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Bladder Chemoprophylaxis Following Ureterorenoscopy in Patients with Upper-Tract Urothelial Carcinoma - Beyond the Abstract

Upper tract urothelial carcinoma (UTUC) is an uncommon genitourinary malignancy accounting for 5–10% of urothelial carcinomas. Although radical nephroureterectomy (RNU) is the gold standard for bulky, high-grade, or invasive UTUC, kidney-sparing procedures for UTUC have increasingly evolved from imperative to elective indications for management of low-risk disease. Ureterorenoscopy (URS) is the most common procedure for the diagnosis, treatment, and surveillance of UTUC. A notable consideration following URS is the demonstrably higher risk of downstream bladder seeding (22–47% rates reported across diagnostic URS series).


In this review, we have compiled the indirect evidence that bladder chemoprophylaxis should be administered immediately after URS performed for the diagnosis or treatment of UTUC. We summarize the salient points below.

First, there is level 1a evidence for the use of an immediate single instillation (SI) of intravesical chemotherapy (mitomycin C [MMC] or gemcitabine) to reduce the risk of bladder recurrences following transurethral resection (TUR) of bladder urothelial carcinoma.1

Second, both the ODMIT-C trial and THP Monotherapy Study Group trial pointed to a reduction in the risk of de novo bladder cancer following RNU when patients are treated postoperatively with intravesical therapy at the time of catheter removal. Specifically, the ODMIT-C trial noted that SI of intravesical MMC yielded absolute (11%) and relative (40%) reductions in the risk of bladder cancer in the first year following RNU.2

Third, there is mounting evidence in both of the above scenarios that immediate early therapy with intravesical agents may be better than delayed treatment, when seeding may have already occurred.3 Bosschieter and colleagues4 reported outcomes from a large prospective trial of more than 2000 bladder tumor resections, for which the difference in time to recurrence was significantly in favor of immediate instillation with MMC (p < 0.001), corresponding to a 25% reduction in risk.

Finally, extrapolative data from the Olympus trial further suggest a potential benefit from chemoprophylaxis after URS.5 With the use of MMC gel for chemoablation of UTUC, bladder recurrences were only noted in 9% of patients at the one-year follow-up.

It is clear that treatment options with a conservative intention for low-risk UTUC will continue to expand. Technological advances in imaging (superior visualization), instrumentation (smaller calibers), and energy devices (photodynamic compounds), as well as novel pharmacologic therapies, will expand the treatment armamentarium.

At present, there are no firm indications for bladder chemoprophylaxis after URS. Nonetheless, the potential to reduce recurrence rates and thus the morbidity and costs associated with treatment is an attractive goal for the management of patients with UTUC.

Written by: Federico Ferraris,1 Jay D. Raman,2 Fabian Yaber3

  1. Sanatorio Dupuytren, Buenos Aires, Argentina
  2. Milton S. Hershey Medical Center, Penn State Health, Hershey, PA, USA
  3. Universidad Nacional de Rosario, Santa Fe, Argentina

References:

  1. Sylvester RJ, Oosterlinck W, Holmang S, et al. Systematic review and individual patient data meta-analysis of randomized trials comparing a single immediate instillation of chemotherapy after trans- urethral resection with transurethral resection alone in patients with stage pTa–pT1 urothelial carcinoma of the bladder: which patients benefit from the instillation? Eur Urol 2016;69:231–44. http://dx.doi.org/10.1016/j.eururo.2015.05.050.
  2. O’Brien T, Ray E, Singh R, et al. Prevention of bladder tumours after nephroureterectomy for primary upper urinary tract urothelial carcinoma: a prospective, multicentre, randomised clinical trial of a single postoperative intravesical dose of mitomycin C (the ODMIT-C Trial). Eur Urol 2011;60:703–10. http://dx.doi.org/10. 1016/j.eururo.2011.05.064.
  3. Bosschieter J, Nieuwenhuijzen JA, van Ginkel T, et al. Value of an immediate intravesical instillation of mitomycin C in patients with non-muscle-invasive bladder cancer: a prospective multicentre randomised study in 2243 patients. Eur Urol 2018;73:226–32. http://dx.doi.org/10.1016/j.eururo.2017.06.038.
  4. Bosschieter J, Nieuwenhuijzen JA, Vis AN, et al. An immediate, single intravesical instillation of mitomycin C is of benefit in patients with non-muscle-invasive bladder cancer irrespective of prognostic risk groups. Urol Oncol 2018;36:400.e7–400.e14. http://dx.doi.org/10. 1016/j.urolonc.2018.05.026.
  5. Kleinmann N, Matin SF, Pierorazio PM, et al. Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open- label, single-arm, phase 3 trial. Lancet Oncol 2020;21:776–85. http://dx.doi.org/10.1016/S1470-2045(20)30147-9.

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