Perioperative treatment to preserve nerve function did not significantly improve erectile function after surgery for prostate cancer, a randomized, placebo-controlled study showed.
Six months after radical prostatectomy, patients treated with erythropoietin (EPO) or placebo had similar scores on a validated scale of erectile function. In fact, the median score favored the placebo group (19 vs 14). Investigators also found no significant difference between groups at 3, 9, and 12 months. Adjustment for nerve-sparing surgery, which was associated with recovery of erectile function, had minimal effect on analyses of primary and secondary endpoints.
The EPO group had significantly higher hemoglobin levels during treatment, consistent with administration of EPO, reported Hiten D. Patel, MD, of Johns Hopkins School of Medicine in Baltimore, and co-authors in the Journal of Urology.
“Unfortunately, ERECT did not confirm an independent benefit for erythropoietin as suggested by retrospective data and highlights the need for high-quality, randomized, placebo-controlled trials prior to widespread implementation of these types of adjuncts,” the authors said. “It is possible the lack of efficacy could be due to the target population destined to do relatively well regardless of additional interventions beyond surgical technique.”
“Cases where complete nerve sparing cannot be achieved or patients with some degree of erectile dysfunction preoperatively may be future populations of interest and better approximate preclinical models, which had more significant cavernous nerve injury,” the researchers continued.
Despite technical advances in surgery for prostate cancer, erectile dysfunction remains a common adverse effect and a barrier for patients who are candidates for radical prostatectomy, according to the authors of an accompanying editorial. The ERECT trial added to a list of adjunctive therapies evaluated (unsuccessfully) to preserve and enhance cavernous nerve restoration, but the search should continue.
“The study failed to show a benefit of erythropoietin on erectile function, but may have been limited by small sample size and confounders, including both patient and technical factors,” wrote Poone S. Shoureshi, MD, and Mark Garzotto, MD, both of Oregon Health & Science University in Portland.
“Peripheral nerve regeneration and neuroprotection are critical areas of research with the potential to change clinical management of post-prostatectomy patients … . Ultimately, it is through progress in these and other areas of research that surgeons will be able to reduce the morbidity and improve patient acceptance of radical prostatectomy,” the editorialists said.
Though a common complication of radical prostatectomy, postoperative erectile dysfunction tends to decline over time. In the randomized PROTECT trial, the incidence of erectile dysfunction decreased from 67% at baseline to 21% at 36 months. However, a substantial proportion of men have long-term erectile dysfunction of varying degrees of severity.
Erectile dysfunction after radical prostatectomy results from surgical injury to erection-producing nerves. The advent and adoption of nerve-sparing surgery substantially improved erectile function outcomes, but no additional intervention has demonstrated ability to alter the natural history of postoperative erectile dysfunction, Patel and colleagues noted. Phosphodiesterase-5 inhibitors aid in erectile function recovery, but placebo-controlled trials showed no permanent benefit.
“Recovery rates for erectile function have flatlined in the past decade despite advancements in surgical and postsurgical care,” the team stated.
EPO is expressed in the central and peripheral nervous systems, and receptors have been identified in human penile tissue and neurovascular bundles. Studies involving a preclinical model of cavernous nerve injury showed that EPO improved erection recovery, suggesting a neurotrophic effect. Additionally, retrospective clinical data showed sustained improvement in the International Index of Erectile Function (IIEF) in men who received subcutaneous injections of EPO prior to radical prostatectomy.
The ERECT trial progressed clinical evaluation of EPO in erectile dysfunction to the phase II setting. The investigators enrolled 63 patients with planned radical prostatectomy for localized prostate cancer and randomized 56 to receive perioperative EPO or placebo.
Randomized treatment consisted of three subcutaneous injections, administered the day before, the day of, and the day after surgery. The primary endpoint was improvement in IIEF scores from baseline to 6 months.
The 56 patients had a median age of about 55, and 50 underwent robot-assisted surgical procedures. Two experienced surgeons rated each procedure for nerve sparing, and both groups had a total score of 9 (very good or excellent).
The study population had a median baseline IIEF score of 12. After 6 months of follow-up, the scores did not differ significantly between the two groups (P=0.50). Scores did not differ at any other prespecified time points, resulting in a cumulative P-value of 0.45.
A nerve-sparing rating of 10 had a significant association with improved IIEF recovery (P=0.022). Patient-reported outcomes, oncologic outcomes, and complications were similar in the two treatment groups.
The study was supported by Johns Hopkins University.
Patel and co-authors noted no disclosures.
Shoureshi and Garzotto noted no disclosures.