# A Review of the Latest Evidence on Prognostic Factors in Locally Advanced and Metastatic Urothelial Carcinoma Treated with Immune Checkpoint Inhibitors

## TL;DR

This review summarizes factors affecting outcomes in advanced urothelial carcinoma patients treated with immune checkpoint inhibitors.

## Contribution

The paper systematically reviews recent evidence on clinical, biochemical, and molecular prognostic factors in urothelial carcinoma immunotherapy.

## Key findings

- Poor ECOG performance status and liver/bone metastases are linked to worse outcomes in immunotherapy-treated urothelial carcinoma.
- Low hemoglobin, high NLR, and low serum sodium are associated with reduced survival in these patients.
- PD-L1 expression and concomitant use of antibiotics or PPIs may influence immunotherapy effectiveness.

## Abstract

Background and Objectives: Urothelial carcinoma (UC) is one of the most prevalent and lethal cancers worldwide. Identifying and understanding the factors that influence treatment outcome is essential for improving therapeutic effectiveness and predicting patient response. The objective of this review is to estimate how clinical, biochemical, molecular and therapeutic factors impact the prognosis of patients with advanced urothelial carcinoma (aUC) and metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs). Methods: A review was performed using PubMed, Scopus and Web of Science databases. All articles were published from 2013 to 2025 focusing on prognostic factors in locally advanced and metastatic urothelial carcinoma treated with ICIs. Results: Clinical prognostic factors for patients treated with ICIs include poor Eastern Cooperative Oncology Group (ECOG) performance status and the presence of liver or bone metastases, both associated with poor outcomes. Low hemoglobin levels and several biochemical markers, such as high neutrophil-to-lymphocyte ratio (NLR), elevated systemic immune-inflammation index (SII) and low serum sodium are also associated with reduced survival. Programmed cell death-ligand 1 (PD-L1) expression shows predictive relevance for ICI response. Concomitant use of antibiotics or proton pump inhibitors (PPIs) may diminish immunotherapy effectiveness. Additionally, sarcopenia and high lactate dehydrogenase (LDH) levels correlate with poorer clinical outcomes. Conclusions: Prognostic outcomes in aUC and mUC are influenced by a complex interaction of clinical, biochemical and molecular factors. Integrative prognostic models are essential to the guidance of personalized immunotherapeutic strategies and the improvement of patient outcomes in aUC and mUC.