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ED after prostate cancer treatment

Published in Efficacy

prostate cancer treatmentAll of the available prostate cancer treatments, including radical prostatectomy, external beam radiation therapy, brachytherapy, cryotherapy, androgen-deprivation therapy, and even active surveillance alone, can result in ED. ED after prostate cancer treatment includes both organic and psychogenic causes, as significant anxiety and depression may result from a diagnosis of prostate cancer, leading to psychogenic ED.

The most important risk for organic ED after prostate cancer treatment of any type is damage to the cavernosal nerves. Walsh first described the technique for sparing the bilateral neurovascular bundles to better preserve erectile function, and a bilateral nerve sparing radical prostatectomy (BNSRP) is the surgical standard for prostate cancer today. Approximately 155,000 prostatectomies were performed in the United States in 2005 according to hospital discharge data. Potency in men after open BNSRP has a wide reported range of 10% to 97% in the literature. Of 1288 men who underwent radical prostatectomy as part of the Prostate Cancer Outcomes Study, only 28% had erections sufficient for intercourse at 5 years.

Cavernosal nerve injury during prostate cancer treatment is a neuropraxia resulting in atrophy of the cavernosal smooth muscle and abnormal deposition of collagen into the corpora cavernosa. Cavernosal hypoxia is another contributing factor in the development of fibrosis post-prostatectomy. The smooth muscle atrophy and fibrosis leads to corporal veno-occlusive dysfunction (CVOD), which is recognized as the primary cause of organic ED after prostate cancer treatment.

There are increasing experimental data that increased concentrations of NO and cGMP have an antifibrotic effect on tissues including the tunica albuginea and corporal tissue, supporting a role for cheap tadalafil to halt the pathophysiologic role of CVOD in post-prostate cancer treatment ED. Kovanecz and colleagues have recently studied the effect of once-daily tadalafil on the prevention of fibrosis and CVOD after cavernosal nerve injury in rats. Male rats had either a bilateral cavernosal nerve resection, unilateral cavernosal nerve resection, or a sham operation, and they were then either untreated or given once-daily tadalafil. CVOD was assessed at 45 days with cavernosometry and histopathology. The authors found that tadalafil (Cialis Super Active) normalized the increase in penile shaft collagen content, normalized the reduction in corporeal smooth muscle content, and improved the lower collagen type III:I ratio, effectively preventing CVOD and underlying corporal fibrosis after cavernosal nerve damage. Similarly, Vignozzi et al also found that once-daily tadalafil given to rats that have undergone bilateral cavernosal nerve resection reversed the decline in cavernosal smooth muscle to collagen ratio.

In the clinical arena, on-demand dosing of tadalafil has been studied for ED secondary to BNSRP and external-beam radiotherapy. Mon-torsi and associates evaluated on-demand dosing of tadalafil 20 mg in men with ED following BNSRP in a randomized, double-blind, placebo controlled, multicentered study of 303 men over 12 weeks. All men had normal erectile function preoperatively and had undergone a BNSRP 12 to 48 months prior to the study. Primary endpoints were IIEF-EF, SEP-Q2, and SEP-Q3, and secondary endpoints were the GAQ and the EDITS questionnaire. Average age was 60 years, and 93% were white men. Almost two-thirds of the participants had some degree of postoperative tumescence at baseline as defined by reporting the ability “to achieve at least some erection” in over half of their sexual encounters on the SEP-Q1. Among all patients, 62% responded to tadalafil on the GAQ compared with 23% placebo (p < 0.001). Of those with some postoperative potency, 71% responded to tadalafil compared with 24% placebo (p < 0.001). The SEP-Q3 revealed 41% of the total group had successful intercourse compared with 19% with placebo (p < 0.001). Over 50% of men with residual function had successful intercourse compared with 26% placebo (p < 0.001). In this trial, canadian tadalafil was successful in producing erections sufficient for intercourse in men with ED after BNSRP, but it was more efficacious in men with some residual potency after surgery prior to treatment.

Sixty patients with ED after external-beam radiotherapy for prostate cancer were randomized to on-demand canadian tadalafil 20 mg or placebo in a double-blind, placebo controlled, crossover study lasting 12 weeks. Efficacy was assessed with the IIEF-EF, SEP, and a GAQ. Average age was higher than most other tadalafil studies at 69 years, the participants’ prostate cancer tumor stages were 37% T1c, 37% T2, and 26% T3, and the baseline mean IIEF-EF score among all men revealed severe ED at 8.4. The IIEF-EF score improved to 17.7 with tadalafil and to 9.5 with placebo (p < 0.0001). The SEP-Q3 data demonstrated 46% of participants successfully had intercourse with tadalafil 20 mg compared with 12% with placebo (p < 0.0001), and 67% of patients taking tadalafil 20 mg responded positively with the GAQ compared with 20% with placebo (p < 0.001). This study was continued as an open-label extension over 6 weeks. Fifty-one of 60 patients (85%) enrolled, who had a higher IIEF-EF score than those who did not enroll (p < 0.05). Tadalafil was equally effective in the double-blind phase as in the open-label phase of the study.

Tadalafil Professional and other PDE5 inhibitors dosed both in continuous fashion and on-demand have been proposed for erectile rehabilitation and ED prophylaxis after BNSRP. In a small, prospective, observational study of 27 patients who underwent BNSRP, tadalafil (Cialis Soft) 20 mg was dosed every 3 days beginning on the first postoperative day. At 6 weeks, 89% of men reported erections, and 50% had successful intercourse. One-hundred percent had erections at 6 months, with 78% reporting successful intercourse. Padma-Nathan and colleagues reported in a multicentered, placebo-controlled, prospective study of prophylactic sildenafil dosed nightly beginning 4 weeks after BNSRP and continuing for 36 weeks that patients taking prophylactic sildenafil had a 27% return of erectile function compared with only 4% in the placebo group (p <0.05). A randomized, double-blind, multicentered study of early postoperative dosing with vardenafil, dosed either once-daily or on-demand and compared with placebo, in 628 men after BNSRP found that on-demand vardenafil treatment resulted in greater IIEF-EF scores and higher SEP-Q3 response rates than once-daily dosing or placebo. Although the efficacy of postoperative treatment with PDE5 inhibitors to prevent CVOD and corporal fibrosis and reduce ED after BNSRP seems clear, it remains uncertain whether a continuous or an on-demand dosing strategy is superior in this setting.