Erection rehabilitation following prostatectomy — current strategies and future directions

Journal name:
Nature Reviews Urology
Year published:
Published online


Despite continued advances in urological surgery, erectile dysfunction (ED) remains a serious adverse effect of radical prostatectomy. In this setting, ED is predominantly caused by injury to the neurovascular bundles, which lie alongside the prostate and are responsible for initiating and maintaining the erectile response. Most men will experience some degree of ED after radical prostatectomy, although erectile function outcomes have already remarkably improved since the development of nerve-sparing surgical techniques. To further improve outcomes, erection rehabilitation strategies are being investigated, which emphasize early treatment regimens with the aim of preventing adverse remodelling after surgery and preserving erectile function. Strategies include pharmacological therapy, mechanical therapy and psychosocial support. In addition, novel therapeutic approaches involving new targets for small-molecule treatments and regenerative medicine therapies are being developed to aid in restoring erectile function. Although ED treatments can be effective following radical prostatectomy, no specific erection rehabilitation regimen has currently been shown to be superior to other investigated rehabilitation regimens. Nevertheless, the different strategies rightfully remain an area of intensive research, as preservation of erectile function is a critical part of providing comprehensive care for men with prostate cancer to ensure their overall well-being, in contrast to just treating a patient's tumour.


  1. Ramsey, S. D. et al. Impact of prostate cancer on sexual relationships: a longitudinal perspective on intimate partners' experiences. J. Sex. Med. 10, 31353143 (2013).
  2. Mulhall, J. P., Bivalacqua, T. J. & Becher, E. F. Standard operating procedure for the preservation of erectile function outcomes after radical prostatectomy. J. Sex. Med. 10, 195203 (2013).
  3. Levinson, A. W., Lavery, H. J., Ward, N. T., Su, L.-M. & Pavlovich, C. P. Is a return to baseline sexual function possible? An analysis of sexual function outcomes following laparoscopic radical prostatectomy. World J. Urol. 29, 2934 (2011).
  4. Menon, M. et al. Vattikuti Institute prostatectomy: contemporary technique and analysis of results. Eur. Urol. 51, 648657; discussion 657658 (2007).
  5. Nelson, C. J., Scardino, P. T., Eastham, J. A. & Mulhall, J. P. Back to baseline: erectile function recovery after radical prostatectomy from the patients' perspective. J. Sex. Med. 10, 16361643 (2013).
  6. Magheli, A. & Burnett, A. L. Erectile dysfunction following prostatectomy: prevention and treatment. Nat. Rev. Urol. 6, 415427 (2009).
  7. Marien, T., Sankin, A. & Lepor, H. Factors predicting preservation of erectile function in men undergoing open radical retropubic prostatectomy. J. Urol. 181, 18171822 (2009).
  8. Woo, S. H. et al. Comprehensive analysis of sexual function outcome in prostate cancer patients after robot-assisted radical prostatectomy. J. Endourol. 28, 172177 (2014).
  9. Sivarajan, G., Prabhu, V., Taksler, G. B., Laze, J. & Lepor, H. Ten-year outcomes of sexual function after radical prostatectomy: results of a prospective longitudinal study. Eur. Urol. 65, 5865 (2014).
  10. Catalona, W. J. & Basler, J. W. Return of erections and urinary continence following nerve sparing radical retropubic prostatectomy. J. Urol. 150, 905907 (1993).
  11. Walsh, P. C., Marschke, P., Ricker, D. & Burnett, A. L. Patient-reported urinary continence and sexual function after anatomic radical prostatectomy. Urology 55, 5861 (2000).
  12. Garcia, F. J. & Brock, G. Current state of penile rehabilitation after radical prostatectomy. Curr. Opin. Urol. 20, 234240 (2010).
  13. Montorsi, F. et al. (eds) Sexual Medicine. Sexual Dysfunctions in Men and Women (Health Publication, 2010).
  14. Montorsi, F. et al. 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, 14081410 (1997).
  15. Padma-Nathan, H. et al. Randomized, double-blind, placebo-controlled study of postoperative nightly sildenafil citrate for the prevention of erectile dysfunction after bilateral nerve-sparing radical prostatectomy. Int. J. Impot. Res. 20, 479486 (2008).
  16. Rosen, R. C. et al. The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology 49, 822830 (1997).
  17. Cappelleri, J. C. & Rosen, R. C. The Sexual Health Inventory for Men (SHIM): a 5-year review of research and clinical experience. Int. J. Impot. Res. 17, 307319 (2005).
  18. Litwin, M. S. et al. Prostate Cancer Index: development, reliability, and validity of a health-related quality of life measure. Med. Care 36, 10021012 (1998).
  19. Wei, J. T., Dunn, R. L., Litwin, M. S., Sandler, H. M. & Sanda, M. G. Development and validation of the expanded prostate cancer index composite (EPIC) for comprehensive assessment of health-related quality of life in men with prostate cancer. Urology 56, 899905 (2000).
  20. Chipman, J. J. et al. Measuring and predicting prostate cancer related quality of life changes using EPIC for clinical practice. J. Urol. 191, 638645 (2014).
  21. Iacono, F. et al. Histological alterations in cavernous tissue after radical prostatectomy. J. Urol. 173, 16731676 (2005).
  22. Kendirci, M., Bejma, J. & Hellstrom, W. J. Update on erectile dysfunction in prostate cancer patients. Curr. Opin. Urol. 16, 186195 (2006).
  23. Jänig, W.& McLachlan, E. M. Organization of lumbar spinal outflow to distal colon and pelvic organs. Physiol. Rev. 67, 13321404 (1987).
  24. Walsh, P. C. & Donker, P. J. Impotence following radical prostatectomy: insight into etiology and prevention. J. Urol. 128, 492497 (1982).
  25. Gillitzer, R. & Thüroff, J. W. Relative advantages and disadvantages of radical perineal prostatectomy versus radical retropubic prostatectomy. Crit. Rev. Oncol. Hematol. 43, 167190 (2002).
  26. Akingba, A. G. & Burnett, A. L. Endothelial nitric oxide synthase protein expression, localization, and activity in the penis of the alloxan-induced diabetic rat. Mol. Urol. 5, 189197 (2001).
  27. User, H. M., Hairston, J. H., Zelner, D. J., McKenna, K. E. & McVary, K. T. Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction. J. Urol. 169, 11751179 (2003).
  28. Scheib, J. & Höke, A. Advances in peripheral nerve regeneration. Nat. Rev. Neurol. 9, 668676 (2013).
  29. Klein, L. T. et al. Apoptosis in the rat penis after penile denervation. J. Urol. 158, 626630 (1997).
  30. Leungwattanakij, S. et al. Cavernous neurotomy causes hypoxia and fibrosis in rat corpus cavernosum. J. Androl. 24, 239245 (2003).
  31. Hatzimouratidis, K. et al. Phosphodiesterase type 5 inhibitors in postprostatectomy erectile dysfunction: a critical analysis of the basic science rationale and clinical application. Eur. Urol. 55, 334347 (2009).
  32. Mulhall, J. P. et al. Erectile dysfunction after radical prostatectomy: hemodynamic profiles and their correlation with the recovery of erectile function. J. Urol. 167, 13711375 (2002).
  33. Calenda, G. et al. Whole genome microarray of the major pelvic ganglion after cavernous nerve injury: new insights into molecular profile changes after nerve injury. BJU Int. 109, 15521564 (2012).
  34. Tsujimura, A. et al. Significance of electrostimulation in detecting neurovascular bundle during radical prostatectomy. Int. J. Urol. 13, 926931 (2006).
  35. Burnett, A. L., Teloken, P. E., Briganti, A., Whitehurst, T. & Montorsi, F. Intraoperative assessment of an implantable electrode array for cavernous nerve stimulation. J. Sex. Med. 5, 19491954 (2008).
  36. Klotz, L. & Herschorn, S. Early experience with intraoperative cavernous nerve stimulation with penile tumescence monitoring to improve nerve sparing during radical prostatectomy. Urology 52, 537542 (1998).
  37. Takenaka, A. et al. Pelvic autonomic nerve mapping around the prostate by intraoperative electrical stimulation with simultaneous measurement of intracavernous and intraurethral pressure. J. Urol. 177, 225229; discussion 229 (2007).
  38. Klotz, L. et al. A randomized phase 3 study of intraoperative cavernous nerve stimulation with penile tumescence monitoring to improve nerve sparing during radical prostatectomy. J. Urol. 164, 15731578 (2000).
  39. Hu, J. C. et al. Comparative effectiveness of minimally invasive versus open radical prostatectomy. JAMA 302, 15571564 (2009).
  40. Gandaglia, G. et al. Comparative effectiveness of robot-assisted and open radical prostatectomy in the postdissemination era. J. Clin. Oncol. 32, 14191426 (2014).
  41. Huang, K.-H., Carter, S. C., Shih, Y.-C. T. & Hu, J. C. Robotic and standard open radical prostatectomy: oncological and quality-of-life outcomes. J. Comp. Eff. Res. 2, 293299 (2013).
  42. Ficarra, V. et al. Long-term evaluation of survival, continence and potency (SCP) outcomes after robot-assisted radical prostatectomy (RARP). BJU Int. 112, 338345 (2013).
  43. Haglind, E. et al. Urinary incontinence and erectile dysfunction after robotic versus open radical prostatectomy: a prospective, controlled, nonrandomised trial. Eur. Urol. 68, 216225 (2015).
  44. Suardi, N. et al. Nerve-sparing approach during radical prostatectomy is strongly associated with the rate of postoperative urinary continence recovery. BJU Int. 111, 717722 (2013).
  45. Medina, M., Paddock, H. N., Connolly, R. J. & Schwaitzberg, S. D. Novel antiadhesion barrier does not prevent anastomotic healing in a rabbit model. J. Invest. Surg. 8, 179186 (1995).
  46. Becker, J. M. et al. Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-blind multicenter study. J. Am. Coll. Surg. 183, 297306 (1996).
  47. Adanali, G., Verdi, M., Tuncel, A., Erdogan, B. & Kargi, E. Effects of hyaluronic acid-carboxymethylcellulose membrane on extraneural adhesion formation and peripheral nerve regeneration. J. Reconstr. Microsurg. 19, 2936 (2003).
  48. Park, J. S., Lee, J. H., Han, C. S., Chung, D. W. & Kim, G. Y. Effect of hyaluronic acid-carboxymethylcellulose solution on perineural scar formation after sciatic nerve repair in rats. Clin. Orthop. Surg. 3, 315324 (2011).
  49. Joung, J. Y. et al. Use of a hyaluronic acid-carboxymethylcellulose adhesion barrier on the neurovascular bundle and prostatic bed to facilitate earlier recovery of erectile function after robot-assisted prostatectomy: an initial experience. J. Endourol. 27, 12301235 (2013).
  50. Patel, V. R. et al. Dehydrated human amnion/chorion membrane allograft nerve wrap around the prostatic neurovascular bundle accelerates early return to continence and potency following robot-assisted radical prostatectomy: propensity score-matched analysis. Eur. Urol. 67, 3335 (2015).
  51. Briganti, A. et al. Predicting erectile function recovery after bilateral nerve sparing radical prostatectomy: a proposal of a novel preoperative risk stratification. J. Sex. Med. 7, 25212531 (2010).
  52. Gandaglia, G. et al. Preoperative erectile function is the only predictor of the use of a high number of phosphodiesterase type-5 inhibitors after bilateral nerve-sparing radical prostatectomy. Int. J. Impot. Res. 26, 201204 (2014).
  53. Faller, H. et al. Effects of psycho-oncologic interventions on emotional distress and quality of life in adult patients with cancer: systematic review and meta-analysis. J. Clin. Oncol. 31, 782793 (2013).
  54. Lafaye, A. et al. Dyadic effects of coping strategies on emotional state and quality of life in prostate cancer patients and their spouses. Psychooncology 23, 797803 (2014).
  55. Zisman, A., Leibovici, D., Kleinmann, J., Siegel, Y. I. & Lindner, A. The impact of prostate biopsy on patient well-being: a prospective study of pain, anxiety and erectile dysfunction. J. Urol. 165, 445454 (2001).
  56. Turns, D. Psychosocial issues: pelvic exenterative surgery. J. Surg. Oncol. 76, 224236 (2001).
  57. Burnett, A. L. Current rehabilitation strategy: clinical evidence for erection recovery after radical prostatectomy. Transl. Androl. Urol. 2, 2431 (2013).
  58. Teloken, P., Mesquita, G., Montorsi, F. & Mulhall, J. Post-radical prostatectomy pharmacological penile rehabilitation: practice patterns among the International Society for Sexual Medicine practitioners. J. Sex. Med. 6, 20322038 (2009).
  59. Mulhall, J., Land, S., Parker, M., Waters, W. B. & Flanigan, R. C. The use of an erectogenic pharmacotherapy regimen following radical prostatectomy improves recovery of spontaneous erectile function. J. Sex. Med. 2, 532540; discussion 540542 (2005).
  60. Kovanecz, I. et al. Chronic daily tadalafil prevents the corporal fibrosis and veno-occlusive dysfunction that occurs after cavernosal nerve resection. BJU Int. 101, 203210 (2008).
  61. Ferrini, M. G. et al. Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat. Urology 68, 429435 (2006).
  62. Montorsi, F. et al. Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy. Eur. Urol. 54, 924931 (2008).
  63. Montorsi, F. et al. Effects of tadalafil treatment on erectile function recovery following bilateral nerve-sparing radical prostatectomy: a randomised placebo-controlled study (REACTT). Eur. Urol. 65, 587596 (2014).
  64. Virag, R. Intracavernous injection of papaverine for erectile failure. Lancet 2, 938 (1982).
  65. Ruiz Rubio, J. L. et al. Mechanisms of prostaglandin E1-induced relaxation in penile resistance arteries. J. Urol. 171, 968973 (2004).
  66. Coombs, P. G., Heck, M., Guhring, P., Narus, J. & Mulhall, J. P. A review of outcomes of an intracavernosal injection therapy programme. BJU Int. 110, 17871791 (2012).
  67. Raina, R. et al. Long-term efficacy and compliance of intracorporeal (IC) injection for erectile dysfunction following radical prostatectomy: SHIM (IIEF-5) analysis. Int. J. Impot. Res. 15, 318322 (2003).
  68. Costabile, R. A. et al. Efficacy and safety of transurethral alprostadil in patients with erectile dysfunction following radical prostatectomy. J. Urol. 160, 13251328 (1998).
  69. McCullough, A. R. et al. Recovery of erectile function after nerve sparing radical prostatectomy and penile rehabilitation with nightly intraurethral alprostadil versus sildenafil citrate. J. Urol. 183, 24512456 (2010).
  70. US National Library of Medicine. [online], (2015).
  71. Hong, S. K., Han, B. K., Jeong, S. J., Byun, S.-S. & Lee, S. E. Effect of statin therapy on early return of potency after nerve sparing radical retropubic prostatectomy. J. Urol. 178, 613616 (2007).
  72. Segal, R. L., Bivalacqua, T. J. & Burnett, A. L. Irbesartan promotes erection recovery after nerve-sparing radical retropubic prostatectomy: a retrospective long-term analysis. BJU Int. 110, 17821786 (2012).
  73. Allaf, M. E., Hoke, A. & Burnett, A. L. Erythropoietin promotes the recovery of erectile function following cavernous nerve injury. J. Urol. 174, 20602064 (2005).
  74. Liu, T., Allaf, M. E., Lagoda, G. & Burnett, A. L. Erythropoietin receptor expression in the human urogenital tract: immunolocalization in the prostate, neurovascular bundle and penis. BJU Int. 100, 11031106 (2007).
  75. Burnett, A. L., Allaf, M. E. & Bivalacqua, T. J. Erythropoietin promotes erection recovery after nerve-sparing radical retropubic prostatectomy: a retrospective analysis. J. Sex. Med. 5, 23922398 (2008).
  76. Lehrfeld, T. & Lee, D. I. The role of vacuum erection devices in penile rehabilitation after radical prostatectomy. Int. J. Impot. Res. 21, 158164 (2009).
  77. Welliver, R. C., Mechlin, C., Goodwin, B., Alukal, J. P. & McCullough, A. R. A pilot study to determine penile oxygen saturation before and after vacuum therapy in patients with erectile dysfunction after radical prostatectomy. J. Sex. Med. 11, 10711077 (2014).
  78. Raina, R. et al. Early use of vacuum constriction device following radical prostatectomy facilitates early sexual activity and potentially earlier return of erectile function. Int. J. Impot. Res. 18, 7781 (2006).
  79. Köhler, T. S. et al. A pilot study on the early use of the vacuum erection device after radical retropubic prostatectomy. BJU Int. 100, 858862 (2007).
  80. Engel, J. D. Effect on sexual function of a vacuum erection device post-prostatectomy. Can. J. Urol. 18, 57215725 (2011).
  81. Cormie, P., Turner, B., Kaczmarek, E., Drake, D. & Chambers, S. K. A qualitative exploration of the experience of men with prostate cancer involved in supervised exercise programs. Oncol. Nurs. Forum 42, 2432 (2015).
  82. Gilbert, S. M. Shifting focus to cancer survivorship in prostate cancer: challenges and opportunities. Curr. Opin. Urol. 18, 326332 (2008).
  83. Wittmann, D. et al. Exploring the role of the partner in couples' sexual recovery after surgery for prostate cancer. Support. Care Cancer 22, 25092515 (2014).
  84. Wittmann, D. et al. What couples say about their recovery of sexual intimacy after prostatectomy: toward the development of a conceptual model of couples' sexual recovery after surgery for prostate cancer. J. Sex. Med. 12, 494504 (2015).
  85. Walker, L. M., Wassersug, R. J. & Robinson, J. W. Psychosocial perspectives on sexual recovery after prostate cancer treatment. Nat. Rev. Urol. 12, 167176 (2015).
  86. Albersen, M. et al. Injections of adipose tissue-derived stem cells and stem cell lysate improve recovery of erectile function in a rat model of cavernous nerve injury. J. Sex. Med. 7, 33313340 (2010).
  87. Kim, S. J., Park, S. H., Sung, Y. C.& Kim, S. W. Effect of mesenchymal stem cells associated to matrixen on the erectile function in the rat model with bilateral cavernous nerve crushing injury. Int. Braz. J. Urol. 38, 833841 (2012).
  88. Fandel, T. M. et al. Recruitment of intracavernously injected adipose-derived stem cells to the major pelvic ganglion improves erectile function in a rat model of cavernous nerve injury. Eur. Urol. 61, 201210 (2013).
  89. Qiu, X. et al. Both immediate and delayed intracavernous injection of autologous adipose-derived stromal vascular fraction enhances recovery of erectile function in a rat model of cavernous nerve injury. Eur. Urol. 62, 720727 (2012).
  90. Sopko, N. A. et al. Bone marrow support of the heart in pressure overload is lost with aging. PLoS ONE 5, e15187 (2010).
  91. Dong, F. et al. Myocardial CXCR4 expression is required for mesenchymal stem cell mediated repair following acute myocardial infarction. Circulation 126, 314324 (2012).
  92. Puliafico, S. B., Penn, M. S. & Silver, K. H. Stem cell therapy for heart disease. J. Gen. Intern. Med. 28, 13531363 (2013).
  93. Melman, A., Bar-Chama, N., McCullough, A., Davies, K. & Christ, G. The first human trial for gene transfer therapy for the treatment of erectile dysfunction: preliminary results. Eur. Urol. 48, 314318 (2005).
  94. Melman, A. & Davies, K. P. Gene therapy in the management of erectile dysfunction (ED): past, present, and future. ScientificWorldJournal 9, 846854 (2009).
  95. Zhu, X. et al. Improving erectile function of spontaneously hypertensive rats by silencing ROCK2. Urology 84, 983.e11983.e18 (2014).
  96. Yin, G. N. et al. Inhibition of Ninjurin 1 restores erectile function through dual angiogenic and neurotrophic effects in the diabetic mouse. Proc. Natl Acad. Sci. USA 111, E2731E2740 (2014).
  97. Sopko, N. A., Hannan, J. L. & Bivalacqua, T. J. Understanding and targeting the Rho kinase pathway in erectile dysfunction. Nat. Rev. Urol. 11, 622628 (2014).
  98. Chitaley, K. et al. Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway. Nat. Med. 7, 119122 (2001).
  99. Mulhall, J. P. Penile rehabilitation following radical prostatectomy. Curr. Opin. Urol. 18, 613620 (2008).
  100. Segal, R. L., Bivalacqua, T. J. & Burnett, A. L. Current penile-rehabilitation strategies: clinical evidence. Arab J. Urol. 11, 230236 (2013).
  101. Hinh, P. & Wang, R. Overview of contemporary penile rehabilitation therapies. Adv. Urol. 2008, 481218 (2008).
  102. Basal, S., Wambi, C., Acikel, C., Gupta, M. & Badani, K. Optimal strategy for penile rehabilitation after robot-assisted radical prostatectomy based on preoperative erectile function. BJU Int. 111, 658665 (2013).

Download references

Author information


  1. The James Buchanan Brady Urological Institute, The Johns Hopkins School of Medicine, 1800 Orleans Street, Baltimore, Maryland 21287, USA.

    • Nikolai A. Sopko
  2. Department of Urology, The Johns Hopkins School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287–2411, USA.

    • Arthur L. Burnett


Both authors researched data for the article, substantially contributed to discussion of the content, wrote and reviewed/edited the manuscript before submission.

Competing interests statement

N.A.S. declares no competing interests. A.L.B. is a consultant and/or advisor for Astellas and Genomic Health, is involved in scientific study and/or trial for Acorda Therapeutics, American Medical Systems, Auxilium, Coloplast, Endo Pharmaceuticals, Medispec, National Institutes of Health, Pfizer, Reflexonic and Vivus, is a member of the steering committee of the New England Research Institute, has a leadership position with The Center for Intimacy after Cancer Therapy, and is editorial board member for Andrology, European Urology, International Urology and Nephrology, The Journal of Sexual Medicine and Faculty Member of Practical Reviews in Urology.

Corresponding author

Correspondence to:

Author details

  • Nikolai A. Sopko

    Nikolai A. Sopko is a Resident in the James Brady Buchanan Urological Institute and Department of Urology at the Johns Hopkins School of Medicine in Baltimore, Maryland, USA. He received his PhD in stem cell biology and his MD from Case Western Reserve University in Cleveland, Ohio, USA, in 2012 through the NIH-funded Medical Scientist Training Program. His research interests include the molecular biology of erectile dysfunction with attention to the role of nerve injury and rehabilitation.

  • Arthur L. Burnett

    Arthur L. Burnett received his medical degree from Johns Hopkins University in Baltimore, Maryland, USA, in 1988. He is a Professor in the Department of Urology at Johns Hopkins Medical School. He is also the Director of the Basic Science Laboratory in Neurourology and the Male Sexual Dysfunction Clinic in the Department of Urology at Johns Hopkins University Hospital.

Additional data