High-grade T1 Urothelial Carcinoma: Where Do We Stand?
- 53 Downloads
Purpose of Review
Bladder cancer is a deadly and common malignancy, with 24% of new cases presenting as T1 disease. High-grade T1 in particular represents a difficult entity to treat due to its clinical variability and known risks of recurrence, progression, and cancer-specific mortality. The differences in guidelines from major urologic organizations underscore this variability, and the past year has seen another BCG shortage, further complicating management. Advances have been made in the molecular and genomic characterization of high-grade T1, and new clinical trials are available to investigate alternative therapies. In this review, we summarize the variations in guidelines, alternatives to BCG, emerging molecular and genomic discoveries, and recent clinical trials.
Adherence to guidelines for non-muscle-invasive bladder cancer in the community among practicing urologists remains low, in part due to the variations in available guidelines. In the era of a BCG shortage, decreased dosing schedules and alternative intravesical options are increasingly being used. New biomarkers are being discovered to better risk-stratify patients, with future therapies aimed at targeting aggressive disease.
HGT1 urothelial carcinoma remains a highly variable and aggressive disease, but we are making significant progress in better characterizing the clinical and molecular factors that influence recurrence and progression, to better guide management.
KeywordsHigh-grade T1 Bladder cancer BCG
Compliance with Ethical Standards
Conflict of Interest
Wesley Yip and Akbar Ashrafi each declare no potential conflicts of interest. Siamak Daneshmand is a section editor for Current Urology Reports.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
- 1.Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34.Google Scholar
- 7.Chang SS, Boorjian SA, Chou R, Clark PE, Daneshmand S, Konety BR, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol. 2016;196(4):1021–9.Google Scholar
- 8.Babjuk M, Burger M, Compérat EM, Gontero P, Mostafid AH, Palou J, van Rhijn BWG, Rouprêt M, Shariat SF, Sylvester R, Zigeuner R. EAU guidelines on non-muscle-invasive bladder cancer (TaT1 and CIS). In: Non-muscle-invasive bladder cancer. European Association of Urology. 2017. https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer. .
- 9.Flaig TW, Spiess PE, Agarwal N, Bangs R, Boorjian SA, Buyyounouski MK, Chang SS, Downs TM, Efstathiou JA, Friedlander T, Greenberg RE, Guru KA, Herr HW, Hoimes C, Inman BA, Jimbo M, Kader AK, Lele SM, Meeks JJ, Michalski J, Montgomery JS, Nandagopal L, Pagliaro LC, Pal SK, Patterson A, Plimack ER, Pohar KS, Porter MP, Preston MA, Sexton WJ, Siefker-Radtke AO, Tward J, Wright JL, Gurski LA, Johnson-Chilla A. Bladder cancer. In: NCCN clinical practice guidelines. National Comprehensive Cancer Network. 2019. https://www.nccn.org/professionals/physician_gls/PDF/bladder.pdf. Accessed 27 Jul 2019.
- 11.Martínez-Piñeiro JA, Martínez-Piñeiro L, Solsona E, Rodríguez RH, Gómez JM, Martín MG, et al. Has a 3-fold decreased dose of Bacillus Calmette-Guerin the same efficacy against recurrences and progression of T1G3 and Tis bladder tumors than the standard dose? Results of a prospective randomized trial. J Urol. 2005;174(4 Pt 1):1242–7.PubMedGoogle Scholar
- 14.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(2):247–56.PubMedGoogle Scholar
- 15.Lammers RJ, Witjes JA, Inman BA, Leibovitch I, Laufer M, Nativ O, et al. 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(1):81–93.Google Scholar
- 16.Arends TJ, Nativ O, Maffezzini M, de Cobelli O, Canepa G, Verweij F, et al. Results of a randomised controlled trial comparing intravesical chemohyperthermia with mitomycin C versus Bacillus Calmette-Guérin for adjuvant treatment of patients with intermediate- and high-risk non-muscle-invasive bladder cancer. Eur Urol. 2016;69(6):1046–52.PubMedGoogle Scholar
- 26.May M, Bastian PJ, Brookman-May S, Burger M, Bolenz C, Trojan L, et al. Pathological upstaging detected in radical cystectomy procedures is associated with a significantly worse tumour-specific survival rate for patients with clinical T1 urothelial carcinoma of the urinary bladder. Scand J Urol Nephrol. 2011;45(4):251–7.PubMedGoogle Scholar
- 27.Martin-Doyle W, Leow JJ, Orsola A, Chang SL, Bellmunt J. Improving selection criteria for early cystectomy in high-grade t1 bladder cancer: a meta-analysis of 15,215 patients. J Clin Oncol. 2015;33(6):643–50.Google Scholar
- 28.D Andrea D, Abufaraj M, Susani M, Ristl R, Foerster B, Kimura S, Mari A, Soria F, Briganti A, Karakiewicz PI, Gust KM, Rouprêt M, Shariat SF. Accurate prediction of progression to muscle-invasive disease in patients with pT1G3 bladder cancer: a clinical decision-making tool. Urol Oncol. 2018;36(5):239.e1–239.e7.Google Scholar
- 29.Gontero P, Sylvester R, Pisano F, Joniau S, Vander Eeckt K, Serretta V, et al. Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guérin: results of a retrospective multicenter study of 2451 patients. Eur Urol. 2015;67(1):74–82.PubMedGoogle Scholar
- 35.Mano R, Zilber S, Di Natale RG, Kedar D, Lifshitz DA, Yossepowitch O, et al. Heat shock proteins 60 and 70 are associated with long-term outcome of T1-stage high-grade urothelial tumors of the bladder treated with intravesical Bacillus Calmette-Guérin immunotherapy. Urol Oncol. 2018;36(12):531.e9–531.e17.Google Scholar