REVIEW URRENT C OPINION
Rectourethral fistulas in the cancer survivor Jennifer M. Hanna a, Andrew C. Peterson b, and Christopher Mantyh a
Purpose of review Iatrogenic rectourethral fistulas (RUFs) are a rare but challenging complication that can follow the treatment of prostate cancer. We review the literature regarding the surgical management of RUFs and subsequent outcomes, focusing on a cause-specific approach. Recent findings Iatrogenic RUFs are reported to occur in approximately 1% of patients treated with external-beam radiation therapy, in 1–6% of patients after radical prostatectomy, and in 5–9% following brachytherapy or cryotherapy after prostate cancer. Most of these patients will require surgical treatment at some point. Though there have been multiple surgical procedures described with varying degrees of success, there is no consensus as to the procedure of choice, though authors now agree on the importance of the interposition of healthy tissue in radiation-induced fistulas. Summary The current literature regarding surgical approaches to the iatrogenic RUF in the prostate cancer patient highlights the importance of a cause-specific and often multidisciplinary approach, as well as the one that is most familiar to the individual surgeon, because there is often little difference in the approaches in terms of recurrence. However, given the high success rate and low complication rate, muscle transposition flap repairs remain an attractive surgical option for fistulas with unfavorable local conditions such as those present after radiation. Keywords gracilis interposition graft, prostate cancer, rectourethral fistula, York-Mason repair
INTRODUCTION Adenocarcinoma of the prostate is the most common urologic malignancy in the USA and the third leading cause of cancer death in men [1]. With improved screening methods and the advent of the prostate-specific antigen (PSA) blood test, an increasing number of patients have been diagnosed with clinically localized disease. Local therapy for T1–2N0 disease results in greater than 90% 10-year disease-specific survival [2]. Consequently, toxicity and quality of life following therapy are important in treatment selection. Several reports have shown the utility of therapeutic options, including radical prostatectomy and radiotherapy [external-beam radiotherapy (EBRT) or brachytherapy], for patients with localized prostate cancer and a low risk of biochemical failure after treatment [3,4]. More advanced carcinomas require higher doses for adequate treatment [5,6]. One strategy for dose escalation uses EBRT in conjunction with brachytherapy. This approach is intended to improve local control and disease-free survival [3,4]. Combined EBRT and brachytherapy, however, can be associated with an increased risk of rectal toxicity www.co-urology.com
compared with either modality alone. Severe sideeffects may substantially alter the patient’s quality of life and require significant healthcare resource use. Iatrogenic rectourethral fistulas (RUFs) are a rare but challenging problem observed by urological and colorectal surgeons, and a debilitating complication that can follow the treatment of prostate cancer. Although uncommon, these RUFs may occur following radical prostatectomy [7], EBRT [8], cryosurgery [9], brachytherapy, or combination therapy for the treatment of prostate carcinoma. It is reported to occur in approximately 1% of patients treated with EBRT, in 1–6% of patients after radical
a
Section of Colon and Rectal Surgery, Department of Surgery and Division of Urology, Duke University Medical Center, Durham, North Carolina, USA b
Correspondence to Christopher Mantyh, MD, Duke University Medical Center, Box 3117, Durham, NC 27710, USA. Tel: +1 919 681 3977; fax: +1 919 681 7934; e-mail: [email protected] Curr Opin Urol 2014, 24:382–388 DOI:10.1097/MOU.0000000000000073 Volume 24 Number 4 July 2014
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Rectourethral fistulas in the cancer survivor Hanna et al. &
KEY POINTS Iatrogenic rectourethral fistulas are a rare and increasingly challenging complication that can follow the treatment of prostate cancer, with an increasing incidence secondary to the use of combination, radiation-based, and salvage therapies. Most patients will require surgical treatment of their RUF at some point because of the exceedingly rare rate of spontaneous healing. However, there is no consensus regarding the procedure of choice. Interposition of healthy tissue using muscle transposition flap repairs remain an attractive surgical option for fistulas with unfavorable local conditions, such as those present after radiation. A cause-specific, algorithmic, and often multidisciplinary approach with an emphasis on the techniques that are most familiar to the individual surgeon is important in achieving favorable outcomes.
prostatectomy, and in 5–9% following brachytherapy or cryotherapy after prostate cancer [10–13]. Advanced local disease, radiotherapy of the pelvis, bacterial prostatitis, or transurethral resection of the prostate before radical prostatectomy have been reported as predisposing factors for RUF [7–13]. Recently, Thomas et al. [14] reported that prostate cancer was locally advanced in 62% of their series of RUFs after radical prostatectomy. Additionally, they detected no additional risk factors including diabetes mellitus, antihormonal therapy, or former bowel, prostate, or bladder surgery. Therefore, adherence of the prostate to the rectum and wide surgical resection may have been contributing factors for rectal injury. Thomas et al. [14] further report that 54% of the patients in whom RUF developed actually experience an overt intraoperative rectal injury. Therefore, iatrogenic rectal injury during radical prostatectomy is a major risk factor for RUF. Harpster et al. [10] also demonstrated a higher incidence of RUF after perineal radical prostatectomy compared with retropubic radical prostatectomy. This may be attributable to difficult transection of the rectourethralis muscle and mobilization of the rectum as initial steps in perineal prostatectomy to gain access to the prostate.
THE CHANGING PROBLEM Of the 315 cases of RUF reported through 1997, only 12 (3.8%) involved radiation to the pelvis [15–19]. From 1998 through 2012 and including a recent study at our institution, 184 of the 360 reported cases (52.6%) have involved exposure to pelvic
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radiation [8,9,11,20–30,31 ,32,33,34 ]. Though some of this increase may be attributable to reporting bias, it is likely that the increased use of brachytherapy and combined brachytherapy and EBRT for prostate cancer would appear to contribute to the increasing incidence of RUFs. In fact, we recently noted an increase in the number of men presenting to our institution with RUF following radiation therapy for prostate cancer, particularly brachytherapy or a combination of EBRT and brachytherapy, as well as those presenting after salvage therapy have been used for biochemical or histologically confirmed recurrence. Prostatectomy, cryosurgery, brachytherapy, and high-intensity focused ultrasound (HIFU) have been used as salvage methods after failed EBRT. Indeed, with the unprecedented volume of primary radiation, salvage radiation, and combination therapy use in the last decade, along with the adjuncts of cryotherapy and HIFU, a dramatic change in the complexity of the lesion has developed. In addition, the rates of RUF after these salvage methods have been reported to be approximately 3–6% but as high as 60% when patients are treated with primary combination therapy [33,35– 37]. In most of these conditions, the fistula is usually large and the quality and healing ability of local tissues is poor with extensive radiation, eliminating any attempts at local repair. A concomitant urethral stricture, rectal stricture, and urethral or anal sphincteric dysfunction are other factors that may add to the complexity of this problem. As such, patients in whom a RUF develops have a prolonged clinical course, often requiring several surgical procedures. The basis of the challenge in these cases is an inaccessible, fibrotic, and adherent space containing anal and urinary sphincter as well as erectile anatomy with the potential of injury to these structures [30,38].
A CAUSE-SPECIFIC TIME COURSE The development of RUFs can be variable depending on its cause. Though RUF mostly develops 2–3 weeks after radical prostatectomy [39], it is important to note that the average time between last radiotherapy session and the diagnosis of fistula has been reported to range from 14 months to as long as 14 years, supporting the notion that RUF can be a late complication of radiotherapy [40,41]. The extended interval between radiotherapy and the development of complications warrants caution in performing rectal procedures in patients with an irradiated pelvis. Although some investigators have advocated the use of brachytherapy in patients who have cancer recurrence after full-dose EBRT, but many radiation oncologists discourage this practice for fear of injury to the rectum or bladder [5,6].
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It is also important to note that not all RUF in patients with a history of radiotherapy can be attributable only to this cause. Prior surgery or instrumentation as well as anterior biopsy of the rectum is believed to be associated with an increased risk of RUF. In at least 22 of the previously reported cases, other treatments or procedures were performed in the lower urinary tract or rectum [22]. Chrouser et al. [30] observed that in 81% of the patients with RUF after EBRT, brachytherapy, or EBRT and brachytherapy, a history of transurethral resection of the prostate, prostate biopsies, rectal stricture, urethral stricture, and rectal argon beam therapy was performed. Two studies have suggested that biopsy may be necessary when faced with endoscopic findings and a clinical situation consistent with radiation proctitis [8,16,42]. Shakespeare and Miller point to the concern of secondary colorectal carcinomas in patients with persistent rectal bleeding after radiotherapy as the impetus for early rectal biopsy. However, these authors argue against performing such procedures, as the increased incidence of carcinomas occur at 5–15 years following EBRT [42,43]. Such biopsies may actually facilitate fistula formation [44]. In these so-called vulnerable patients, the development of fistula after the biopsy or rectal surgery has been previously reported in the literature to be a mean of 4 months, compared with the relatively longer interval mean of 22.6 months after EBRT [40]. These data support the argument that the rectal biopsy or rectal surgery was the final event that facilitated fistula formation. The latency between the completion of EBRT and the onset of the RUF suggests that elective rectal surgery should be minimized even several years after radiotherapy. However, once RUFs are diagnosed in patients with a history of prostatic malignancy, some advocate a preoperative biopsy of the fistulous tract to exclude recurrent cancer [20].
THE MANAGEMENT DEBATE Spontaneous closure of an iatrogenic RUF can occur with the placement of an indwelling catheter in 25% of cases [45], but is exceedingly rare in radiated patients [21,23]. Some authors have suggested that the iatrogenic fistula must close within 6 weeks of the original surgery, prior to complete epithelialization of the track [46]. Although symptoms such as pneumaturia, fecaluria, and the passage of urine through the rectum are often alleviated by fecal and urinary diversion, these fistulas seldom spontaneously heal [21]. Even when diverted, patients may continue to develop recurrent urinary tract infections resistant to medical therapy [18]. Thus, most of these patients will eventually require 384
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surgical treatment. However, the problems of repair in such situations include difficult accessibility compounded by a previously operated on and sometimes irradiated field. As such, achieving a high fistula closure rate together with normal postoperative urinary and bowel function is a real challenge. Numerous surgical procedures have been described for the treatment of rectourethral fistula [7,21,15,47–49]. These include fecal diversion, primary repairs including the anterior transanorectal approach (sphincter divided), the Kraske laterosacral approach (sphincter not divided), the transanal approach and the posterior sagittal or York-Mason approach [15,21,23,50], endorectal advancement flaps, coloanal sleeve anastomoses [51], transposition flaps (e.g., omental), and various muscle flaps: bulbocavernosus, rectus abdominis, sartorius, gluteus, and gracilis [52–57]. However, all of these series are small and no consensus regarding management has been achieved. The lack of consensus on the optimal surgical option for closure of RUFs has resulted in the description of a myriad of techniques reflecting the uncertainty produced by limited small series without regard for cause and comorbidities [21]. In fact, Munoz et al. [58] described 40 different techniques highlighting the lack of consensus about the optimal treatment strategy. Overall, the ultimate goal of treatment for such an injury would be fistula closure with the restoration of bowel and bladder function, if possible. The role of fecal diversion as the treatment of choice in the healing of RUFs is unclear. Though previous studies have shown that it probably has no role as the sole modality of treatment [21], diversion may serve as an initial stage in preparation for reconstruction and repair and for control of sepsis in the region of the fistula [59]. However, even this role has been questioned [60–62]. In our opinion, diversion should be used as the initial operation in the presence of sepsis, primary repair of large fistulas, or when the healing capacity of the tissues is in doubt, such as in irradiated tissue. Indeed, rates of permanent fecal diversion as high as 31% have been reported for patients with complex RUFs because of an injured noncompliant rectum or severe anosphincteric dysfunction even when healing is observed [63]. Therefore, in these cases, if fecal and urinary diversion has not already been performed before referral, we generally perform a diverting ileostomy or colostomy and place a suprapubic tube or urethral catheter at the same time as a diagnostic cystoscopy and proctoscopy in all patients soon after presentation to prevent sepsis and decrease inflammation in the area of the fistula. Previous investigators have almost unanimously supported initial fecal and urinary diversion Volume 24 Number 4 July 2014
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as well, although one group recommended diversion before definitive surgery only in septic cases and diversion at definitive surgery in all others [21]. In the setting of obvious severe injury to the rectal sphincter, end colostomy is generally used because it would be anticipated to be permanent. If a colonic pull-through procedure is anticipated, ileostomy is preferred. Fecaluria seems to be a poor prognostic sign and should be considered a contraindication for immediate surgical fistula closure without proximal fecal diversion [14]. Conservative treatment by transurethral or suprapubic urinary diversion for at least 4 weeks is usually the first attempt in patients without signs of sepsis and fecaluria. As previously reported, the best time for fistula closure is 2–3 months after fecal diversion [14,64]. The control of local inflammation around the fistula seems to be the single most important factor for successful fistula closure. A modified York-Mason (posterior sagittal, transanal, and transrectal) approach has been the most widely used approach in the last decade. This approach allows for rapid access and excellent exposure through unscarred tissue planes, allowing for excision of the fistulous tract as well as a wide working space and thus easy manipulation of instruments (Supplementary Digital Content 1, http://links.lww.com/COU/A5) [65]. The posterolateral rectal innervations, urinary continence, and potency have been consistently preserved by maintaining a midline sagittal dissection and avoiding the lateral pelvic and pararectal space. When a midline transsphincteric incision is used, with careful tagging of the sphincteric muscle components and anastomotic restoration of the rectal wall, it does not result in fecal incontinence. For patients who have surgically acquired fistulas, which are often relatively small and surrounded by healthy tissue, this type of repair is associated with excellent success rates [65–68]. For nonirradiated fistulas, transanal and transsphincteric approaches to the rectal lumen with a rectal advancement flap are also well tolerated and have led to successful repairs in between 75 and 100% of cases [15,21]. Treatment in the patient with radiation-induced RUF is dictated by the clinical situation, life expectancy, premorbid urinary and bowel function, continence, and local anatomy. In cases of an irradiated rectourethral septum, fibrotic perineal body and septum, or traumatized tissue, as is the case in patients treated for prostate cancer, there often is inadequate viable tissue for any local repair to close fistulas. In these cases, it is often essential to separate the organs and interpose healthy tissue with an independent blood supply [52,53,69,70].
Unfortunately, radiotherapy-induced RUFs have a higher recurrence rate with such approaches, thought to be related to a lack of sufficient tissue interposition and vascularity. Indeed, even those who have reported excellent results with primary and one-stage repairs caution the use of these in complicated situations of irradiated tissue, and advocate for diversion and tissue interposition, as these patients often have large and necrotic fistulas [65]. Additionally, the prone position prohibits concomitant complex urethral reconstruction, the use of interposition muscle flaps, and the adjunct of a buccal mucosal graft onlay urethroplasty in large fistulas (larger than 2 cm) in which the urethral defect is not amenable to primary closure. Moreover, the procedure may be complicated by a 9–26% reported incidence of fecal transanal fistulization when fecal diversion is not used, and should not be offered to patients with known anorectal dysfunction in whom rectal continence may be impaired [71]. Optimal surgical approaches for these complex RUFs use the interposition of healthy tissue, such as omentum or gracilis muscle, into the plane between the rectum and urethra [20,21]. These tissues are placed over the urethral defect, which is usually not amenable to primary closure because of adjacent tissue fixation. Zmora et al. [20] described a series of 11 men with iatrogenic RUFs after surgery or pelvic radiotherapy for prostate cancer. Eightythree percent of 12 transposition flaps resulted in complete healing, although in two cases further surgical procedures were required, with eventual complete healing. This success rate in repairing iatrogenic RUFs is consistent with the reported 83–100% in the literature for this group of patients [20,21,63,72]. The additional advantage of the gracilis muscle interposition flap, in particular, is that it is done using a perineal approach. The urologist’s familiarity with the perineal approach can result in good exposure for identification, dissection, excision, and repair of the area extending from the bulbar urethra to the bladder neck and the related area of the rectum. Distal urethral mobilization is feasible through the same exposure, which allows for successful repair when associated urethral pathologic features are present. Moreover, there is preservation of urinary and rectal function.
CONCLUSION Patients with a RUF have to deal with a prolonged clinical course and side-effects of their therapy. In addition, they have to wait several months for definitive cure, often on average 3 months for successful fistula closure and longer for colostomy
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Reconstructive urology and the cancer survivor
Suspected rectourethral fistula
Appointment with urology
Patients should have voiding diary, 24-hr pad weight, AUA symptom score, IIEF-5 score, ICS male SF questionnaire, RUG, cytoscopy, check nutrition labs, +/– smoking referral Uppertract evaluation
Suprapubic tube +/– nutritional evaluation
Referral to colorectal surgery
Wexner symptom score, proctoscopy +/– anal manometry
Fecal diversion +/– nutritional evaluation
Nonradiated RUF*
PostRadiation/HIFU/Cryoablation RUF*
Suprapubic tube or Foley, Heal x3 months
Heal x4–6 months
Cystoscopy, RUG/VCUG, proctoscopy +/– nutrition labs
Cysto, RUG/VCUG, +/– urodynamics, pelvic MRI, proctoscopy, +/– nutrition labs
< 2cm, no stricture, no BNC, distal rectal RUF, good anal function
> 2cm orin proximal location
Consider perineal repair +/– plastic surgery involvement
York Mason Repair
Foley x3 weeks; suprapubic tube x4 weeks
Appointment with plastic surgery
If prostatic RUF: (1) Salvage prostatectomy (2) Omental vs gracilis flap
If < 2cm: (1) Primary urethra repair (2) Gracilis flap
If > 2cm or BNC or membrane strictures (1) Buccal only (2) Gracilis flap
Foley x6 weeks, suprapubic tube x8 weeks Pericath RUG/VCUG, proctoscopy
If ablative therapy: (1) Transperineal +/– transabdominal excision of cavity (2) Inferior pubectomy (3) Rectal closure (4) Omental vs gracilis flap (5) Vesicourethral anastamosis (6) Wound drainage
If > 3cm or fixed tissues, distal fistula, poor rectal tone
Pelvic exenteration with plastic surgery, urology, and colorectal surgery
Pericath RUG/VCUG
Consider reversal of fecal diversion Heal x6 months If urinary incontinence, consider artificial urinary sphincter at least 6 months after RUF repair
Gastografin enema, proctoscopy Cystoscopy, RUG, urodynamics, voiding diary, pad weights, quality of life questionnaires
If urinary incontinence, consider artificial urinary sphincter at least 6 months after RUF repair
Consider reversal of fecal diversion
FIGURE 1. Algorithm for the surgical management of rectourethral fistula. AUA, American Urological Association; BNC, bladder neck contracture; HIFU, high-intensity focused ultrasound; IIEF-5, International Index of Erectile Function-5; ICS, International Continence Society; RUG, retrograde urethrogram; RUF, rectourethral fistula; SF, short form; VCUG, voiding cystourethrogram. On the basis of clinical indications, consider fistula biopsy: (1) positive margins or (2) rising prostatespecific antigen.
closure. These time frames can be further prolonged in patients with radiotherapy-induced RUFs with longer times to healing. The multiplicity of 386
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approaches which exist for the repair of RUFs is testimony to the technical difficulty encountered and to the high recurrence rates [46,59,62,73–81]. Volume 24 Number 4 July 2014
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Rectourethral fistulas in the cancer survivor Hanna et al.
Because of multiple different approaches, our urology and colorectal surgery team at Duke have developed an algorithm for all patients with a newly diagnosed RUF based on a review of our own retrospective data as well as the previously published literature that uses a multidisciplinary approach to optimize results of surgery for RUFs (Fig. 1) [34 ]. Local tissues are evaluated by both urologic and colorectal surgeons. Fecal diversion is our preference for all fistulas. It is always performed in cases of a tenuous repair, active infection, previous failed attempts at closure, large fistulas, as well as in complex cases caused by radiation or cryosurgery. This prevents rectal wall distention and pressure during healing and minimizes rectal wall dehiscence and infection, which is critical for successful complex fistula closure. Careful consideration is given before bowel diversion is reversed, as patients with RUFs can require permanent fecal diversion because of an injured noncompliant rectum or severe anosphincteric dysfunction despite RUF healing [34 ]. In our own series of 37 patients, we demonstrate excellent results for even the most devastating radiationinduced fistulas using a cause-specific approach to closure of iatrogenic RUFs that is optimized by using a team of urologists, plastic surgeons, and colorectal surgeons. Using such an approach, 67% of irradiated patients demonstrated healing of their RUF, and all patients who developed an RUF after prostatectomy for prostate cancer demonstrated healing [34 ]. We additionally advocate an approach that is most familiar to the individual surgeon, as there is often little difference between transanal, posterior parasacral, transperineal, or transabdominal approaches in terms of recurrence [21]. However, given the high success rate and low complication rate, muscle transposition flap repairs are an attractive surgical option for fistulas with unfavorable local conditions such as those present after radiation or subsequent to long-term persistent infection, and especially after failed previous repairs. Although the numbers are small, it seems that bringing new muscle between the rectum and urethra gives sufficient bulk to prevent a recurrence and brings in a new blood supply in the case of irradiated tissue. Successful reconstruction strategies further avoid permanent urinary diversion, cystoprostatectomy, or proctectomy in the presence of an intact anal sphincter. This combination of techniques has been the most effective approach to the management of all RUFs, with excellent results for even the most devastating radiation or ablative fistulas with unprecedented success rates and minimal morbidity. &
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Acknowledgements None.
Conflicts of interest There are no conflicts of interest.
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50. Hudson CN. Rectovaginal and other fistulae between the intestine and genital tract. In: Fob C, Smith R, editors. Operative surgery: colon, rectum and anus. 3rd ed. Boston: Butterworths; 1997. 51. MacRae HM, McLeod RS, Cohen Z, et al. Treatment of rectovaginal fistulas that has failed previous repair attempts. Dis Colon Rectum 1995; 38:921– 925. 52. Stirnemann H. Treatment of recurrent recto-vaginal fistula by interposition of a gluteus maximus muscle flap. Am J Proctol 1969; 20:52–54. 53. Zacharin RF. Grafting as a principle in the surgical management of vesicovaginal and rectovaginal fistulae. Aust N Z J Obstet Gynaecol 1980; 20:10–17. 54. McCall ML, Bolten KA. Martin’s gynecological operations with emphasis on topographical anatomy. Boston: Little Brown & Co; 1957. 55. Parks AG, Allen CL, Frank JD, Mcpartlin JF. A method of treating postirradiation rectovaginal fistulas. Br J Surg 1978; 65:417–421. 56. Byron RL Jr, Ostergord DR. Sartorius muscle interposition for the treatment of the radiation-induced vaginal fistula. Am J Obstet Gynecol 1969; 104:104– 107. 57. Ryan JA Jr, Beebe HG, Gibbons RP. Gracilis muscle flap for closure of rectourethral fistula. J Urol 1979; 122:124–125. 58. Munoz M, Nelson H, Harrington J, et al. Management of acquired rectourinary fistulas: outcome according to cause. Dis Colon Rectum 1998; 41:1230– 1238. 59. Mason AY. Rectoprostatic and rectourethral fistulae. J R Soc Med 1973; 66:245–256. 60. Lewis LG. Repair of recto-urethral fistulas. J Urol 1947; 57:1173–1183. 61. Morgan C Jr. Dorsal rectotomy and full thickness skin graft for repair of prostatic urethrorectal fistula. J Urol 1975; 113:207–209. 62. Wood TW, Middleton RG. Single stage transrectal transsphincteric (modified York-Mason) repair of rectourinary fistulas. Urology 1990; 35:27–30. 63. Vanni AJ, Buckley JC, Zinman LN. Management of surgical and radiation induced rectourethral fistulas with an interposition muscle flap and selective buccal mucosal onlay graft. J Urol 2010; 184:2400–2404. 64. Gupta G, Kumar S, Kekre N, et al. Surgical management of rectourethral fistula. Urology 2008; 71:267–271. 65. Renschler TD, Middleton RG. 30 Years of experience with York-Mason repair of recto-urinary fistulas. J Urol 2003; 170:1222–1225. 66. Bukowski TP, Chakrabarty A, Powell IJ, et al. Acquired rectourethral fistula: methods of repair. J Urol 1995; 153:730–733. 67. Fengler SA, Abcarian H. The York Mason approach to repair of iatrogenic rectourinary fistulae. Am J Surg 1997; 173:213–217. 68. Kasraeian A, Rozet F, Cathelineau X, et al. Modified York-Mason technique for repair of iatrogenic rectourinary fistula: the Montsouris experience. J Urol 2009; 181:1178–1183. 69. Gorenstein L, Boyd JB, Ross TM. Gracilis muscle repair of rectovaginal fistula after restorative proctocolectomy: report of two cases. Dis Colon Rectum 1988; 31:730–734. 70. Boronow RC. Repair of the radiation-induced vaginal fistula utilizing the Martius technique. World J Surg 1986; 10:237–248. 71. Thompson BW, Tucker WE. Transsphincteric approach to lesions of the rectum. South Med J 1987; 80:41–43. 72. Ghoniem G, Elmissiry M, Weiss E, et al. Transperineal repair of complex rectourethral fistula using gracilis muscle flap interposition – can urinary and bowel functions be preserved? J Urol 2008; 179:1882–1886. 73. Culp OS, Calhoon HW. A variety of rectourethral fistulas: experiences with 20 cases. J Urol 1964; 91:560–571. 74. Turner-Varwick R. The use of pedicled grafts in the repair of urinary tract fistulae. Br J Urol 1972; 44:644–656. 75. Antony J. A method of repair of recurrent recto-vesicoprostatic fistula following prostatectomy. J Urol 1980; 124:936–937. 76. Trippitelli A, Barbagli G, Lenzi R, et al. Surgical treatment of rectourethral fistulae. Eur Urol 1985; 11:388–391. 77. Venable DD. Modification of the anterior perineal transanorectat approach for complicated urethrorectal fistula repair. J Urol 1989; 142:381–384. 78. Gecelter L. Transanorectal approach to the posterior urethra and bladder neck. J Urol 1973; 109:1011–1016. 79. Vose SN. A technique for the repair of recto-urethral fistulas. J Urol 1949; 61:790–794. 80. Kilpatrick FR, Thompson HR. Postoperative recto-prostatic fistula and closure by Kraske’s approach. Br J Urol 1962; 34:470–474. 81. Prasad ML, Nelson R, Hambrick E, Abcarian H. York Mason procedure for repair of postoperative rectoprostatic urethral fistula. Dis Colon Rectum 1983; 26:716–720.
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Rectourethral fistulas in the cancer survivor Jennifer M. Hanna a, Andrew C. Peterson b, and Christopher Mantyh a
Purpose of review Iatrogenic rectourethral fistulas (RUFs) are a rare but challenging complication that can follow the treatment of prostate cancer. We review the literature regarding the surgical management of RUFs and subsequent outcomes, focusing on a cause-specific approach. Recent findings Iatrogenic RUFs are reported to occur in approximately 1% of patients treated with external-beam radiation therapy, in 1–6% of patients after radical prostatectomy, and in 5–9% following brachytherapy or cryotherapy after prostate cancer. Most of these patients will require surgical treatment at some point. Though there have been multiple surgical procedures described with varying degrees of success, there is no consensus as to the procedure of choice, though authors now agree on the importance of the interposition of healthy tissue in radiation-induced fistulas. Summary The current literature regarding surgical approaches to the iatrogenic RUF in the prostate cancer patient highlights the importance of a cause-specific and often multidisciplinary approach, as well as the one that is most familiar to the individual surgeon, because there is often little difference in the approaches in terms of recurrence. However, given the high success rate and low complication rate, muscle transposition flap repairs remain an attractive surgical option for fistulas with unfavorable local conditions such as those present after radiation. Keywords gracilis interposition graft, prostate cancer, rectourethral fistula, York-Mason repair
INTRODUCTION Adenocarcinoma of the prostate is the most common urologic malignancy in the USA and the third leading cause of cancer death in men [1]. With improved screening methods and the advent of the prostate-specific antigen (PSA) blood test, an increasing number of patients have been diagnosed with clinically localized disease. Local therapy for T1–2N0 disease results in greater than 90% 10-year disease-specific survival [2]. Consequently, toxicity and quality of life following therapy are important in treatment selection. Several reports have shown the utility of therapeutic options, including radical prostatectomy and radiotherapy [external-beam radiotherapy (EBRT) or brachytherapy], for patients with localized prostate cancer and a low risk of biochemical failure after treatment [3,4]. More advanced carcinomas require higher doses for adequate treatment [5,6]. One strategy for dose escalation uses EBRT in conjunction with brachytherapy. This approach is intended to improve local control and disease-free survival [3,4]. Combined EBRT and brachytherapy, however, can be associated with an increased risk of rectal toxicity www.co-urology.com
compared with either modality alone. Severe sideeffects may substantially alter the patient’s quality of life and require significant healthcare resource use. Iatrogenic rectourethral fistulas (RUFs) are a rare but challenging problem observed by urological and colorectal surgeons, and a debilitating complication that can follow the treatment of prostate cancer. Although uncommon, these RUFs may occur following radical prostatectomy [7], EBRT [8], cryosurgery [9], brachytherapy, or combination therapy for the treatment of prostate carcinoma. It is reported to occur in approximately 1% of patients treated with EBRT, in 1–6% of patients after radical
a
Section of Colon and Rectal Surgery, Department of Surgery and Division of Urology, Duke University Medical Center, Durham, North Carolina, USA b
Correspondence to Christopher Mantyh, MD, Duke University Medical Center, Box 3117, Durham, NC 27710, USA. Tel: +1 919 681 3977; fax: +1 919 681 7934; e-mail: [email protected] Curr Opin Urol 2014, 24:382–388 DOI:10.1097/MOU.0000000000000073 Volume 24 Number 4 July 2014
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Rectourethral fistulas in the cancer survivor Hanna et al. &
KEY POINTS Iatrogenic rectourethral fistulas are a rare and increasingly challenging complication that can follow the treatment of prostate cancer, with an increasing incidence secondary to the use of combination, radiation-based, and salvage therapies. Most patients will require surgical treatment of their RUF at some point because of the exceedingly rare rate of spontaneous healing. However, there is no consensus regarding the procedure of choice. Interposition of healthy tissue using muscle transposition flap repairs remain an attractive surgical option for fistulas with unfavorable local conditions, such as those present after radiation. A cause-specific, algorithmic, and often multidisciplinary approach with an emphasis on the techniques that are most familiar to the individual surgeon is important in achieving favorable outcomes.
prostatectomy, and in 5–9% following brachytherapy or cryotherapy after prostate cancer [10–13]. Advanced local disease, radiotherapy of the pelvis, bacterial prostatitis, or transurethral resection of the prostate before radical prostatectomy have been reported as predisposing factors for RUF [7–13]. Recently, Thomas et al. [14] reported that prostate cancer was locally advanced in 62% of their series of RUFs after radical prostatectomy. Additionally, they detected no additional risk factors including diabetes mellitus, antihormonal therapy, or former bowel, prostate, or bladder surgery. Therefore, adherence of the prostate to the rectum and wide surgical resection may have been contributing factors for rectal injury. Thomas et al. [14] further report that 54% of the patients in whom RUF developed actually experience an overt intraoperative rectal injury. Therefore, iatrogenic rectal injury during radical prostatectomy is a major risk factor for RUF. Harpster et al. [10] also demonstrated a higher incidence of RUF after perineal radical prostatectomy compared with retropubic radical prostatectomy. This may be attributable to difficult transection of the rectourethralis muscle and mobilization of the rectum as initial steps in perineal prostatectomy to gain access to the prostate.
THE CHANGING PROBLEM Of the 315 cases of RUF reported through 1997, only 12 (3.8%) involved radiation to the pelvis [15–19]. From 1998 through 2012 and including a recent study at our institution, 184 of the 360 reported cases (52.6%) have involved exposure to pelvic
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radiation [8,9,11,20–30,31 ,32,33,34 ]. Though some of this increase may be attributable to reporting bias, it is likely that the increased use of brachytherapy and combined brachytherapy and EBRT for prostate cancer would appear to contribute to the increasing incidence of RUFs. In fact, we recently noted an increase in the number of men presenting to our institution with RUF following radiation therapy for prostate cancer, particularly brachytherapy or a combination of EBRT and brachytherapy, as well as those presenting after salvage therapy have been used for biochemical or histologically confirmed recurrence. Prostatectomy, cryosurgery, brachytherapy, and high-intensity focused ultrasound (HIFU) have been used as salvage methods after failed EBRT. Indeed, with the unprecedented volume of primary radiation, salvage radiation, and combination therapy use in the last decade, along with the adjuncts of cryotherapy and HIFU, a dramatic change in the complexity of the lesion has developed. In addition, the rates of RUF after these salvage methods have been reported to be approximately 3–6% but as high as 60% when patients are treated with primary combination therapy [33,35– 37]. In most of these conditions, the fistula is usually large and the quality and healing ability of local tissues is poor with extensive radiation, eliminating any attempts at local repair. A concomitant urethral stricture, rectal stricture, and urethral or anal sphincteric dysfunction are other factors that may add to the complexity of this problem. As such, patients in whom a RUF develops have a prolonged clinical course, often requiring several surgical procedures. The basis of the challenge in these cases is an inaccessible, fibrotic, and adherent space containing anal and urinary sphincter as well as erectile anatomy with the potential of injury to these structures [30,38].
A CAUSE-SPECIFIC TIME COURSE The development of RUFs can be variable depending on its cause. Though RUF mostly develops 2–3 weeks after radical prostatectomy [39], it is important to note that the average time between last radiotherapy session and the diagnosis of fistula has been reported to range from 14 months to as long as 14 years, supporting the notion that RUF can be a late complication of radiotherapy [40,41]. The extended interval between radiotherapy and the development of complications warrants caution in performing rectal procedures in patients with an irradiated pelvis. Although some investigators have advocated the use of brachytherapy in patients who have cancer recurrence after full-dose EBRT, but many radiation oncologists discourage this practice for fear of injury to the rectum or bladder [5,6].
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It is also important to note that not all RUF in patients with a history of radiotherapy can be attributable only to this cause. Prior surgery or instrumentation as well as anterior biopsy of the rectum is believed to be associated with an increased risk of RUF. In at least 22 of the previously reported cases, other treatments or procedures were performed in the lower urinary tract or rectum [22]. Chrouser et al. [30] observed that in 81% of the patients with RUF after EBRT, brachytherapy, or EBRT and brachytherapy, a history of transurethral resection of the prostate, prostate biopsies, rectal stricture, urethral stricture, and rectal argon beam therapy was performed. Two studies have suggested that biopsy may be necessary when faced with endoscopic findings and a clinical situation consistent with radiation proctitis [8,16,42]. Shakespeare and Miller point to the concern of secondary colorectal carcinomas in patients with persistent rectal bleeding after radiotherapy as the impetus for early rectal biopsy. However, these authors argue against performing such procedures, as the increased incidence of carcinomas occur at 5–15 years following EBRT [42,43]. Such biopsies may actually facilitate fistula formation [44]. In these so-called vulnerable patients, the development of fistula after the biopsy or rectal surgery has been previously reported in the literature to be a mean of 4 months, compared with the relatively longer interval mean of 22.6 months after EBRT [40]. These data support the argument that the rectal biopsy or rectal surgery was the final event that facilitated fistula formation. The latency between the completion of EBRT and the onset of the RUF suggests that elective rectal surgery should be minimized even several years after radiotherapy. However, once RUFs are diagnosed in patients with a history of prostatic malignancy, some advocate a preoperative biopsy of the fistulous tract to exclude recurrent cancer [20].
THE MANAGEMENT DEBATE Spontaneous closure of an iatrogenic RUF can occur with the placement of an indwelling catheter in 25% of cases [45], but is exceedingly rare in radiated patients [21,23]. Some authors have suggested that the iatrogenic fistula must close within 6 weeks of the original surgery, prior to complete epithelialization of the track [46]. Although symptoms such as pneumaturia, fecaluria, and the passage of urine through the rectum are often alleviated by fecal and urinary diversion, these fistulas seldom spontaneously heal [21]. Even when diverted, patients may continue to develop recurrent urinary tract infections resistant to medical therapy [18]. Thus, most of these patients will eventually require 384
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surgical treatment. However, the problems of repair in such situations include difficult accessibility compounded by a previously operated on and sometimes irradiated field. As such, achieving a high fistula closure rate together with normal postoperative urinary and bowel function is a real challenge. Numerous surgical procedures have been described for the treatment of rectourethral fistula [7,21,15,47–49]. These include fecal diversion, primary repairs including the anterior transanorectal approach (sphincter divided), the Kraske laterosacral approach (sphincter not divided), the transanal approach and the posterior sagittal or York-Mason approach [15,21,23,50], endorectal advancement flaps, coloanal sleeve anastomoses [51], transposition flaps (e.g., omental), and various muscle flaps: bulbocavernosus, rectus abdominis, sartorius, gluteus, and gracilis [52–57]. However, all of these series are small and no consensus regarding management has been achieved. The lack of consensus on the optimal surgical option for closure of RUFs has resulted in the description of a myriad of techniques reflecting the uncertainty produced by limited small series without regard for cause and comorbidities [21]. In fact, Munoz et al. [58] described 40 different techniques highlighting the lack of consensus about the optimal treatment strategy. Overall, the ultimate goal of treatment for such an injury would be fistula closure with the restoration of bowel and bladder function, if possible. The role of fecal diversion as the treatment of choice in the healing of RUFs is unclear. Though previous studies have shown that it probably has no role as the sole modality of treatment [21], diversion may serve as an initial stage in preparation for reconstruction and repair and for control of sepsis in the region of the fistula [59]. However, even this role has been questioned [60–62]. In our opinion, diversion should be used as the initial operation in the presence of sepsis, primary repair of large fistulas, or when the healing capacity of the tissues is in doubt, such as in irradiated tissue. Indeed, rates of permanent fecal diversion as high as 31% have been reported for patients with complex RUFs because of an injured noncompliant rectum or severe anosphincteric dysfunction even when healing is observed [63]. Therefore, in these cases, if fecal and urinary diversion has not already been performed before referral, we generally perform a diverting ileostomy or colostomy and place a suprapubic tube or urethral catheter at the same time as a diagnostic cystoscopy and proctoscopy in all patients soon after presentation to prevent sepsis and decrease inflammation in the area of the fistula. Previous investigators have almost unanimously supported initial fecal and urinary diversion Volume 24 Number 4 July 2014
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as well, although one group recommended diversion before definitive surgery only in septic cases and diversion at definitive surgery in all others [21]. In the setting of obvious severe injury to the rectal sphincter, end colostomy is generally used because it would be anticipated to be permanent. If a colonic pull-through procedure is anticipated, ileostomy is preferred. Fecaluria seems to be a poor prognostic sign and should be considered a contraindication for immediate surgical fistula closure without proximal fecal diversion [14]. Conservative treatment by transurethral or suprapubic urinary diversion for at least 4 weeks is usually the first attempt in patients without signs of sepsis and fecaluria. As previously reported, the best time for fistula closure is 2–3 months after fecal diversion [14,64]. The control of local inflammation around the fistula seems to be the single most important factor for successful fistula closure. A modified York-Mason (posterior sagittal, transanal, and transrectal) approach has been the most widely used approach in the last decade. This approach allows for rapid access and excellent exposure through unscarred tissue planes, allowing for excision of the fistulous tract as well as a wide working space and thus easy manipulation of instruments (Supplementary Digital Content 1, http://links.lww.com/COU/A5) [65]. The posterolateral rectal innervations, urinary continence, and potency have been consistently preserved by maintaining a midline sagittal dissection and avoiding the lateral pelvic and pararectal space. When a midline transsphincteric incision is used, with careful tagging of the sphincteric muscle components and anastomotic restoration of the rectal wall, it does not result in fecal incontinence. For patients who have surgically acquired fistulas, which are often relatively small and surrounded by healthy tissue, this type of repair is associated with excellent success rates [65–68]. For nonirradiated fistulas, transanal and transsphincteric approaches to the rectal lumen with a rectal advancement flap are also well tolerated and have led to successful repairs in between 75 and 100% of cases [15,21]. Treatment in the patient with radiation-induced RUF is dictated by the clinical situation, life expectancy, premorbid urinary and bowel function, continence, and local anatomy. In cases of an irradiated rectourethral septum, fibrotic perineal body and septum, or traumatized tissue, as is the case in patients treated for prostate cancer, there often is inadequate viable tissue for any local repair to close fistulas. In these cases, it is often essential to separate the organs and interpose healthy tissue with an independent blood supply [52,53,69,70].
Unfortunately, radiotherapy-induced RUFs have a higher recurrence rate with such approaches, thought to be related to a lack of sufficient tissue interposition and vascularity. Indeed, even those who have reported excellent results with primary and one-stage repairs caution the use of these in complicated situations of irradiated tissue, and advocate for diversion and tissue interposition, as these patients often have large and necrotic fistulas [65]. Additionally, the prone position prohibits concomitant complex urethral reconstruction, the use of interposition muscle flaps, and the adjunct of a buccal mucosal graft onlay urethroplasty in large fistulas (larger than 2 cm) in which the urethral defect is not amenable to primary closure. Moreover, the procedure may be complicated by a 9–26% reported incidence of fecal transanal fistulization when fecal diversion is not used, and should not be offered to patients with known anorectal dysfunction in whom rectal continence may be impaired [71]. Optimal surgical approaches for these complex RUFs use the interposition of healthy tissue, such as omentum or gracilis muscle, into the plane between the rectum and urethra [20,21]. These tissues are placed over the urethral defect, which is usually not amenable to primary closure because of adjacent tissue fixation. Zmora et al. [20] described a series of 11 men with iatrogenic RUFs after surgery or pelvic radiotherapy for prostate cancer. Eightythree percent of 12 transposition flaps resulted in complete healing, although in two cases further surgical procedures were required, with eventual complete healing. This success rate in repairing iatrogenic RUFs is consistent with the reported 83–100% in the literature for this group of patients [20,21,63,72]. The additional advantage of the gracilis muscle interposition flap, in particular, is that it is done using a perineal approach. The urologist’s familiarity with the perineal approach can result in good exposure for identification, dissection, excision, and repair of the area extending from the bulbar urethra to the bladder neck and the related area of the rectum. Distal urethral mobilization is feasible through the same exposure, which allows for successful repair when associated urethral pathologic features are present. Moreover, there is preservation of urinary and rectal function.
CONCLUSION Patients with a RUF have to deal with a prolonged clinical course and side-effects of their therapy. In addition, they have to wait several months for definitive cure, often on average 3 months for successful fistula closure and longer for colostomy
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Suspected rectourethral fistula
Appointment with urology
Patients should have voiding diary, 24-hr pad weight, AUA symptom score, IIEF-5 score, ICS male SF questionnaire, RUG, cytoscopy, check nutrition labs, +/– smoking referral Uppertract evaluation
Suprapubic tube +/– nutritional evaluation
Referral to colorectal surgery
Wexner symptom score, proctoscopy +/– anal manometry
Fecal diversion +/– nutritional evaluation
Nonradiated RUF*
PostRadiation/HIFU/Cryoablation RUF*
Suprapubic tube or Foley, Heal x3 months
Heal x4–6 months
Cystoscopy, RUG/VCUG, proctoscopy +/– nutrition labs
Cysto, RUG/VCUG, +/– urodynamics, pelvic MRI, proctoscopy, +/– nutrition labs
< 2cm, no stricture, no BNC, distal rectal RUF, good anal function
> 2cm orin proximal location
Consider perineal repair +/– plastic surgery involvement
York Mason Repair
Foley x3 weeks; suprapubic tube x4 weeks
Appointment with plastic surgery
If prostatic RUF: (1) Salvage prostatectomy (2) Omental vs gracilis flap
If < 2cm: (1) Primary urethra repair (2) Gracilis flap
If > 2cm or BNC or membrane strictures (1) Buccal only (2) Gracilis flap
Foley x6 weeks, suprapubic tube x8 weeks Pericath RUG/VCUG, proctoscopy
If ablative therapy: (1) Transperineal +/– transabdominal excision of cavity (2) Inferior pubectomy (3) Rectal closure (4) Omental vs gracilis flap (5) Vesicourethral anastamosis (6) Wound drainage
If > 3cm or fixed tissues, distal fistula, poor rectal tone
Pelvic exenteration with plastic surgery, urology, and colorectal surgery
Pericath RUG/VCUG
Consider reversal of fecal diversion Heal x6 months If urinary incontinence, consider artificial urinary sphincter at least 6 months after RUF repair
Gastografin enema, proctoscopy Cystoscopy, RUG, urodynamics, voiding diary, pad weights, quality of life questionnaires
If urinary incontinence, consider artificial urinary sphincter at least 6 months after RUF repair
Consider reversal of fecal diversion
FIGURE 1. Algorithm for the surgical management of rectourethral fistula. AUA, American Urological Association; BNC, bladder neck contracture; HIFU, high-intensity focused ultrasound; IIEF-5, International Index of Erectile Function-5; ICS, International Continence Society; RUG, retrograde urethrogram; RUF, rectourethral fistula; SF, short form; VCUG, voiding cystourethrogram. On the basis of clinical indications, consider fistula biopsy: (1) positive margins or (2) rising prostatespecific antigen.
closure. These time frames can be further prolonged in patients with radiotherapy-induced RUFs with longer times to healing. The multiplicity of 386
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approaches which exist for the repair of RUFs is testimony to the technical difficulty encountered and to the high recurrence rates [46,59,62,73–81]. Volume 24 Number 4 July 2014
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Rectourethral fistulas in the cancer survivor Hanna et al.
Because of multiple different approaches, our urology and colorectal surgery team at Duke have developed an algorithm for all patients with a newly diagnosed RUF based on a review of our own retrospective data as well as the previously published literature that uses a multidisciplinary approach to optimize results of surgery for RUFs (Fig. 1) [34 ]. Local tissues are evaluated by both urologic and colorectal surgeons. Fecal diversion is our preference for all fistulas. It is always performed in cases of a tenuous repair, active infection, previous failed attempts at closure, large fistulas, as well as in complex cases caused by radiation or cryosurgery. This prevents rectal wall distention and pressure during healing and minimizes rectal wall dehiscence and infection, which is critical for successful complex fistula closure. Careful consideration is given before bowel diversion is reversed, as patients with RUFs can require permanent fecal diversion because of an injured noncompliant rectum or severe anosphincteric dysfunction despite RUF healing [34 ]. In our own series of 37 patients, we demonstrate excellent results for even the most devastating radiationinduced fistulas using a cause-specific approach to closure of iatrogenic RUFs that is optimized by using a team of urologists, plastic surgeons, and colorectal surgeons. Using such an approach, 67% of irradiated patients demonstrated healing of their RUF, and all patients who developed an RUF after prostatectomy for prostate cancer demonstrated healing [34 ]. We additionally advocate an approach that is most familiar to the individual surgeon, as there is often little difference between transanal, posterior parasacral, transperineal, or transabdominal approaches in terms of recurrence [21]. However, given the high success rate and low complication rate, muscle transposition flap repairs are an attractive surgical option for fistulas with unfavorable local conditions such as those present after radiation or subsequent to long-term persistent infection, and especially after failed previous repairs. Although the numbers are small, it seems that bringing new muscle between the rectum and urethra gives sufficient bulk to prevent a recurrence and brings in a new blood supply in the case of irradiated tissue. Successful reconstruction strategies further avoid permanent urinary diversion, cystoprostatectomy, or proctectomy in the presence of an intact anal sphincter. This combination of techniques has been the most effective approach to the management of all RUFs, with excellent results for even the most devastating radiation or ablative fistulas with unprecedented success rates and minimal morbidity. &
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Acknowledgements None.
Conflicts of interest There are no conflicts of interest.
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