Phosphodiesterases 5 inhibitors and erectile dysfunction recovery after pelvic surgery: future perspectives for new drugs and new formulations

BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5I) represent the first-line treatment in the management of post-operative erectile dysfunction (ED) after pelvic oncological surgery. The aim of our study is to evaluate the available evidence on the efficacy of PDE5Is, including new formulations and penile rehabilitation post-pelvic surgery. EVIDENCE ACQUISITION: A systematic review of the literature was performed until May 2020. The following databases were searched: Scopus, Medline and Web of Science. The MeSH search was conducted by combining the following terms: 'erectile dysfunction', 'radical prostatectomy' 'pelvic' 'bladder' 'phosphodiesterase' inhibitors' 'avanafil' 'sildenafil' 'tadalafil' 'lodenafil' 'mirodenafil' 'udenafil' 'vardenafil' 'sublingual' 'orodispersible' 'penile' 'rehabilitation'. EVIDENCE SYNTHESIS: Sildenafil, Tadalafil, vardenafil and Avanafil improve EF compared with placebo in men with all levels of ED severity after radical prostatectomy with good tolerability. No specific recommendations can be suggested regarding the superiority of a drug over the other. The optimal dose, continuous vs. on-demand and duration of treatment, is still under investigation. In vitro and preclinical studies suggest the possible role for lodenafil, mirodenafil and oro-dispersible formulations in patients undergoing oncological pelvic surgery. Few studies demonstrated the efficacy of udenafil in improving ED after rectal surgery or radical prostatectomy. Complete recovery of EF after surgery is still an unmet need in the field of penile rehabilitation after pelvic surgery. CONCLUSION: PDE5Is have a crucial role in the management of post pelvic surgery of ED. New drugs and new formulations have shown excellent results in patients with ED; however, data in patients after surgery is still scarce. Further well designed RCT should clarify the role of these new compounds and oro-dispersible formulations in the management of ED in patients undergoing pelvic surgery.