An Update on the Use of Mitomycin C for Endoscopic Management of Vesicourethral Anastomotic Stenosis and Bladder Neck Contracture
By: Jack G. Campbell, MD; Alex J. Vanni, MD, FACS | Posted on: 05 Oct 2021
Contracture of the posterior urethra at the junction with the bladder includes both vesicourethral anastomotic stenosis (VUAS) after prostatectomy for prostate cancer and bladder neck contracture (BNC) resulting from endoscopic intervention for benign prostate disease. Additionally, pelvic radiotherapy can lead to posterior urethral stenosis in up to 32% of patients, particularly when associated with radical prostatectomy.1 The goal of treating VUAS and BNC is to restore physiological voiding, prevent urinary retention, maintain urinary continence and avoid the need for intermittent or indwelling catheterization. Although most VUAS/BNC will resolve after a single procedure, maximizing the efficacy of endoscopic management with adjuncts to reduce scar formation for recurrent VUAS/BNC is appealing in order to avoid the complexity and comorbidity of open or robotic bladder neck reconstruction.
Mitomycin C (MMC) is an antibiotic with antiproliferative properties including inhibition of fibroblast proliferation and collagen deposition that has been employed in clinical medicine for over 50 years. It has been widely used in the management of various diseases of scarring or contracture and was first described for the management of VUAS and BNC in 2011.2 Since the initial description, multiple cohort studies have evaluated endoscopic incision, dilation or resection of the vesicourethral anastomosis or bladder neck with MMC injection, as summarized in the table.2–9
Table. Summary of studies using MMC for VUAS/BNC management
|Source||Technique||No.||Total Dosage/Concentration||Median Followup (mos)||No. Serious Adverse Events||% Results after 1 or 2 Treatments|
|Vanni2||CKI, MMCI × 3–4 incision sites||18||NR / 0.3–0.4 mg/ml||12||0||1: 72
|Lyon3||Bipolar TUIBN, MMCI × 4 sites||13||2 mg / 0.4 mg/ml)||16.5||0||1: 62
|Redshaw4||TUR or TUI, MMCI at incision sites||55||0.4–10 mg (0.1–1 mg/ml)||8.6||4 (7%)||1: 58
|Nagpal5||CKI, MMCI × 3–4 incision sites||40||NR / 0.3–0.4 mg/ml)||20.5||0||1: 75
|Farrell6||CKI × 4 sites, MMCI at incision sites, daily CIC||11*||4 mg (0.4 mg/ml)||23†||0||1: 64
|Koslov7||HKI × 3 sites, MMCI at incision sites||9||0.5 mg||20||0||1: 89|
|Sourial8||MMCI × 3 sites, dilation to 26 Fr||29||0.1 mg (0.05 mg/ml)||12||0||1: 79
|Rozanski9||CKI, MMCI × 3–4 incision sites||86||NR / 0.3–0.4 mg/ml||21.1||0||1: 65
|CKI, cold knife incision. HKI, hot knife incision. TUIBN, transurethral incision bladder neck.
*VUAS/BNC patients in a total cohort of 37.
† Includes entire cohort, not only VUAS/BNC.
Despite differences in surgical technique and dosage, overall success after 1 and 2 treatments is 58%–75% and 73%–89%, respectively, in this difficult patient cohort. In the largest multi-institutional series, overall patency at median followup of 21.1 months was 90% when allowing for patients receiving 3 or more treatments, including an overall success rate of 76% in 24 irradiated patients.9 While studies on the efficacy of endoscopic MMC do not usually describe the rate and degree of stress incontinence, the rate of all patients treated with urethrotomy and MMC who go on to receive artificial urinary sphincter is 25%–45%.4,8
To our knowledge, only 1 study has reported adverse events potentially related to MMC in endoscopic management of VUAS/BNC. A study of patients from 6 institutions observed severe adverse events in 4/55 (7%) patients including the devastating complications of rectourethral fistula, osteitis pubis and necrosis of the trigone.4 It is important to note, however, that the technique of incisions was not standardized in the group (hot and cold knife), and the dosing of MMC in these patients ranged from 2–4.5 mg with 3 of 4 patients receiving at least 4 mg. These complications highlight the importance of a standardized protocol in terms of the urethrotomy type, location of incision and dose of MMC. Our technique is to incise (cold knife is our preference) through the contracture, but not so deeply as to be in the surrounding structures. Additionally, it is important to avoid incisions at both the 6 o’clock and 12 o’clock positions to avoid the proximity of the rectum and pubic symphysis.
The existing data on the optimal endoscopic management of VUAS/BNC are limited due to a lack of randomized trials, variance in followup and definition of success, different incision or resection techniques and lack of stratification between VUAS and BNC. Of note, the management of these patients is addressed with 3 guideline statements in the AUA 2016 Male Urethral Stricture Guidelines, which allow for dilation, incision or resection of the vesicourethral anastomosis or bladder neck, or for open reconstruction.10 Adjunctive endoscopic therapies, including MMC, are not directly addressed. Thus, studies directly comparing various techniques and treatment modalities are important moving forward. Although we offer robotic bladder neck reconstruction or urinary diversion to patients with recurrent VAUS/BNC (required in some cases, ie obliterated bladder neck), we believe there is utility with urethrotomy and low-dose MMC injection for recalcitrant VUAS/BNC due to the low morbidity and proven success rate demonstrated in multiple studies2–9 as the vast majority of patients avoid intermittent or indwelling catheterization or more complex reconstructive procedures. As with all complex medical conditions, thorough patient counseling and shared decision making are imperative when deciding how to treat our patient’s recurrent VUAS/BNC.
- Browne BM and Vanni AJ: Management of urethral stricture and bladder neck contracture following primary and salvage treatment of prostate cancer. Curr Urol Rep 2017; 18: 76.
- Vanni AJ, Zinman LN and Buckley JC: Radial urethrotomy and intralesional mitomycin C for the management of recurrent bladder neck contractures. J Urol 2011; 186: 156.
- Lyon TD, Ayyash OM, Ferroni MC et al: Bipolar transurethral incision of bladder neck stenoses with mitomycin C injection. Adv Urol 2015; 2015: 758536.
- Redshaw JD, Broghammer JA, Smith TG et al: Intralesional injection of mitomycin C at transurethral incision of bladder neck contracture may offer limited benefit: TURNS Study Group. J Urol 2015; 193: 87.
- Nagpal K, Zinman LN, Lebeis C et al: Durable results of mitomycin C injection with internal urethrotomy for refractory bladder neck contractures: multi-institutional experience. Urol Pract 2015; 2: 250.
- Farrell MR, Sherer BA and Levine LA: Visual internal urethrotomy with intralesional mitomycin C and short-term clean intermittent catheterization for the management of recurrent urethral strictures and bladder neck contractures. Urology 2015; 85: 1494.
- Koslov DS, Kovell R, Wood KD et al: Adjunctive intralesional antifibrotics following transurethral incision of bladder neck contractures. Int J Urol Nephrol 2015; 3: 97.
- Sourial MW, Richard PO, Bettez M et al: Mitomycin-C and urethral dilatation: a safe, effective, and minimally invasive procedure for recurrent vesicourethral anastomotic stenoses. Urol Oncol 2017; 35: 672.
- Rozanski AT, Zhang LT, Holst DD et al: The effect of radiation therapy on the efficacy of internal urethrotomy with intralesional mitomycin C for recurrent vesicourethral anastomotic stenoses and bladder neck contractures: a multi-institutional experience. Urology 2021; 147: 294.
- Wessells H, Angermeier KW, Elliott S et al: Male urethral stricture: American Urological Association guideline. J Urol 2017; 197: 182.