G. Zanni

The ageing male and erectile dysfunction.

Erectile dysfunction is common in the ageing man and reliable therapies are needed. The pathophysiology of erectile dysfunction in this group mainly includes chronic ischaemia, which triggers the deterioration of cavernosal smooth muscle and the development of corporeal fibrosis. Assessing the ageing man with erectile dysfunction who seeks medical treatment should comprise a thorough medical and sexual history, a systemic and focused physical examination and selected blood tests. Oral drug therapy represents a safe and effective option for most ageing men.

Prophylaxis of Erectile Function After Radical Prostatectomy with Phosphodiesterase Type 5 Inhibitors

Erectile dysfunction (ED) is one of the most challenging complications associated with radical prostatectomy (RP) for clinically localized prostate cancer. Currently, a broad spectrum of therapeutic options are available to improve sexual health after surgical treatment. Several basic science reports highlighted a potential role for phosphodiesterase type 5 inhibitors in the prevention of endothelial damage related to ischemia reperfusion and/or denervation following surgery. Recent studies have shown that pharmacological prophylaxis soon after RP can significantly improve the rate at which erectile function is recovered after surgery. Use of on-demand treatments for ED in patients who have undergone RP has been shown to be highly effective. In this context, pharmacological prophylaxis potentially may have a significantly expanded role in future strategies aimed at preserving postoperative erectile function. We analyzed the factors affecting erectile function after RP and evaluated the evidence suggesting the role of pharmacological prophylaxis and treatment of ED after surgery.

The case for postoperative PDE-5 inhibitor drug treatment after radical prostatectomy.

TREATMENT OF ERECTILE DYSFUNCTION (ED) after radical prostatectomy (RP) represents a challenging field for practicing urologists. To date, several pharmacologic treatment protocols have been proposed.1–3 Among these, on-demand or chronic administration of proerectile drugs, such as phosphodiesterase type 5 inhibitors (PDE5-I), have been gaining increasing acceptance. The rationale for chronic use of PDE5-I has been recently elucidated. Behr-Roussel and associates4 studied the effect of an 8week treatment with sildenafil (60 mg/kg/d subcutaneously) in male rats on electrically induced erectile response in vivo before and after an acute intravenous injection of sildenafil (0.3 mg/kg). In addition, endothelial-dependent and -independent relaxations of strips of corpus cavernosum were examined in vitro and compared with cavernosal strips of untreated rats. Endothelial relaxation induced by acetylcholine was significantly enhanced in rats treated chronically with sildenafil compared with untreated rats. Conversely, relaxations elicited by the calcium ionophore A23187 or by sodium nitroprusside were similar in tissues from chronically salineor sildenafil-treated animals. These findings imply that either muscarinic receptors or the transduction mechanisms leading to the activation of endothelial nitric oxide synthase are up-regulated by chronic sildenafil treatment.4 Moreover, functional in vivo evaluations showed that chronic administration of sildenafil significantly enhanced frequency-dependent erectile response and was associated with a greater response to an acute injection of sildenafil in treated rats compared with controls. Therefore, chronic sildenafil seems to induce profound and structural modification of the erectile tissue that goes beyond PDE5 inhibition. This study provided the first experimental support for the chronic administration of sildenafil and suggested that such treatment could be associated with a higher rate of erectile function recovery after RP. Padma-Nathan and colleagues5 reported on the daily administration of sildenafil (50 or 100 mg) v placebo, taken at bedtime, in patients undergoing bilateral nerve-sparing radical retropubic prostatectomy (NSRRP) who were potent preoperatively. Four weeks after surgery, patients were randomized to receive either sildenafil or placebo, which was then administered for 36 weeks. Whereas 27% of the patients receiving sildenafil were responders (i.e., demonstrated return of spontaneous normal erectile function), only 4% of the placebo patients were (P 0.01). Postoperative nocturnal penile tumescence assessments were supportive of the data originating from sexual activity. In the hands of experienced surgeons, a 27% overall rate of return to normal erectile function after a bilateral NSRRP is far from impressive, but the important message is that daily bedtime administration of sildenafil (50 or 100 mg) after bilateral NSRRP is able to improve the baseline results of surgeons with a large volume of patients. Although similar data are not yet available for tadalafil and vardenafil, one could expect similar findings with these drugs. The rationale for PDE5-I administration at bedtime in patients undergoing NSRRP was also evaluated in a well-designed study by Bannowsky and coworkers.6 In a cohort of 27 patients undergoing NSRRP, nocturnal penile tumescence recording during the acute phase after surgery showed residual erectile function as early as the first night after catheter removal. In contrast, in a small control group of four patients treated with non-NSRRP, no nocturnal erections were recorded during the same time interval. The authors concluded that in cases of recovery of early nocturnal tumescence, administration of a PDE5-I can support successive organ rehabilitation, whereas the use of intracavernous injection therapy was advocated in patients who do not show any spontaneous erectile activity. Other studies have indicated that early use of sildenafil after NSRRP appears to be associated with preservation of smooth muscle content within human corpora cavernosa. Schwartz and associates7 enrolled 40 potent patients with localized prostate cancer who underwent NSRRP at a single institution and were subsequently treated with either 50 or 100 mg of sildenafil every other day for 6 months, starting from the day of catheter removal. Patients underwent percutaneous penile biopsy both at the time of surgery and 6 months after surgery. None of these patients showed a postoperative decrease of smooth muscle content. In patients in the 50-mg group, there was no statistically significant change in the mean intracavernosal smooth muscle content between the preoperative and postoperative mea-

636 INSURANCE STATUS IS A DETERMINANT OF THE STAGE AT PRESENTATION AND OF CANCER CONTROL IN EUROPEAN MEN SUBJECTED TO RADICAL PROSTATECTOMY FOR CLINICALLY LOCALIZED PROSTATE CANCER

Andrea Gallina*‡, Pierre I. Karakiewicz*, Felix K.-H. Chun*†, Alberto Briganti*‡, Markus Graefen¶, Francesco Montorsi‡, Jochen Walz†, Claudio Jeldres*, Andreas Erbersdobler§, Andrea Salonia‡, Nazareno Suardi‡, Federico Deho‡, Thorsten Schlomm†, Vincenzo Scattoni‡, Alexander Haese†, Hans Heinzer†, Luc Valiquette*, Patrizio Rigatti‡ and Hartwig Huland†¶ *Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal, Quebec, Canada, †Department of Urology, ¶Martini Clinic – Prostate Cancer Center, and §Institute of Pathology, University of Hamburg, Hamburg, Germany, and ‡Department of Urology, Vita-Salute University, Milan, Italy