Correspondence Department of Urology, St James' University Hospital, Leeds LS9 7TF, UK

Email ian.eardley@btinternet.com

Original article

Mulhall J et al. (2005) The use of an erectogenic pharmacotherapy regimen following radical prostatectomy improves recovery of spontaneous erectile function. J Sex Med 2: 532–542   PubMed

Synopsis

Background

Radical prostatectomy (RP) can cause erectile dysfunction (ED). Some studies have indicated that early pharmacologic intervention in men undergoing RP could promote return of erectile function.

Objective

To determine whether a pharmacologic penile rehabilitation program improves long-term erectile function after RP.

Design

This nonrandomized, prospective study recruited men scheduled to undergo RP for clinically localized prostate cancer between 1998 and 2001. Those who described their preoperative erections as fully functional, and had not received androgen-deprivation or pelvic-radiation therapy, were eligible. Before surgery, patients were introduced to the concept of penile rehabilitation. Patients then chose to enter one of two treatment groups: rehabilitation, or no rehabilitation. Postoperative erectile function was evaluated every 4 months, using a rigidity visual analog scale and the INTERNATIONAL INDEX OF ERECTILE FUNCTION (IIEF) questionnaire. Only patients who presented for follow-up 6 months after RP, and had 3 separate IIEF scores and 18 months' follow-up were included in the analysis.

Intervention

Men who agreed to participate in the penile rehabilitation program received oral sildenafil (100 mg, given on four occasions) soon after RP. These men were instructed to use pharmacologic intervention to obtain three erections per week for 12 months, with sildenafil or, if they failed to respond to sildenafil, penile injection therapy (30 mg/ml papaverine, 1 mg/ml phentolamine and 10g/ml prostaglandin E1; or 30 mg/ml papaverine and 1 mg/ml phentolamine). Men in the no-rehabilitation group did not follow the protocol, but presented for follow-up assessments of erectile function.

Outcome measures

The primary endpoint was postoperative return of spontaneous erectile function.

Results

Of 132 men (mean age 5910.6 years), 58 chose to participate in the rehabilitation program, and 74 opted for no rehabilitation. The rehabilitation and no-rehabilitation groups were similar in age and intraoperative nerve-sparing status. At 18 months after surgery, 52% of men in the rehabilitation group were able to achieve functional erections without medical assistance, compared with 19% of men in the no-rehabilitation group (P <0.001). The proportion of patients responsive to sildenafil and intracavernosal injections was 64% and 95%, respectively, in the rehabilitation group, compared with 24% and 76%, respectively, in the no-rehabilitation group (P <0.001 and P <0.01, respectively). Men in the rehabilitation group became responsive to sildenafil more rapidly (9 4 months versus 13 3 months, P = 0.02). At 18 months, the mean number of erections per week was significantly greater in the rehabilitation group (1.9 vs 0.4, P <0.001), as were visual-analog-scale scores (53 21% vs 26 43%, P <0.01), and IIEF erectile-function-domain scores (22 6 vs 12 14, P = 0.01).

Conclusion

Pharmacologic penile rehabilitation improved postoperative recovery of spontaneous erectile function, and postoperative responsiveness to erectogenic drugs.

Commentary

For men who choose RP as treatment for localized prostate cancer, one of the most common potential complications is ED. Predictors for the preservation and return of erectile function in such men include the patient's age, his preoperative erectile function, the presence of any preoperative risk factors for ED, and the nerve-sparing status of the procedure. Erectile function may take up to 18 months (and perhaps longer) to return, even in men in whom bilateral nerve sparing is achieved. In those men who do develop ED, a number of pathophysiologic mechanisms have been implicated, including unrecognized nerve injury, arterial injury, and veno-occlusive dysfunction caused by structural alterations in the cavernosal smooth muscle.

In 1997, Montorsi and colleagues first raised the possibility of so-called 'rehabilitation' as a means of preserving erectile function.¹ In a small, prospective, randomized, controlled trial, they demonstrated the potential for early, regular, intracavernosal injection therapy with prostaglandin E1 to prevent ED. It was thought that regular erections (albeit induced pharmacologically) resulted in regular cavernosal oxygenation, which, in turn, promoted preservation of cavernosal smooth muscle and erectile function. In a subsequent randomized, placebo-controlled trial, nightly sildenafil resulted in a higher return of spontaneous erectile function 9 months after nerve-sparing RP, compared with placebo.² Sildenafil's mechanism of action in this setting is less clear, and it has been suggested that preservation of endothelial function and even promotion of neurogenesis may be involved. This study has thus far only been published in abstract form, but it has had a considerable effect upon urological practice.³

The paper by Mulhall and colleagues follows up on these findings. It is essentially a prospective, nonrandomized study of potent men who underwent RP. Men who underwent non-nerve-sparing surgery were included, in addition to men who underwent bilateral and unilateral nerve-sparing procedures. In the postoperative period, the men chose to enter a program of rehabilitation for their erectile function, or to use erectogenic treatment as and when required. The objective of the rehabilitation program was to achieve at least three erections per week, either by oral pharmacotherapy with sildenafil, or, if that was ineffective, by intracavernosal injection therapy. The majority (77%) of men in the rehabilitation group initially needed to use intracavernosal injection therapy to achieve regular erections. The outcome of the trial indicated a clear advantage for rehabilitation, with 52% of men in the rehabilitation program having spontaneous, functionally useful erections at 18 months, compared with 19% of those who were treated only as required (P <0.01). The success rates in terms of the proportion of men who were responsive to oral pharmacotherapy were 64% and 24%, respectively (P <0.01).

While this paper was not a prospective, randomized, controlled trial, it does support earlier studies in suggesting that early rehabilitation programs are beneficial in preserving erectile function in men who have undergone RP. The optimal program, however, is undefined. In this study, most men used intracavernosal injection therapy, and it is not clear whether simply using oral phosphodiesterase type 5 inhibitors would be as effective. At this time, there is a relative paucity of robust, prospective, randomized trials in this field. In the absence of such studies, the regimen used in this paper appears to be the optimal approach for a patient who is anxious to maximize his chances of normal erectile function following RP.

Acknowledgments

The synopsis was written by Sandra Ford, Associate Editor, Nature Clinical Practice.

References

1. Montorsi F et al. (1997) Recovery of spontaneous erectile function after nerve-sparing radical retropubic prostatectomy with and without early intracavernous injections of alprostadil: results of a prospective, randomized trial. J Urol 158: 1408–1410 | Article | PubMed | ISI | ChemPort |
2. Padma-Nathan H et al. (2003) Postoperative nightly administration of sildenafil citrate significantly improves the return of normal spontaneous erectile function after bilateral nerve-sparing radical prostatectomy [abstract]. J Urol 169 (Suppl): S375
3. Schiff JD and Mulhall JP (2005) Neuroprotective strategies in radical prostatectomy. BJU Int 95: 11–14 | Article | PubMed | ISI |

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Subject areas under which this article appears: Sexual dysfunction | Prostate cancer