Penile Rehabilitation After Prostate Cancer Treatment: Outcomes and Practical Algorithm

Urologic Clinics of North America

Volumn 38, Issue 2, 2011, Pages 105-118

  Mazzola, Clarisse ^a   Mulhall, John P ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

Erectile dysfunction; Penile rehabilitation; Prostate cancer; Radical prostatectomy

Indexed keywords

ENDOTHELIN B RECEPTOR; INDUCIBLE NITRIC OXIDE SYNTHASE; NITRIC OXIDE; PHOSPHODIESTERASE V INHIBITOR; PLACEBO; PROSTAGLANDIN E1; SILDENAFIL; TADALAFIL; TRANSFORMING GROWTH FACTOR BETA; VARDENAFIL;

ACCESSORY PUDENDAL ARTRERY; APOPTOSIS; ARTERY; CAVERNOUS NERVE; CORPUS CAVERNOSUM; DRUG DOSE COMPARISON; DRUG DOSE INCREASE; DRUG DOSE TITRATION; DRUG SUBSTITUTION; DRUG WITHDRAWAL; ENDOTHELIAL PROGENITOR CELL; ERECTILE DYSFUNCTION; EVENING DOSAGE; HUMAN; HYPERBARIC OXYGEN; HYPOXIA; LOW DRUG DOSE; MEAN ARTERIAL PRESSURE; MEDICAL APPARATUS, EQUIPMENT AND SUPPLIES; NERVE CRUSH; NERVE TRANSECTION; NEUROPROTECTION; NONHUMAN; OXYGEN TENSION; PARASYMPATHETIC NERVE; PATHOPHYSIOLOGY; PATIENT COMPLIANCE; PENILE FIBROSIS; PENILE REHABILITATION; PENIS ERECTION; PRIORITY JOURNAL; PROSTATE CANCER; PROSTATECTOMY; PULMONARY HYPERTENSION; RADICAL RETROPUBIC PROSTATECTOMY; REHABILITATION; REVIEW; SEXUAL INTERCOURSE; SMOOTH MUSCLE; TISSUE OXYGENATION; VACUUM DEVICE; VEIN OCCLUSION;

ALGORITHMS; ANIMALS; APOPTOSIS; COITUS; ERECTILE DYSFUNCTION; HUMANS; MALE; MUSCLE, SMOOTH; OXYGEN; PENIS; PROSTATECTOMY; PROSTATIC NEOPLASMS; RECOVERY OF FUNCTION;

EID: 79957517732     PISSN: 00940143     EISSN: 1558318X     Source Type: Journal    
DOI: 10.1016/j.ucl.2011.03.002     Document Type: Review

References (92)

1. Tal R., Alphs H.H., Krebs P., et al. Erectile function recovery rate after radical prostatectomy: a meta-analysis. J Sex Med 2009, 6:2538-2546.
2. Quinlan D.M., Epstein J.I., Carter B.S., et al. Sexual function following radical prostatectomy: influence of preservation of neurovascular bundles. J Urol 1991, 145:998-1002.
3. Marien T., Sankin A., Lepor H. Factors predicting preservation of erectile function in men undergoing open radical retropubic prostatectomy. J Urol 2009, 181:1817-1822.
4. Catalona W.J., Carvalhal G.F., Mager D.E., et al. Potency, continence and complication rates in 1,870 consecutive radical retropubic prostatectomies. J Urol 1999, 162:433-438.
5. Walsh P.C., Partin A.W., Epstein J.I. Cancer control and quality of life following anatomical radical retropubic prostatectomy: results at 10 years. J Urol 1994, 152:1831-1836.
6. Zippe C.D., Kedia A.W., Kedia K., et al. Treatment of erectile dysfunction after radical prostatectomy with sildenafil citrate (Viagra). Urology 1998, 52:963-966.
7. Moskovic D.J., Alphs H., Nelson C.J., et al. Subjective characterization of nerve sparing predicts recovery of erectile function after radical prostatectomy: defining the utility of a nerve sparing grading system. J Sex Med 2011, 8(1):255-260.
8. Masterson T.A., Serio A.M., Mulhall J.P., et al. Modified technique for neurovascular bundle preservation during radical prostatectomy: association between technique and recovery of erectile function. BJU Int 2008, 101:1217-1222.
9. Katz D., Bennett N.E., Stasi J., et al. Chronology of erectile function in patients with early functional erections following radical prostatectomy. J Sex Med 2010, 7:803-809.
10. Leungwattanakij S., Bivalacqua T.J., Usta M.F., et al. Cavernous neurotomy causes hypoxia and fibrosis in rat corpus cavernosum. J Androl 2003, 24:239-245.
11. User H.M., Hairston J.H., Zelner D.J., et al. Penile weight and cell subtype specific changes in a post-radical prostatectomy model of erectile dysfunction. J Urol 2003, 169:1175-1179.
12. Ferrini M.G., Davila H.H., Kovanecz I., et al. Vardenafil prevents fibrosis and loss of corporal smooth muscle that occurs after bilateral cavernosal nerve resection in the rat. Urology 2006, 68:429-435.
13. Ferrini M.G., Kovanecz I., Sanchez S., et al. Fibrosis and loss of smooth muscle in the corpora cavernosa precede corporal veno-occlusive dysfunction (CVOD) induced by experimental cavernosal nerve damage in the rat. J Sex Med 2009, 6:415-428.
14. Kovanecz I., Rambhatla A., Ferrini M.G., et al. Chronic daily tadalafil prevents the corporal fibrosis and veno-occlusive dysfunction that occurs after cavernosal nerve resection. BJU Int 2008, 101:203-210.
15. Mulhall J.P., Muller A., Donohue J.F., et al. The functional and structural consequences of cavernous nerve injury are ameliorated by sildenafil citrate. J Sex Med 2008, 5:1126-1136.
16. Klein L.T., Miller M.I., Buttyan R., et al. Apoptosis in the rat penis after penile denervation. J Urol 1997, 158:626-630.
17. Lysiak J.J., Yang S.K., Klausner A.P., et al. Tadalafil increases Akt and extracellular signal-regulated kinase 1/2 activation, and prevents apoptotic cell death in the penis following denervation. J Urol 2008, 179:779-785.
18. Podlasek C.A., Gonzalez C.M., Zelner D.J., et al. Analysis of NOS isoform changes in a post radical prostatectomy model of erectile dysfunction. Int J Impot Res 2001, 13(Suppl 5):S1-S15.
19. Canguven O., Burnett A. Cavernous nerve injury using rodent animal models. J Sex Med 2008, 5:1776-1785.
20. Mullerad M., Donohue J.F., Li P.S., et al. Functional sequelae of cavernous nerve injury in the rat: is there model dependency. J Sex Med 2006, 3:77-83.
21. Jin H.R., Chung Y.G., Kim W.J., et al. A mouse model of cavernous nerve injury-induced erectile dysfunction: functional and morphological characterization of the corpus cavernosum. J Sex Med 2010, 7(10):3351-3364.
22. Iacono F., Giannella R., Somma P., et al. Histological alterations in cavernous tissue after radical prostatectomy. J Urol 2005, 173:1673-1676.
23. Rambhatla A., Kovanecz I., Ferrini M., et al. Rationale for phosphodiesterase 5 inhibitor use post-radical prostatectomy: experimental and clinical review. Int J Impot Res 2008, 20:30-34.
24. Mulhall J.P., Secin F.P., Guillonneau B. Artery sparing radical prostatectomy-myth or reality?. J Urol 2008, 179:827-831.
25. Secin F.P., Karanikolas N., Touijer A.K., et al. Anatomy of accessory pudendal arteries in laparoscopic radical prostatectomy. J Urol 2005, 174:523-526. [discussion: 526].
26. Secin F.P., Karanikolas N., Kuroiwa K., et al. Positive surgical margins and accessory pudendal artery preservation during laparoscopic radical prostatectomy. Eur Urol 2005, 48:786-792. [discussion: 793].
27. Polascik T.J., Walsh P.C. Radical retropubic prostatectomy: the influence of accessory pudendal arteries on the recovery of sexual function. J Urol 1995, 154:150-152.
28. Rogers C.G., Trock B.P., Walsh P.C. Preservation of accessory pudendal arteries during radical retropubic prostatectomy: surgical technique and results. Urology 2004, 64:148-151.
29. Droupy S., Hessel A., Benoit G., et al. Assessment of the functional role of accessory pudendal arteries in erection by transrectal color Doppler ultrasound. J Urol 1999, 162:1987-1991.
30. Matin S.F. Recognition and preservation of accessory pudendal arteries during laparoscopic radical prostatectomy. Urology 2006, 67:1012-1015.
31. Rosen M.P., Greenfield A.J., Walker T.G., et al. Arteriogenic impotence: findings in 195 impotent men examined with selective internal pudendal angiography. Young Investigator's Award. Radiology 1990, 174:1043-1048.
32. Gray R.R., Keresteci A.G., St Louis E.L., et al. Investigation of impotence by internal pudendal angiography: experience with 73 cases. Radiology 1982, 144:773-780.
33. Benoit G., Droupy S., Quillard J., et al. Supra and infralevator neurovascular pathways to the penile corpora cavernosa. J Anat 1999, 195(Pt 4):605-615.
34. Breza J., Aboseif S.R., Orvis B.R., et al. Detailed anatomy of penile neurovascular structures: surgical significance. J Urol 1989, 141:437-443.
35. Box G.N., Kaplan A.G., Rodriguez E., et al. Sacrifice of accessory pudendal arteries in normally potent men during robot-assisted radical prostatectomy does not impact potency. J Sex Med 2010, 7:298-303.
36. Moreland R.B., Albadawi H., Bratton C., et al. O2-dependent prostanoid synthesis activates functional PGE receptors on corpus cavernosum smooth muscle. Am J Physiol Heart Circ Physiol 2001, 281:H552-H558.
37. Moreland R.B., Gupta S., Goldstein I., et al. Cyclic AMP modulates TGF-beta 1-induced fibrillar collagen synthesis in cultured human corpus cavernosum smooth muscle cells. Int J Impot Res 1998, 10:159-163.
38. Muller A., Tal R., Donohue J.F., et al. The effect of hyperbaric oxygen therapy on erectile function recovery in a rat cavernous nerve injury model. J Sex Med 2008, 5:562-570.
39. Vignozzi L., Morelli A., Filippi S., et al. Effect of sildenafil administration on penile hypoxia induced by cavernous neurotomy in the rat. Int J Impot Res 2008, 20:60-67.
40. Kim N., Vardi Y., Padma-Nathan H., et al. Oxygen tension regulates the nitric oxide pathway. Physiological role in penile erection. J Clin Invest 1993, 91:437-442.
41. Tal R., Mueller A., Mulhall J.P. The correlation between intracavernosal pressure and cavernosal blood oxygenation. J Sex Med 2009, 6:2722-2727.
42. Lue T.F., Takamura T., Schmidt R.A., et al. Potential preservation of potency after radical prostatectomy. Urology 1983, 22:165-167.
43. Knispel H.H., Andresen R. Evaluation of vasculogenic impotence by monitoring of cavernous oxygen tension. J Urol 1993, 149:1276-1279.
44. Ghofrani H.A., Voswinckel R., Reichenberger F., et al. Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension: a randomized prospective study. J Am Coll Cardiol 2004, 44:1488-1496.
45. Nehra A., Goldstein I., Pabby A., et al. Mechanisms of venous leakage: a prospective clinicopathological correlation of corporeal function and structure. J Urol 1996, 156:1320-1329.
46. Mulhall J.P., Graydon R.J. The hemodynamics of erectile dysfunction following nerve-sparing radical retropubic prostatectomy. Int J Impot Res 1996, 8:91-94.
47. Mulhall J.P., Slovick R., Hotaling J., et al. Erectile dysfunction after radical prostatectomy: hemodynamic profiles and their correlation with the recovery of erectile function. J Urol 2002, 167:1371-1375.
48. Mulhall J., Barnas J., Aviv N., et al. Sildenafil citrate response correlates with the nature and the severity of penile vascular insufficiency. J Sex Med 2005, 2:104-108.
49. Zhang R., Wang Y., Zhang L., et al. Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats. Stroke 2002, 33:2675-2680.
50. Becher E.F., Toblli J.E., Castronuovo C., et al. Expression of caveolin-1 in penile cavernosal tissue in a denervated animal model after treatment with sildenafil citrate. J Sex Med 2009, 6:1587-1593.
51. Kovanecz I., Rambhatla A., Ferrini M., et al. Long-term continuous sildenafil treatment ameliorates corporal veno-occlusive dysfunction (CVOD) induced by cavernosal nerve resection in rats. Int J Impot Res 2008, 20:202-212.
52. Vignozzi L., Filippi S., Morelli A., et al. Effect of chronic tadalafil administration on penile hypoxia induced by cavernous neurotomy in the rat. J Sex Med 2006, 3:419-431.
53. Magee T.R., Ferrini M., Garban H.J., et al. Gene therapy of erectile dysfunction in the rat with penile neuronal nitric oxide synthase. Biol Reprod 2002, 67:1033-1041.
54. Valente E.G., Vernet D., Ferrini M.G., et al. L-arginine and phosphodiesterase (PDE) inhibitors counteract fibrosis in the Peyronie's fibrotic plaque and related fibroblast cultures. Nitric Oxide 2003, 9:229-244.
55. Gonzalez-Cadavid N.F., Rajfer J. The pleiotropic effects of inducible nitric oxide synthase (iNOS) on the physiology and pathology of penile erection. Curr Pharm Des 2005, 11:4041-4046.
56. Padma-Nathan H., McCullough A.R., Levine L.A., 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 2008, 20:479-486.
57. Parsons J.K., Marschke P., Maples P., et al. Effect of methylprednisolone on return of sexual function after nerve-sparing radical retropubic prostatectomy. Urology 2004, 64:987-990.
58. Bannowsky A., Schulze H., van der Horst C., et al. Recovery of erectile function after nerve-sparing radical prostatectomy: improvement with nightly low-dose sildenafil. BJU Int 2008, 101:1279-1283.
59. Penson D.F., McLerran D., Feng Z., et al. 5-year urinary and sexual outcomes after radical prostatectomy: results from the prostate cancer outcomes study. J Urol 2005, 173:1701-1705.
60. Rozet F., Galiano M., Cathelineau X., et al. Extraperitoneal laparoscopic radical prostatectomy: a prospective evaluation of 600 cases. J Urol 2005, 174:908-911.
61. Stanford J.L., Feng Z., Hamilton A.S., et al. Urinary and sexual function after radical prostatectomy for clinically localized prostate cancer: the Prostate Cancer Outcomes Study. JAMA 2000, 283:354-360.
62. Das A., Xi L., Kukreja R.C. Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling. J Biol Chem 2005, 280:12944-12955.
63. Fisher P.W., Salloum F., Das A., et al. Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity. Circulation 2005, 111:1601-1610.
64. Kukreja R., Salloum F., Xi L. Anti-ischemic effects of sildenafil, vardenafil and tadalafil in heart. Int J Impot Res 2007, 19:226-227.
65. Salloum F.N., Ockaili R.A., Wittkamp M., et al. Vardenafil: a novel type 5 phosphodiesterase inhibitor reduces myocardial infarct size following ischemia/reperfusion injury via opening of mitochondrial K(ATP) channels in rabbits. J Mol Cell Cardiol 2006, 40:405-411.
66. Salloum F.N., Takenoshita Y., Ockaili R.A., et al. Sildenafil and vardenafil but not nitroglycerin limit myocardial infarction through opening of mitochondrial K(ATP) channels when administered at reperfusion following ischemia in rabbits. J Mol Cell Cardiol 2007, 42:453-458.
67. Behr-Roussel D., Gorny D., Mevel K., et al. Chronic sildenafil improves erectile function and endothelium-dependent cavernosal relaxations in rats: lack of tachyphylaxis. Eur Urol 2005, 47:87-91.
68. Musicki B., Champion H.C., Becker R.E., et al. Erection capability is potentiated by long-term sildenafil treatment: role of blood flow-induced endothelial nitric-oxide synthase phosphorylation. Mol Pharmacol 2005, 68:226-232.
69. Bivalacqua T.J., Liu T., Musicki B., et al. Endothelial nitric oxide synthase keeps erection regulatory function balance in the penis. Eur Urol 2007, 51:1732-1740.
70. De Young L.X., Domes T., Lim K., et al. Endothelial rehabilitation: the impact of chronic PDE5 inhibitors on erectile function and protein alterations in cavernous tissue of diabetic rats. Eur Urol 2008, 54:213-220.
71. Foresta C., De Toni L., Di Mambro A., et al. The PDE5 inhibitor sildenafil increases circulating endothelial progenitor cells and CXCR4 expression. J Sex Med 2009, 6:369-372.
72. Foresta C., Di Mambro A., Caretta N., et al. Effect of vardenafil on endothelial progenitor cells in hypogonadotrophic hypogonadal patients: role of testosterone treatment. Clin Endocrinol 2009, 71:412-416.
73. Foresta C., Ferlin A., De Toni L., et al. Circulating endothelial progenitor cells and endothelial function after chronic Tadalafil treatment in subjects with erectile dysfunction. Int J Impot Res 2006, 18:484-488.
74. Foresta C., Lana A., Cabrelle A., et al. PDE-5 inhibitor, Vardenafil, increases circulating progenitor cells in humans. Int J Impot Res 2005, 17:377-380.
75. Foresta C., Caretta N., Lana A., et al. Relationship between vascular damage degrees and endothelial progenitor cells in patients with erectile dysfunction: effect of vardenafil administration and PDE5 expression in the bone marrow. Eur Urol 2007, 51:1411-1417. [discussion: 1417-9].
76. Aicher A., Heeschen C., Mildner-Rihm C., et al. Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells. Nat Med 2003, 9:1370-1376.
77. Montorsi F., Guazzoni G., Strambi L.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 1997, 158:1408-1410.
78. Schwartz E.J., Wong P., Graydon R.J. Sildenafil preserves intracorporeal smooth muscle after radical retropubic prostatectomy. J Urol 2004, 171:771-774.
79. Mulhall J., Land S., Parker M., et al. The use of an erectogenic pharmacotherapy regimen following radical prostatectomy improves recovery of spontaneous erectile function. J Sex Med 2005, 2:532-540. [discussion: 540-2].
80. Mulhall J.P., Parker M., Waters B.W., et al. The timing of penile rehabilitation after bilateral nerve-sparing radical prostatectomy affects the recovery of erectile function. BJU Int 2010, 105:37-41.
81. Montorsi F., Brock G., Lee J., et al. Effect of nightly versus on-demand vardenafil on recovery of erectile function in men following bilateral nerve-sparing radical prostatectomy. Eur Urol 2008, 54:924-931.
82. Mulhall J.P. Does on-demand vardenafil improve erectile function recovery after radical prostatectomy?. Nat Clin Pract Urol 2009, 6:14-15.
83. Mulhall J.P., Bella A.J., Briganti A., et al. Erectile function rehabilitation in the radical prostatectomy patient. J Sex Med 2010, 7:1687-1698.
84. Bosshardt R.J., Farwerk R., Sikora R., et al. Objective measurement of the effectiveness, therapeutic success and dynamic mechanisms of the vacuum device. Br J Urol 1995, 75:786-791.
85. Raina R., Agarwal A., Ausmundson S., 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 2006, 18:77-81.
86. Dalkin B.L., Christopher B.A. Preservation of penile length after radical prostatectomy: early intervention with a vacuum erection device. Int J Impot Res 2007, 19:501-504.
87. Kohler T.S., Pedro R., Hendlin K., et al. A pilot study on the early use of the vacuum erection device after radical retropubic prostatectomy. BJU Int 2007, 100:858-862.
88. Yuan J., Lin H., Li P., et al. Molecular mechanisms of vacuum therapy in penile rehabilitation: a novel animal study. Eur Urol 2010, 58:773-780.
89. Costabile R.A., Spevak M., Fishman I.J., et al. Efficacy and safety of transurethral alprostadil in patients with erectile dysfunction following radical prostatectomy. J Urol 1998, 160:1325-1328.
90. Raina R., Agarwal A., Zaramo C.E., et al. Long-term efficacy and compliance of MUSE for erectile dysfunction following radical prostatectomy: SHIM (IIEF-5) analysis. Int J Impot Res 2005, 17:86-90.
91. Raina R., Pahlajani G., Agarwal A., et al. The early use of transurethral alprostadil after radical prostatectomy potentially facilitates an earlier return of erectile function and successful sexual activity. BJU Int 2007, 100:1317-1321.
92. McCullough A.R., Hellstrom W.G., Wang R., et al. Recovery of erectile function after nerve sparing radical prostatectomy and penile rehabilitation with nightly intraurethral alprostadil versus sildenafil citrate. J Urol 2010, 183:2451-2456.