Non-surgically Related Causes of Erectile Dysfunction After Bilateral Nerve-sparing Radical Prostatectomy

G Gandaglia; G Lista; N Fossati; N Suardi; A Gallina; M Moschini; L Bianchi; MS Rossi; R Schiavina; SF Shariat; A Salonia; F Montorsi; A Briganti


Prostate Cancer Prostatic Dis. 2016;19(2):185-190. 

In This Article


Although RP is generally associated with excellent long-term oncologic outcomes in men with clinically localized PCa, a significant proportion of patients would not recover EF and urinary continence after surgery.[2,4,7–9] Meticulous surgical approaches aimed at the preservation of the neurovascular structures deputed to EF are of fundamental importance in order to achieve satisfactory long-term functional results.[4,6,7,10,17] This concept is further stressed in the robotic technique, where the enhanced view, together with the lower risk of bleeding and better visualization of anatomical structures, allows for an accurate sparing of the neurovascular bundles, thus resulting into higher EF recovery rates.[6–8] Nonetheless, more than 10% of the patients treated with BNSRP experience postoperative ED at long-term follow-up, even when a meticulous surgical approach is performed by experienced surgeons.[4,6–8] In light of this situation, we hypothesized that non-surgical related variables (namely, preoperative functional status, depression and the administration of aRT) might have a role in the recovery of EF after surgery. Therefore, we tested the impact of these variables in a large contemporary cohort of patients treated with open or robot-assisted BNSRP at a high-volume tertiary center.

Our analyses show that age and preoperative functional status as measured by the IIEF-EF represent important predictors of EF recovery after surgery. Particularly, patients with mild and no ED at baseline had approximately 2- and 3-fold higher probability of recovering EF after BSNRP as compared with their counterparts with preoperative ED. These findings are in line with previous studies showing a significant association between baseline IIEF-EF, age at surgery and postoperative EF recovery.[7,18–20] In addition, previous investigations also supported the role of these parameters in predicting urinary continence recovery.[21] As such, age and preoperative EF have been proposed as markers of a pelvic vascular disease that might impair functional outcomes after surgery.[21] Although these observations might lead to the conclusion that a nerve-sparing approach is not beneficial in elderly and impotent patients, the preservation of the neurovascular bundles might improve urinary continence recovery after surgery even in patients with poor erections at baseline.[17,22] As a consequence, this surgical approach should be always considered when feasible, regardless of preoperative functional status.

Our analyses were also able to demonstrate an impact of the depressive status on the probability of recovering EF after BNSRP. Previous investigations reported an association between ED and the development of psychological distress and depression after RP.[23] For example, Weber et al.[23] showed that men with less sexual bother after surgery were 55% less likely to have depressive symptoms. In addition, several studies reported an association between depression and ED in the general population,[24,25] where depressed men were twice as likely to complain ED as compared with their non-depressed counterparts.[24] Nonetheless, at the best of authors' knowledge our investigation represents the first available evidence proving a role of preoperative depression as measured by objective scores on the recovery of EF after surgery. This observation has also important clinical implications with regard to the identification of men who might benefit the most from mental health support at PCa diagnosis and after RP.[26]

Of note, we observed a detrimental impact of aRT on EF recovery in PCa patients undergoing BNSRP. Although previous investigations demonstrated that patients receiving aRT after surgery are at increased risk of urinary incontinence,[27] the role of this multimodal approach on EF is still debated.[28–30] For example, the only randomized trial reporting data on ED during follow-up failed to show significant differences between patients treated with immediate radiotherapy and initial observation.[31] In addition, retrospective investigations failed to show an increased risk of sexual dysfunction among patients managed with aRT.[28–30] Nonetheless, these studies are based on historic patients or on population-based cohorts. As such, the inclusion of men treated with different surgical approaches and the adoption of heterogeneous definitions of aRT, as well as the lack of validated definitions of postoperative quality of life end points might limit the generalizability of these observations. On the contrary, our study represents one of the first available evidence showing a detrimental impact of aRT on EF recovery. The inclusion of a large cohort of contemporary patients treated with BNSRP in a high-volume center and the assessment of postoperative ED using a validated questionnaire-based definition over a long follow-up period represent the main strengths of our analyses. Moreover, we were able to adjust our analyses for preoperative sexual function, depressive status and the surgical approach, which represent independent predictors of EF recovery. From a biological standpoint, the pathophysiology of ED after aRT might be multifactorial and include both vasculogenic and neurogenic components. In particular, fibrosis and ischemia of endothelial cells in penile arteries and sinusoids of the corpora cavernosum changes caused by radiation therapy might substantially impair EF recovery. Additionally, the administration of radiotherapy might cause ultrastructural changes that would ultimately generate corporal fibrosis, venous leakage, and, in turn, inability to maintain erections. A direct neurogenic mechanism has also been hypothesized.[32–34]

Finally, although this goes beyond the initial scope of our investigation, our analyses confirm that robot-assisted surgery confers a significant benefit in terms of EF recovery in men with clinically localized PCa.[6–8] This observation is consistent with the results of a recent randomized controlled trial that demonstrated that robot-assisted RP was beneficial in preserving EF as compared with the traditional approach.[6] However, it is worth mentioning that this advantage varies according to baseline patient characteristics, where men with worse preoperative general health status (that is, older and sicker patients with baseline ED) might not experience any of the benefits associated with the adoption of this surgical technique.[8]

Despite several strengths, our study is not devoid of limitations. First, it is limited by its retrospective nature. For example, we cannot exclude that selection bias might in part explain the association between aRT and EF recovery. Nonetheless, we tried to circumvent this limitation adjusting our multivariable models for potential confounders. Second, although all patients included in our study were strongly encouraged to use PDE5-Is in an on-demand or daily fashion, due to the retrospective nature of our analyses young, non-depressed, preoperatively potent patients might be more likely to start penile rehabilitation protocols.[35] Third, previous studies demonstrated an impact of surgical volume on the probability of recovering EF after RP.[36] However, we were not able to adjust our analyses for this confounder. Nonetheless, we included patients treated by six experienced surgeons in a high-volume center for both open and robot-assisted surgeries. Fourth, all patients were asked to complete preoperative questionnaires at the time of hospital admission. This timing might have overestimate ED and depression due to psychogenic issues after PCa diagnosis.[37] This might also explain why a small proportion of the patients with preoperative ED were able to recover a satisfactory EF after surgery. Finally, our results were obtained in a high-volume tertiary referral center. Therefore, they might not be generalizable to other settings.