Prognostic Factors for Overall Survival in the VESPER Trial: Basal Molecular Subtype Is a Relevant Key Factor

Area of Science:

• Oncology
• Urothelial Carcinoma Research
• Clinical Trial Analysis

Background:

• Muscle-invasive bladder cancer (MIBC) treatment often involves neoadjuvant chemotherapy (NAC) followed by cystectomy.
• Identifying prognostic factors for overall survival (OS) is crucial for treatment stratification.
• The VESPER trial evaluated different NAC regimens in MIBC patients.

Purpose of the Study:

• To identify prognostic factors for overall survival (OS) in MIBC patients treated with NAC and cystectomy within the VESPER trial.
• To assess the predictive value of clinical, biological, pathological, and molecular characteristics on OS.
• To determine the most significant prognostic factors for OS in this patient cohort.

Main Methods:

• Analysis of the NAC VESPER trial population (n=437), comparing dose-dense MVAC with gemcitabine/cisplatin.
• Central review of tumor slides and blocks from 297 urothelial carcinoma cases.
• Investigation of clinical, pathological, and molecular features for their effect on OS using univariate and multivariable analyses.

Main Results:

• Univariate analysis revealed creatinine clearance, lymphovascular invasion, perineural invasion, and molecular subtype as significant prognostic factors for OS.
• Basal/squamous molecular subtype demonstrated high prognostic value, particularly within the first 1-5 years post-randomization.
• Multivariable analysis confirmed these four factors are complementary for OS prediction; patients with two or more factors had significantly lower 5-year OS rates (38%) compared to those with none (72%) or one factor (67%).

Conclusions:

• Four key prognostic factors for OS were identified in MIBC patients treated with NAC in the VESPER trial.
• Basal molecular subtype emerged as the most significant prognostic factor, independent of treatment arm.
• These findings highlight the importance of these factors for improving prognostic accuracy and potentially guiding treatment decisions in MIBC.