Findings from a meta-analysis show that, while phosphodiesterase type 5 (PDE-5) inhibitor use is associated with a statistically significant increased risk of melanoma, they do not support a causal relationship, said lead author Stacy Loeb, MD, MSc, of NYU School of Medicine, New York.
The research, published online in the Journal of the National Cancer Institute (May 19, 2017), represents the first meta-analysis of published studies investigating PDE-5 inhibitors and melanoma, and its objective was to determine whether there was an association that meets Hill’s criteria for causality. It included three case-control and two cohort studies with 866,049 men, of whom 41,874 had a diagnosis of melanoma.
Using random effects models to calculate summary statistics, the overall analysis found an increased risk of melanoma in men using a PDE-5 inhibitor (relative risk [RR]=1.11, 95% confidence interval [CI]=1.02-1.22). Results of other analyses showed that the association between PDE-5 inhibitor use and melanoma, however, did not meet five of nine Hill’s causal criteria.
“We believe that physicians and patients should not be concerned about using PDE-5 inhibitors on account of worry about melanoma,” said Dr. Loeb. “Nevertheless, men should continue to be careful about the risk of any kind of skin cancer from excessive sun exposure and use sun protection.”
The investigation of causality between PDE-5 inhibitor use and melanoma included analyses looking for dose-response, biologic gradient, and specificity.
Analyses with men categorized based on extent of PDE-5 inhibitor exposure showed a statistically significant increased risk of melanoma only among men who took lower amounts of the medication (RR=1.15, 95% CI=1.01-1.31), but not in those with high exposure (RR=1.09, 95% CI=0.97-1.23).
Analyses using information from two studies reporting data on melanoma stage did not find any evidence of biologic gradient. High PDE-5 inhibitor exposure was associated with an increased risk of stage 0 melanoma (RR=1.45, 95% CI=1.09-1.92), but the risk of stage II to IV melanoma was actually decreased in men with high PDE-5 inhibitor exposure (RR=0.67, 95% CI=0.46-0.97).
Lack of specificity was demonstrated by an analysis that showed risk of basal cell carcinoma was also increased among PDE-5 inhibitor users and by a magnitude similar to that observed for melanoma (RR=1.16, 95% CI=1.13-1.20).