Analysis of MRE11 and Mortality Among Adults With Muscle-Invasive Bladder Cancer Managed With Trimodality Therapy

Area of Science:

• Oncology
• Biomarker Discovery
• Genitourinary Cancer Research

Background:

• Muscle-invasive bladder cancer (MIBC) treatment often involves radical cystectomy, but bladder-preserving trimodality therapy offers an alternative.
• Biomarkers are crucial for selecting patients who will benefit most from trimodality therapy.
• MRE11, a DNA repair protein, is a potential response biomarker but requires validation in prospective studies.

Purpose of the Study:

• To assess the prognostic value of MRE11 expression in patients with MIBC undergoing trimodality therapy.
• To utilize automated quantitative image analysis for standardized MRE11 expression measurement.
• To correlate MRE11 expression levels with disease-specific mortality (DSM).

Main Methods:

• A pooled analysis of 135 patients with MIBC from 6 prospective trimodality therapy trials (RTOG 8802, 8903, 9506, 9706, 9906, 0233).
• MRE11 expression was quantified using immunofluorescence and automated image analysis, calculating a nuclear-to-cytoplasmic (NC) signal ratio.
• Association between MRE11 NC ratio and disease-specific mortality (DSM) was evaluated.

Main Results:

• Patients with higher MRE11 NC signal ratios (above the first quartile of 1.49) demonstrated significantly lower disease-specific mortality (HR, 0.50; P=.03).
• The 4-year DSM was 21.0% for patients with high MRE11 NC ratios versus 41.0% for those with lower ratios.
• MRE11 expression was not significantly associated with overall survival.

Conclusions:

• Elevated MRE11 nuclear-to-cytoplasmic signal ratios are associated with improved disease-specific survival following trimodality therapy for MIBC.
• A low MRE11 NC ratio identifies a subgroup of patients with poor prognosis who might benefit from intensified treatment strategies.
• MRE11 expression serves as a valuable prognostic biomarker for guiding treatment decisions in bladder cancer patients receiving trimodality therapy.