Erectile dysfunction following radical prostatectomy represents a major concern for patients and physicians and generates much of the controversy associated with the treatment of low risk disease. Spontaneous return of erectile function after the procedure is awaited during the first 4 years and is affected by several factors. Some of these factors are patient dependent and others are the results of the surgeon expertise and the surgical technique applied.
As such, younger and healthier patients with no cardiovascular morbidities have better sexual outcome as their older and sicker counterparts. Preoperative erectile function is another important variable affecting postoperative erectile recovery. Motivated patients with sexually functional partner and a preoperative IIEF-EF score ≥26 have the best results in terms of postoperative satisfactory sexual activity. Bilateral high anterior release nerve sparing procedure performed by experienced surgeons in order to avoid stretching, heating and/or crushing the neurovascular bundles as well as to preserve any accessory cavernosal artery yields the highest erectile function recovery rates. However, these rates are unsatisfactory as only one third of potent patients will recover their preoperative status. The substantial burden on the quality of life of the remaining patients had urged the scientific community to understand the pathophysiology of surgically induced erectile dysfunction.
Animal models reproducing cavernous nerve damage occurring during radical prostatectomy have demonstrated that temporary loss of erection results into decreased oxygenation. The temporary state of constant low oxygen supply leads to endothelial cell dysfunction, smooth muscle apoptosis and fibrotic changes in the corpora cavernosa as well as disrupts veno-occlusive mechanism. These irreversible structural and hemodynamic changes rendered uneventful spontaneous recovery of erectile function even after the disappearance of neurapraxia. The concept of cavernosal tissue oxygenation during this period raised hope by preserving endothelial and smooth muscle function while awaiting the return of cavernous neural transmission. As such, hyperbaric oxygen therapy after cavernous nerve crush in rats improved erectile function. Based on these rationales, several authors translated the concept of early oxygenation to humans applied marketed drugs and/or devices used to treat erectile dysfunction. These authors found controversial results as highlighted in our recently published review article [1]. Additionally, the largest study to date found no long term effect of PDE5I administration following radical prostatectomy compared to placebo and high quality studies for other available drugs or devices are lacking. However, despite the absence of proper data, penile rehabilitation is recommended by the majority of scientific societies and practitioners are divided according to the optimal rehabilitation program.
It is well known that oxygen tension in the flaccid penis is in the hypoxic range and that oxygenation occurs during the erect state [2]. However, to date, no studies have proven an in vivo derangement of endothelial or smooth muscle cell metabolism secondary to a prolonged flaccid state. Recently, Martinez-Salamanca et al. have demonstrated that endothelial function and cavernosal sensitivity to PDE5I are preserved in erectile tissue of patients suffering from erectile dysfunction after radical prostatectomy [3]. The content of fibrosis and the amount of smooth muscle apoptosis in their penile tissues were not significantly different from those in normal patients without erectile dysfunction. Their results do not support and even challenge the concept of penile rehabilitation to avoid hypoxia induced apoptosis and fibrosis using PDE5I. However, it suggests that if PDE5I are efficacious in penile rehabilitation programs following nerve sparing radical prostatectomy, another mechanism could be solicited.
Thus, practitioner must remain vigilant about flawed animal models and their limitations. Reversely, positive clinical bedside findings that were not predicted by animal testing-such as negative results of PDE5I in clinical studies- should backtracked the bridge of translational gap and be used to refine the preclinical models. By doing so, we can add some solid evidence to our current standards.
Written by: Fouad Aoun, MD, MSc - from Jules Bordet Institute
References
1- Aoun F, Peltier A, van Velthoven R. Penile rehabilitation after pelvic cancer surgery. Scientific World Journal. 2015;2015:876046.
2- Kim N, Vardi Y, Padma-Nathan H, Daley J, Goldstein I, Saenz de Tejada I. Oxygen tension regulates the nitric oxide pathway. Physiological role in penile erection. J Clin Invest. 1993;91:437-42.
3- Martínez-Salamanca JI, La Fuente JM, Fernández A, Martínez-Salamanca E, Pepe-Cardoso AJ, Carballido J, Angulo J. Nitrergic function is lost but endothelial function is preserved in the corpus cavernosum and penile resistance arteries of men after radical prostatectomy. J Sex Med. 2015;12:590-9.