The authors of this study comment that their results should be interpreted cautiously and are insufficient to alter clinical recommendations; nevertheless they provide epidemiological evidence on possible skin adverse effects of PDE5A inhibitors, and support continued investigation of this observed association. Further studies are needed to confirm these findings in other patient populations, to assess the effect of dose, and to investigate underlying biological mechanisms.
A related Commentary states that these findings suggest a new biologic basis for the sex survival disparity in melanoma, by demonstrating promotion of melanoma cell invasion with sildenafil. An vitro study demonstrated that phosphodiesterase (PDE) 5A was downregulated in a substantial collection of melanoma lines expressing oncogenic BRAF, indicating that this inherent phenotype may provide a biomarker for enhanced invasiveness and poor prognostic outcome. Since PDE5A drugs are used mainly as needed rather than persistently and are cleared rapidly, any systemic effect would be intermittent.