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  • Review Article
  • Published:

BCG-unresponsive non-muscle-invasive bladder cancer: recommendations from the IBCG

Nature Reviews Urology volume 14, pages 244–255 (2017)Cite this article

Subjects

Key Points

  • Intravesical immunotherapy in the form of BCG is the only effective adjuvant therapy for high-risk NMIBC (non-muscle-invasive bladder cancer) that reduces progression of disease

  • Response to salvage therapies after BCG are highly dependent on pattern of tumour recurrence after BCG, especially with regards to dose, duration, and schedule of BCG administration and timing of tumour recurrence after BCG therapy

  • For a patient to be considered BCG-unresponsive, they must have received ≥1 induction course (6 weeks) and one maintenance course (3 weeks) and either have refractory tumour (no disease-free interval) or have recurrence of high-grade tumour within 6 months of their last BCG exposure

  • In true BCG-unresponsive patients, the only standard therapy is radical cystectomy

  • No salvage medical or intravesical treatments have been shown to have durable efficacy in true BCG-unresponsive patients, although some show efficacy in select subgroups of patients

  • Options presented to patients who have high-grade tumour recurrence after adequate BCG therapy should factor in the risk of invasive and metastatic disease, balanced with the potential benefit of bladder salvage

Abstract

Intravesical immunotherapy with live attenuated BCG remains the standard of care for patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Most patients initially respond, but recurrence is frequent and progression to invasive cancer is a concern. No established and effective intravesical therapies are available for patients whose tumours recur after BCG, representing a clinically important unmet need. Development and discovery of treatment options for BCG-unresponsive NMIBC is a high priority in order to decrease the morbidity, burden of health-care expenditures, and mortality related to bladder cancer. This Review of treatment options after BCG failure focuses on principles of optimal management emerging therapies, thus enabling a synthesis of recommendations for management for such patients.

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Figure 1: Classification of patients with high-risk NMIBC after intravesical BCG and types of BCG failure.
Figure 2: Recommendations for management of patients after BCG failure.

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Authors and Affiliations

  1. Department of Urology, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1373, Houston, 77054, Texas, USA

    Ashish M. Kamat & Debasish Sundi

  2. Department of Urology, Claude Bernard University, Hôpital Edouard Herriot, Urologie — Pavillon V, 5 Place d'Arsonval, Lyon, 69003, France

    Marc Colombel

  3. Department of Surgery, University of Arizona and BCG Oncology, 3815 East Bell Road, Suite 1210, Phoenix, 85032, Arizona, USA

    Donald Lamm

  4. Department of Urology, HELIOS Agnes Karll Hospital, Am Hochkamp 21, 23611, Bad Schwartau, Germany

    Andreas Boehle

  5. Department of Urology, AUSL Modena, B. Ramazzini Hospital, Via G. Molinari, 1, 41012, Carpi-Modena, Italy

    Maurizio Brausi

  6. Department of Urology, North York General Hospital, 1333 Sheppard Avenue East, Suite 222, North York, M2J 1V1, Ontario, Canada

    Roger Buckley

  7. Department of Urology/Surgery, Southmead Hospital & Bristol Urological Institute, Brunel Building, Southmead Road, Bristol, BS10 5NB, UK

    Raj Persad

  8. Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Carrer de Cartagena, 340–350, Barcelona, 08025, Spain

    Joan Palou

  9. Division of Urologic Oncology, Memorial Cancer Institute, Memorial Health System, 20801 Biscayne Boulevard, Suite 203, Aventura, 33180, Florida, USA

    Mark Soloway

  10. Department of Urology, Radboud University Nijmegen Medical Centre, PO Box 9101, Nijmegen, 6500 HGB, Netherlands

    J. Alfred Witjes

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  1. Ashish M. Kamat
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  3. Debasish Sundi
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  4. Donald Lamm
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  6. Maurizio Brausi
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  7. Roger Buckley
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  11. J. Alfred Witjes
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Contributions

All authors researched data for the article, made a substantial contribution to discussions of content, and wrote and reviewed or edited the manuscript before submission.

Corresponding author

Correspondence to Ashish M. Kamat.

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Competing interests

A.K. declares that he has acted as a consultant for Cepheid, Photocure,Telesta Therapeutics, Sanofi, Merck, Abbott Molecular, Theralase, Heat Biologics, Spectrum Pharmaceuticals, and Oncogenix. He has received grant support from FKD Industries, Photocure, Merck, and Heat Biologics, and he has a patent pending for a cytokine assay for BCG (CYPRIT) with the University of Texas MD Anderson Cancer Center. J.A.W. declares that he has acted as an adviser for MEL. J.P. declares clinical trial collaborations with Combat Medical and Presurgery. D.L. declares research collaborations with Vicinium and Cold Genesys-CG0070. R.B. declares that he has acted as a consultant for Sanofi. The other authors declare no competing interests.

PowerPoint slides

Glossary

BCG intolerant

Scenario when a patient cannot receive BCG owing to treatment-related adverse effects.

BCG refractory

Presence of persistent high-grade cancer 6 months after the start of induction therapy, or cancers that have progressed by grade or stage 3 months after the start of induction therapy.

BCG relapse

Indicates cancer recurrence after achieving a disease-free state at 6 months after treatment.

BCG unresponsive

Denotes the group of patients with BCG-refractory tumours and those who are BCG-relapsing within 6 months of their last BCG exposure.

Type I error, α

Probability of incorrectly rejecting a true null hypothesis (false positive).

Type II error, β

Probability of incorrectly accepting a false null hypothesis (false negative).

Power, 1-β

The chance that a study will successfully demonstrate a true result.

Intradermal priming

Intradermal injection of BCG vaccine in order to induce BCG-specific memory T cells

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Kamat, A., Colombel, M., Sundi, D. et al. BCG-unresponsive non-muscle-invasive bladder cancer: recommendations from the IBCG. Nat Rev Urol 14, 244–255 (2017). https://doi.org/10.1038/nrurol.2017.16

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