ESSM Newsletter # 40

17 ESSM Today Penile rehabilitation following radical prostatectomy: What do we know so far? one might wonder why many urologists still offer penile rehabilitation. The answer may rely on the evidence proven in animal and histological data. RP creates a series of histological alterations in cavernous tissue which include marked increase in collagen fibers along with a decrease of elas- ticity and smooth muscle cell fibers. Kovanecz et al studied the temporal relationship in the corpora between the expression of inducible ni- tric oxide synthase, histological and biochemical changes, and the development of corporal veno- occlusive dysfunction after bilateral cavernosal nerve resection (BCNR) [16]. They compared histological penile tissue sections from rats who underwent either BCNR or sham operation and after treating the rats with sildenafil, their results revealed that sildenafil had a myogenic effect on the tissues [16]. These changes with sildenafil were also observed when translated to human subjects. A penile biopsy performed during and 6 months after RP revealed no smooth muscle loss after 6 months in patients taking sildenafil 50mg and a significant increase of smooth mus- cle in those taking sildenafil 100mg (p<0.05) [17]. Other animal studies have shown multi- ple beneficial effects of PDE5i in nerve crush models [8]. PDE5i have been shown to not only promote smooth muscle content, but also ame- liorate the fibrotic degeneration normally seen in the corpora cavernosa after BCNR. This oc- curs through modulation of extracellular matrix and gene expression of tissue growth factors which protect against smooth muscle loss and fibrosis after RP [18]. Other positive effects in- clude decrease in oxidative stress, endothelial cell apoptosis, penile shaft collagen content and hypoxia along with prevention of venous leakage through cGMP-related mechanisms dependent and independent of inducible nitric oxide syn- thase induction [19,20]. All these mechanisms, in combination with the neuroprotective effects of PDE5is, have been proven to improve overall erectile function [8]. Another negative impact of RP on sexual func- tion is penile shortening. Savoie and colleagues [21] prospectively measured the penis of 124 men before and at 3-months after RP. Peyro- nie’s disease and patients with history of penile or urethral surgery were excluded. Their results showed that the size of the penis was smaller after RP with a significant difference for flaccid, stretched, pre-pubic fat pad and penile circum- ference measurements. This led investigators to assess the impact of penile rehabilitation on penile length in the clinical setting and at the molecular level in animal models with bi- lateral cavernosal nerve injury. The REACTT study clearly showed that penile length loss was significantly reduced with daily tadalafil com- pared with placebo and on demand groups [12]. Yuan et al. noted that VED therapy preserved EF through anti-hypoxic, antiapoptotic and antifi- brotic mechanisms [22]. These findings were later confirmed with penile blood gas analysis which showed an increase in cavernous blood oxygen saturation after VED therapy [23]. The penile tissue and size preservation with VED are proven in multiple randomized and case series clinical trials [24, 25]. Currently, there is no standard treatment algo- rithm or established clinical guidelines for EF recovery after RP because of controversial evi- dence related to penile rehabilitation. The con- troversy of penile rehabilitation will continue until better modalities become available. For now, it is clear that basic scientific studies show that penile rehabilitation programs have a theoretical benefit on EF and clinically proven effect on pe- nile tissue preservation. However, patients should be informed that current rehabilitation programs have not been clinically proven to significantly improve unassisted erections. In our practice, we believe that any rehabilitation is undeniably better than no action at all. We have also noted that patients with high pre-surgery sexual desire, confidence to get and maintain an erection and pre-surgery intercourse satisfaction are the ones who will benefit the most from early rehabilitation after nerve-sparing RP. Given that the current literature lacks irrefutable evidence regarding the effectiveness of penile rehabilitation modalities, there still remains an opportunity for the develop- ment of larger trials with sufficiently long-term follow-up to convince the urologic community that penile rehabilitation is inarguably effective. References 1. What are the key statistics about pros- tate cancer? American Cancer Society. Available only: https://www.cancer.org/can- cer/prostate-cancer/about/key-statistics. html. Last accessed on 2018 August 2. 2. Sanda MG, Dun RL, Michalski J, Sandler HM, Northouse L, Hembroff L, et al. Quality of life and satisfaction with outcome among prostate – cancer survivors . N Engl J Med 2008; 358: 1250-61. 3. Clavell-Hernandez J, Wang R. The contro- versy surrounding penile rehabilitation after radical prostatectomy . Transl Androl Urol 2017;6(1): 2-11. 4. Salonia A, Castagna G, Capogrosso P, Castiglione F, Briganti A, Montorsi F. Prevention and management of post prostatectomy erectile dysfunction. Transl Androl Urol 2015;4(4): 421-37. 5. Burnett AL, Aus G, Canby-Hagino ED, Cookson MS, D’Amico AV, Dmochowski RR, et al. Erectile function outcome re- porting after clinically localized pros- tate cancer treatment. J Urol 2007;178: 597-601. 6. Mulhall JP. Defining and reporting erec- tile function outcomes after radical prostatectomy: challenges and mis- conceptions. J Urol 2009;181: 462-71.