REVIEW URRENT C OPINION
Bladder neck contractures and the prostate cancer survivor Joseph S. Song, Jairam R. Eswara, and Steven B. Brandes
Purpose of review To summarize the cause and diagnostic and treatment concerns for bladder neck contractures (BNCs) in the prostate cancer survivor. Recent findings BNC rates have decreased significantly in the last 2 decades, likely because of improvement in the surgical technique and increased utilization of laparoscopic and robotic surgery, which may allow better visualization of the vesicourethral anastomosis. Despite these improvements, risk factors such as smoking and coronary artery disease contribute to BNC development. Furthermore, although recent reports have questioned the classical tenets of anastomotic technique such as water-tight anastomoses, there is no evidence that these principles contribute to the risk of BNC development and should continue to be observed. The results of minimally invasive procedures such as urethral dilation and transurethral incision of the bladder neck may be improved with the use of injectable agents. Summary There is little consensus regarding BNC therapy. Although several risk factors contributing to BNC development have been identified, strategies to reduce the risk are unclear. A number of therapeutic options are available, however. In the event of BNC development, treatment should be structured in a hierarchical fashion which minimizes the risk of urinary incontinence. Keywords anastomotic stenosis, bladder neck contracture, bladder neck stenosis, vesicourethral anastomosis
INTRODUCTION As the most common cancer in men, there were more than 400 000 malignancies of the prostate diagnosed in Europe in 2012 [1]. Indeed, some 1.5 million Europeans have developed prostate cancer within the last 5 years [2]. At the same time, survival rates for prostate cancer have increased dramatically over the last 3 decades [3], leaving significant numbers of people to struggle with the sequelae of the disease. One of the most vexing issues for prostate cancer survivors is bladder neck contracture (BNC) after radical prostatectomy. BNCs, also known as bladder neck stenosis or anastomotic stenosis, occur when scar tissue forms at the vesicourethral anastomotic site after radical prostatectomy. Although refinements to the surgical technique have decreased the rate of BNCs from 20% in the 1990s to 1–3% currently [4–6], it continues to be one of the most common complications after radical prostatectomy [7,8,9 ]. Despite its prevalence and impact on the quality of life (QOL), BNCs remain a topic on which there is little consensus. From prevention to treatment, BNC &
remains both enigmatic and problematic. Here, we attempt to organize and summarize the current opinion on BNCs as it relates to the prostate cancer survivor.
PATIENT RISK FACTORS FOR BLADDER NECK CONTRACTURE Although declining rates of BNC have highlighted the impact of technique on BNC occurrence, multiple patient factors, such as a history of smoking, cardiovascular disease, or a hypertrophic healing response, have been linked to BNC development [10,11]. In the case of patients with a smoking history, Borboroglu et al. [11] showed that current smokers Barnes Jewish Hospital, Washington University, St. Louis, Missouri, USA Correspondence to Joseph S. Song, Washington University School of Medicine, Campus Box 8242, 4960 Children’s Place, St. Louis, MO 63110, USA. Tel: +1 314 362 8227; e-mail: [email protected] Curr Opin Urol 2014, 24:389–394 DOI:10.1097/MOU.0000000000000065
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KEY POINTS Patient factors such as smoking status and obesity are significant drivers in BNC development. Although it is unclear which individual components of anastomotic technique decrease BNC risk, the importance of surgical technique is underscored by lower rates of BNC formation in high-volume centers. The most common presenting symptom of BNC is decreased stream 4–5 months after radical prostatectomy, though paradoxical urinary incontinence may also be present. Initial management of BNC should focus on minimally invasive techniques such as urethral dilation or TUIBN, which have lower risks for incontinence; multiple treatments may be required for resolution of BNC. Treatment-resistant BNC can be managed with deep TUIBN, stenting, or open repair, but patients should be educated regarding the high likelihood of urinary incontinence and the possible need for an artificial urinary sphincter.
have a 26% chance of developing BNC, nearly three times the risk of nonsmokers. In former smokers, however, the risk for BNC development was comparable to patients who had never smoked, suggesting that the detriments of tobacco consumption are not permanent. How long it takes to return to a baseline risk for BNC development is unknown. Additionally, patients with a history of coronary artery disease (CAD) have a 26% chance of developing BNC, a significant increase over patients without CAD, although increasing age and BMI are also associated with increased risk for BNC [11,12]. Today, it is widely accepted that vasculopathies which decrease blood flow to the anastomotic site increase the risk of BNC formation and recurrence [13 ]. Furthermore, those with an increased scar response, defined as a midline scar of greater than 10 mm, are eight-fold more likely to develop a BNC [10]. Whether other patients with hypertrophic scar responses, such as patients with a history of keloids, are at increased risk for BNC development is unknown. &
OPERATIVE RISK FACTORS FOR BLADDER NECK CONTRACTURE FORMATION In addition to the patient characteristics, high intraoperative blood loss is also linked to BNC development [5,11,14]. Also, postoperative extravasation has been shown to correlate with BNC risk, possibly 390
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because of disruption and inflammation of the anastomotic site [15]. Also important is anastomotic technique, which remains one of the primary predictors of BNC occurrence. Open radical prostatectomy (ORP) is associated with higher rates of BNC occurrence, with a 1–32% occurrence rate versus 0–3% after laparoscopic and robotic-assisted laparoscopic radical prostatectomy (RALP) [6,11,16,17]. This difference is attributed to better visualization of the vesicourethral anastomotic site during lap and robotic cases, leading to better approximation of the tissue, although whether this is true is unknown. Multiple changes in anastamotic technique and surgical approaches have been proposed to improve the vesicourethral anastomosis, with varying results [14,17,18 ,19–21]. Recently, classical risks for BNC occurrence, such as anastomotic leak, have been called into question [22]. Although these findings cloud the water regarding BNC prevention, it is likely that the optimal anastomosis remains one that correctly aligns the urethra, approximates mucosa, and strikes a balance between being tension-free and water tight [23 ]. Ultimately, the role of technique in BNC prevention is underscored by the negative correlation between surgical volume and BNC occurrence, with highvolume practices having generally lower rates of BNC after prostatectomy [10,24]. &
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SYMPTOMS AND DIAGNOSIS OF BLADDER NECK CONTRACTURE BNCs occur 4–5 months after prostatectomy on average, though some patients can develop symptoms as early as 1 month or as late as 1 year after surgery [6,10]. In general, most strictures are diagnosed within the first 6 months, after which, there is a steady decline in risk until the likelihood of BNC development is negligible after 2 years [12]. The most common symptom of BNC is a slow or diminished stream, which is present in approximately 60% of patients diagnosed with a BNC [4]. Other lower urinary tract symptoms (LUTS) are also common, such as frequency, incontinence, or retention. It is important to note that, despite the obstructive nature of BNC, paradoxical urinary incontinence is a common finding. This stems from both fibrotic scar tissue disrupting the function of the external sphincter as well as overflow incontinence resulting from urinary retention. Although BNCs can lead to emergencies like acute retention, they are often more striking in their effects on patient’s QOL. Whereas few studies have examined the QOL components for patients with BNCs specifically, some have highlighted the impact of LUTS on QOL, particularly after prostatectomy. Volume 24 Number 4 July 2014
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Bladder neck contractures Song et al.
Nocturia and weak stream, for instance, are the core symptoms of LUTS, and elimination of these greatly improves the QOL [25]. At the same time, the treatment for BNC itself can impact QOL. Patients who undergo multiple treatments or are on a regimen of clean intermittent catheterization (CIC) are especially affected [26]. Before treatment, however, many urologists utilize an array of diagnostic tests to confirm BNC. One common method is to attempt passage of a 16 or 18 French cystoscope, with failure to pass the scope or visualization of a pinpoint stricture diagnostic of BNC. Alternatively, retrograde urethrograms and voiding cystourethrograms can also be used to differentiate between BNCs and radiation-induced strictures, which can occur elsewhere along the urethra. Lastly, urodynamics and postvoid residuals can also be used to diagnose and follow BNCs, with high postvoid residuals, low Qmax, and obstructive uroflowmetry patterns classic for BNC.
TREATMENT OF BLADDER NECK CONTRACTURE One of the most frustrating aspects of BNC is its tendency to recur. As a result, there are multiple options for the management of BNCs, depending on the severity and resistance to treatment of the disease. These treatment modalities can generally be divided into four categories: dilation, transurethral incision of the bladder neck (TUIBN), urethral stenting, and open urethral reconstruction. Currently, there is no consensus as to the best treatment regimen. However, these approaches lie on a spectrum regarding both invasiveness and outcomes. Lessinvasive procedures like dilation are associated with higher rates of BNC recurrence but lower risks for incontinence. More invasive procedures like urethral stenting are associated with much higher risks of incontinence, but are more effective in treating recalcitrant disease. As a result, treatment of BNCs can be placed into a hierarchy (Fig. 1), with less-invasive procedures utilized on newly diagnosed BNCs before proceeding to other treatments only after multiple treatment failures or rapid recurrence of BNCs.
Dilation A common first step in BNC treatment is urethral dilation with a course of CIC. Dilation is a minimally invasive procedure which can be performed in the office with filiform and followers, graduated sounds, or balloons. Aside from its ease of access, dilation is also associated with a nearly zero risk of de novo incontinence [11,14,27]. These benefits, however, come at a price – BNCs recur commonly after dilation and some reports suggest that as many
as 94% of patients can require a second treatment [27]. Furthermore, although BNC-free rates increase with multiple courses of dilation [10,14,28], repeat dilation increases the risk for urethral trauma and urinary infection [5]. Some authors have attempted to address this issue by improving the efficacy of dilation through CIC [10,28]. Although these studies showed eventual success rates over 90%, it is unclear whether CIC truly improves dilation results as there have been no trials comparing the effectiveness of dilation with or without CIC. In addition to CIC, anti-inflammatory agents have also been used to augment dilation. Early reports suggest that agents such as methylprednisolone may dramatically improve the effectiveness of dilation [29]. Although these reports require more investigation, they suggest that medical adjuvants may play an important role in improving BNC dilation result.
Transurethral incision of the bladder neck TUIBN is a commonly utilized operative treatment of BNC, in which either a scalpel or a electrocautery is used to incise the contracted scar tissue. Although TUIBN is more invasive than dilation, it remains a same-day procedure with minimal recovery time. Furthermore, TUIBN has been shown to have higher success rates than dilation, with general initial success rates of 50–80% [30–32]. The downside is that TUIBN is also associated with increased risk for urinary incontinence, as the incision may adversely affect sphincter function. In general, this risk is low, as most reports indicate a less than 15% risk for incontinence [29,32]. Similar to dilation, multiple attempts have been made to improve the outcomes after TUIBN. By deepening the incision, even highly resistant BNCs can be managed with TUIBN [33,34,35 ]. However, this procedure results in high rates of incontinence that may require artificial urinary sphincter (AUS) implantation and complicate the treatment of recurrent BNC. As a result, adjuvants to TUIBN have been proposed to avoid the incontinence associated with deep TUIBN. Eltahawy et al. [31] injected triamcinolone to the incision sites after holmium laser TUIBN and reported an 83% success rate in patients with previous treatment-resistant BNC. Similarly, Vanni et al. [32] achieved a 72% success rate using mitomycin C in patients with recurrent BNC. Of note, both these reports achieved incontinence rates similar to that seen after classic TUIBN, while achieving high success rates in the setting of recurrent disease. These agents have not been tested in a controlled fashion, but these early findings are promising.
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Workup of BNC: History and physical Postvoid residual Urodynamics Retrograde urethrogram/voiding cystourethrogram Cystoscopy
Diagnosis of BNC
BNC resolution
Dilation + CIC
BNC recurrence
BNC resolution
TUIBN
BNC recurrence
BNC resolution
-or-
Stent
BNC recurrence
BNC resolution
Deep TUIBN
BNC resolution
BNC recurrence
Open repair
BNC recurrence
Urinary diversion
FIGURE 1. Proposed guideline flowchart for the treatment of postprostatectomy bladder neck contractures; the flowchart is designed to minimize the risk of incontinence through a gradual escalation in invasiveness of treatment.
Urethral stenting Similar to deep TUIBN, urethral stenting may result in significant disruption of the external sphincter and subsequent incontinence. As a result, this procedure is generally reserved for recurrent or treatment-resistant BNC, in which they can achieve eventual BNC resolution in 76–100% of cases [36,37]. As with deep TUIBN, the timing of when an AUS should be placed can be problematic and can complicate BNC management. As a result, attempts have been made to decrease incontinence by placing 392
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the stent more proximally [38]. However, even in patients in whom stent placement does not impact continence, high rates of stent migration, erosion, and ingrowth can result in stent failure, decreasing its long-term efficacy [37,39].
Open urethral reconstruction As a last resort, urethral reconstruction via open repair can be considered. This approach is significantly more invasive, but can result in resolution of Volume 24 Number 4 July 2014
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Bladder neck contractures Song et al.
BNC in 60–100% of patients [40,41]. Of note, the patients in these studies had multiple treatment failures, with as many as 10 prior failed attempts to manage BNC in a less-invasive fashion. Additionally, the results of urethral reconstruction can be further improved with follow-up TUIBN, in which Pfalzgraf et al. [40] showed raised eventual success rate from 60 to 95%. Similar to deep TUIBN and stent placement, however, urethral reconstruction also results in high rates of incontinence, ranging from 36 to 100% [41]. As a result, patients who undergo open repair should be prepared for the possibility of major sphincter dysfunction and the need for AUS implantation.
CONCLUSION Despite declining rates, BNC remains a significant source of morbidity for prostate cancer survivors. Although BNC can be minimized with improved surgical technique, patient factors are still a driver in BNC development. If a BNC does develop, it is important to utilize less-invasive techniques such as urethral dilation or TUIBN first, as they have smaller risk for incontinence. Furthermore, eventual success rates can be increased with multiple dilations or TUIBNs. Stenting or open repair should be reserved only as a last resort after multiple treatment failures, as these procedures carry high risk for urinary incontinence; patients undergoing these procedures should be prepared for the possibility of requiring an AUS implantation. Acknowledgements None. Conflicts of interest There are no conflicts of interest.
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. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 2013; 49:1374–1403. 2. Bray F, Ren J-S, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 2013; 132:1133– 1145. 3. Rachet B, Maringe C, Nur U, et al. Population-based cancer survival trends in England and Wales up to 2007: an assessment of the NHS cancer plan for England. Lancet Oncol 2009; 10:351–369. 4. Breyer BN, Davis CB, Cowan JE, et al. Incidence of bladder neck contracture after robot-assisted laparoscopic and open radical prostatectomy. BJU Int 2010; 106:1734–1738. 5. Surya BV, Provet J, Johanson KE, Brown J. Anastomotic strictures following radical prostatectomy: risk factors and management. J Urol 1990; 143:755– 758.
6. Msezane LP, Reynolds WS, Gofrit ON, et al. Bladder neck contracture after robot-assisted laparoscopic radical prostatectomy: evaluation of incidence and risk factors and impact on urinary function. J Endourol 2008; 22:377–383. 7. Ghazi A, Scosyrev E, Patel H, et al. Complications associated with extraperitoneal robot-assisted radical prostatectomy using the standardized Martin classification. Urology 2013; 81:324–331. 8. Koc¸ G, Tazeh NN, Joudi FN, et al. Lower extremity neuropathies after robotassisted laparoscopic prostatectomy on a split-leg table. J Endourol 2012; 26:1026–1029. 9. Yuh B, Ruel N, Muldrew S, et al. Complications and outcomes of robot& assisted salvage radical prostatectomy: a single institution experience. BJU Int 2013. doi: 10.1111/bju.12595. A recent study on outcomes after robotic salvage prostatectomy which demonstrates that bladder neck contracture remains the most common complication after prostatectomy, despite modern advances in approach and technique. 10. Park R, Martin S, Goldberg JD. Anastomotic strictures following radical continence, and factors predisposing to occurrence. [date unknown]. p. 4295. 11. Borboroglu PG, Sands JP, Roberts JL, Amling CL. Stricture after radical prostatectomy. 2000. p. 4295. 12. 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; discussion 534. 13. Ramirez D, Zhao LC, Bagrodia A, et al. Deep lateral transurethral incisions for & recurrent bladder neck contracture: promising 5-year experience using a standardized approach. Urology 2013; 82:1430–1435. A good study which shows both the high rate of BNC resolution after deep TUIBN as well as the increased risk smoking places on BNC recurrence. 14. Thiel DD, Igel TC, Brisson TE, Heckman MG. Outcomes with an alternative anastomotic technique after radical retropubic prostatectomy: 10-year experience. Urology 2006; 68:132–136. 15. Huang G, Lepor H. Factors predisposing to the development of anastomotic strictures in a single-surgeon series of radical retropubic prostatectomies. BJU Int 2006; 97:255–258. 16. Popken G, Sommerkamp H, Schultze-Seemann W, et al. Anastomotic stricture after radical prostatectomy. Incidence, findings and treatment. Eur Urol 1998; 33:382–386. 17. Webb DR, Sethi K, Gee K. An analysis of the causes of bladder neck contracture after open and robot-assisted laparoscopic radical prostatectomy. BJU Int 2009; 103:957–963. 18. Ouzaid I, Xylinas E, Ploussard G, et al. Anastomotic stricture after minimally & invasive radical prostatectomy: what should be expected from the Van Velthoven single-knot running suture? J Endourol 2012; 26:1020–1025. Multiple anastomotic techniques have been developed as potential ways to lower BNC risk. However, as this study demonstrates, even large cohorts of patients can have relatively low (43 in this case) rates of BNC occurrence and it can be difficult to compare different techniques because of heterogeneity in patient populations, institutional differences, and variability in surgeon experience. 19. Garg T, See Wa. Bladder neck contracture after radical retropubic prostatectomy using an intussuscepted vesico-urethral anastomosis: incidence with long-term follow-up. BJU Int 2009; 104:925–928. 20. 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. 21. Miki T, Okihara K, Ukimura O, et al. Running suture for vesicourethral anastomosis in minilaparotomy radical retropubic prostatectomy. Urology 2006; 67:410–412. 22. Hanson GR, Odom E, Borden LS, et al. Postoperative drain output as a predictor of bladder neck contracture following radical prostatectomy. Int Urol Nephrol 2008; 40:351–354. 23. Cho HJ, Jung TY, Kim DY, et al. Prevalence and risk factors of bladder neck & contracture after radical prostatectomy. Korean J Urol 2013; 54:297–302. Although some recent studies question the role of anastomotic leak in BNC development, other reports maintain that one of the most important indicators for BNC development is urinary leak. Ultimately, water-tight anastamoses are unlikely to be detrimental and have the potential of decreasing the BNC formation. 24. Kundu SD, Roehl KA, Eggener SE, et al. Potency, continence and complications in 3477 consecutive radical retropubic prostatectomies. J Urol 2004; 172:2227–2231. 25. Lee SW, Doo SW, Yang WJ, Song YS. Importance of relieving the most bothersome symptom for improving quality of life in male patients with lower urinary tract symptoms. Urology 2012; 80:684–687. 26. Lubahn JD, Zhao LC, Scott JF, et al. Poor quality of life in patients with urethral stricture treated with intermittent self-dilation. J Urol 2014; 191:143–147. 27. Giannarini G, Manassero F, Mogorovich A, et al. Cold-knife incision of anastomotic strictures after radical retropubic prostatectomy with bladder neck preservation: efficacy and impact on urinary continence status. Eur Urol 2008; 54:647–656. 28. Besarani D, Amoroso P, Kirby R. Bladder neck contracture after radical retropubic prostatectomy. BJU Int 2004; 94:1245–1247. 29. Kravchick S, Lobik L, Peled R, Cytron S. Transrectal ultrasonography-guided injection of long-acting steroids in the treatment of recurrent/resistant anastomotic stenosis after radical prostatectomy. J Endourol 2013. doi: 10.1089/end.2012.0661.
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Reconstructive urology and the cancer survivor 30. 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. 31. 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. 32. Vanni AJ, Zinman LN, Buckley JC. Radial urethrotomy and intralesional mitomycin C for the management of recurrent bladder neck contractures. J Urol 2011; 186:156–160. 33. Gousse AE, Tunuguntla HSGR, Leboeuf L. Two-stage management of severe postprostatectomy bladder neck contracture associated with stress incontinence. Urology 2005; 65:316–319. 34. Anger JT, Raj GV, Delvecchio FC, Webster GD. Anastomotic contracture and incontinence after radical prostatectomy: a graded approach to management. J Urol 2005; 173:1143–1146. 35. Brede C, Angermeier K, Wood H. Continence outcomes after treatment of & recalcitrant postprostatectomy bladder neck contracture and review of the literature. Urology 2013. doi: 10.1016/j.urology.2013.10.042. A large cohort of 63 patients with at least one failure of BNC treatment. This study demonstrates the conundrum of escalated treatment; although deep bladder neck incision was sufficient to resolve BNC in a majority (66%) of patients with treatment-resistant BNCs, it also resulted in AUS requirement in 74% of patients.
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36. 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. 37. Magera JS, 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. 38. Erickson Ba, McAninch JW, Eisenberg ML, et al. Management for prostate cancer treatment related posterior urethral and bladder neck stenosis with stents. J Urol 2011; 185:198–203. 39. Borawski K, Webster G. 1097 Long term consequences in the management of the devastated, obstructed outlet using combined urolume stent with subsequent artificial urinary Ssphincter placement. J Urol 2010; 183: e427. 40. Pfalzgraf D, Beuke M, Isbarn H, et al. Open retropubic reanastomosis for highly recurrent and complex bladder neck stenosis. J Urol 2011; 186:1944– 1947. 41. Simonato A, Gregori A, Lissiani A, Carmignani G. Two-stage transperineal management of posterior urethral strictures or bladder neck contractures associated with urinary incontinence after prostate surgery and endoscopic treatment failures. Eur Urol 2007; 52:1499–1504.
Volume 24 Number 4 July 2014
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Bladder neck contractures and the prostate cancer survivor Joseph S. Song, Jairam R. Eswara, and Steven B. Brandes
Purpose of review To summarize the cause and diagnostic and treatment concerns for bladder neck contractures (BNCs) in the prostate cancer survivor. Recent findings BNC rates have decreased significantly in the last 2 decades, likely because of improvement in the surgical technique and increased utilization of laparoscopic and robotic surgery, which may allow better visualization of the vesicourethral anastomosis. Despite these improvements, risk factors such as smoking and coronary artery disease contribute to BNC development. Furthermore, although recent reports have questioned the classical tenets of anastomotic technique such as water-tight anastomoses, there is no evidence that these principles contribute to the risk of BNC development and should continue to be observed. The results of minimally invasive procedures such as urethral dilation and transurethral incision of the bladder neck may be improved with the use of injectable agents. Summary There is little consensus regarding BNC therapy. Although several risk factors contributing to BNC development have been identified, strategies to reduce the risk are unclear. A number of therapeutic options are available, however. In the event of BNC development, treatment should be structured in a hierarchical fashion which minimizes the risk of urinary incontinence. Keywords anastomotic stenosis, bladder neck contracture, bladder neck stenosis, vesicourethral anastomosis
INTRODUCTION As the most common cancer in men, there were more than 400 000 malignancies of the prostate diagnosed in Europe in 2012 [1]. Indeed, some 1.5 million Europeans have developed prostate cancer within the last 5 years [2]. At the same time, survival rates for prostate cancer have increased dramatically over the last 3 decades [3], leaving significant numbers of people to struggle with the sequelae of the disease. One of the most vexing issues for prostate cancer survivors is bladder neck contracture (BNC) after radical prostatectomy. BNCs, also known as bladder neck stenosis or anastomotic stenosis, occur when scar tissue forms at the vesicourethral anastomotic site after radical prostatectomy. Although refinements to the surgical technique have decreased the rate of BNCs from 20% in the 1990s to 1–3% currently [4–6], it continues to be one of the most common complications after radical prostatectomy [7,8,9 ]. Despite its prevalence and impact on the quality of life (QOL), BNCs remain a topic on which there is little consensus. From prevention to treatment, BNC &
remains both enigmatic and problematic. Here, we attempt to organize and summarize the current opinion on BNCs as it relates to the prostate cancer survivor.
PATIENT RISK FACTORS FOR BLADDER NECK CONTRACTURE Although declining rates of BNC have highlighted the impact of technique on BNC occurrence, multiple patient factors, such as a history of smoking, cardiovascular disease, or a hypertrophic healing response, have been linked to BNC development [10,11]. In the case of patients with a smoking history, Borboroglu et al. [11] showed that current smokers Barnes Jewish Hospital, Washington University, St. Louis, Missouri, USA Correspondence to Joseph S. Song, Washington University School of Medicine, Campus Box 8242, 4960 Children’s Place, St. Louis, MO 63110, USA. Tel: +1 314 362 8227; e-mail: [email protected] Curr Opin Urol 2014, 24:389–394 DOI:10.1097/MOU.0000000000000065
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KEY POINTS Patient factors such as smoking status and obesity are significant drivers in BNC development. Although it is unclear which individual components of anastomotic technique decrease BNC risk, the importance of surgical technique is underscored by lower rates of BNC formation in high-volume centers. The most common presenting symptom of BNC is decreased stream 4–5 months after radical prostatectomy, though paradoxical urinary incontinence may also be present. Initial management of BNC should focus on minimally invasive techniques such as urethral dilation or TUIBN, which have lower risks for incontinence; multiple treatments may be required for resolution of BNC. Treatment-resistant BNC can be managed with deep TUIBN, stenting, or open repair, but patients should be educated regarding the high likelihood of urinary incontinence and the possible need for an artificial urinary sphincter.
have a 26% chance of developing BNC, nearly three times the risk of nonsmokers. In former smokers, however, the risk for BNC development was comparable to patients who had never smoked, suggesting that the detriments of tobacco consumption are not permanent. How long it takes to return to a baseline risk for BNC development is unknown. Additionally, patients with a history of coronary artery disease (CAD) have a 26% chance of developing BNC, a significant increase over patients without CAD, although increasing age and BMI are also associated with increased risk for BNC [11,12]. Today, it is widely accepted that vasculopathies which decrease blood flow to the anastomotic site increase the risk of BNC formation and recurrence [13 ]. Furthermore, those with an increased scar response, defined as a midline scar of greater than 10 mm, are eight-fold more likely to develop a BNC [10]. Whether other patients with hypertrophic scar responses, such as patients with a history of keloids, are at increased risk for BNC development is unknown. &
OPERATIVE RISK FACTORS FOR BLADDER NECK CONTRACTURE FORMATION In addition to the patient characteristics, high intraoperative blood loss is also linked to BNC development [5,11,14]. Also, postoperative extravasation has been shown to correlate with BNC risk, possibly 390
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because of disruption and inflammation of the anastomotic site [15]. Also important is anastomotic technique, which remains one of the primary predictors of BNC occurrence. Open radical prostatectomy (ORP) is associated with higher rates of BNC occurrence, with a 1–32% occurrence rate versus 0–3% after laparoscopic and robotic-assisted laparoscopic radical prostatectomy (RALP) [6,11,16,17]. This difference is attributed to better visualization of the vesicourethral anastomotic site during lap and robotic cases, leading to better approximation of the tissue, although whether this is true is unknown. Multiple changes in anastamotic technique and surgical approaches have been proposed to improve the vesicourethral anastomosis, with varying results [14,17,18 ,19–21]. Recently, classical risks for BNC occurrence, such as anastomotic leak, have been called into question [22]. Although these findings cloud the water regarding BNC prevention, it is likely that the optimal anastomosis remains one that correctly aligns the urethra, approximates mucosa, and strikes a balance between being tension-free and water tight [23 ]. Ultimately, the role of technique in BNC prevention is underscored by the negative correlation between surgical volume and BNC occurrence, with highvolume practices having generally lower rates of BNC after prostatectomy [10,24]. &
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SYMPTOMS AND DIAGNOSIS OF BLADDER NECK CONTRACTURE BNCs occur 4–5 months after prostatectomy on average, though some patients can develop symptoms as early as 1 month or as late as 1 year after surgery [6,10]. In general, most strictures are diagnosed within the first 6 months, after which, there is a steady decline in risk until the likelihood of BNC development is negligible after 2 years [12]. The most common symptom of BNC is a slow or diminished stream, which is present in approximately 60% of patients diagnosed with a BNC [4]. Other lower urinary tract symptoms (LUTS) are also common, such as frequency, incontinence, or retention. It is important to note that, despite the obstructive nature of BNC, paradoxical urinary incontinence is a common finding. This stems from both fibrotic scar tissue disrupting the function of the external sphincter as well as overflow incontinence resulting from urinary retention. Although BNCs can lead to emergencies like acute retention, they are often more striking in their effects on patient’s QOL. Whereas few studies have examined the QOL components for patients with BNCs specifically, some have highlighted the impact of LUTS on QOL, particularly after prostatectomy. Volume 24 Number 4 July 2014
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Bladder neck contractures Song et al.
Nocturia and weak stream, for instance, are the core symptoms of LUTS, and elimination of these greatly improves the QOL [25]. At the same time, the treatment for BNC itself can impact QOL. Patients who undergo multiple treatments or are on a regimen of clean intermittent catheterization (CIC) are especially affected [26]. Before treatment, however, many urologists utilize an array of diagnostic tests to confirm BNC. One common method is to attempt passage of a 16 or 18 French cystoscope, with failure to pass the scope or visualization of a pinpoint stricture diagnostic of BNC. Alternatively, retrograde urethrograms and voiding cystourethrograms can also be used to differentiate between BNCs and radiation-induced strictures, which can occur elsewhere along the urethra. Lastly, urodynamics and postvoid residuals can also be used to diagnose and follow BNCs, with high postvoid residuals, low Qmax, and obstructive uroflowmetry patterns classic for BNC.
TREATMENT OF BLADDER NECK CONTRACTURE One of the most frustrating aspects of BNC is its tendency to recur. As a result, there are multiple options for the management of BNCs, depending on the severity and resistance to treatment of the disease. These treatment modalities can generally be divided into four categories: dilation, transurethral incision of the bladder neck (TUIBN), urethral stenting, and open urethral reconstruction. Currently, there is no consensus as to the best treatment regimen. However, these approaches lie on a spectrum regarding both invasiveness and outcomes. Lessinvasive procedures like dilation are associated with higher rates of BNC recurrence but lower risks for incontinence. More invasive procedures like urethral stenting are associated with much higher risks of incontinence, but are more effective in treating recalcitrant disease. As a result, treatment of BNCs can be placed into a hierarchy (Fig. 1), with less-invasive procedures utilized on newly diagnosed BNCs before proceeding to other treatments only after multiple treatment failures or rapid recurrence of BNCs.
Dilation A common first step in BNC treatment is urethral dilation with a course of CIC. Dilation is a minimally invasive procedure which can be performed in the office with filiform and followers, graduated sounds, or balloons. Aside from its ease of access, dilation is also associated with a nearly zero risk of de novo incontinence [11,14,27]. These benefits, however, come at a price – BNCs recur commonly after dilation and some reports suggest that as many
as 94% of patients can require a second treatment [27]. Furthermore, although BNC-free rates increase with multiple courses of dilation [10,14,28], repeat dilation increases the risk for urethral trauma and urinary infection [5]. Some authors have attempted to address this issue by improving the efficacy of dilation through CIC [10,28]. Although these studies showed eventual success rates over 90%, it is unclear whether CIC truly improves dilation results as there have been no trials comparing the effectiveness of dilation with or without CIC. In addition to CIC, anti-inflammatory agents have also been used to augment dilation. Early reports suggest that agents such as methylprednisolone may dramatically improve the effectiveness of dilation [29]. Although these reports require more investigation, they suggest that medical adjuvants may play an important role in improving BNC dilation result.
Transurethral incision of the bladder neck TUIBN is a commonly utilized operative treatment of BNC, in which either a scalpel or a electrocautery is used to incise the contracted scar tissue. Although TUIBN is more invasive than dilation, it remains a same-day procedure with minimal recovery time. Furthermore, TUIBN has been shown to have higher success rates than dilation, with general initial success rates of 50–80% [30–32]. The downside is that TUIBN is also associated with increased risk for urinary incontinence, as the incision may adversely affect sphincter function. In general, this risk is low, as most reports indicate a less than 15% risk for incontinence [29,32]. Similar to dilation, multiple attempts have been made to improve the outcomes after TUIBN. By deepening the incision, even highly resistant BNCs can be managed with TUIBN [33,34,35 ]. However, this procedure results in high rates of incontinence that may require artificial urinary sphincter (AUS) implantation and complicate the treatment of recurrent BNC. As a result, adjuvants to TUIBN have been proposed to avoid the incontinence associated with deep TUIBN. Eltahawy et al. [31] injected triamcinolone to the incision sites after holmium laser TUIBN and reported an 83% success rate in patients with previous treatment-resistant BNC. Similarly, Vanni et al. [32] achieved a 72% success rate using mitomycin C in patients with recurrent BNC. Of note, both these reports achieved incontinence rates similar to that seen after classic TUIBN, while achieving high success rates in the setting of recurrent disease. These agents have not been tested in a controlled fashion, but these early findings are promising.
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Workup of BNC: History and physical Postvoid residual Urodynamics Retrograde urethrogram/voiding cystourethrogram Cystoscopy
Diagnosis of BNC
BNC resolution
Dilation + CIC
BNC recurrence
BNC resolution
TUIBN
BNC recurrence
BNC resolution
-or-
Stent
BNC recurrence
BNC resolution
Deep TUIBN
BNC resolution
BNC recurrence
Open repair
BNC recurrence
Urinary diversion
FIGURE 1. Proposed guideline flowchart for the treatment of postprostatectomy bladder neck contractures; the flowchart is designed to minimize the risk of incontinence through a gradual escalation in invasiveness of treatment.
Urethral stenting Similar to deep TUIBN, urethral stenting may result in significant disruption of the external sphincter and subsequent incontinence. As a result, this procedure is generally reserved for recurrent or treatment-resistant BNC, in which they can achieve eventual BNC resolution in 76–100% of cases [36,37]. As with deep TUIBN, the timing of when an AUS should be placed can be problematic and can complicate BNC management. As a result, attempts have been made to decrease incontinence by placing 392
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the stent more proximally [38]. However, even in patients in whom stent placement does not impact continence, high rates of stent migration, erosion, and ingrowth can result in stent failure, decreasing its long-term efficacy [37,39].
Open urethral reconstruction As a last resort, urethral reconstruction via open repair can be considered. This approach is significantly more invasive, but can result in resolution of Volume 24 Number 4 July 2014
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Bladder neck contractures Song et al.
BNC in 60–100% of patients [40,41]. Of note, the patients in these studies had multiple treatment failures, with as many as 10 prior failed attempts to manage BNC in a less-invasive fashion. Additionally, the results of urethral reconstruction can be further improved with follow-up TUIBN, in which Pfalzgraf et al. [40] showed raised eventual success rate from 60 to 95%. Similar to deep TUIBN and stent placement, however, urethral reconstruction also results in high rates of incontinence, ranging from 36 to 100% [41]. As a result, patients who undergo open repair should be prepared for the possibility of major sphincter dysfunction and the need for AUS implantation.
CONCLUSION Despite declining rates, BNC remains a significant source of morbidity for prostate cancer survivors. Although BNC can be minimized with improved surgical technique, patient factors are still a driver in BNC development. If a BNC does develop, it is important to utilize less-invasive techniques such as urethral dilation or TUIBN first, as they have smaller risk for incontinence. Furthermore, eventual success rates can be increased with multiple dilations or TUIBNs. Stenting or open repair should be reserved only as a last resort after multiple treatment failures, as these procedures carry high risk for urinary incontinence; patients undergoing these procedures should be prepared for the possibility of requiring an AUS implantation. Acknowledgements None. Conflicts of interest There are no conflicts of interest.
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