Penson et al. analyzed the data from the large Prostate Cancer Outcomes Study which included 1,213 men who underwent prostatectomy for prostate cancer. They reported on urinary and sexual outcomes at up to 5 years postopera- tively. Compared to baseline rates of 81% with erections firm enough for penetration, rates at 6, 12, 24 and 60 months were 9, 17, 22, and 28% respectively. Notably, the data was collected on men diagnosed from 1994 to 1995 and the 60 month survey was distributed in 2000. Thus, all patients theoretically were exposed to intracavernous injection in the early postoperative period, but sildenafil was not available until around 3 years postoperatively. Consequently, this provides a relatively good estimation of the natural history of erectile dysfunction post- prostatectomy, though the improvement in erec- tile function seen between years 2–5 could have been significantly affected by the introduction of PDE5 inhibitors. Indeed, 43% of the study patients had used sildenafil at least one time and of these 520 patients, 32% reported achieving an erection suitable for intercourse. Of the technologies available around the beginning of the study, intracavernous injection was tried by 17%, vacuum erection devices were tried by 25%, “other” therapies including MUSE™ were used in 7%, and penile prostheses were implanted in 4% of the men.

Treatment of erectile dysfunction in post-prostatectomy men is unique compared with ED caused by other factors; in that rehabilitation (ED recovery) from treatment induced nerve and vascular injury are plausible. Thus, treatment of post-prostatectomy ED must keep two goals in mind: immediate erectile function facilitated by medication use and ultimate return to pre-pros- tatectomy erection status without use of adjunctive medications.

Penile injections do not require neuronal integrity to function. Injections have been shown to have the highest functional erection success rates following RRP with multiple studies showing ³90% efficacy at 6 months post-op. Like penile injections, MUSE™ works independent of nerve status. This medication has been shown to be effec- tive in men with ED after RRP, producing an erection thought to be sufficient for intercourse in the clinic in 70% of subjects, and leading to successful intercourse at home in 40% of subjects compared to 7% in placebo. Similar results were found in a study where 55% of subjects had successful intercourse and 48% effectively used MUSE™ long term (2 years) after RRP.

The potential to regain some erectile function with time (typically maximized at 18–24 months) after radical prostatectomy is well established in the literature. The potential of pharmacotherapy to aid in return to pre-op, baseline erectile function status with return of spontaneous, medication unassisted erections adequate for penetration is not only theoretically intuitive, but also has been reported in numerous small studies. The theoretical support is drawn from the results of denervating the cavernosum of rats and observation of the ensuing hypoxia and fibrosis coupled with the knowledge that erections increase the oxygenation of the cavernosum.

Phosphodiesterase inhibitors are likely the most commonly used rehabilitative pharmaceutical though they have lower theoretical rehabilitative potential than ICI or MUSE™ as they require a threshold level of neural integrity to be effective. McCullough et al. published a study using 50 and 100 mg nightly doses of sildenafil followed by an 8 week washout period. This study showed that men on daily sildenafil treatment had much higher rates of erectile function than those taking placebo, namely 24% for 50 mg sildenafil and 33% for 100 mg sildenafil versus 5% for placebo. Rates of return to spontaneous erection with ICI and MUSE™ should theoretically be higher because they are more effective at producing erections during the neurapraxic period post pros-tatectomy. Montorsi et al. published one of the first papers on erectile rehabilitation comparing 3 months of t.i.w. ICI alprostadil to patients receiving no treatment. Patients were assessed at a 6 month follow up, i.e. after a 2 month period without t.i.w. alprostadil. Eight (67%) were noted to have return of spontaneous erection which only required the use of ICI alprostadil one in 4.2 times for successful intercourse. The other four patients in the ICI group reported needing to use ICI greater than 50% of the time to achieve successful intercourse.

Only 20% of the placebo group reported spontaneous erections that were sufficient for intercourse. This study, although often cited, likely suffers from methodological flaws as no other studies have replicated these impressive results. A larger study by Mulhall et al. examined a group of men with functional preoperative erections prior to prostatectomy and who were non-responders to sildenafil in the early post- operative period. At 18 months postop, men who followed a regimen of t.i.w. ICI were compared to those who did not follow the protocol. Of the 58 men in the protocol group, 52% had a return of spontaneous erections compared to 19% of the 74 men in the non-protocol group. Althoughencouraging, this study suffers from a high degree of self selection bias, as the patients who were not hav- ing success and ultimately stopped treatment, but adhered to follow-up were simply included in the non-protocol group. The efficacy of MUSE™ in penile rehabilitation has also been tested. Raina et al. reported on 97 men post-prostatectomy, 56 of whom used t.i.w. MUSE™ for 6 months and 35 of whom used only p.r.n. erectile aids. Those who used MUSE™ attained a fourfold higher rate of spontaneous erections than those who did not (40% vs. 11%).