Recent evidence of a causal link between Phosphodiesterase-5-inhibitor (PDE-5i) use and melanoma has caused concern in PDE-5i use and was even addressed in the 2018 American Urological Association guideline on erectile dysfunction (ED). Given that several studies have affirmed this low probability but statistically significant association, one might expect a shift in melanoma diagnoses since PDE-5is were introduced in 1998. We sought to determine if the introduction of PDE-5i drugs for ED treatment increased incidence of melanoma.
The Surveillance, Epidemiology, and End Results (SEER) database was used to compare the incidence of melanoma diagnosis in American men between 1973 and 2015, providing over a decade of data before and after PDE-5i introduction in 1998. Interrupted time-series and logistic regression were used to assess this relationship.
Over 43 years, the SEER database has reported 292,166 cases of Melanoma, with males accounting for 53.7% of cases (Standard deviation [SD] 3%, Range 47.5–58.3%). After the introduction of PDE-5i, there was no proportional increase in melanoma diagnoses, in fact demonstrating a 2% lower incidence from prediction models (p < 0.05).
Our analysis of the SEER database demonstrates that the trend in incidence of melanoma has fallen in the era of PDE-5i use for ED. These findings may be of value in counseling patients anxious about the potential association between PDE-5i use and skin cancer; however, continued research analyzing individual-level risk are needed.
- • Introduction of PDE-5i for ED was not shown to increase incidence of melanoma.
• History of prostate cancer did not increase subsequent diagnosis of melanoma.
- • Patient counseling can help ease concern about melanoma risk and PDE-5i use.
Phosphodiesterase-5 inhibitor (PDE-5i) therapy is an established standard care for patients with erectile dysfunction (ED). More than 20 million men were treated with Sildenafil in the first 6 years after the drug was introduced into the market in 1998 . In 2002, the National Health and Nutrition Examination Survey (NHANES) reported the overall prevalence of ED in men over the age of 20 was 18.4% . Meanwhile, in 2011, the Global Online Sexual Survey (GOSS) found that 23.7% of surveyed men in the US were consistently using PDE-5i . Even when considering its additional off-label uses, such as pulmonary hypertension (pHTN) and congestive heart failure (CHF), the number of patients with ED using PDE-5i has increased drastically since being introduced . Additionally, more than one-third of men who undergo radical prostatectomy (RP) for prostate cancer (PCa) experience ED, and PDE-5i therapy is used as a safe and effective treatment in these patients .
The incidence of melanoma and its associated mortality has been increasing for the past 2 decades, with the majority of new diagnoses being made among males over the age of 50 . In 2021, the new cases in males is estimated to be 62,260 compared to 29,000 in 2001 . The association of PDE-5i and melanoma was first suggested based on the observation that in melanoma cells, oncogenic BRAF induces invasion through downregulation of phosphodiesterase-5A (PDE5A), the same biochemical pathway through which PDE-5i drugs act . Given the proposed association between PDE-5i and melanoma, along with the rise in PDE-5i use, one might expect a shift in melanoma diagnoses since the introduction of PDE-5i. We thus looked at the SEER database to see if the incidence of melanoma changed among the patient population after the introduction of PDE-5i.