Currently phosphodiesterase type PDE inhibitors are used
Currently, phosphodiesterase type 5 (PDE-5) inhibitors are used widely as the first- line oral treatment for erectile dysfunction of varying causes. Radical prostatectomy for the treatment of prostate cancer is frequently associated with erectile dysfunction, and this type of erectile dysfunction is attributed mainly to intraoperative damage to the neurovascular system. The efficacy of PDE-5 inhibitors in the treatment of erectile dysfunction after radical prostatectomy has been demonstrated., , However, the administration of the PDE-5 inhibitor to patients with rectal cancer has been reported rarely.
Udenafil (Zydena, Dong-A, Seoul, Korea) is an oral selective PDE-5 inhibitor that was developed recently. It is rapidly absorbed, reaches maximal concentration within 1–1.5 hours after administration, and has a relatively long PNU-120596 (11–13 h). In previous clinical trials, udenafil was demonstrated to be safe and effective as a once-daily prescription for patients with erectile dysfunction of various causes., The aim of this randomized, double-blind, placebo-controlled trial was to explore the efficacy of udenafil in the treatment of erectile dysfunction, as well as its safety in male patients who underwent TME for rectal cancer.
Discussion Operative resection is the most important treatment for patients with rectal cancer. Although TME technique has improved nerve preservation, as well as cancer control, various degrees of sexual dysfunction have been reported. Therefore, in addition to TME, surgeons have been trying to improve nerve sparing by using operative techniques such as electrical stimulation of the autonomic nerve system or a surgical robot for clear visualization.17, 18 However, the effect of these techniques is yet to be revealed. Similar to what is observed in rectal cancer surgery, erectile dysfunction after radical prostatectomy is associated with intraoperative injury to the nerves. Recovery of erectile function after such injury requires a certain convalescence period. PDE-5 inhibitors have been used to improve erectile function after prostatectomy. There have been only 2 studies that evaluated PDE-5 inhibitors in patients with erectile dysfunction after rectal resection, both of which used sildenafil (Viagra, Pfizer, New York, NY).10, 19 In a recent randomized, controlled trial, the efficacy of sildenafil was investigated in 32 patients with erectile dysfunction after rectal resection for rectal cancer or inflammatory bowel disease. The response rate to sildenafil was favorable, and 79% of 14 patients responded positively to GAQ. In a more recent study that used sildenafil after rectal cancer surgery, 70% of 16 patients responded to the medication. In our study, at the end of the period of treatment with udenafil, the IIEF-5 scores were significantly higher in the udenafil group than they were in the placebo group, and 85% of the patients in the udenafil group responded positively to medication. Studies seeking to treat sexual dysfunction using PDE-5 inhibitors after rectal cancer surgery are limited in number, and the pathophysiologic mechanisms in these patients have not been determined. However, because erectile dysfunction after rectal cancer surgery is correlated with autonomic nerve injury, the mechanisms are expected to be similar to that involved in treatment of patients with erectile dysfunction after radical prostatectomy for prostate cancer. During a prostatectomy, nerve injury can occur by stretching, heat, ischemia, and inflammation, after which nitric oxide production decreases. The nitric oxide released from nerves triggers a rise in cyclic guanosine monophosphate, which induces smooth relaxation and penile erection. PDE-5 inhibitors prevent degradation of cyclic guanosine monophosphate, compensating for the reduced level of nitric oxide, thus allowing improved penile erection. The idea of penile rehabilitation after radical prostatectomy was first introduced in 1997. Early use of intracavernosal alprostadil injection improved the recovery of SEs compared with an untreated group. After this study, penile rehabilitation strategies have been advocated.21, 22, 23 The aim of penile rehabilitation after radical prostatectomy is to prevent changes in the functional smooth muscle during a period of neuropraxia, such as fibrosis and atrophy. Experimental data from animal studies suggest that penile rehabilitation using PDE-5 inhibitors might protect the cavernosal smooth muscle from permanent pathophysiologic changes. However, the evidence obtained in humans remains controversial.24, 25 The largest randomized, placebo-controlled study, which included 423 patients who underwent nerve-sparing prostatectomy, did not show improvements in erectile function after the 9-week washout period. In our study, continuous medication with udenafil for 12 weeks did not show significant long-term efficacy after washout period. This result may be explained by the fact that sexual dysfunction is usually temporary in most patients if the autonomic nerve system is completely preserved during surgery. Drug dosage and timing of treatment onset may also have affected our results. We administered a fixed dose, which may not have been sufficient for some patients. Regarding the timing of treatment onset, sildenafil medication was started as early as 4 weeks for the treatment of erectile dysfunction after radical prostatectomy. Future studies must take into consideration the pathophysiologically degenerative change in penile muscles after rectal cancer surgery, the timing of treatment onset, and the dosage of the PDE-5 inhibitor in question.