Predicting response to bacillus Calmette-Guerin in high-risk non-muscle invasive bladder cancer

Sep 21, 2026

Bladder cancer is a common malignancy, with many new diagnoses falling under non-muscle invasive bladder cancer (NMIBC), where recurrence is frequent and the risk is highest in high-risk NMIBC. Intravesical bacillus Calmette-Guerin (BCG) is standard care to reduce recurrence, yet a substantial subset lacks a durable response and may progress to muscle-invasive disease. Reliable predictive tools are therefore needed to identify non-responders and guide alternative treatments. This review evaluates clinical and molecular risk factors for forecasting BCG response, emphasizing high-risk T1 cancers.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Burden and classification of bladder cancer

NMIBC risk groups and role of BCG

Rationale for predicting BCG response

Predicting response to bacillus Calmette-Guerin in high-risk non-muscle invasive bladder cancer Amir M. Soltani-Tehrani, Aman Kumar, Kamal S. Pohar Department of Urology, Ohio State University Wexner Medical Centre/The James Cancer Hospital, Columbus, OH, USA Contributions: (I) Conception and design: All authors; (II) Administrative support: KS Pohar; (III) Provision of study materials or patients: All authors;(IV) Collection and assembly of data: AM Soltani-Tehrani, A Kumar; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Kamal S. Pohar, MD. Department of Urology, The Ohio State University Wexner Medical Center/The James Cancer Hospital, 460 W 10th Ave, Columbus, OH 43210, [USA. Email: kamal.pohar@osumc.edu](USA. Email: kamal.pohar@osumc.edu). Abstract: Bladder cancer is a commonly diagnosed cancer, especially in men, and 70% of new diagnoses are considered non-muscle invasive bladder cancer (NMIBC) . Bladder cancer is prone to high rates of recurrence, and this risk is greatest in high risk NMIBC. Intravesical bacillus Calmette-Guerin (BCG) is standard of care for reducing rates of recurrence for high risk NMIBC. Despite its favorable efficacy a significant proportion of patients do not have durable prolonged response to BCG and some patients progress to muscle invasive bladder cancer worsening prognosis. Predictive tools are needed in clinical practice to identify patients who are not likely to respond to BCG and need alternative treatments. The European Organization for Research and Treatment of Cancer (EORTC) and Club Urologico Espanol de Tratamiento Oncologico (CUETO) have proposed outcome prediction tables for NMIBC patients, providing risk stratification and recurrence and progression probability scores. While valuable in clinical practice, these tables have limitations and overestimate recurrence and progression for high risk NMIBC. Several efforts have attempted to refine our ability to better understand which patients derive the greatest benefit from BCG. T1 pathologic substaging, tumor budding, and artificial intelligence techniques studying pathologic features of the tumor and the microenvironment have been applied to high risk NMIBC as a means of identifying patients less likely to respond to BCG. Molecular markers, genomic alterations and transcriptomic signatures are promising and hold the potential to aid in forecasting tumor progression and response to therapy. However, their application is still in its initial phases and necessitates additional validation through further studies. This review describes both clinical and molecular risk factors that could prove beneficial in anticipating the response to BCG, with a particular focus on high-risk T1 bladder cancers. Keywords: Bladder cancer; bacillus Calmette-Guerin (BCG); non-muscle invasive bladder cancer (NMIBC); urine cytokine; molecular markers Submitted Jan 26, 2024. Accepted for publication Jun 05, 2024. Published online Jul 30, 2024. doi: 10.21037/tcr-24-180 View this article at: [https://dx.doi.org/10.21037/tcr-24-180](https://dx.doi.org/10.21037/tcr-24-180) Introduction Bladder cancer is the 9th most common malignancy with 573,000 new cases and 213,000 deaths reported worldwide in 2020 (1,2) . Cancer of the bladder is often categorized as either non-muscle invasive bladder cancer (NMIBC) or muscle invasive bladder cancer (MIBC) . NMIBC encompasses 70% of newly detected cases and includes stage Ta (tumor confined to the epithelium; non-invasive), T1 [invasive to lamina propria (LP)] and Tis [carcinoma in situ (CIS)], and in general is associated with favorable prognosis (3,4) . MIBC implies cancer invasion of the muscularis propria, perivesical fat or surrounding organs © AME Publishing Company. Transl Cancer Res 2024;13(11):6489-6502 | [https://dx.doi.org/10.21037/tcr-24-180](https://dx.doi.org/10.21037/tcr-24-180)

FAQs

Why is predicting response to BCG important in high-risk NMIBC?

High-risk NMIBC has the greatest likelihood of recurrence and progression. Although BCG is standard care, many patients do not achieve a durable response and some progress to muscle-invasive disease, worsening prognosis.

What limitations do current NMIBC outcome prediction tables have?

EORTC and CUETO tables provide risk stratification and recurrence/progression probabilities, but they can overestimate recurrence and progression in high-risk NMIBC.

Which approaches are discussed for improving prediction of BCG response?

The review highlights clinical pathologic factors such as T1 substaging and tumor budding, artificial intelligence methods using tumor and microenvironment features, and molecular markers including genomic alterations and transcriptomic signatures that require further validation.

Sep 21, 2026

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