a 7% decreased risk between 24 and 30 months.
The study, which was published online ahead of print in the Journal of Clinical Oncology, demonstrated no association between cumulative use of other antidiabetic drugs and either PCa-specific or all-cause mortality.
The Mayo Clinic study, which included 12,052 patients, found no significant reduction in the risk of biochemical recurrence, systemic progression, or all-cause mortality associated with metformin use, according an online report in Urologic Oncology. In addition, the investigators found no significant association between metformin use and final pathologic Gleason score, disease stage, rate of positive surgical margins, or tumor volume. The study population included 885 diabetics (7.3%), of whom 323 were taking metformin and 562 were not.
The findings of Dr. Margel’s group are consistent with a previous study showing that metformin use is associated with improved PCa-specific survival and other outcomes in men who underwent external beam radiotherapy for localized PCa. That study, by Daniel E. Spratt, MD, and collaborators at Memorial-Sloan Kettering Cancer Center in New York, included 2,901 patients who had a median follow-up of 8.7 years. The 10-year PCa-specific mortality actuarial rates were 2.7% among the 157 diabetics taking metformin compared with 21.9% and 8.2% for the 162 diabetics not taking metformin and 2,582 non-diabetic controls, respectively. Compared with the diabetic non-metformin group, the metformin users were twice as likely to be alive without PSA recurrence and 3.7 times as likely to be alive and free of distant metastases, according to a report in European Urology (2013;63:709-716). Metformin users were 5.1 times less likely die from PCa.