Progress in the development of tissue-based biomarkers for urothelial cancer

ABSTRACT

Introduction

As the understanding of molecular mechanisms of bladder cancer advances, molecularly-guided precision medicine becomes increasingly relevant. Biomarkers play a critical role in this setting, predicting treatment response and identifying candidates for targeted therapies.

Areas covered

Current literature on biomarkers in their role in disease prognosis and response to neoadjuvant and adjuvant therapies. In non-muscle invasive bladder cancer, particular focus is on markers of disease progression, and response to intravesical therapy. In muscle invasive and advanced bladder cancer, particular emphasis is on markers associated with neoadjuvant chemotherapy, as well as systemic immunotherapy. We discuss current shortcomings and pitfalls in contemporary markers, and future avenues of prospective research.

Expert opinion

The focus on biomarkers has moved from immunohistochemical analysis and tumor-related phenotypic changes to examining genetic alterations. Single marker analysis has been shown to be insufficient in predicting both disease course and response to therapy, and studies have shifted toward examining marker combinations and genetic classifiers. Ultimately, significant progress in implementing biomarkers into clinical guidelines remains elusive, largely due to lack of prospective studies in well-defined patient cohorts and with clinically meaningful endpoints. Until then, despite their promising value, tissue markers should be limited to experimental settings and clinical trials.

KEYWORDS:

• Biomarkers
• response to intravesical therapy
• bladder cancer
• immunotherapy
• muscle invasive bladder cancer
• neoadjuvant chemotherapy

Article highlights

• Tissue based biomarkers in bladder cancer have transitioned from single marker analysis to marker combinations and genetic classifiers

• Markers remain challenging in non-muscle invasive bladder cancer with an absence of robust studies

• Genomic classifiers and molecular subtyping have shown promise in identifying responders to neoadjuvant chemotherapy in muscle invasive bladder cancer, but the need for robust validation studies remains

• Despite approval of several systemic immunotherapies in the first line cisplatin ineligible and second line settings, understanding of biomarkers in the era of immunotherapy remains limited

Declaration of interest

Y Lotan is a consultant for Nanorobotics, C2I genomics, Photocure, Astra-Zeneca, Merck, Fergene, Abbvie, Cleveland Diagnostics, Ambu, Seattle Genetics, Hitachi, Ferring Research, Verity Pharmaceuticals, Virtuoso Surgical, Stimit, Urogen, Vessi, CAPs medical, and BMS. Y Lotan has received payments from C2I genomics and currently has stock options with no value with C2I genomics.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper received no funding.