ICUD Consultation on Urethral Strictures: Posterior Urethral Stenosis After Treatment of Prostate Cancer

Supplement Article Chapter 8: Posterior Urethral Stenosis After Treatment of Prostate Cancer Sender Herschorn, Sean Elliott, Michael Coburn, Hunter Wessells, and Leonard Zinman Posterior urethral stenosis can result from radical prostatectomy in approximately 5%-10% of patients (range 1.4%-29%). Similarly, 4%-9% of men after brachytherapy and 1%-13% after external beam radiotherapy will develop stenosis. The rate will be greater after combination therapy and can exceed 40% after salvage radical prostatectomy. Although postradical prostatectomy stenoses mostly develop within 2 years, postradiotherapy stenoses take longer to appear. Many result in storage and voiding symptoms and can be associated with incontinence. The evaluation consists of a workup similar to that for lower urinary tract symptoms, with additional testing to rule out recurrent or persistent prostate cancer. Treatment is usually initiated with an endoscopic approach commonly involving dilation, visual urethrotomy with or without laser treatment, and, possibly, UroLume stent placement. Open surgical urethroplasty has been reported, as well as urinary diversion for recalcitrant stenosis. A proposed algorithm illustrating a graded approach has been provided. UROLOGY -: -e-, 2013.
2013 Elsevier Inc.

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ccording to data published for 2010 by the American Cancer Society, prostate cancer affects 217,730 men annually, and the median age at diagnosis is 68 years.1 The 5-year relative survival for localized disease has been 99.1%, and only 1 in 6 men diagnosed with prostate cancer will die of prostate cancer. According to the 2007 Surveillance Epidemiology and End Results database, among men newly diagnosed with prostate cancer, radical prostatectomy (RP) will be selected as the initial therapy for 36%, external beam radiotherapy (EBRT) in 20%, brachytherapy (BT) in 10%, and BT plus EBRT in 4% (Elliott SP, M.D., Jarosek SA, R.N., Virnig BA, Ph.D., M.P.H., written communication, October 10, 2011.). Cryotherapy and thermal ablation have been used less commonly. Because these data only follow-up patients through 6 months, it has been difficult to calculate how many, in the modern era, subsequently undergo additional therapy. Treatment trends in the management of low-risk prostate cancer have also varied over time, as reflected in the Cancer of the Prostate Strategic Urologic Research Endeavour database report (Fig. 1).2

Chairs: Sender Herschorn, Canada, and Sean Elliott, United States Members: Michael Coburn, United States, Hunter Wessells, United States, and Leonard Zinman, United States Financial Disclosure: S.H. receives royalties from Cook Medical. The remaining authors declare that they have no relevant financial interests. From the Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada; the Department of Urology, University of Minnesota, Minneapolis, MN; the Division of Urology, Baylor College of Medicine, Houston, TX; the Department of Urology, University of Washington, Seattle, Washington; and the Lahey Clinic Medical Center, Burlington, MA. Reprint requests: Sender Herschorn, B.Sc., M.D.C.M., F.R.C.S.C., University of Toronto, Sunnybrook Health Sciences Centre, Room A309, 2075 Bayview Avenue, Toronto, ON M4N 3M5 Canada. E-mail: [email protected] Submitted: June 5, 2013, accepted (with revisions): August 16, 2013

ª 2013 Elsevier Inc. All Rights Reserved

As the male urethra courses through the prostate, it is susceptible to injury during prostate cancer treatment. Stenosis of the posterior urethra can lead to recurring problems of urinary retention, dysuria, and urinary frequency and incontinence, with a negative effect on patients’ quality of life. Because the probability of long-term survival after prostate cancer treatment is high, it is important for practitioners to understand the frequency with which posterior urethral stenosis (PUS) occurs after prostate cancer treatment to properly counsel patients regarding the implications of their treatment choice. It is likewise critical to better define the comparative effectiveness of treatment options to manage therapy-related PUS.

MATERIAL AND METHODS The committee assessed and reviewed the epidemiology, evaluation, and management of PUS after localized treatment of prostate cancer. Studies from the past 15 years from peerreviewed journals, abstracts from scientific meetings, and published data searches manually and electronically formed the basis of the present review. The search terms used included “prostate cancer,” “radical prostatectomy,” “radiation, brachytherapy,” “cryotherapy,” and “high-intensity focused ultrasound (HIFU).” As a general term, PUS can be subdivided into bladder neck, vesicourethral anastomotic, prostatic urethral, membranous, prostatomembranous, and bulbomembranous (BM) stenoses. Obliterative lesions can be seen in virtually all these entities. The published data have not always differentiated among the various anatomic locations for stenosis. However, post-RP stenosis will usually be located at the vesicourethral anastomosis and in the sections discussing RP, it is referred to as such. Specific recommendations and grades of recommendations (GR) were made in accordance with the published results and were determined by the levels of evidence (LE).3 Consensus of the committee determined the recommendations, which can be 0090-4295/13/$36.00 http://dx.doi.org/10.1016/j.urology.2013.08.036

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with a perineal or robotic compared with than an open retropubic approach.7,15,16 The risk of complications is much greater after salvage RP than after primary RP, and BNC can occur in 42% of such patients. It has been well documented that most BNC after RP occurs within 2 years of surgery.6,19 Overall, the likelihood of BNC after RP ranges from 1.4%-29% of patients. Most contemporary series have reported BNC rates of 5%-10%.4,10 Publications of robotic-assisted prostatectomy to date7,20 have suggested that BNC rates of 1%-3% are common; however, longer follow-up is needed to confirm these results.

Figure 1. Treatment trends among patients with low-risk prostate cancer aged 75 years. P values for significant trends were as follows: external beam radiotherapy (EBRT), P ¼ .0005; brachytherapy (Brachy), P ¼ .0001; primary androgen deprivation therapy (PADT), P ¼ .0492; and watchful waiting (WW), P ¼ .0048. The trend for radical prostatectomy (RP) was not significant (P ¼ .96). Data reprinted with permission from Cooperberg et al.2 found at the end of the present report. Recommendations for future research were also included.

EPIDEMIOLOGY AND RISK FACTORS Radical Prostatectomy PUS after RP manifests as a narrowing of the anastomosis between the bladder neck and the membranous urethra, commonly termed “bladder neck contracture” (BNC), which occurs in 1.4%-29% of patients after RP (Table 1).4-8 The number of RPs performed in the United States exceeded 80,000 in 2001 and has continued to remain constant despite concerns about the public health benefit of prostate-specific antigen screening. Using conservative estimates from published studies, it has been calculated that >5000 men will require treatment each year for post-RP strictures of the posterior urethra and bladder neck. BNC after RP results from fibrotic narrowing of the reconfigured and/or spared bladder neck.6,9 The proposed mechanisms have included anastomotic tension, inflammation from urinary extravasation, poor tissue handling, and ischemia. The risk factors identified in case series and large prospective studies can be divided into preoperative, intraoperative, and postoperative categories and have included excessive blood loss, type of bladder neck dissection, postoperative urinary leakage, adjuvant radiotherapy (RT), previous transurethral resection of the prostate (TURP), current cigarette smoking, older age, obesity, and surgeon experience4-6,8-18 (Table 2). Better visualization for accomplishing an epithelial-toepithelial anastomosis might explain the lower BNC rates 2

Radiotherapy RT can be delivered by way of an external beam source (EBRT) or using brachytherapy seeds (BT). BT can be delivered as short-acting nonpermanent seeds (high-doserate BT [HDR-BT]) or longer half-life seeds that are permanently implanted (low-dose-rate BT [LDR-BT]). Radiation causes its therapeutic effect by damaging the deoxyribonucleic acid of actively dividing cells. The longterm effect results from the persistent effect of oxidative stress. Adverse effects such as PUS are secondary to chronic fibrosis and progressive endarteritis in poorly oxygenated submucosal and muscular tissues, with eventual tissue scarring.21,22 Although surgical PUS occurs primarily within the first 2 years after treatment,6,19 PUS due to RT continues to accumulate during the long term. Because of the high prevalence of patients living long term after pelvic RT and the accumulation of urinary RT adverse effects over an extended time horizon, it is imperative that we better understand the delayed urinary adverse effects of pelvic RT, including PUS. Incidence After BT. Numerous reports have shown that urethral stenosis is the most frequent late complication reported in patients after BT.23-25 The incidence of urethral stenosis after HDR-BT in published studies has been 0%-14%,25-27 with most series reporting rates of 4%-9% at 5 years. The rate has been slightly greater when combined with EBRT.28 The urethral stricture rates reported in RT studies have generally identified only strictures resulting in symptoms and might therefore have underestimated the true rate of urethral stricture development. Incidence After EBRT. Urethral stenosis occurs after 3dimensional conformal RT in 1%-13% of patients, and the risk increases with long-term follow-up: <7% with <5 years of follow-up but 10%-18% with 5-10 years of follow-up.29-32 The risk of stenosis is increased in those with a history of TURP before EBRT.30 Although intensity-modulated RT has successfully reduced rectal toxicity through improved targeting of RT beams, urinary symptoms can actually be worse after intensity-modulated RT than after 3-dimensional conformal RT.32 UROLOGY

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Table 1. Incidence of bladder neck contracture after radical prostatectomy Investigator Year Modality Borboroglu 2000 et al4

RP

Design Retrospective cohort

n 467

Hu et al5 Erickson et al6

2003 2009

Carlsson et al7 Gillitzer et al8

2010 ORRP vs Retrospective 1738 (485 open, LARRP cohort 1253 robotic) 2010 RPP vs Retrospective 2918 (866 RPP RRP cohort vs 2052 RRP)

RP RRP

Retrospective cohort

2,292 4,132

Rate (%)

Follow-up

Accrual

Comment

>12 mo 1991-1999 Risk factors: current smoking, CAD, and EBL in MVLR model Univariate: also DM, OR time; obesity was not recorded 22-28 <2 y 2.5 44 mo 1983-2000 Multivariate predictors: year of surgery and nonenerve-sparing approach 4.5 and 0.2 2002-2007 No risk factors crude discussed 3.8 (RPP); Median 1997-2007 Multivariate logistic 5.5 (RRP) 52 mo regression risk factors: Gleason score, TURP, prostate volume, tumor stage and grade, transfusions, acute urinary retention treated with suprapubic tube, surgical technique 11

CAD, coronary artery disease; DM, diabetes mellitus; EBL, estimated blood loss; LARRP, laparoscopically assisted robotic radical prostatectomy; MVLR, multivariate logistic regression model; OR, operation time; ORRP, open radical retropubic prostatectomy; RP, radical prostatectomy (retropubic, perineal, or unspecified); RPP, radical perineal prostatectomy; RRP, radical retropubic prostatectomy; TURP, transurethral resection of the prostate.

The incidence of PUS after adjuvant or salvage EBRT has been 3%-8.5%.33,34

patients developed urethral strictures, and all were in the BM urethra.

Urethral Stricture due to BT. Pathophysiology. Urethral obstruction immediately after BT implantation is due to therapy-induced inflammation of the prostate. Although the problem is common, it is generally self-limited.35 However, urethral stenosis can develop and is the most common long-term serious urinary adverse effect of BT. This underscores the importance of understanding the delayed urinary adverse effects of pelvic RT.

Risk Factors After BT. The risk factors for urethral stricture after BT included older age, nonwhite race, low income, more comorbidities, combination therapy with EBRT or hormonal therapy, and a history of previous TURP. Older age was not found to be a significant risk factor in the series by Pellizzon et al.39 Several other series have confirmed that the risk of urethral stricture after BT is increased by combination therapy with EBRT. A review of the Cancer of the Prostate Strategic Urologic Research Endeavour multi-institutional registry revealed a crude risk of treatment of urethral stricture of 1.8% after BT and 5.2% after BT pus EBRT, with a median followup of 2.7 years. Most of the strictures have occurred at the membranous urethra, and early investigators noted the risk was related to the dose delivered to the prostatic apex.37,40,41 Others have countered that the apical dose does not matter; however, a close read of these more recent series will demonstrate that their apical dose was much lower than that in the earlier series.26,27 Of the suggested clinical predictive factors for urethral strictures after prostate BT, previous TURP has consistently been a risk factor for late genitourinary toxicity in patients receiving either HDR-BT or LDR-BT.38 Retrospective data have suggested that EBRT or LDRBT for prostate carcinoma in those with a history of

Time Frame After BT. A Surveillance Epidemiology and End ResultseMedicare examination showed that within 2 years of BT, 30% of patients were listed with a diagnosis of urinary obstruction and 10% had a claim for a procedure performed for obstruction, most often dilation of a urethral stricture.28 This compares with median latency periods of 24-36 months in the HDRBT population.24,36 Stricture Location After BT. The relatively specific sensitivity of the BM urethra to RT damage appears paradoxical, because this area (lying approximately 20 mm distal to the prostatic apex) should theoretically receive a far lower radiation dose than the prostatic urethra, which rarely develops stenosis.25,37 In the study by Sullivan et al,38 the stricture location was the BM urethra in 92.1%. In the study by Merrick et al,37 29 of 1186 UROLOGY

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Table 2. Risk factors for vesicourethral anastomotic stenosis after radical prostatectomy Investigator

Risk Factor

n

VUAS Rate (%)

48 467 467

Higher with increased age

4592 8837 246 467 2918 90 143 100 4132

Lower with MIS

Preoperative 17

Thiel et al Borboroglu et al4 Borboroglu et al4

Age Comorbidity Smoking Intraoperative

16

Rabbani et al Hu et al15 Thiel et al17 Borboroglu et al4 Gillitzer et al8 Gallo et al12 Levy et al18 Srougi et al13 Erickson et al6

Open vs MIS Blood loss Anastomosis Vest sutures BN eversion Surgeon volume

Higher with more EBL No difference Worse with vest sutures No difference Lower with high volume

Postoperative 9

Surya et al Levy et al18 Ozu et al14 Gillitzer et al8

Extravasation Catheter removal Acute retention

156 143 55 2918

Conflicting No difference Higher if treated with suprapubic vs Foley catheter

BN, bladder neck; MIS, minimally invasive surgery; VUAS, vesicourethral anastomotic stenosis; other abbreviation as in Table 1.

previous TURP resulted in a 15% risk of developing a urethral stricture or BNC, significantly greater than the 6% rate for those without a history of TURP.42 In another series of >400 patients receiving HDR-BT, all patients with late grade 3 and 4 genitourinary complications (including 7.4% with urethral strictures) had undergone either TURP or urethrotomy within 1 year before or after BT.43 Patients should be counseled regarding their increased risk of urethral stricture formation when considering BT. A history of hypertension was also a significant predictive factor for stricture formation38 and a plausible finding based on toxicity studies from other tumor sites in which hypertension has been shown to increase late severe toxicity, especially in conjunction with diabetes mellitus.44 It seems prudent, however, to manage vascular risk factors aggressively in patients scheduled to undergo HDR-BT. Compared with HDR-BT, urethral strictures seem to occur less frequently as a complication after LDR-BT and conformal EBRT. Modern LDR-BT series have reported an incidence of 0%-5.5%.26,37,45 Cryotherapy Cryotherapy involves the ablation of tissue by local induction of extremely low temperatures and is used a therapeutic modality for prostate cancer. In 1996, the American Urological Association recognized cryotherapy as a therapeutic option for prostate cancer and removed the “investigational” label from this procedure. Improvements in the technology of cryotherapy have allowed more efficient freezing of the prostate gland and reduced damage to the surrounding tissues. Thus, this modality offers a minimally invasive treatment with 4

low morbidity, minimal blood loss, a short hospital stay, and high rates of negative post-treatment biopsy findings.46-49 The main mechanism of cytotoxicity produced by cryotherapy is the induction of targeted areas of coagulative necrosis in the prostate gland. The freezing injury comprises direct mechanical shock, osmotic shock, and cellular hypoxia. The mechanisms of action include protein denaturation by dehydration, transfer of water from the intracellular space to the extracellular space, rupture of cell membranes from ice crystal expansion, a toxic concentration of cellular constituents, thermal shock from rapid super-cooling, slow thawing, vascular stasis, and increased apoptosis.46,50 One of the most important recent advances has been real-time ultrasound-guided placement of the cryoprobes and continuous visualization of the freezing. Biplanar transrectal ultrasonography allows for transverse and longitudinal views of the prostate and of the frozen area. The views are interchangeable during the procedure. Frozen tissue differs from unfrozen tissue in sound impedance, resulting in a strong echo reflection at the interface of the normal and frozen tissue.46 To protect the urethra and external urinary sphincter, minimize urethral sloughing, and prevent urinary incontinence, a urethral warming device should be used during prostate cryotherapy.46 Urethral Sloughing and/or Urethral Stricture After Cryotherapy. Tissue sloughing has been reported to occur in 3.8%-23% of cases.49,51 With the current refinement of the freezing technique, however, symptomatic sloughing has been a minor and infrequent event, occurring in <3% of patients. Treatment consists of antibiotics and adequate urinary drainage. Intermittent self-catheterization UROLOGY

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can lead to spontaneous tissue dislodgment. However, transurethral resection or removal of the necrotic tissue could be required if the condition persists.46 Urethral stricture rarely forms after cryotherapy if an effective urethral warming device has been used.46 However, if extensive tissue sloughing occurs, stricture at the bladder neck or the middle of the prostatic urethra can occur. In those cases of stenosis, transurethral incision or balloon dilation will usually be successful. Calcification of the stricture can also occur, necessitating transurethral resection. The use of an effective urethral warming catheter is essential to minimize the risk of tissue sloughing.46,52,53 Rectourethral fistula has been reported to occur in 0%-3% of patients.48,49,53 It has most commonly been seen in patients who had previously undergone RT. In recent series, the rate has been 0% owing to the high accuracy using transrectal ultrasonography and temperature monitoring of the rectal wall.46

High-intensity Focused Ultrasound HIFU is a new technology, and, with time, the incidence of urethral stricture could decrease, just as it did with BT and cryotherapy. However, with the present technology, PUS has been reported to occur in 7%-30% of those undergoing HIFU as first-line treatment54,55 and in 20% of those undergoing salvage HIFU.56,57 Epidemiology and Risk Factors With HIFU. HIFU is a minimally invasive alternative technique for the management of both benign prostatic hypertrophy (or hyperplasia [BPH]) and localized primary or recurrent prostate cancer.58 It was originally introduced in 1992 as a thermoablation treatment option for BPH. The target effect is achieved by the emission of a high-energy ultrasound beam, which is focused on the prostate through a transrectal probe imaging the lesion using simultaneous ultrasonography, and delivering a generated temperature in the range of 100 C, leading to immediate coagulative necrosis.59 The most common adverse effect is the development of bladder outlet obstruction from edema and sloughing of necrotic tissue. To reduce the incidence of urinary retention, the concept of combined TURP and HIFU in 1 session was introduced.60,61 This reduced the catheterization time to 7 days, with subsequent reports having similar findings, revealing a decrease in the rate of bladder outlet obstruction of 2%-8% by adding initial TURP to HIFU therapy. Long-term follow-up, however, might demonstrate a delayed appearance of bladder outlet obstruction, because many patients do not develop obstructive disease for 15 months to 9 years.62 A trend was seen toward lower rates of bladder outlet obstruction (12.5%) when a longer interval between TURP and HIFU was used, especially if a large amount of tissue had been resected. The long-term effect of HIFU on the prostate is increased fibrosis, leading to 80%-100% of UROLOGY

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bladder neck scarring in patients with multiple previous episodes of recurrent obstruction. HIFU Summary. Bladder outlet obstruction occurred in 25% of patients after the first HIFU thermal ablation of localized prostatic cancer, and 5% had obstruction from multiple episodes. Necrotic tissue accounted for most of the first episodes. TURP performed 3 months after HIFU resulted in a marked decrease in bladder outlet obstruction (30% vs 12.5%). The presence of late post-HIFU BNC has varied from 3.6%-4.8%, irrespective of the addition of TURP to the original HIFU. These were classic vesical neck stenoses requiring conventional remedies of cold knife or laser urethrotomy.

Post-transurethral Prostatectomy BNC has been a disappointing, but consistently occurring, complication of all forms of prostate surgery.63 The etiology is not well understood but is undoubtedly related to the type of procedure (surgical, endoscopic, or ablative), prostate size, extravasation of urine, catheterization duration, and a history of previous prostate surgery. BNC can develop as late as 15-19 months after TURP but most cases develop within 2-8 months. BNC is usually identified by the development or persistence of voiding or storage symptoms after initial improvement.64 In the presence of continued bladder overactivity or a large postvoid residual urine volume, bladder dysfunction should first be distinguished from obstructing BNC.65 A meta-analysis of randomized controlled trials of various forms of surgical techniques used for BPH reported an overall rate of 2%-4%.66,67 The occurrence of BNC after TURP has changed during the past 2 decades, from 15% reported in a randomized prospective trial in 199568 to the significant decrease of 3.4% reported in 2004.68,69 That study also confirmed the observation that the prostate volume had a significant effect on the incidence of this complication. Patients with a low prostate resection weight (average 11  3.7 g) will be predisposed to bladder neck stenosis. The development of BNC had no correlation with surgeon experience or time of resection. The one most consistent observation was the development of BNC in those with a small prostate. The mechanism leading to this complication after TURP is still unclear, but the key factors proposed have included extensive resection and fulguration at the bladder neck, undermining the bladder neck, a large resection loop that generates excessive heat, and the presence of a small intraurethral adenoma.70 Transurethral incision of the prostate, introduced by Orandi71 in 1973 as an alternative to TURP, has been used primarily in patients with BPH if the gland does not exceed 30 g.72 Lee et al,64 in a study of 1470 patients, showed that TURP plus transurethral incision of the prostate could completely prevent the incidence of BNC if the resected adenoma weight was >30 g; the incidence of BNC was 7.7% if the resected weight was <30 g.69 5

Table 3. Suggested workup for posterior urethral stenosis after treatment of prostate cancer

History Physical examination: general, abdominal, genital, perineal, rectal, and neurologic, as required Laboratory testing Urinalysis with or without urine culture PSA measurement to rule out persistent or recurrent cancer Renal function tests (creatinine, BUN), if clinically indicated Uroflowmetry and post-void residual measurement Cystoscopy: retrograde and antegrade (if necessary) Imaging studies If unable to delineate length, location, severity, and complexity of stenosis: Retrograde urethrography and, possibly, voiding cystourethrography Renal and/or ureteral ultrasonography, if indicated Prostate imaging (TRUS), if necessary Other (CT/MRI) if disease is thought to be outside urinary tract (eg, cancer, abscess, prostatic calcification, fistula) Urodynamic evaluation, if necessary BUN, blood urea nitrogen; CT/MRI, computed tomography/magnetic resonance imaging; PSA, prostate-specific antigen; TRUS, transrectal ultrasonography.

EVALUATION AND PREOPERATIVE MANAGEMENT Men who develop PUS after treatment of prostate cancer can present with lower urinary tract symptoms (LUTS), both storage and voiding. The usual timing of the onset of the stenosis is dependent on the type of treatment administered. With RT, both EBRT and BT, it usually occurs within a few years. After RP (with or without EBRT), TURP, or interventions such as HIFU and cryotherapy that result in tissue sloughing, the symptoms of obstructed voiding can occur immediately after catheter removal or, more likely, within the first year. As yet, no evidenced-based recommended workup is available for new or persistent LUTS after treatment of prostate cancer. The following recommendations were determined from the recommendations for evaluation of LUTS in older men from the Sixth International Consultation on New Developments in Prostate Cancer and Prostate Diseases.73 These recommendations were also incorporated into the updated American Urological Association “Clinical Guidelines in the Management of BPH.”74 Additional recommendations represent the consensus of the committee. The workup for LUTS after treatment of prostate cancer is determined by the onset and severity of the symptoms. The development of PUS is usually associated with de novo, recurrent, or persistent LUTS. The main complaint can relate to an obstructed voiding pattern, such as a reduced force of stream, although other voiding and/or storage symptoms can predominate. A careful evaluation before the initiation of intervention should be undertaken. The timing of the intervention should be determined by the severity of the symptoms and evaluation findings. As an example, acute urinary retention after Foley catheter removal after radical retropubic prostatectomy might merit immediate cystoscopy and recatheterization. 6

In general, evaluation of suspected PUS after the treatment of prostate cancer includes (Table 3) the following: History (LUTS, validated questionnaires, voiding diary); the reader is also referred to Chapter 2, “Evaluation and Follow-up” Physical examination: general, abdominal, genital, perineal, rectal, and neurologic, as required Laboratory investigations Urinalysis: the presence of hematuria could indicate additional pathologic features, such as bladder tumor or complications of bladder outlet obstruction with a bladder calculus Urine culture and sensitivity (or leukocyte esterase screening test): this is necessary before instrumentation; infection could represent or contribute to the underlying cause of the voiding symptoms Prostate-specific antigen measurement to rule out persistent or recurrent cancer Renal function tests should be considered (creatinine, blood urea nitrogen), if clinically indicated Uroflowmetry and postvoid residual urine volume measurement Cystoscopy: allows lower urinary tract evaluation to assess for anterior urethral pathologic findings, sphincter integrity, foreign bodies, calculi, recurrent cancer, and other areas of stenosis and/or stricture Antegrade endoscopy should be considered to assess the anatomy proximal to the stenosis Imaging If unable to delineate the length, location, severity, and complexity of the stenosis Retrograde urethrography and, possibly, voiding cystourethrography, depending on the complexity. UROLOGY

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In general, imaging should be reserved for cases in which complete cystourethroscopy cannot be performed for various reasons (multiple strictures encountered, complete urethral obliteration, patient unwilling to undergo procedure in ambulatory setting). Performed separately, each provides useful information in evaluating the level of the stricture, but both done simultaneously could allow for evaluation of the whole urinary tract proximal and distal to the stricture level Renal and/or ureteral ultrasonography, if clinically indicated Prostate imaging (transrectal ultrasonography), if necessary to exclude abscess, calcification, and cancer recurrence Other (computed tomography/magnetic resonance imaging): if disease is believed to be more extensive (eg, cancer, abscess, prostatic calcification, fistula) Urodynamic evaluation: Reserved for specific cases to evaluate all types of voiding dysfunction, as needed

TREATMENT Strictures related to prostate cancer therapy result from a number of interacting mechanisms, including anatomic tissue loss from surgery, postoperative fibrosis, ionizing radiation, and electrical injury. Thus, treatment must take into consideration the surrounding anatomic characteristics, capacity for healing, and ability to support transfer of adjacent or distant donor tissue sites. The continence status of the patient and the relationship of the stricture to the external sphincter further complicate decision making about the treatment of PUS. Taken together, the many variables influencing patient choice argue for an individualized approach to the problem. Treatment Approach After RT The increased rate of complications associated with reconstruction of the radiated urethra underlies the initial selection of endoscopic therapy for the management of strictures after all RT modalities. Strictures after primary EBRT or BT most commonly involve the membranous or bulbar urethra.75 Rectourethral fistulas can complicate such strictures, but their treatment is beyond the scope of our report. Endoscopic treatment of radiation-induced PUS has been associated with recurrence rates of approximately 40%-60%, regardless of the location or etiology.76,77 In a large series reporting the stricture rate after BT,38 PUS was initially treated with either dilation (n ¼ 15) or internal urethrotomy (n ¼ 20). With a median follow-up of 16 months, 49% required second-line endoscopic therapy and 9% had third-line therapy in the form of intermittent self-catheterization (ISC) or urethroplasty. Overall, 10.5% of the patients with stricture developed urinary incontinence severe enough to require daily pad use. UROLOGY

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Urethroplasty might prove successful when endoscopic approaches fail. In case series, the success rates have been 73%-90%.75,78,79 Excision and primary anastomosis of radiation-induced stenosis proved more successful than other techniques, including stents.80 Just as in other parts of the urethra, success is more likely with shorter strictures. EBRT was identified as a consistent risk factor for failure.75,78 Management of Post-RP Vesicourethral Anastomotic Strictures The definitive management of post-RP vesicourethral anastomotic strictures (VUASs) generally requires endourologic or open surgical intervention. Local urethral dilation might facilitate temporary urethral catheter drainage or the initiation of intermittent selfcatheterization. A critical consideration in the treatment of these strictures is the risk of urinary incontinence. Surgical Management—Endourologic. Interruption of the stenotic bladder neck is the central premise of endourologic procedures for VUAS. Most anastomotic strictures after radical retropubic prostatectomy occur within 6 months. For early postoperative stenoses, urethral dilation is indicated. In all such cases, cystoscopic placement of a guidewire and the use of sounds, straight or curved co-axial dilators,81,82 or long filiform will reduce the risk of false passage or disruption of a recent anastomosis. The success of dilation in these circumstances has varied, although they usually allow spontaneous voiding, and some series have reported longterm favorable outcomes with this approach.81,83,84 For strictures that fail initial dilation or occur >6 weeks after RP, a stepwise approach with the goal of preserving urinary continence is advocated. Reported series of patients treated with endourologic techniques are listed in Table 4.4,9,11,17,20,81,82,84-92 A low-energy incision has been recommended: either direct vision internal urethrotomy (DVIU) or holmium:yttrium-aluminum-garnet laser.86-88 Dalkin11 described deep incisions at the 4- and 8-o’clock positions with a cold-knife urethrotome from the proximal area of the contracture to its distal extent. The incisions should be continued down to bleeding tissue, and a monopolar cautery electrode can be used if hemostasis is required.93 The role of intermittent self-catheterization in reducing recurrence after dilation has not been established for VUAS. Transurethral electrosurgical incision has been used when dilation and DVIU have failed. The greater risk of incontinence should be considered against the likelihood of long-term urethral patency.94 Highly symptomatic patients are generally willing to accept the risks of incontinence and the necessity of subsequent artificial urinary sphincter or male sling surgery. The outcomes of endourologic treatment of post-RP VUAS are listed in Table 4. Failure of repeated DVIU for VUAS is an extremely challenging problem. Because most open reconstructive techniques compromise 7

Table 4. Endourologic management of vesicourethral anastomotic stenosis Treatment Dilation

Investigators

Ramchandani et al,83 1994 Geary et al,84 1995 Thiel et al,17 2006 Park et al,81 2001 Herschorn et al,82 2007 DVIU Surya et al,9 1990 Dalkin,11 1996 Borboroglu et al,4 2000 Gonzalgo et al,20 2005 TUR Popken et al,85 1998 Ho:YAG laser Hayashi et al,86 2005 Lagerveld et al,87 2005 Eltahawy et al,88 2008 Endourethroplasty Chiou et al,89 1996 Kuyumcuoglu et al,90 2010 UroLume Elliott et al,91 2002 Magera et al,92 2009 Endourethroplasty Chiou et al,89 1996 Kuyumcuoglu et al,90 2010

n

Success (%) Evidence

27

59

80

38

3

43 100 26

92.3

18 18

62

3

17 52

88 58

3 3

24 100

3

3 100

4

10 100

4

24

83

3

2 100

4

11

55

9

88

25

52

2 100 11

55

3

4 3

DVIU, direct vision internal urethrotomy; Ho, holmium; TUR, transurethral resection; YAG, yttrium-aluminum-garnet.

continence,94,95 alternatives such as endourethroplasty89,90 and stenting have been proposed as adjuncts to DVIU. Vanni et al96 reported using a triradial incision in the bladder neck at the 9-, 12-, and 3-o’clock positions, preceded and followed by interstitial injection of mitomycin C as an antiproliferative agent to prevent recurrence. A full-thickness incision with a cold knife through the fibrotic ring into the periprostatic fat was then followed by 10 days of an indwelling catheter. This approach has had a success rate of 84% in patients with refractory BNC that has failed previous DVIU. The permanent metallic UroLume stent (American Medical Systems, Minnetonka, MN) has been used sparingly because of challenges with tissue regrowth or intrusion and migration into the bladder. In selected cases of refractory VUAS, several investigators have described successful UroLume implantation.91,92 Although the UroLume has usually been described in conjunction with immediate or subsequent anti-incontinence surgery, the 8

Table 5. Open surgical management of vesicourethral anastomotic stenosis Treatment Urethroplasty

Success (%) Approach Evidence

Investigator

n

Wessells et al,95 1998 Theodoros et al,97 2000 Elliott et al,78 2006 Herschorn,98 2007

4

100

AP or P

4

6

83

AP

4

10

70

AP

3

5

100

A or AP

4

A, abdominal; AP, abdominoperineal; P, perineal.

use of the shortest possible UroLume stent might preserve sphincter function. Surgical Management—Open. The most severe postradical retropubic prostatectomy anastomotic stenoses require an aggressive reconstructive approach. Temporary suprapubic cystostomy drainage will allow planning for reconstruction or diversion. In selected patients, suprapubic drainage might be the best long-term strategy. The published data outlining surgical reconstruction consists of case series and has been summarized in Table 5. The variability of the approach reflects the considerations of surgical exposure, amount of scar to be excised, and sources of healthy vascularized tissue for transfer into the diseased bladder neck region. Patient age, previous surgery or RT, cancer stage, and life expectancy must be assessed before intervention. The primary goal should be urethral patency, with many men requiring insertion of an artificial urinary sphincter at a later date.95,97 When repeat vesicourethral anastomosis using a retropubic or abdominal approach is possible without extensive urethral mobilization, preservation of continence can be possible.98 In most series, incontinence resulted because of sphincter deficiency due to RP; the need for extensive mobilization of the anterior urethra for reanastomosis; or the effects of previous repeated transurethral incision. Urinary diversion, leaving the bladder in situ, has been reported for patients with radiation necrosis of the bladder neck or urethra, severe bladder dysfunction, complex fistulas, or other factors that make reconstruction of the urethra impractical or impossible.99

CONCLUSION The risk factors for the development of VUAS identified in case series and large prospective RP studies can be divided into preoperative, intraoperative, and postoperative categories and include excessive blood loss, type of bladder neck dissection, postoperative urinary leakage, adjuvant RT, previous TURP, smoking, older age, obesity, and surgeon experience (LE 2-3). Other risk factors include open vs minimally invasive surgery UROLOGY

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Bulbar, Bulbomembranous, Membranous

Bladder Neck, Prostatic

Dilation

Dilation

Cold- or hot-knife incision Success

Cold- or hot-knife incision/ TUR ± self-dilation

Failure Repeat incision, ± Self-dilation

Success

Failure Transurethral resection

Success

Failure Open surgical reconstruction vs. UroLume vs. suprapubic (SP) or supravesical (SV) diversion

UroLume vs. “salvage” prostatectomy/ anastomosis vs. SP or SV diversion

Figure 2. Proposed algorithm for postradiotherapy (external beam radiotherapy, brachytherapy, combined modality) vesicourethral stenosis (“prostate in”).

Figure 3. Proposed algorithm for vesicourethral anastomotic stricture. CIC, clean intermittent catheterization; DVIU, direct vision internal urethrotomy; SP, suprapubic. (Color version available online.)

(LE 2-3) and acute postoperative retention treated with suprapubic tube placement (LE 3). After BT, stenosis is the most common long-term serious urinary adverse effect (LE 2-3). Most stenoses will develop within 2-5 years and will be in the BM region (LE 2-3). The risk factors included older age, nonwhite race, low income, more comorbidities, UROLOGY

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combination therapy with EBRT or hormonal therapy, and a history of previous TURP (LE 2-3). Urethral stenosis after EBRT also increases with longterm follow-up (LE 2-3), with salvage RP associated with the greatest stenosis rate (LE 3). After cryotherapy, prostatic obstruction can occur with tissue sloughing (LE 3). Urethral warming should be used 9

to minimize sloughing and prevent stricture occurrence (LE 3). After HIFU, necrotic sloughing of the prostate can occur, necessitating TURP (LE 3). Pre- or post-HIFU TURP can decrease the development of bladder outflow obstruction (LE 3). However, long-term BNC can still occur (LE 3). Patients with a low prostate resection weight (at TURP for BPH) are predisposed to BNC (LE 2-3). Before surgery, a basic patient evaluation should consist of history and physical examination, urinalysis, and postvoid residual urine measurement (LE 1-2, GR A). Urine (urinalysis, culture, and sensitivity/leukocyte esterase screening test) and blood (blood urea nitrogen, creatinine, glucose, prostate-specific antigen) testing is recommended. Cystoscopy and appropriate imaging studies of the urinary tract will be helpful in guiding therapy (LE 2-3, GR B). Urodynamics can be helpful to evaluate voiding dysfunction and/or incontinence (LE 3, GR C). After RT (Fig. 2), a graded approach to management, beginning with endourologic procedures, should be done. This can be combined with self-dilation. Management failures can necessitate more invasive approaches, including stents, open reconstruction, or diversion (LE 3, GR C). For VUAS after RP (Fig. 3), a graded approach to management, beginning with endourologic procedures, is recommended. This can be combined with self-dilation. Management failures might necessitate more invasive approaches, including stents, open reconstruction, or diversion (LE 3, GR C). Concomitant or resultant urinary incontinence will require additional evaluation and surgery (LE 3, GR C).

Recommendations Continue to document risk factors and associations with localized treatment of prostate cancer Standardization is needed in reporting complications from all sources, including surgeons and radiation oncologists An anatomic classification system is needed to define the location of PUS. The classification could also include a description of incremental anatomic severity. Higher grade lesions would thus be associated with greater morbidity, warrant more complex treatment, and might have a worse prognosis. No accepted grading system is yet available for VUAS Identify intraoperative techniques of RP that are associated with a lower risk of VUAS Standardization is needed in the workup for accurate delineation of the stenosis and its morbidity A registry is needed of surgical cases of stenoses after RP and RT to create larger cohorts Randomized trials of interventional techniques, both endourologic and open, are needed 10

References 1. American Cancer Society. Cancer facts & figures 2010. 2010:23e37. Available at: http://www.cancer.org/acs/groups/content/@nho/ documents/document/acspc-024113.pdf. Accessed March 30, 2012. 2. Cooperberg MR, Lubeck DP, Meng MV, et al. The changing face of low-risk prostate cancer: trends in clinical presentation and primary management. J Clin Oncol. 2004;22:2141-2149. 3. Levels of evidence. BJU Int. 2008;101:1333. 4. Borboroglu PG, Sands JP, Roberts JL, et al. Risk factors for vesicourethral anastomotic stricture after radical prostatectomy. Urology. 2000;56:96-100. 5. Hu JC, Gold KF, Pashos CL, et al. Role of surgeon volume in radical prostatectomy outcomes. J Clin Oncol. 2003;21:401-405. 6. Erickson BA, Meeks JJ, Roehl KA, et al. Bladder neck contracture after retropubic radical prostatectomy: incidence and risk factors from a large single-surgeon experience. BJU Int. 2009;104:1615-1619. 7. Carlsson S, Nilsson AE, Schumacher MC, et al. Surgery-related complications in 1253 robot-assisted and 485 open retropubic radical prostatectomies at the Karolinska University Hospital, Sweden. Urology. 2010;75:1092-1097. 8. Gillitzer R, Thomas C, Wiesner C, et al. Single center comparison of anastomotic strictures after radical perineal and radical retropubic prostatectomy. Urology. 2010;76:417-422. 9. Surya BV, Provet J, Johanson KE, et al. Anastomotic strictures following radical prostatectomy: risk factors and management. J Urol. 1990;143:755-758. 10. Besarani D, Amoroso P, Kirby R. Bladder neck contracture after radical retropubic prostatectomy. BJU Int. 2004;94:1245-1247. 11. Dalkin BL. Endoscopic evaluation and treatment of anastomotic strictures after radical retropubic prostatectomy. J Urol. 1996;155: 206-208. 12. Gallo L, Perdon
a S, Autorino R, et al. Vesicourethral anastomosis during radical retropubic prostatectomy: does the number of sutures matter? Urology. 2007;69:547-551. 13. Srougi M, Paranhos M, Leite KM, et al. The influence of bladder neck mucosal eversion and early urinary extravasation on patient outcome after radical retropubic prostatectomy: a prospective controlled trial. BJU Int. 2005;95:757-760. 14. Ozu C, Hagiuda J, Nakagami Y, et al. Radical retropubic prostatectomy with running vesicourethral anastomosis and early catheter removal: our experience. Int J Urol. 2009;16:487-492. 15. Hu JC, Gu X, Lipsitz SR, et al. Comparative effectiveness of minimally invasive vs open radical prostatectomy. JAMA. 2009; 302:1557-1564. 16. Rabbani F, Yunis LH, Pinochet R, et al. Comprehensive standardized report of complications of retropubic and laparoscopic radical prostatectomy. Eur Urol. 2010;57:371-386. 17. Thiel DD, Igel TC, Brisson TE, et al. Outcomes with an alternative anastomotic technique after radical retropubic prostatectomy: 10year experience. Urology. 2006;68:132-136. 18. Levy JB, Ramchandani P, Berlin JW, et al. Vesicourethral healing following radical prostatectomy: is it related to surgical approach? Urology. 1994;44:888-892. 19. Elliott SP, Meng MV, Elkin EP, et al. Incidence of urethral stricture after primary treatment for prostate cancer: data from CaPSURE. J Urol. 2007;178:529-534. 20. Gonzalgo ML, Pavlovich CP, Trock BJ, et al. Classification and trends of perioperative morbidities following laparoscopic radical prostatectomy. J Urol. 2005;174:135-139. 21. Crew JP, Jephcott CR, Reynard JM. Radiation-induced haemorrhagic cystitis. Eur Urol. 2001;40:111-123. 22. deVries CR, Freiha FS. Hemorrhagic cystitis: a review. J Urol. 1990; 143:1-9. 23. Mate TP, Gottesman JE, Hatton J, et al. High dose-rate afterloading 192 Iridium prostate brachytherapy: feasibility report. Int J Radiat Oncol Biol Phys. 1998;41:525-533. 24. Astr€om L, Pedersen D, Mercke C, et al. Long-term outcome of high dose rate brachytherapy in radiotherapy of localised prostate cancer. Radiother Oncol. 2005;74:157-161.

UROLOGY

-

(-), 2013

25. Morton GC. The emerging role of high-dose-rate brachytherapy for prostate cancer. Clin Oncol (R Coll Radiol). 2005;17:219-227. 26. Allen ZA, Merrick GS, Butler WM, et al. Detailed urethral dosimetry in the evaluation of prostate brachytherapy-related urinary morbidity. Int J Radiat Oncol Biol Phys. 2005;62:981-987. 27. Zelefsky MJ, Yamada Y, Cohen GN, et al. Five-year outcome of intraoperative conformal permanent I-125 interstitial implantation for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2007;67:65-70. 28. Chen AB, D’Amico AV, Neville BA, et al. Patient and treatment factors associated with complications after prostate brachytherapy. J Clin Oncol. 2006;24:5298-5304. 29. Lawton CA, Bae K, Pilepich M, et al. Long-term treatment sequelae after external beam irradiation with or without hormonal manipulation for adenocarcinoma of the prostate: analysis of Radiation Therapy Oncology Group studies 85-31, 86-10, and 92-02. Int J Radiat Oncol Biol Phys. 2008;70:437-441. 30. Gardner BG, Zietman AL, Shipley WU, et al. Late normal tissue sequelae in the second decade after high dose radiation therapy with combined photons and conformal protons for locally advanced prostate cancer. J Urol. 2002;167:123-126. 31. Chism DB, Horwitz EM, Hanlon AL, et al. Late morbidity profiles in prostate cancer patients treated to 79-84 Gy by a simple four-field coplanar beam arrangement. Int J Radiat Oncol Biol Phys. 2003;55:71-77. 32. Zelefsky MJ, Levin EJ, Hunt M, et al. Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys. 2008;70:1124-1129. 33. MacDonald OK, Lee RJ, Snow G, et al. Prostate-specific antigen control with low-dose adjuvant radiotherapy for high-risk prostate cancer. Urology. 2007;69:295-299. 34. Cozzarini C, Fiorino C, Di Muzio N, et al. Hypofractionated adjuvant radiotherapy with helical tomotherapy after radical prostatectomy: planning data and toxicity results of a phase I-II study. Radiother Oncol. 2008;88:26-33. 35. Merrick GS, Butler WM, Lief JH, et al. Temporal resolution of urinary morbidity following prostate brachytherapy. Int J Radiat Oncol Biol Phys. 2000;47:121-128. 36. Martinez A, Gonzalez J, Spencer W, et al. Conformal high dose rate brachytherapy improves biochemical control and cause specific survival in patients with prostate cancer and poor prognostic factors. J Urol. 2003;169:974-979. 37. Merrick GS, Butler WM, Wallner KE, et al. Risk factors for the development of prostate brachytherapy related urethral strictures. J Urol. 2006;175:1376-1380. 38. Sullivan L, Williams SG, Tai KH, et al. Urethral stricture following high dose rate brachytherapy for prostate cancer. Radiother Oncol. 2009;91:232-236. 39. Pellizzon AC, Salvajoli JV, Maia MA, et al. Late urinary morbidity with high dose prostate brachytherapy as a boost to conventional external beam radiation therapy for local and locally advanced prostate cancer. J Urol. 2004;171:1105-1108. 40. Wallner K, Roy J, Harrison L. Tumor control and morbidity following transperineal iodine 125 implantation for stage T1/T2 prostatic carcinoma. J Clin Oncol. 1996;14:449-453. 41. Merrick GS, Butler WM, Tollenaar BG, et al. The dosimetry of prostate brachytherapy-induced urethral strictures. Int J Radiat Oncol Biol Phys. 2002;52:461-468. 42. Seymore CH, el-Mahdi AM, Schellhammer PF. The effect of prior transurethral resection of the prostate on post radiation urethral strictures and bladder neck contractures. Int J Radiat Oncol Biol Phys. 1986;12:1597-1600. 43. Deger S, Boehmer D, Roigas J, et al. High dose rate (HDR) brachytherapy with conformal radiation therapy for localized prostate cancer. Eur Urol. 2005;47:441-448. 44. Chon BH, Loeffler JS. The effect of nonmalignant systemic disease on tolerance to radiation therapy. Oncologist. 2002;7:136-143. 45. Grills IS, Martinez AA, Hollander M, et al. High dose rate brachytherapy as prostate cancer monotherapy reduces toxicity

UROLOGY

-

(-), 2013

46.

47.

48.

49.

50. 51.

52. 53.

54.

55.

56.

57.

58.

59.

60.

61.

62.

63.

64.

65.

66.

compared to low dose rate palladium seeds. J Urol. 2004;171: 1098-1104. Lam JS, Pisters LL, Belldegrun AS. Cryotherapy for prostate cancer. In: Wein AJ, Kavoussi LR, Novick AC, et al., eds. Campbell-Walsh Urology. 9th ed. Philadelphia: Saunders Elsevier; 2007:3032-3052. Koppie TM, Grossfeld GD, Miller D, et al. Patterns of treatment of patients with prostate cancer initially managed with surveillance: results from the CaPSURE database. Cancer of the Prostate Strategic Urological Research Endeavor. J Urol. 2000;164:81-88. Long JP, Bahn D, Lee F, et al. Five-year retrospective, multiinstitutional pooled analysis of cancer-related outcomes after cryosurgical ablation of the prostate. Urology. 2001;57:518-523. Han KR, Cohen JK, Miller RJ, et al. Treatment of organ confined prostate cancer with third generation cryosurgery: preliminary multicenter experience. J Urol. 2003;170(4 Pt 1):1126-1130. Cooper IS, Hirose T. Application of cryogenic surgery to resection of parenchymal organs. N Engl J Med. 1966;274:15-18. Long JP, Fallick ML, LaRock DR, et al. Preliminary outcomes following cryosurgical ablation of the prostate in patients with clinically localized prostate carcinoma. J Urol. 1998;159:477-484. Pisters LL. Cryotherapy for prostate cancer: ready for prime time? Curr Opin Urol. 2010;20:218-222. Izawa JI, Ajam K, McGuire E, et al. Major surgery to manage definitively severe complications of salvage cryotherapy for prostate cancer. J Urol. 2000;164:1978-1981. Ahmed HU, Ishaq A, Zacharakis E, et al. Rectal fistulae after salvage high-intensity focused ultrasound for recurrent prostate cancer after combined brachytherapy and external beam radiotherapy. BJU Int. 2009;103:321-323. Challacombe BJ, Murphy DG, Zakri R, et al. High-intensity focused ultrasound for localized prostate cancer: initial experience with a 2year follow-up. BJU Int. 2009;104:200-204. Murat FJ, Poissonnier L, Rabilloud M, et al. Mid-term results demonstrate salvage high-intensity focused ultrasound (HIFU) as an effective and acceptably morbid salvage treatment option for locally radiorecurrent prostate cancer. Eur Urol. 2009;55:640-647. Chalasani V, Martinez CH, Lim D, et al. Salvage HIFU for recurrent prostate cancer after radiotherapy. Prostate Cancer Prostatic Dis. 2009;12:124-129. Chaussy C, Thüroff S. High-intensity focused ultrasound in the management of prostate cancer. Expert Rev Med Devices. 2010;7: 209-217. Thüroff S, Chaussy C, Vallancien G, et al. High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study. J Endourol. 2003;17:673-677. Madersbacher S, Schatzl G, Djavan B, et al. Long-term outcome of transrectal high-intensity focused ultrasound therapy for benign prostatic hyperplasia. Eur Urol. 2000;37:687-694. Uchida T, Ohkusa H, Nagata Y, et al. Treatment of localized prostate cancer using high-intensity focused ultrasound. BJU Int. 2006;97:56-61. Chaussy C, Thüroff S. The status of high-intensity focused ultrasound in the treatment of localized prostate cancer and the impact of a combined resection. Curr Urol Rep. 2003;4:248-252. Wei JT, Calhoun E, Jacobsen SJ. Urologic diseases in America project: benign prostatic hyperplasia. J Urol. 2005;173: 1256-1261. Lee YH, Chiu AW, Huang JK. Comprehensive study of bladder neck contracture after transurethral resection of prostate. Urology. 2005;65:498-503. Rassweiler J, Seemann O, Schulze M, et al. Laparoscopic versus open radical prostatectomy: a comparative study at a single institution. J Urol. 2003;169:1689-1693. American Urological Association Education and Research, Inc. Results of the treatment outcomes analyses. 2003. Available at: http://www.auanet.org/content/guidelines-and-quality-care/clinicalguidelines/main-reports/bph-management/chapt_3_appendix.pdf. Accessed October 10, 2010.

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67. Tan A, Liao C, Mo Z, et al. Meta-analysis of holmium laser enucleation versus transurethral resection of the prostate for symptomatic prostatic obstruction. Br J Surg. 2007;94:1201-1208. 68. Riehmann M, Knes JM, Heisey D, et al. Transurethral resection versus incision of the prostate: a randomized, prospective study. Urology. 1995;45:768-775. 69. Al-Singary W, Arya M, Patel HR. Bladder neck stenosis after transurethral resection of prostate: does size matter? Urol Int. 2004; 73:262-265. 70. Varkarakis J, Bartsch G, Horninger W. Long-term morbidity and mortality of transurethral prostatectomy: a 10-year follow-up. Prostate. 2004;58:248-251. 71. Orandi A. Transurethral incision of the prostate. J Urol. 1973;110: 229-231. 72. Kletscher BA, Oesterling JE. Transurethral incision of the prostate: a viable alternative to transurethral resection. Semin Urol. 1992;10: 265-272. 73. Abrams P, Chapple C, Khoury S, et al. Evaluation and treatment of lower urinary tract symptoms in older men. J Urol. 2009;181: 1779-1787. 74. McVary KT, Roehrborn CG, Avins AL, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185:1793-1803. 75. Glass AS, McAninch JW, Zaid UB, et al. Urethroplasty after radiation therapy for prostate cancer. Urology. 2012;79:1402-1405. 76. Bullock TL, Brandes SB. Adult anterior urethral strictures: a national practice patterns survey of board certified urologists in the United States. J Urol. 2007;177:685-690. 77. G omez-Iturriaga Piña A, Crook J, Borg J, et al. Median 5 year followup of 125iodine brachytherapy as monotherapy in men aged < or ¼ 55 years with favorable prostate cancer. Urology. 2010;75:1412-1416. 78. Elliott SP, McAninch JW, Chi T, et al. Management of severe urethral complications of prostate cancer therapy. J Urol. 2006; 176(6 Pt 1):2508-2513. 79. Meeks JJ, Brandes SB, Morey AF, et al. Urethroplasty for radiotherapy induced bulbomembranous strictures: a multi-institutional experience. J Urol. 2011;185:1761-1765. 80. Eisenberg ML, Elliott SP, McAninch JW. Preservation of lower urinary tract function in posterior urethral stenosis: selection of appropriate patients for urethral stents. J Urol. 2007;178:2456-2460. 81. Park R, Martin S, Goldberg JD, et al. Anastomotic strictures following radical prostatectomy: insights into incidence, effectiveness of intervention, effect on continence, and factors predisposing to occurrence. Urology. 2001;57:742-746. 82. Herschorn S, Carrington E. S-shaped coaxial dilators for male urethral strictures. Urology. 2007;69:1199-1201. 83. Ramchandani P, Banner MP, Berlin JW, et al. Vesicourethral anastomotic strictures after radical prostatectomy: efficacy of transurethral balloon dilation. Radiology. 1994;193:345-349.

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84. Geary ES, Dendinger TE, Freiha FS, et al. Incontinence and vesical neck strictures following radical retropubic prostatectomy. Urology. 1995;45:1000-1006. 85. Popken G, Sommerkamp H, Schultze-Seemann W, et al. Anastomotic stricture after radical prostatectomy: incidence, findings and treatment. Eur Urol. 1998;33:382-386. 86. Hayashi T, Yoshinaga A, Ohno R, et al. Successful treatment of recurrent vesicourethral stricture after radical prostatectomy with holmium laser: report of three cases. Int J Urol. 2005;12:414-416. 87. Lagerveld BW, Laguna MP, Debruyne FM, et al. Holmium:YAG laser for treatment of strictures of vesicourethral anastomosis after radical prostatectomy. J Endourol. 2005;19:497-501. 88. Eltahawy E, Gur U, Virasoro R, et al. Management of recurrent anastomotic stenosis following radical prostatectomy using holmium laser and steroid injection. BJU Int. 2008;102:796-798. 89. Chiou RK, Howe S, Morton JJ, et al. Treatment of recurrent vesicourethral anastomotic stricture after radical prostatectomy with endourethroplasty. Urology. 1996;47:422-425. 90. Kuyumcuoglu U, Eryildirim B, Tarhan F, et al. Antegrade endourethroplasty with free skin graft for recurrent vesicourethral anastomotic strictures after radical prostatectomy. J Endourol. 2010;24:63-67. 91. Elliott DS, Boone TB. Combined stent and artificial urinary sphincter for management of severe recurrent bladder neck contracture and stress incontinence after prostatectomy: a long-term evaluation. J Urol. 2001;165:413-415. 92. Magera JS Jr, Inman BA, Elliott DS. Outcome analysis of urethral wall stent insertion with artificial urinary sphincter placement for severe recurrent bladder neck contracture following radical prostatectomy. J Urol. 2009;181:1236-1241. 93. Yurkanin JP, Dalkin BL, Cui H. Evaluation of cold knife urethrotomy for the treatment of anastomotic stricture after radical retropubic prostatectomy. J Urol. 2001;165:1545-1548. 94. Anger JT, Raj GV, Delvecchio FC, et al. Anastomotic contracture and incontinence after radical prostatectomy: a graded approach to management. J Urol. 2005;173:1143-1146. 95. Wessells H, Morey AF, McAninch JW. Obliterative vesicourethral strictures following radical prostatectomy for prostate cancer: reconstructive armamentarium. J Urol. 1998;160:1373-1375. 96. Vanni A, Zinman L, Buckley J. Management of recurrent bladder neck contractures with urethrotomy and mitomycin C [abstract]. J Urol. 2010;183:e426. 97. Theodoros C, Katsifotis C, Stournaras P, et al. Abdomino-perineal repair of recurrent and complex bladder neck-prostatic urethra contractures. Eur Urol. 2000;38:734-740. 98. Herschorn S. Management of post-radical prostatectomy complete bladder neck occlusion [abstract]. J Urol. 2007;177:14. 99. Ullrich NF, Wessells H. A technique of bladder neck closure combining prostatectomy and intestinal interposition for unsalvageable urethral disease. J Urol. 2002;167(2 Pt 1):634-636.

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