Intravesical Instillation Therapy
Transurethral resection of a bladder tumor (TURBT) is the gold-standard treatment for non-muscle-invasive bladder cancer (NMIBC); however, the recurrence rate is as high as 80%. Immediate post-TURBT intravesical chemotherapy (PIC) is focused on control of local recurrence of NMIBC. Current evidence in a large meta-analysis has shown that immediate PIC reduces the recurrence rate, especially in low-risk patients, but the quality of the evidence was low. The optimal dosage, number, and timing of treatments are still controversial. Both the American Urological Association (AUA) and the European Association of Urology (EAU) guidelines support immediate postoperative intravesical chemotherapy in NMIBC. The EAU has recommended immediate PIC in low- to intermediate-risk patients. The AUA has recommended PIC only in small-volume low-grade Ta-stage urothelial carcinoma tumors of the bladder (Chang et al., J Urol 196:1021–1029, 2016). Contraindications to PIC include deep muscle resection, bladder perforation, and prior allergy to the chemotherapy agent (Kulkarni et al., Eur Urol 57:60–70, 2010).
In patients with high-risk NMIBC, intravesical instillation (of bacillus Calmette–Guérin (BCG) immunotherapy or chemotherapeutic agents) and radical cystectomy are treatment options. Intravesical BCG has been shown to reduce tumor progression and recurrence. If high-grade NMIBC patients want bladder preservation, intravesical instillation of BCG is a good treatment option. However, because it uses a live strain of Mycobacterium bovis, caution is needed regarding possible side effects. BCG-unresponsive NMIBC and BCG shortages are other issues that can arise. Intravesical BCG instillation is associated with better oncological outcomes than intravesical chemotherapy, which is thus sometimes considered as an alternative treatment when patients cannot tolerate BCG or are unresponsive to it. Novel methods for administering mitomycin C (MMC), such as electromotive drug administration (EMDA) and chemohyperthermia (C-HT), provide promising results equivalent to those of BCG immunotherapy.
KeywordsIntravesical therapy BCG MMC BCG shortage BCG failure BCG unresponsive Electromotive drug administration Chemohyperthermia
- 1.Sylvester RJ, Oosterlinck W. A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a meta-analysis of published results of randomized clinical trials. J Urol. 2004;171:2186–90. https://doi.org/10.1097/01.ju.0000125486.92260.b2.CrossRefPubMedGoogle Scholar
- 2.Perlis N, Zlotta AR, Beyene J, Finelli A. Immediate post–transurethral resection of bladder tumor intravesical chemotherapy prevents non-muscle-invasive bladder cancer recurrences: an updated meta-analysis on 2548 patients and quality-of-evidence review. Eur Urol. 2013;64:421–30. https://doi.org/10.1016/j.eururo.2013.06.009.CrossRefPubMedGoogle Scholar
- 3.Sylvester RJ, Oosterlinck W, Holmang S, Sydes MR, Birtle A, Gudjonsson S, et al. Systematic review and individual patient data meta-analysis of randomized trials comparing a single immediate instillation of chemotherapy after transurethral resection with transurethral resection alone in patients with stage pTa–pT1 urothelial carcinoma. Eur Urol. 2016;69:231–44. https://doi.org/10.1016/j.eururo.2015.05.050.CrossRefPubMedGoogle Scholar
- 10.Stasi SMDI, Giannantoni A, Stephen RL, Capelli G, Navarra P, Massoud R, et al. Intravesical electromotive mitomycin C versus passive transport mitomycin C for high risk superficial bladder cancer: a prospective randomized study. J Urol. 2003;170:777–82. https://doi.org/10.1097/01.ju.0000080568.91703.18.CrossRefPubMedGoogle Scholar
- 11.Di Stasi SM, Valenti M, Verri C, Liberati E, Giurioli A, Leprini G, et al. Electromotive instillation of mitomycin immediately before transurethral resection for patients with primary urothelial non-muscle invasive bladder cancer: a randomised controlled trial. Lancet Oncol. 2011;12:871–9. https://doi.org/10.1016/S1470-2045(11)70190-5.CrossRefPubMedGoogle Scholar
- 12.Lammers RJM, Witjes JA, Inman BA, Leibovitch I. The role of a combined regimen with intravesical chemotherapy and hyperthermia in the management of non-muscle-invasive bladder cancer: a systematic review. Eur Urol. 2011;60:81–93. https://doi.org/10.1016/j.eururo.2011.04.023.CrossRefPubMedGoogle Scholar
- 14.Sylvester RJ, van der Meijden APM, Lamm DL. Intravesical bacillus Calmette-Guérin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol. 2002;168:1964–70. https://doi.org/10.1097/01.ju.0000034450.80198.1c.CrossRefPubMedGoogle Scholar
- 17.Lamm DL, Blumenstein BA, Crissman JD, Montie JE, Gottesman JE, Lowe BA, et al. Maintenance bacillus Calmette-Guérin immunotherapy for recurrent Ta, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group study. J Urol. 2000;163:1124–9. https://doi.org/10.1016/S0022-5347(05)67707-5.CrossRefPubMedGoogle Scholar
- 19.Malmström PU, Sylvester RJ, Crawford DE, Friedrich M, Krege S, Rintala E, et al. An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette–Guérin for non-muscle-invasive bladder cancer. Eur Urol. 2009;56:247–56. https://doi.org/10.1016/j.eururo.2009.04.038.CrossRefPubMedGoogle Scholar
- 20.Hinotsu S, Akaza H, Naito S, Ozono S, Sumiyoshi Y, Noguchi S, et al. Maintenance therapy with bacillus Calmette–Guérin Connaught strain clearly prolongs recurrence-free survival following transurethral resection of bladder tumour for non-muscle-invasive bladder cancer. BJU Int. 2011;108:187–95. https://doi.org/10.1111/j.1464-410X.2010.09891.x.CrossRefPubMedGoogle Scholar
- 21.Oddens J, Brausi M, Sylvester R, Bono A, Van De Beek C, Van Andel G, et al. Final results of an EORTC-GU Cancers Group randomized study of maintenance bacillus Calmette–Guérin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance. Eur Urol. 2013;63:462–72. https://doi.org/10.1016/j.eururo.2012.10.039.CrossRefPubMedGoogle Scholar
- 22.Van der Meijden APM, Sylvester RJ, Oosterlinck W, Hoeltl W, Bono AV. Maintenance bacillus Calmette-Guérin for Ta T1 bladder tumors is not associated with increased toxicity: results from a European Organisation for Research and Treatment of Cancer Genito-urinary Group phase III trial. Eur Urol. 2003;44:429–34. https://doi.org/10.1016/S0302-2838(03)00357-9.CrossRefPubMedGoogle Scholar