Let’s rethinking about the safety of phosphodiesterase type 5 inhibitor in the patients with erectile dysfunction after radical prostatectomy

As the radical prostatectomy (RP) for the patient diagnosed as localized prostate cancer has been increasing, erectile dysfunction (ED) associated with RP is increased and ED after RP is a significant risk factor to reduce the quality of life for the patient after RP. Therefore, the treatment concept called penile rehabilitation was introduced and phosphodiesterase type 5 inhibitor (PDE5I) is used widely for the prostate cancer patient after RP. Generally PDE5I is considered as safe and effective drug for the prostate cancer patient after RP. Recently, a report against the general opinion that PDE5I use is safe in the patient with prostate cancer was reported and the analysis of 5-yr biochemical recurrence-free survival after RP between the PDE5I users and non-PDE5I users after bilateral nerve sparing RP showed decreased 5-yr biochemical recurrence-free survival in the PDE5I users. In addition, a longitudinal cohort study reported that sildenafil, a kind of PDE5I, use might be associated with the development of melanoma and this result suggested the possibility of adverse effect of PDE5I on some kinds of cancers as well as prostate cancer. Moreover, the studies to evaluate the influence of nitric oxide (NO) and guanosine monophosphate (cGMP) signaling pathway associated with PDE5 showed both cancer reduction and cancer development. Therefore, the role of NO and cGMP signaling pathway in cancer was reviewed based on the previous studies and suggested the necessity of further clinical studies concerning about the safety of PDE5I in prostate cancer.