# Prognostic and predictive factors of immune checkpoint inhibitor therapy in urinary bladder cancer

## TL;DR

This review summarizes factors that predict how well immunotherapy works for bladder cancer patients, aiming to help choose the best treatments.

## Contribution

The paper offers a comprehensive overview of both established and emerging biomarkers for predicting immune checkpoint inhibitor response in urothelial bladder cancer.

## Key findings

- PD-L1 immunohistochemistry and tumor mutational burden are established biomarkers for ICI response.
- Serum inflammatory markers, molecular subtypes, and microbiome features are emerging as potential predictive factors.
- Current biomarkers have limitations, and more research is needed to improve personalized treatment selection.

## Abstract

Immune checkpoint inhibitor (ICI) therapy has become a firmly integrated component of the systemic treatment repertoire for locally advanced and metastatic urothelial bladder cancer (UBC). Over the past decade, multiple ICIs have demonstrated meaningful clinical activity, and their indications have expanded across treatment lines, including second-line therapy after platinum, first-line therapy for cisplatin-ineligible disease, avelumab maintenance following chemotherapy, and, more recently, combination strategies such as pembrolizumab plus enfortumab vedotin. Despite these advances, patient responses to ICIs remain highly heterogeneous. While a subset of patients achieves substantial tumor regression and long-term survival, a considerable proportion derives little or no benefit. The rapidly evolving therapeutic landscape - encompassing antibody-drug conjugates, targeted agents, and perioperative ICI approvals - further emphasizes the need to identify which patients are most likely to respond to immunotherapy. Given the marked variability in therapeutic sensitivity and the increasing availability of alternative effective treatments, accurate prediction of ICI efficacy is becoming increasingly crucial for personalized treatment selection. In this review, we provide a comprehensive overview of currently established and emerging biomarkers of ICI response in UBC, including PD-L1 immunohistochemistry, serum inflammatory markers, tumor mutational burden, histology and molecular subtypes, gene expression patterns and microbiome features. We discuss their strengths, limitations, and potential translational relevance, highlighting ongoing challenges and future directions.