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Recurrence mechanisms of non-muscle-invasive bladder cancer — a clinical perspective

Nature Reviews Urology volume 19, pages 280–294 (2022)Cite this article

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Abstract

Non-muscle-invasive bladder cancer (NMIBC) is an early-stage cancer without invasion into the detrusor muscle layer. Transurethral resection of bladder tumour (TURBT) is a diagnostic and potentially curative procedure for NMIBC, but has some limitations, including difficulties in ascertaining complete tumour removal upon piecemeal resection and the possibility of tumour re-implantation after the procedure. The oncological control of NMIBC is far from satisfactory, with a 1-year recurrence rate of 15–61%, and a 5-year recurrence rate of 31–78%. Various recurrence mechanisms have been described for NMIBC, such as undetected tumours upon cystoscopy, incomplete resection during TURBT, tumour re-implantation after TURBT, drop metastasis from upper tract urothelial carcinoma and field change cancerization. Understanding the recurrence mechanisms from a clinical perspective has strong implications for the optimization of NMIBC oncological outcomes, as a cure for patients with NMIBC can only be achieved by tackling all possible recurrence mechanisms in a comprehensive manner.

Key points

  • Undetected cancer upon cystoscopy, local residual disease after transurethral resection and tumour re-implantation might cause early disease recurrence of non-muscle-invasive bladder cancer (NMIBC), whereas field change cancerization effects could lead to late disease recurrence.

  • Drop metastasis from upper tract urothelial carcinoma can cause NMIBC recurrence, although it is unlikely to be the predominant recurrence mechanism.

  • Recurrence mechanisms should be managed in a comprehensive manner in order to optimize the oncological outcomes of NMIBC.

  • Molecular classification of NMIBC as well as treatment with immunotherapy and other novel therapeutic agents might have important implications in the future management of NMIBC.

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Fig. 1: Conventional transurethral resection of bladder tumour and non-muscle-invasive bladder cancer recurrence.
Fig. 2: En bloc resection and NMIBC recurrence.
Fig. 3: Field change cancerization effect.

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Authors and Affiliations

  1. S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China

    Jeremy Yuen-Chun Teoh

  2. European Association of Urology-Young Academic Urologists (EAU-YAU) Urothelial Cancer Working Group, Amsterdam, Netherlands

    Jeremy Yuen-Chun Teoh

  3. The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Ashish M. Kamat

  4. Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada

    Peter C. Black

  5. Division of Oncology, Department of Medicine, University of Washington, Washington, USA

    Petros Grivas

  6. Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, WA, USA

    Petros Grivas

  7. Department of Urology, Medical University of Vienna, Vienna, Austria

    Shahrokh F. Shariat & Marek Babjuk

  8. Department of Urology, Weill Cornell Medical College, New York, NY, USA

    Shahrokh F. Shariat

  9. Department of Urology, University of Texas Southwestern, Dallas, TX, USA

    Shahrokh F. Shariat

  10. Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia

    Shahrokh F. Shariat

  11. Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan

    Shahrokh F. Shariat

  12. Department of Urology, 2nd Faculty of Medicine, Hospital Motol, Charles University, Prague, Czech Republic

    Shahrokh F. Shariat & Marek Babjuk

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  1. Jeremy Yuen-Chun Teoh
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J.Y.-C.T. researched data for the article. All authors contributed substantially to discussion of the content. All authors wrote the article. All authors reviewed and edited the manuscript before submission.

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Correspondence to Jeremy Yuen-Chun Teoh.

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Competing interests

J.Y.-C.T. holds investigator grants from Baxter, Bristol-Myers Squibb, Janssen, Ferring, Merck Sharp & Dohme, Storz and Olympus, is an advisory board member for Astellas, Ferring and Janssen, is a consultant for Astellas, Ferring, Janssen and MRI PRO and received an honorarium from Astellas, Boston Scientific, Combat Medical, Ferring, Janssen, Olympus and Sanofi. A.M.K. holds investigator grants from FKD Industries, Merck, Photocure, BMS, SWOG, NIH, AIBCCR, Heat Biologics, Adolor, Alere, Pacific Edge, Telesta, Celgene, TetraLogic and FAMRI and is an advisory board member for Merck, BMS, Eisai, Arquer, MDx Health, Photocure, AstraZeneca, Abbott Molecular, US Biotest, Ferring, BioClin, FKD Industries, Genentech, Allergan, Incyte, Telesta, Aurasence, Taris, Oncogenex, Sanofi, Pfizer, Theralase, Cepheid, Medac, Asieris, Synergo, Combat and Imagin. P.C.B. holds investigator grants from iProgen, GSK and GenomeDx Biosciences, is an advisory board member for Astellas, AbbVie, AstraZeneca, Bayer, Biosyent, BMS, Ferring, Janssen, MDxHealth, Merck, Roche, Sanofi and UroGen and is a consultant for Bayer, Janssen, Roche and Sanofi. P.G. holds investigator grants from Bavarian Nordic, Bristol Myers Squibb, Clovis Oncology, Debiopharm, EMD Serono, GlaxoSmithKline, Immunomedics/Gilead, Merck, Mirati Therapeutics, Pfizer, QED Therapeutics and G1 Therapeutics, and is a consultant for AstraZeneca, Astellas Pharma, Bayer, Bristol Myers Squibb, Clovis Oncology, Dyania Health, EMD Serono, Exelixis, Foundation Medicine, Genentech/Roche, Genzyme, GlaxoSmithKline, Guardant Health, Immunomedics/Gilead, Infinity Pharmaceuticals, Janssen, Merck, Mirati Therapeutics, Pfizer, QED Therapeutics, Regeneron Pharmaceuticals, Seattle Genetics, 4D Pharma PLC and UroGen. S.F.S., is a consultant for Olympus and Janssen and received an honorarium from Astellas, AstraZeneca, Bayer, BMS, Cepheid, Ferring, Ipsen, Janssen, Lilly and UroGen Pharma. M.B. is a consultant for Astellas and Ipsen and received an honorarium from Ipsen, Janssen, Olympus and Astellas.

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Nature Reviews Urology thanks P. U. Malmstrom, M. Oya and M. O’Donnell for their contribution to the peer review of this work.

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Teoh, J.YC., Kamat, A.M., Black, P.C. et al. Recurrence mechanisms of non-muscle-invasive bladder cancer — a clinical perspective. Nat Rev Urol 19, 280–294 (2022). https://doi.org/10.1038/s41585-022-00578-1

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