REVIEW URRENT C OPINION
Current management of erectile dysfunction in prostate cancer survivors Benjamin A. Sherer and Laurence A. Levine
Purpose of review Although no standard management of erectile dysfunction in prostate cancer (CaP) survivors exists, many treatment options are available. This review summarizes the current understanding of the cause and management of erectile dysfunction in CaP survivors. Recent findings Erectile dysfunction after radical therapy for CaP may be more common than previously thought. Genetics and vascular comorbidities may have a significant impact on erectile dysfunction after CaP treatment. Although penile rehabilitation with medical modalities show good efficacy in motivated patients, the return of erectile function is never guaranteed with nonsurgical management. Penile prosthesis placement results in early return to sexual function after CaP treatment with high patient satisfaction rates. Various techniques allow safe placement of a three-piece penile prosthesis in patients with a history of pelvic surgery. Summary To optimize recovery of erectile function and prevent loss of penile length, penile rehabilitation should be initiated expeditiously after prostatectomy or radiation. In patients with refractory erectile dysfunction, dexterous and motivated patients remain excellent candidates for first and second-line medical therapies. However, early placement of a penile prosthesis following radical prostatectomy is now a proven and viable option. Keywords erectile dysfunction, penile prosthesis, penile rehabilitation, prostate cancer
INTRODUCTION Prostate cancer (CaP) remains the most common nonskin cancer in men in the USA. Men with CaP often struggle with sexual dysfunction, both before and after treatment. Effectively treating erectile dysfunction after radical prostatectomy or radiation therapy (XRT) can be a challenge. In this review, we focus on the most recent literature and summarize the current understanding of the cause and management of erectile dysfunction in CaP survivors. We also share management strategies for this difficult patient population. Following CaP treatment, 70% of men complain of worsening sexual function, which is frequently attributed to surgery or XRT [1]. However, as with all patients presenting with erectile dysfunction, it is important to view erectile dysfunction in cancer patients as multifactorial, with both psychogenic and organic components. Many CaP patients have vascular comorbidities (hypertension, diabetes, hyperlipidemia, smoking history) that are known risk factors for erectile dysfunction in all men. Helfand et al. recently reported
that men with biopsy-proven CaP had significantly worse decline in postbiopsy International Index of Erectile Function (IIEF) scores compared to men without cancer (10.1 versus 1.0, respectively). They concluded that a CaP diagnosis (not the biopsy itself) has a real adverse effect on sexual function, likely due to psychological distress associated with the diagnosis [2 ]. &
ERECTILE DYSFUNCTION AFTER RADICAL PROSTATECTOMY After Walsh et al. first introduced the nerve-sparing approach to radical prostatectomy, return of postprostatectomy erectile function became an attainable goal [3,4]. Unfortunately, nerve sparing is not Rush University Medical Center, Chicago, Illinois, USA Correspondence to Laurence Levine, 1725 W Harrison St Suite 352, Chicago, IL 60612, USA. Tel: +1 312 563 3480; fax: +1 312 563 5007; e-mail: [email protected] Curr Opin Urol 2014, 24:401–406 DOI:10.1097/MOU.0000000000000072
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KEY POINTS Erectile dysfunction in CaP survivors is often multifactorial and more common than previously thought.
seems to be directly related to the amount of radiation given near the penile bulb. This was recently confirmed by a review of eight previous studies describing EBRT-induced erectile dysfunction [13]. Erectile dysfunction after XRT may also have a strong genetic component. Kerns et al. [14 ] recently completed a two-stage genome-wide association study in men with new-onset erectile dysfunction after XRT. They identified 12 single-nucleotide polymorphisms of interest that were all located near genes involved in erectile function and concluded that some patients may be genetically susceptible to erectile dysfunction after XRT [14 ]. We are also learning that vascular comorbidities may have a significant role in erectile dysfunction after XRT. Wang et al. [15 ] recently reported data from 732 patients treated for CaP with XRT. Patients with three vascular comorbidities were almost twice (75%) as likely to develop erectile dysfunction at 4 years after XRT compared to patients with no vascular comorbidities (44%) [15 ]. &
Early penile rehabilitation should be initiated in men with erectile dysfunction after radical therapy for CaP to help optimize preservation or return of erectile function. Therapy should be directed based on patient goals, and medical options include PDE5is, ICI, and VED therapy. IPP implantation is a well established, effective treatment option for CaP survivors with erectile dysfunction and can be performed safely in patients with a history of pelvic surgery. In select patients, IPP placement as a first-line option for post radical prostatectomy erectile dysfunction has become a viable option.
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always successful. Among experienced surgeons (>1000 cases), potency rates range from 40 to 86% [5–7], and 90% of men will experience some level of erectile dysfunction in the early recovery phase [8,9]. Erectile dysfunction after radical prostatectomy is primarily caused by neuronal and vascular injury near the cavernous neurovascular bundle at the time of surgery. Subsequent neuropraxia, inflammation, and ischemia result in failure of spontaneous erections, which can lead to persistent hypoxia and corporal fibrosis. Without early intervention and penile rehabilitation, these pathophysiologic changes may be irreversible [8–11]. Earlier this year, van Den Bergh et al. compared erectile function in CaP patients on active surveillance versus patients treated with radical therapy. In the surveillance group, 20–30% of the men were sexually inactive as a result of erectile dysfunction compared to 86–91% in the radical prostatectomy group and 56–60% in the XRT group. Men on active surveillance had less erectile dysfunction, more sustained erections, and more frequent sexual activity [12 ]. With more widespread use of active surveillance for low-risk CaP, perhaps fewer men will suffer from sexual dysfunction caused by overtreatment of CaP. &
ERECTILE DYSFUNCTION AFTER RADIATION THERAPY Radiation therapy-induced erectile dysfunction is likely due to neurovascular bundle injury, and 402
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WORK-UP After a thorough history and physical exam, the following lab values are obtained: serum chemistries, fasting glucose, complete blood count, lipid profile, and morning serum total testosterone. If testosterone is abnormally low, serum-free testosterone, luteinizing hormone, and estradiol are measured.
HYPOGONADISM AND TESTOSTERONE REPLACEMENT Hypogonadism is present in more than 20% of men after radical prostatectomy and is often worsened by androgen deprivation therapy (ADT). Variability in sexual side-effects of ADT is likely attributable to age, testosterone levels, and overall physical functional status. Due to prolonged absence of erections, ADT may lead to corporal fibrosis and decreased penile length [16]. Many urologists avoid testosterone replacement therapy (TRT) in hypogonadal CaP survivors out of fear that TRT will increase the risk of CaP recurrence. This has become a point of controversy. However, current evidence supports the safe use of TRT in hypogonadal CaP survivors [17 ]. Most notably, Pastuszak et al. [18 ,19] recently reported use of TRT in 103 hypogonadal men following radical prostatectomy for CaP. Although TRT use did result in slight PSA elevation, there was no associated increase in cancer recurrence at a median of 27 months of follow-up [18 ]. Similarly, in a separate study, 13 hypogonadal CaP patients after XRT were treated safely with TRT [19]. &
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Erectile dysfunction in prostate cancer survivors Sherer and Levine
PENILE REHABILITATION Management of erectile dysfunction in CaP survivors should focus on preventing and/or reversing the aforementioned pathophysiologic insults caused by radical therapy. Much like an orthopedic patient should expect to undergo rehabilitation after a joint replacement, CaP patients should expect a period of rehabilitation to regain erectile function after CaP treatment. A strategy of staged therapy (with first, second, and third-line interventions) is offered with a detailed discussion of administration, side-effects, reversibility, relative invasiveness, and cost. There is no standard regimen for penile rehabilitation. Approaches are based on patient motivation to regain or maintain erectile function. In the most motivated men, daily evening low-dose phosphodiesterase type 5 inhibitors (PDE5is) are initiated within 1 week of radical prostatectomy. If there is no response to full-dose PDE5i at 1 month after radical prostatectomy, intracorporal injection therapy (ICI) is recommended, with a goal of experiencing 2–3 penetrable erections per week. At 1 month post radical prostatectomy or when urinary control improves (whichever comes first), 10 min of daily vacuum erection device (VED) therapy is introduced to fully engorge the penis. For less motivated patients, we determine patient goals and initiate as needed treatment with PDE5is, ICI, or VED. PDE5is (sildenafil tadalafil, vardenafil) are widely supported as first-line options for postprostatectomy erectile dysfunction. Sildenafil is often used because it is the only PDE5i supported by a randomized, blinded, placebo-controlled trial in this patient group. A study by Padma-Nathan et al. [20] showed a return of spontaneous erections in 27% of patients on sildenafil versus 4% on placebo at 48 months, and a 20% increase in successful vaginal penetration in the sildenafil group after 1 year. Although daily dosing of PDE5is is often prescribed, Montorsi et al. [21] found that vardenafil taken as needed had similar recovery of post radical prostatectomy erectile function when compared to daily use. In practice, tadalafil is frequently used because the extended half-life allows better patient compliance and a longer period of activity which may lead to more spontaneous nocturnal erections. PDE5is can also be used for rehabilitation in CaP patients treated with XRT. A recent systematic review of randomized controlled trials by Yang et al. [22 ] clearly demonstrates significant improvements in IIEF scores in CaP patients treated with PDE5is after XRT. In men poorly responsive to PDE5is, ICI with alprostadil alone or in combination with papaverine &
or phentolamine is an effective option. After radical prostatectomy, over 90% of patients on ICI develop erections sufficient for sexual intercourse. ICI therapy also helps induce recovery of spontaneous erections, but satisfaction rates (40%) tend to be lower than other modalities. Long-term (>3 years) data have revealed high dropout rates (50%), most often attributed to discomfort, fear, or inconvenience associated with injection [23–25]. Only small-scale trials on combination therapy have been completed, but concurrent use of PDE5is and ICI may expedite a return of erectile function, possibly via synergistic mechanisms. Combination therapy is a reasonable second-line approach if there is an inadequate response from either approach individually. Prescribers must be careful with dose titration, as there may be an increased risk of sideeffects when combining oral, injectable, and/or intraurethral agents. Vacuum erection device is also an important component of penile rehabilitation. With early VED use after radical prostatectomy, over 80% of patients successfully have intercourse and 60% have improvement in spontaneous erections. VED users have significant improvements (>10 points) in IIEF scores and less loss of penile length [26]. The device is reliable, relatively easy to use, and has few contraindications. An adequate erection is typically achieved in 1–3 min. Initial costs may be expensive, but devices are durable and are often covered by insurance plans. Disadvantages of VEDs include the indiscreet nature of the device and the development of cool erections, penile discoloration, pivoting of the penis at the base, and inability to ejaculate due to urethral constriction [27].
PENILE PROSTHESIS Inflatable penile prosthesis (IPP) implantation is a well established, well tolerated, and effective treatment option for CaP survivors with erectile dysfunction that is poorly responsive to medical therapy. A prosthesis does not interfere with urination, orgasm, or sensation and allows penile rigidity on an ‘aswanted’ basis. Compared to the aforementioned medical modalities, IPP after radical prostatectomy results in higher patient satisfaction, higher quality erections, greater quality of life, and more frequent sexual contact [23,28]. Despite these benefits, evaluation of the Surveillance Epidemiology and End Results – Medicare database revealed that penile prosthesis placement is severely underutilized in patients with postprostatectomy erectile dysfunction and accounts for only 0.78% of therapy offered to men with erectile dysfunction after radical prostatectomy [29].
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Infection is the most dreaded complication of IPP. Although average infection rates historically do not exceed 2–3%, risk of infection may be higher in those who require replacement or have underlying medical conditions (diabetes, vascular disease, smoking history) that predispose to infection. However, with newer antibiotic impregnated and hydrophilic-coated devices, prostheses are less prone to infection, even after revision/replacement surgery [30]. One year out from radical prostatectomy, many men report a 1–3 cm loss in penile length which can lead to negative self-image and contribute to overall decreased sexual function and desire [31,32]. After IPP placement, many men complain of additional length loss. For men concerned about loss of penile length, external traction therapy should be encouraged prior to prosthesis placement. Men who previously completed traction therapy benefit from maintenance or gain (up to 1.5 cm) of penile length after IPP placement (compared to pretraction stretched penile length) [33]. After radical prostatectomy via the open or robotic-assisted retropubic approach, the space of Retzius may be scarred or obliterated. Some surgeons avoid three-piece prosthesis placement in this setting due to fear of difficult or dangerous reservoir placement. However, Lane et al. [34] reported on a series of 115 successful three-piece IPP implants after radical prostatectomy through a single penoscrotal incision with no complications related to reservoir placement. Traditionally, to enter the space of Retzius, the surgeon first identifies the external inguinal ring. Then, finger pressure, Metzenbaum scissors, or a Kelly clamp is used to perforate the transversalis fascia allowing access to the retropubic space. A group of experienced implanters recently evaluated the space of Retzius in 28 cadavers. They found that the filled urinary bladder is only 2–4 cm from the internal inguinal ring and the external iliac vein is only 2.5–4 cm lateral to the ring. These data emphasize the importance of adequately emptying the bladder and avoiding extensive medial or lateral dissection during reservoir placement [35]. We recently described a modified technique, using Jorgensen scissors, which allows safe entry into the space of Retzius, even in patients with a history of radical prostatectomy. The tips of the Jorgensen scissors are placed at the level of the external inguinal ring just over the superior aspect of the pubis. In an upward lifting motion, the transversalis fascia is perforated with the tips pointing away from vessels, bladder, or bowel that may descend into this area following pelvic surgery [36]. 404
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If the space of Retzius cannot be entered bluntly or sharply due to severe scarring, ectopic reservoir placement is a viable option. In a recent survey of 95 implant surgeons, 81% believed that radical prostatectomy does make traditional reservoir placement more difficult and 97% felt that alternative reservoir placement techniques should be routinely taught [37]. Traditionally, ectopic placement was performed superficial to the posterior rectus sheath via a separate transverse hypogastric incision. New single-incision approaches to ectopic reservoir placement are gaining popularity. Traditional low-lying ectopic reservoir placement may result in a reservoir that is palpable and visible as a lower abdominal deformity. Morey and Wilson [38] have proposed an improved high submuscular placement of the reservoir. Through the penoscrotal incision, a Foerster lung clamp (or sponge clamp) is used to spread and elevate the rectus abdominis to the level of the umbilicus. This allows more cephalad reservoir placement that is invisible and only barely palpable. Morey et al. [39 ] reported successful high ectopic reservoir placement in 74 consecutive IPP patients. Ectopic reservoir placement can also be achieved via an infrapubic approach. Perito has demonstrated successful abdominal wall reservoir placement (typically posterior to the transversalis fascia) in over 2000 patients with minimal complications. In patients with a history of significant pelvic surgery, the reservoir can be placed anterior to the transversalis fascia with only a small increased risk (1.34 versus 0.09%) of future reservoir herniation [40 ,41]. Regardless of approach, IPP placement in CaP survivors is proven to be well tolerated and effective. Yet, many still consider IPP placement to be a thirdline option, used only when primary and secondary medical options fail. Recent literature indicates that urologists should start to more strongly consider earlier intervention with penile prosthesis in select patients. Early prosthesis implantation might prevent long periods of frustration after prostatectomy as men struggle with the delayed, often limited results of medical therapies. Recently, Megas et al. evaluated 54 men with erectile dysfunction after radical prostatectomy and compared those who underwent early IPP placement (6 months after radical prostatectomy, n ¼ 25) versus those taking a PDE5i (tadalafil, n ¼ 29). IIEF scores were significantly higher in the IPP group at 6, 12, and 24 months following IPP placement. The change in IIEF score from the first time-point immediately after radical prostatectomy to 2 years was significantly greater (P < 0.001) in the IPP group (IIEF 20.4 from 1.3) compared with the &
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Erectile dysfunction in prostate cancer survivors Sherer and Levine &&
tadalafil group (IIEF 8.1 from 2.4) [42 ]. These data lend strong support to a new concept of early IPP placement as a first-line option for post-radical prostatectomy erectile dysfunction. Perhaps prosthesis placement should no longer be thought of as a ‘last resort’.
CONCLUSION Erectile dysfunction is common in CaP patients, especially those treated with radical prostatectomy or XRT. Management of erectile dysfunction in CaP survivors can be difficult, but various effective management options exist. To optimize recovery of erectile function and prevent loss of penile length, penile rehabilitation should be initiated expeditiously after prostatectomy or XRT. In patients with refractory erectile dysfunction, dexterous and motivated patients remain excellent candidates for first and second-line medical therapies, whereas other patients might instead benefit from IPP placement. Various techniques are now available to allow safe placement of a three-piece IPP reservoir in patients with prior pelvic surgery. Early placement of an IPP within 1 year following radical prostatectomy is now a proven and viable option, especially in patients with moderate to severe preoperative erectile dysfunction. Acknowledgements None. Conflicts of interest B.A.S.: No conflicts of interest. L.A.L.: Consultant for Coloplast, Consultant for Auxillium, Chief Medical Officer for Absorption Pharmaceuticals, Stock/Stock Options with Absorption Pharmaceuticals.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Meyer JP, Gillat DA, Lockyer R, MacDonagh R. The effect of erectile dysfunction on quality of life of men after radical prostatectomy. BJU Int 2003; 92:929–931. 2. Helfand BT, Glaser AP, Rimar K, et al. Prostate cancer diagnosis is associated & with an increased risk of erectile dysfunction after prostate biopsy. BJU Int 2013; 111:38–43. This prospective study reveals that psychological impact of a cancer diagnosis likely leads to worsening erectile function, even before treatment of CaP. 3. Walsh PC, Donker PJ. Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 1982; 128:492–497. 4. Quinlan DM, Epstein JI, Carter BS, Walsh PC. Sexual function following radical prostatectomy: influence of preservation of neurovascular bundles. J Urol 1991; 145:998–1002. 5. Zippe CD, Pahlajani G. Penile rehabilitation following radical prostatectomy: role of early intervention and chronic therapy. Urol Clin North Am 2007; 34:601–618.
6. Catalona WJ, Basler JW. Return of erections and urinary continence following nerve sparing radical retropubic prostatectomy. J Urol 1993; 150:905– 907. 7. Mulhall JP, Bella AJ, Briganti A, et al. Erectile dysfunction rehabilitation in the radical prostatectomy patient. J Sex Med 2010; 7:1687–1698. 8. Mulhall JP, Mongentalar A. Penile rehabilitation should become the norm for radical prostatectomy patients. J Sex Med 2007; 4:538–543. 9. User HM, Hairston JH, Zelner DJ, et al. Penile weight and cell subtype specific changes in a postradical prostatectomy model of erectile dysfunction. J Urol 2003; 169:1175–1179. 10. Fraiman MC, Lepor H, McCullough AR. Changes in penile morphometrics in men with erectile dysfunction after nerve-sparing radical retropubic prostatectomy. Mol Urol 1999; 3:109–115. 11. Walsh PC, Marschke P, Ricker D, Burnett AL. Patient-reported urinary continence and sexual function after anatomic radical prostatectomy. Urology 2000; 55:58–61. 12. van Den Bergh CN, Korfage IJ, Roobol MJ, et al. Sexual function with localized & prostate cancer: active surveillance vs. radical therapy. BJU Int 2012; 110:1032–1039. This is the first study to compare erectile function in CaP patients undergoing active surveillance versus radical prostatectomy or XRT. The authors confirm that, compared to active surveillance, radical therapy leads to significantly worse erectile function 1 year after CaP treatment. 13. Rivin Del Campo E, Thomas K, Weinberg V, Roach M. Erectile dysfunction after radiotherapy for prostate cancer: a model assessing the conflicting literature on dose-volume effects. Int J Impotence Res 2013; 25:161–165. 14. Kerns SL, Stock R, Stone N, et al. A 2-stage genome-wide association study & to identify single nucleotide polymorphisms associated with development of erectile dysfunction following radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys 2013; 85:e21–e28. This case-control genotyping study reveals 12 single-nucleotide polymorphisms of interest that may contribute to erectile dysfunction after prostate brachytherapy. Future studies linking genetic factors to erectile dysfunction risk may lead to new treatment modalities. 15. Wang Y, Liu T, Rossi PJ, et al. Influence of vascular comorbidities and race on & erectile dysfunction after prostate cancer radiotherapy. J Sex Med 2013; 10:2108–2114. This large-scale retrospective study confirms that patients with multiple vascular comorbidities are at significantly increased risk of erectile dysfunction after prostate XRT. 16. Higano CS. Side effects of androgen deprivation therapy: monitoring and minimizing toxicity. Urology 2003; 61:32–38. 17. Landau D, Tsakok T, Aylwin S, Hughes S. Should testosterone replacement & be offered to hypogonadal men treated previously for prostatic carcinoma? Clin Endocrinol 2012; 76:179–181. This review of CaP patients treated with TRT for hypogonadism after radical CaP treatment reveals a very low-risk CaP recurrence. Collectively, the data from small series included in this review argue against the longstanding taboo that TRT should never be used in CaP patients. 18. Pastuszak A, Pearlman AM, Lai WS, et al. Testosterone replacement therapy && in patients with prostate cancer after radical prostatectomy. J Urol 2013; 190:639–644. This study provides new data that support the safety and efficacy of TRT in hypogonadal men with prostate cancer previously treated with radical prostatectomy. Although TRT increases PSA slightly, there is no obvious increased risk of cancer recurrence in hypogonadal CaP survivors treated with TRT. 19. Pastuszak AW, Perlman AM, Godoy G, et al. Testosterone replacement therapy in the setting of prostate cancer treated with radiation. Int J Impotence Res 2013; 25:24–28. 20. Padma-Nathan H, McCullough AR, Levine LA, et al. Randomized, doubleblind, placebo-controlled study of postoperative nightly sildenafil citrate for prevention of erectile dysfunction after bilateral nerve-sparing radical prostatectomy. Int J Impot Res 2008; 20:479–486. 21. 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. 22. Yang L, Qian S, Liu L, et al. Phosphodiesterase-5 inhibitors could be & efficacious in the treatment of erectile dysfunction after radiotherapy for prostate cancer: a systematic review and meta-analysis. Urol Int 2013; 90:339–347. This systematic review of four randomized controlled trials confirms that PDE5is are an excellent first-line option for CaP patients with erectile dysfunction after XRT. 23. Menard J, Tremeaux JC, Faix A, et al. Erectile function and sexual satisfaction before and after penile prosthesis implantation in radical prostatectomy patients: a comparison with patients with vasculogenic erectile dysfunction. J Sex Med 2011; 8:3479–3486. 24. Montorsi F, Guazzoni G, Strambi LF, 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. 25. Raina R, Lakin MM, Thukral A, 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 2003; 15:318–322.
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Reconstructive urology and the cancer survivor 26. Dalkin BL, Christopher BA. Preservation of penile length after radical prostatectomy: early intervention with a vacuum erection device. Int J Impot Res 2007; 19:501–504. 27. Hoyland K, Vasdev N, Adshead J. The use of vacuum erection devices in erectile dysfunction after radical prostatectomy. Rev Urol 2013; 15:67–71. 28. Ramwash HJ, Morgentaler A, Covino N, et al. Quality of life following simultaneous placement of penile prosthesis with radical prostatectomy. J Urol 2005; 174:1395–1398. 29. Tal R, Jacks LM, Elkin E, Mulhall JP. Penile implant utilization following treatment for prostate cancer: analysis of the SEER-Medicare database. J Sex Med 2011; 8:1797–1804. 30. Nehra A, Carson CC, Chapin AK, Ginkel AM. Long-term infection outcomes of 3-piece antibiotic impregnated penile prostheses used in replacement implant surgery. J Urol 2012; 188:899–903. 31. McCullogh A. Penile change following radical prostatectomy: size, smooth muscle atrophy and curve. Curr Urol Rep 2008; 9:492–499. 32. Gontero P, Galzerano M, Bartoletti R, et al. New insights into the pathogenesis of penile shortening after radical prostatectomy and the role of postoperative sexual function. J Urol 2007; 178:602–607. 33. Levine LA, Rybak J. Traction therapy for men with shortened penis prior to penile prosthesis implantation: a pilot study. J Sex Med 2011; 8:2112–2117. 34. Lane BR, Abouassaly R, Angermeier K, Montague D. Three-piece inflatable penile prostheses can be safely implanted after radical prostatectomy through a transverse scrotal incision. Urology 2007; 70:539–542. 35. Henry G, Hsaio W, Karpman E, et al. A guide for inflatable penile prosthesis reservoir placement: pertinent anatomical measurements of the retropubic space. J Sex Med 2014; 11:273–278. 36. Levine LA, Hoeh MP. Review of penile prosthetic reservoir: complications and presentation of a modified reservoir placement technique. J Sex Med 2012; 9:2759–2769.
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37. Karpman E, Sadeghi-Nejad H, Gerard H, et al. Current opinions on alternative reservoir placement for inflatable penile prosthesis among members of the sexual medicine society of North America. J Sex Med 2013; 10:2115–2120. 38. Morey A, Wilson SK. Submuscular reservoir placement. J Sex Med 2013; 10:1672–1675. 39. Morey A, Cefalu C, Hudak S. High submuscular placement of urologic & prosthetic balloons and reservoirs via transscrotal approach. J Sex Med 2013; 10:603–610. This retrospective review describes successful ectopic reservoir placement in a high submuscular abdominal space. This technique allows a safe alternative to reservoir placement in the space of retzius during three-piece IPP placement via the penoscrotal approach. 40. Stember DS, Garber BB, Perito PE. Outcomes of abdominal wall reservoir & placement in inflatable penile prosthesis implantation: a safe and efficacious alternative to the space of retzius. J Sex Med 2014; 11:605–612. As another alternative to retropubic reservoir placement, this retrospective study describes a safe successful ectopic abdominal reservoir placement either anterior or posterior to the transversalis fascia. 41. Perito EP, Wilson SK. Traditional (retroperitoneal) and abdominal wall (ectopic) reservoir placement. J Sex Med 2011; 8:656–659. 42. Megas G, Papadopoulos G, Stathouros G, et al. Comparison of efficacy and && satisfaction profile, between penile prosthesis implantation and oral PDE5 inhibitor tadalafil therapy, in men with nerve-sparing radical prostatectomy erectile dysfunction. BJU Int 2013; 112:E169–E176. This prospective study compares early IPP placement (within 1 year of radical prostatectomy) versus PDE5i treatment after prostatectomy. Early IPP placement results in superior erectile frequency, firmness, duration, and penetration ability. Early IPP placement after radical prostatectomy is a viable option for patients who wish to remain sexually active without waiting for possibly limited and delayed benefits from medical modalities.
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Current management of erectile dysfunction in prostate cancer survivors Benjamin A. Sherer and Laurence A. Levine
Purpose of review Although no standard management of erectile dysfunction in prostate cancer (CaP) survivors exists, many treatment options are available. This review summarizes the current understanding of the cause and management of erectile dysfunction in CaP survivors. Recent findings Erectile dysfunction after radical therapy for CaP may be more common than previously thought. Genetics and vascular comorbidities may have a significant impact on erectile dysfunction after CaP treatment. Although penile rehabilitation with medical modalities show good efficacy in motivated patients, the return of erectile function is never guaranteed with nonsurgical management. Penile prosthesis placement results in early return to sexual function after CaP treatment with high patient satisfaction rates. Various techniques allow safe placement of a three-piece penile prosthesis in patients with a history of pelvic surgery. Summary To optimize recovery of erectile function and prevent loss of penile length, penile rehabilitation should be initiated expeditiously after prostatectomy or radiation. In patients with refractory erectile dysfunction, dexterous and motivated patients remain excellent candidates for first and second-line medical therapies. However, early placement of a penile prosthesis following radical prostatectomy is now a proven and viable option. Keywords erectile dysfunction, penile prosthesis, penile rehabilitation, prostate cancer
INTRODUCTION Prostate cancer (CaP) remains the most common nonskin cancer in men in the USA. Men with CaP often struggle with sexual dysfunction, both before and after treatment. Effectively treating erectile dysfunction after radical prostatectomy or radiation therapy (XRT) can be a challenge. In this review, we focus on the most recent literature and summarize the current understanding of the cause and management of erectile dysfunction in CaP survivors. We also share management strategies for this difficult patient population. Following CaP treatment, 70% of men complain of worsening sexual function, which is frequently attributed to surgery or XRT [1]. However, as with all patients presenting with erectile dysfunction, it is important to view erectile dysfunction in cancer patients as multifactorial, with both psychogenic and organic components. Many CaP patients have vascular comorbidities (hypertension, diabetes, hyperlipidemia, smoking history) that are known risk factors for erectile dysfunction in all men. Helfand et al. recently reported
that men with biopsy-proven CaP had significantly worse decline in postbiopsy International Index of Erectile Function (IIEF) scores compared to men without cancer (10.1 versus 1.0, respectively). They concluded that a CaP diagnosis (not the biopsy itself) has a real adverse effect on sexual function, likely due to psychological distress associated with the diagnosis [2 ]. &
ERECTILE DYSFUNCTION AFTER RADICAL PROSTATECTOMY After Walsh et al. first introduced the nerve-sparing approach to radical prostatectomy, return of postprostatectomy erectile function became an attainable goal [3,4]. Unfortunately, nerve sparing is not Rush University Medical Center, Chicago, Illinois, USA Correspondence to Laurence Levine, 1725 W Harrison St Suite 352, Chicago, IL 60612, USA. Tel: +1 312 563 3480; fax: +1 312 563 5007; e-mail: [email protected] Curr Opin Urol 2014, 24:401–406 DOI:10.1097/MOU.0000000000000072
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KEY POINTS Erectile dysfunction in CaP survivors is often multifactorial and more common than previously thought.
seems to be directly related to the amount of radiation given near the penile bulb. This was recently confirmed by a review of eight previous studies describing EBRT-induced erectile dysfunction [13]. Erectile dysfunction after XRT may also have a strong genetic component. Kerns et al. [14 ] recently completed a two-stage genome-wide association study in men with new-onset erectile dysfunction after XRT. They identified 12 single-nucleotide polymorphisms of interest that were all located near genes involved in erectile function and concluded that some patients may be genetically susceptible to erectile dysfunction after XRT [14 ]. We are also learning that vascular comorbidities may have a significant role in erectile dysfunction after XRT. Wang et al. [15 ] recently reported data from 732 patients treated for CaP with XRT. Patients with three vascular comorbidities were almost twice (75%) as likely to develop erectile dysfunction at 4 years after XRT compared to patients with no vascular comorbidities (44%) [15 ]. &
Early penile rehabilitation should be initiated in men with erectile dysfunction after radical therapy for CaP to help optimize preservation or return of erectile function. Therapy should be directed based on patient goals, and medical options include PDE5is, ICI, and VED therapy. IPP implantation is a well established, effective treatment option for CaP survivors with erectile dysfunction and can be performed safely in patients with a history of pelvic surgery. In select patients, IPP placement as a first-line option for post radical prostatectomy erectile dysfunction has become a viable option.
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always successful. Among experienced surgeons (>1000 cases), potency rates range from 40 to 86% [5–7], and 90% of men will experience some level of erectile dysfunction in the early recovery phase [8,9]. Erectile dysfunction after radical prostatectomy is primarily caused by neuronal and vascular injury near the cavernous neurovascular bundle at the time of surgery. Subsequent neuropraxia, inflammation, and ischemia result in failure of spontaneous erections, which can lead to persistent hypoxia and corporal fibrosis. Without early intervention and penile rehabilitation, these pathophysiologic changes may be irreversible [8–11]. Earlier this year, van Den Bergh et al. compared erectile function in CaP patients on active surveillance versus patients treated with radical therapy. In the surveillance group, 20–30% of the men were sexually inactive as a result of erectile dysfunction compared to 86–91% in the radical prostatectomy group and 56–60% in the XRT group. Men on active surveillance had less erectile dysfunction, more sustained erections, and more frequent sexual activity [12 ]. With more widespread use of active surveillance for low-risk CaP, perhaps fewer men will suffer from sexual dysfunction caused by overtreatment of CaP. &
ERECTILE DYSFUNCTION AFTER RADIATION THERAPY Radiation therapy-induced erectile dysfunction is likely due to neurovascular bundle injury, and 402
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WORK-UP After a thorough history and physical exam, the following lab values are obtained: serum chemistries, fasting glucose, complete blood count, lipid profile, and morning serum total testosterone. If testosterone is abnormally low, serum-free testosterone, luteinizing hormone, and estradiol are measured.
HYPOGONADISM AND TESTOSTERONE REPLACEMENT Hypogonadism is present in more than 20% of men after radical prostatectomy and is often worsened by androgen deprivation therapy (ADT). Variability in sexual side-effects of ADT is likely attributable to age, testosterone levels, and overall physical functional status. Due to prolonged absence of erections, ADT may lead to corporal fibrosis and decreased penile length [16]. Many urologists avoid testosterone replacement therapy (TRT) in hypogonadal CaP survivors out of fear that TRT will increase the risk of CaP recurrence. This has become a point of controversy. However, current evidence supports the safe use of TRT in hypogonadal CaP survivors [17 ]. Most notably, Pastuszak et al. [18 ,19] recently reported use of TRT in 103 hypogonadal men following radical prostatectomy for CaP. Although TRT use did result in slight PSA elevation, there was no associated increase in cancer recurrence at a median of 27 months of follow-up [18 ]. Similarly, in a separate study, 13 hypogonadal CaP patients after XRT were treated safely with TRT [19]. &
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Erectile dysfunction in prostate cancer survivors Sherer and Levine
PENILE REHABILITATION Management of erectile dysfunction in CaP survivors should focus on preventing and/or reversing the aforementioned pathophysiologic insults caused by radical therapy. Much like an orthopedic patient should expect to undergo rehabilitation after a joint replacement, CaP patients should expect a period of rehabilitation to regain erectile function after CaP treatment. A strategy of staged therapy (with first, second, and third-line interventions) is offered with a detailed discussion of administration, side-effects, reversibility, relative invasiveness, and cost. There is no standard regimen for penile rehabilitation. Approaches are based on patient motivation to regain or maintain erectile function. In the most motivated men, daily evening low-dose phosphodiesterase type 5 inhibitors (PDE5is) are initiated within 1 week of radical prostatectomy. If there is no response to full-dose PDE5i at 1 month after radical prostatectomy, intracorporal injection therapy (ICI) is recommended, with a goal of experiencing 2–3 penetrable erections per week. At 1 month post radical prostatectomy or when urinary control improves (whichever comes first), 10 min of daily vacuum erection device (VED) therapy is introduced to fully engorge the penis. For less motivated patients, we determine patient goals and initiate as needed treatment with PDE5is, ICI, or VED. PDE5is (sildenafil tadalafil, vardenafil) are widely supported as first-line options for postprostatectomy erectile dysfunction. Sildenafil is often used because it is the only PDE5i supported by a randomized, blinded, placebo-controlled trial in this patient group. A study by Padma-Nathan et al. [20] showed a return of spontaneous erections in 27% of patients on sildenafil versus 4% on placebo at 48 months, and a 20% increase in successful vaginal penetration in the sildenafil group after 1 year. Although daily dosing of PDE5is is often prescribed, Montorsi et al. [21] found that vardenafil taken as needed had similar recovery of post radical prostatectomy erectile function when compared to daily use. In practice, tadalafil is frequently used because the extended half-life allows better patient compliance and a longer period of activity which may lead to more spontaneous nocturnal erections. PDE5is can also be used for rehabilitation in CaP patients treated with XRT. A recent systematic review of randomized controlled trials by Yang et al. [22 ] clearly demonstrates significant improvements in IIEF scores in CaP patients treated with PDE5is after XRT. In men poorly responsive to PDE5is, ICI with alprostadil alone or in combination with papaverine &
or phentolamine is an effective option. After radical prostatectomy, over 90% of patients on ICI develop erections sufficient for sexual intercourse. ICI therapy also helps induce recovery of spontaneous erections, but satisfaction rates (40%) tend to be lower than other modalities. Long-term (>3 years) data have revealed high dropout rates (50%), most often attributed to discomfort, fear, or inconvenience associated with injection [23–25]. Only small-scale trials on combination therapy have been completed, but concurrent use of PDE5is and ICI may expedite a return of erectile function, possibly via synergistic mechanisms. Combination therapy is a reasonable second-line approach if there is an inadequate response from either approach individually. Prescribers must be careful with dose titration, as there may be an increased risk of sideeffects when combining oral, injectable, and/or intraurethral agents. Vacuum erection device is also an important component of penile rehabilitation. With early VED use after radical prostatectomy, over 80% of patients successfully have intercourse and 60% have improvement in spontaneous erections. VED users have significant improvements (>10 points) in IIEF scores and less loss of penile length [26]. The device is reliable, relatively easy to use, and has few contraindications. An adequate erection is typically achieved in 1–3 min. Initial costs may be expensive, but devices are durable and are often covered by insurance plans. Disadvantages of VEDs include the indiscreet nature of the device and the development of cool erections, penile discoloration, pivoting of the penis at the base, and inability to ejaculate due to urethral constriction [27].
PENILE PROSTHESIS Inflatable penile prosthesis (IPP) implantation is a well established, well tolerated, and effective treatment option for CaP survivors with erectile dysfunction that is poorly responsive to medical therapy. A prosthesis does not interfere with urination, orgasm, or sensation and allows penile rigidity on an ‘aswanted’ basis. Compared to the aforementioned medical modalities, IPP after radical prostatectomy results in higher patient satisfaction, higher quality erections, greater quality of life, and more frequent sexual contact [23,28]. Despite these benefits, evaluation of the Surveillance Epidemiology and End Results – Medicare database revealed that penile prosthesis placement is severely underutilized in patients with postprostatectomy erectile dysfunction and accounts for only 0.78% of therapy offered to men with erectile dysfunction after radical prostatectomy [29].
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Reconstructive urology and the cancer survivor
Infection is the most dreaded complication of IPP. Although average infection rates historically do not exceed 2–3%, risk of infection may be higher in those who require replacement or have underlying medical conditions (diabetes, vascular disease, smoking history) that predispose to infection. However, with newer antibiotic impregnated and hydrophilic-coated devices, prostheses are less prone to infection, even after revision/replacement surgery [30]. One year out from radical prostatectomy, many men report a 1–3 cm loss in penile length which can lead to negative self-image and contribute to overall decreased sexual function and desire [31,32]. After IPP placement, many men complain of additional length loss. For men concerned about loss of penile length, external traction therapy should be encouraged prior to prosthesis placement. Men who previously completed traction therapy benefit from maintenance or gain (up to 1.5 cm) of penile length after IPP placement (compared to pretraction stretched penile length) [33]. After radical prostatectomy via the open or robotic-assisted retropubic approach, the space of Retzius may be scarred or obliterated. Some surgeons avoid three-piece prosthesis placement in this setting due to fear of difficult or dangerous reservoir placement. However, Lane et al. [34] reported on a series of 115 successful three-piece IPP implants after radical prostatectomy through a single penoscrotal incision with no complications related to reservoir placement. Traditionally, to enter the space of Retzius, the surgeon first identifies the external inguinal ring. Then, finger pressure, Metzenbaum scissors, or a Kelly clamp is used to perforate the transversalis fascia allowing access to the retropubic space. A group of experienced implanters recently evaluated the space of Retzius in 28 cadavers. They found that the filled urinary bladder is only 2–4 cm from the internal inguinal ring and the external iliac vein is only 2.5–4 cm lateral to the ring. These data emphasize the importance of adequately emptying the bladder and avoiding extensive medial or lateral dissection during reservoir placement [35]. We recently described a modified technique, using Jorgensen scissors, which allows safe entry into the space of Retzius, even in patients with a history of radical prostatectomy. The tips of the Jorgensen scissors are placed at the level of the external inguinal ring just over the superior aspect of the pubis. In an upward lifting motion, the transversalis fascia is perforated with the tips pointing away from vessels, bladder, or bowel that may descend into this area following pelvic surgery [36]. 404
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If the space of Retzius cannot be entered bluntly or sharply due to severe scarring, ectopic reservoir placement is a viable option. In a recent survey of 95 implant surgeons, 81% believed that radical prostatectomy does make traditional reservoir placement more difficult and 97% felt that alternative reservoir placement techniques should be routinely taught [37]. Traditionally, ectopic placement was performed superficial to the posterior rectus sheath via a separate transverse hypogastric incision. New single-incision approaches to ectopic reservoir placement are gaining popularity. Traditional low-lying ectopic reservoir placement may result in a reservoir that is palpable and visible as a lower abdominal deformity. Morey and Wilson [38] have proposed an improved high submuscular placement of the reservoir. Through the penoscrotal incision, a Foerster lung clamp (or sponge clamp) is used to spread and elevate the rectus abdominis to the level of the umbilicus. This allows more cephalad reservoir placement that is invisible and only barely palpable. Morey et al. [39 ] reported successful high ectopic reservoir placement in 74 consecutive IPP patients. Ectopic reservoir placement can also be achieved via an infrapubic approach. Perito has demonstrated successful abdominal wall reservoir placement (typically posterior to the transversalis fascia) in over 2000 patients with minimal complications. In patients with a history of significant pelvic surgery, the reservoir can be placed anterior to the transversalis fascia with only a small increased risk (1.34 versus 0.09%) of future reservoir herniation [40 ,41]. Regardless of approach, IPP placement in CaP survivors is proven to be well tolerated and effective. Yet, many still consider IPP placement to be a thirdline option, used only when primary and secondary medical options fail. Recent literature indicates that urologists should start to more strongly consider earlier intervention with penile prosthesis in select patients. Early prosthesis implantation might prevent long periods of frustration after prostatectomy as men struggle with the delayed, often limited results of medical therapies. Recently, Megas et al. evaluated 54 men with erectile dysfunction after radical prostatectomy and compared those who underwent early IPP placement (6 months after radical prostatectomy, n ¼ 25) versus those taking a PDE5i (tadalafil, n ¼ 29). IIEF scores were significantly higher in the IPP group at 6, 12, and 24 months following IPP placement. The change in IIEF score from the first time-point immediately after radical prostatectomy to 2 years was significantly greater (P < 0.001) in the IPP group (IIEF 20.4 from 1.3) compared with the &
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Erectile dysfunction in prostate cancer survivors Sherer and Levine &&
tadalafil group (IIEF 8.1 from 2.4) [42 ]. These data lend strong support to a new concept of early IPP placement as a first-line option for post-radical prostatectomy erectile dysfunction. Perhaps prosthesis placement should no longer be thought of as a ‘last resort’.
CONCLUSION Erectile dysfunction is common in CaP patients, especially those treated with radical prostatectomy or XRT. Management of erectile dysfunction in CaP survivors can be difficult, but various effective management options exist. To optimize recovery of erectile function and prevent loss of penile length, penile rehabilitation should be initiated expeditiously after prostatectomy or XRT. In patients with refractory erectile dysfunction, dexterous and motivated patients remain excellent candidates for first and second-line medical therapies, whereas other patients might instead benefit from IPP placement. Various techniques are now available to allow safe placement of a three-piece IPP reservoir in patients with prior pelvic surgery. Early placement of an IPP within 1 year following radical prostatectomy is now a proven and viable option, especially in patients with moderate to severe preoperative erectile dysfunction. Acknowledgements None. Conflicts of interest B.A.S.: No conflicts of interest. L.A.L.: Consultant for Coloplast, Consultant for Auxillium, Chief Medical Officer for Absorption Pharmaceuticals, Stock/Stock Options with Absorption Pharmaceuticals.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Meyer JP, Gillat DA, Lockyer R, MacDonagh R. The effect of erectile dysfunction on quality of life of men after radical prostatectomy. BJU Int 2003; 92:929–931. 2. Helfand BT, Glaser AP, Rimar K, et al. Prostate cancer diagnosis is associated & with an increased risk of erectile dysfunction after prostate biopsy. BJU Int 2013; 111:38–43. This prospective study reveals that psychological impact of a cancer diagnosis likely leads to worsening erectile function, even before treatment of CaP. 3. Walsh PC, Donker PJ. Impotence following radical prostatectomy: insight into etiology and prevention. J Urol 1982; 128:492–497. 4. Quinlan DM, Epstein JI, Carter BS, Walsh PC. Sexual function following radical prostatectomy: influence of preservation of neurovascular bundles. J Urol 1991; 145:998–1002. 5. Zippe CD, Pahlajani G. Penile rehabilitation following radical prostatectomy: role of early intervention and chronic therapy. Urol Clin North Am 2007; 34:601–618.
6. Catalona WJ, Basler JW. Return of erections and urinary continence following nerve sparing radical retropubic prostatectomy. J Urol 1993; 150:905– 907. 7. Mulhall JP, Bella AJ, Briganti A, et al. Erectile dysfunction rehabilitation in the radical prostatectomy patient. J Sex Med 2010; 7:1687–1698. 8. Mulhall JP, Mongentalar A. Penile rehabilitation should become the norm for radical prostatectomy patients. J Sex Med 2007; 4:538–543. 9. User HM, Hairston JH, Zelner DJ, et al. Penile weight and cell subtype specific changes in a postradical prostatectomy model of erectile dysfunction. J Urol 2003; 169:1175–1179. 10. Fraiman MC, Lepor H, McCullough AR. Changes in penile morphometrics in men with erectile dysfunction after nerve-sparing radical retropubic prostatectomy. Mol Urol 1999; 3:109–115. 11. Walsh PC, Marschke P, Ricker D, Burnett AL. Patient-reported urinary continence and sexual function after anatomic radical prostatectomy. Urology 2000; 55:58–61. 12. van Den Bergh CN, Korfage IJ, Roobol MJ, et al. Sexual function with localized & prostate cancer: active surveillance vs. radical therapy. BJU Int 2012; 110:1032–1039. This is the first study to compare erectile function in CaP patients undergoing active surveillance versus radical prostatectomy or XRT. The authors confirm that, compared to active surveillance, radical therapy leads to significantly worse erectile function 1 year after CaP treatment. 13. Rivin Del Campo E, Thomas K, Weinberg V, Roach M. Erectile dysfunction after radiotherapy for prostate cancer: a model assessing the conflicting literature on dose-volume effects. Int J Impotence Res 2013; 25:161–165. 14. Kerns SL, Stock R, Stone N, et al. A 2-stage genome-wide association study & to identify single nucleotide polymorphisms associated with development of erectile dysfunction following radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys 2013; 85:e21–e28. This case-control genotyping study reveals 12 single-nucleotide polymorphisms of interest that may contribute to erectile dysfunction after prostate brachytherapy. Future studies linking genetic factors to erectile dysfunction risk may lead to new treatment modalities. 15. Wang Y, Liu T, Rossi PJ, et al. Influence of vascular comorbidities and race on & erectile dysfunction after prostate cancer radiotherapy. J Sex Med 2013; 10:2108–2114. This large-scale retrospective study confirms that patients with multiple vascular comorbidities are at significantly increased risk of erectile dysfunction after prostate XRT. 16. Higano CS. Side effects of androgen deprivation therapy: monitoring and minimizing toxicity. Urology 2003; 61:32–38. 17. Landau D, Tsakok T, Aylwin S, Hughes S. Should testosterone replacement & be offered to hypogonadal men treated previously for prostatic carcinoma? Clin Endocrinol 2012; 76:179–181. This review of CaP patients treated with TRT for hypogonadism after radical CaP treatment reveals a very low-risk CaP recurrence. Collectively, the data from small series included in this review argue against the longstanding taboo that TRT should never be used in CaP patients. 18. Pastuszak A, Pearlman AM, Lai WS, et al. Testosterone replacement therapy && in patients with prostate cancer after radical prostatectomy. J Urol 2013; 190:639–644. This study provides new data that support the safety and efficacy of TRT in hypogonadal men with prostate cancer previously treated with radical prostatectomy. Although TRT increases PSA slightly, there is no obvious increased risk of cancer recurrence in hypogonadal CaP survivors treated with TRT. 19. Pastuszak AW, Perlman AM, Godoy G, et al. Testosterone replacement therapy in the setting of prostate cancer treated with radiation. Int J Impotence Res 2013; 25:24–28. 20. Padma-Nathan H, McCullough AR, Levine LA, et al. Randomized, doubleblind, placebo-controlled study of postoperative nightly sildenafil citrate for prevention of erectile dysfunction after bilateral nerve-sparing radical prostatectomy. Int J Impot Res 2008; 20:479–486. 21. 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. 22. Yang L, Qian S, Liu L, et al. Phosphodiesterase-5 inhibitors could be & efficacious in the treatment of erectile dysfunction after radiotherapy for prostate cancer: a systematic review and meta-analysis. Urol Int 2013; 90:339–347. This systematic review of four randomized controlled trials confirms that PDE5is are an excellent first-line option for CaP patients with erectile dysfunction after XRT. 23. Menard J, Tremeaux JC, Faix A, et al. Erectile function and sexual satisfaction before and after penile prosthesis implantation in radical prostatectomy patients: a comparison with patients with vasculogenic erectile dysfunction. J Sex Med 2011; 8:3479–3486. 24. Montorsi F, Guazzoni G, Strambi LF, 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. 25. Raina R, Lakin MM, Thukral A, 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 2003; 15:318–322.
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Reconstructive urology and the cancer survivor 26. Dalkin BL, Christopher BA. Preservation of penile length after radical prostatectomy: early intervention with a vacuum erection device. Int J Impot Res 2007; 19:501–504. 27. Hoyland K, Vasdev N, Adshead J. The use of vacuum erection devices in erectile dysfunction after radical prostatectomy. Rev Urol 2013; 15:67–71. 28. Ramwash HJ, Morgentaler A, Covino N, et al. Quality of life following simultaneous placement of penile prosthesis with radical prostatectomy. J Urol 2005; 174:1395–1398. 29. Tal R, Jacks LM, Elkin E, Mulhall JP. Penile implant utilization following treatment for prostate cancer: analysis of the SEER-Medicare database. J Sex Med 2011; 8:1797–1804. 30. Nehra A, Carson CC, Chapin AK, Ginkel AM. Long-term infection outcomes of 3-piece antibiotic impregnated penile prostheses used in replacement implant surgery. J Urol 2012; 188:899–903. 31. McCullogh A. Penile change following radical prostatectomy: size, smooth muscle atrophy and curve. Curr Urol Rep 2008; 9:492–499. 32. Gontero P, Galzerano M, Bartoletti R, et al. New insights into the pathogenesis of penile shortening after radical prostatectomy and the role of postoperative sexual function. J Urol 2007; 178:602–607. 33. Levine LA, Rybak J. Traction therapy for men with shortened penis prior to penile prosthesis implantation: a pilot study. J Sex Med 2011; 8:2112–2117. 34. Lane BR, Abouassaly R, Angermeier K, Montague D. Three-piece inflatable penile prostheses can be safely implanted after radical prostatectomy through a transverse scrotal incision. Urology 2007; 70:539–542. 35. Henry G, Hsaio W, Karpman E, et al. A guide for inflatable penile prosthesis reservoir placement: pertinent anatomical measurements of the retropubic space. J Sex Med 2014; 11:273–278. 36. Levine LA, Hoeh MP. Review of penile prosthetic reservoir: complications and presentation of a modified reservoir placement technique. J Sex Med 2012; 9:2759–2769.
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37. Karpman E, Sadeghi-Nejad H, Gerard H, et al. Current opinions on alternative reservoir placement for inflatable penile prosthesis among members of the sexual medicine society of North America. J Sex Med 2013; 10:2115–2120. 38. Morey A, Wilson SK. Submuscular reservoir placement. J Sex Med 2013; 10:1672–1675. 39. Morey A, Cefalu C, Hudak S. High submuscular placement of urologic & prosthetic balloons and reservoirs via transscrotal approach. J Sex Med 2013; 10:603–610. This retrospective review describes successful ectopic reservoir placement in a high submuscular abdominal space. This technique allows a safe alternative to reservoir placement in the space of retzius during three-piece IPP placement via the penoscrotal approach. 40. Stember DS, Garber BB, Perito PE. Outcomes of abdominal wall reservoir & placement in inflatable penile prosthesis implantation: a safe and efficacious alternative to the space of retzius. J Sex Med 2014; 11:605–612. As another alternative to retropubic reservoir placement, this retrospective study describes a safe successful ectopic abdominal reservoir placement either anterior or posterior to the transversalis fascia. 41. Perito EP, Wilson SK. Traditional (retroperitoneal) and abdominal wall (ectopic) reservoir placement. J Sex Med 2011; 8:656–659. 42. Megas G, Papadopoulos G, Stathouros G, et al. Comparison of efficacy and && satisfaction profile, between penile prosthesis implantation and oral PDE5 inhibitor tadalafil therapy, in men with nerve-sparing radical prostatectomy erectile dysfunction. BJU Int 2013; 112:E169–E176. This prospective study compares early IPP placement (within 1 year of radical prostatectomy) versus PDE5i treatment after prostatectomy. Early IPP placement results in superior erectile frequency, firmness, duration, and penetration ability. Early IPP placement after radical prostatectomy is a viable option for patients who wish to remain sexually active without waiting for possibly limited and delayed benefits from medical modalities.
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