Bladder neck contracture, posterior urethral stenosis, and vesicourethral anastomotic stricture are all well-described complications following surgical management for benign and malignant conditions of the prostate. These are particularly prevalent after radical or simple prostatectomy or transurethral resection of the prostate, with an incidence of up to 17% being reported in some studies.¹

Accepted initial management for bladder neck contractures often involves repeated endoscopic procedures including dilations and transurethral incision; however, patency rates vary and recalcitrant strictures are often challenging to manage, recur rapidly, and are resistant to further interventions. More definitive treatment modalities encompassing bladder neck reconstruction are technically demanding, and patients are often left dependent upon self-catheterization regimens, suprapubic drainage, or urinary diversion.

The necessity of less morbid treatment options with improved durability has led to the implementation of mitomycin C as an injectable adjunct to transurethral incision, aiming to harness its antifibrotic properties to reduce and prevent contracture recurrence.

Mitomycin C is an alkylating antiproliferative agent, first isolated by Japanese microbiologists in 1958 from Streptomyces caespitosus, with an active metabolite that causes DNA cross-linking, leading to selective interruption of DNA replication and inhibition of mitosis and protein synthesis. This mechanism forms the basis of its ability to prevent fibroblast proliferation independent of the cell cycle in addition to suppressing endothelial cell growth, collagen deposition, and scar formation. Successfully introduced in 1963 for pterygium surgery, over the last 25 years it has become widely used during glaucoma and corneal refractive surgery and for cicatricial eye disease, conjunctival neoplasia, and allergic eye disease.² It has also been administered intravenously to treat upper gastrointestinal, anal, and breast cancers. In addition to its role in the management of noninvasive bladder cancer via intravesical instillation, mitomycin C has been utilized for the treatment of bladder neck contractures since the late 2000s. Other treatments have been employed in the management of posterior urethral stenosis including intralesional steroid injections with moderate success,³ and urethral stents (no longer available); however, mitomycin C is currently the most commonly used adjunct with the largest accumulated evidence base.

Figure 2. Bladder neck contracture cannulated with hydrophilic guidewire under direct vision.

Results of the addition of mitomycin C injection to direct vision internal urethrotomy have been promising in small studies of patients with recurrent bladder neck contractures. An early retrospective review in 2011 of 18 patients with severe, recurrent contractures undergoing urethrotomy plus mitomycin C injection revealed 72% of patients had a patent bladder neck after 1 procedure at a median follow-up of 12 months, with successful treatment defined as a bladder neck patent to >17Fr navigable via flexible cystoscopy without the need for catheter or dilation.¹ These results were subsequently reproduced in 2015 in a similar study of 40 patients, 75% of whom were demonstrated to have a stable bladder neck following a single procedure with a median follow-up of 20.5 months.⁴ Further improvements in durable bladder neck patency rates of up to 89% following repeat procedures have also been observed.^1,5

Figure 3. Plasma cut utilized to incise bladder neck contracture at 8 o’clock position.

Figure 4. Full-thickness 8 and 4 o’clock incisions performed down to fat, ensuring avoidance of bleeding and visualization of healthy tissue at proximal and distal extents of incisions. Twelve and 6 o’clock incisions are avoided to prevent urosymphyseal fistula and rectal injury, respectively.

Figure 5. Mitomycin C injections into bilateral urethrotomies. Foley catheter was maintained for 72 h postoperatively.

Cumulative success rates have also been encouraging in radiated patients with recurrent bladder neck contractures, with up to 90% experiencing durable improvement in bladder neck patency, and higher overall success rates observed in nonradiated patients compared with radiated patients (94% vs 76%).^6,7 The management of stress urinary incontinence following the establishment of a stable, widely patent bladder neck in such patients has also been investigated, with 45% of patients subsequently undergoing artificial urinary sphincter placement in 1 study with adequate postoperative continence.⁵

Some analyses have, however, reported lower efficacy than previously estimated, with a 2015 multicenter retrospective study of 55 patients by the TURNS (Trauma and Urologic Reconstructive Network of Surgeons) group demonstrating only 58% bladder neck patency rates after 1 procedure at a median follow-up of 9.2 months with 42% of patients experiencing contracture recurrence at a median of 3.7 months.⁵ Seven percent of patients also experienced significant complications including osteitis pubis, bladder neck necrosis, and rectourethral fistula.

The particular structure and function of the posterior urethra and bladder neck including the transitional epithelium, lack of surrounding corpus spongiosum, and specific etiology of contractures require treatment recommendations to be distinct from those governing the management of anterior urethral strictures. However, the somewhat inconclusive evidence for the benefit of mitomycin C for use in the bladder neck, as seen via mixed results from small retrospective reviews and the lack of larger prospective randomized trials, is reflected in the absence of clear national guidelines.

The AUA notes “there is conflicting data about the utility of mitomycin C for the treatment of recurrent vesicourethral stenosis, with further study necessary to validate its use,” while the European Association of Urology “recommends against the use of mitomycin C outside of clinical trials.”

Studies have also varied widely in their methods of assessing postoperative bladder neck patency, as well as in operative technique including number, location, and method of incisions (cold knife vs electrocautery), and volume and concentration of mitomycin C utilized. Studies comparing incision plus mitomycin C injection to incision alone in the management of treatment-naïve bladder neck contracture are also missing.

Prospective randomized trials are needed, as is the optimization of a standardized surgical technique, and currently, given the high success rates of direct vision internal urethrotomy alone, the addition of mitomycin C may potentially only be of marginal benefit and add to health care costs. However, the procedure of injection is technically simple and safe to perform as an adjunct, and has achieved some durable success rates with minimal morbidity.