Incorporating Metastatic Disease Burden into Prognostic Assessment in Metastatic Castration-Resistant Prostate Cancer: The MIRA Score

Background: Prognostic assessment in metastatic castration-resistant prostate cancer (mCRPC) remains important, but metastatic burden is not routinely captured as a simple combined measure. This exploratory study developed the Metastatic Integrated Risk Assessment (MIRA) score using disease burden and routine variables. Methods: Anonymised placebo-arm individual patient data from D4320C00014/ENTHUSE-M1 were analysed. Baseline variables were assessed for association with overall survival (OS) using Cox regression. A hierarchical composite tumour-burden variable combined bone-metastasis categories with RECIST target-lesion presence and sum of longest diameters (SLD). Selected variables formed an additive score, stratified into three risk groups, and were compared with the reconstructed Halabi classification using Harrell’s C-index. The final multivariate Cox model underwent internal validation using 1000 bootstrap resamples. Results: Among 266 placebo-treated patients, 133 deaths occurred, and median OS was 22.21 months. Composite tumour burden showed the strongest prognostic association and remained independently associated with OS. MIRA risk groups showed clear OS separation. In this derivation cohort, MIRA showed higher apparent discrimination than the reconstructed Halabi classification, with C-indices of 0.755 and 0.646, respectively; the paired difference was statistically significant (p < 0.001). For the final multivariate Cox model, the apparent C-index was 0.779, and the optimism-corrected C-index was 0.760; the optimism-corrected calibration slope was 0.841. Conclusions: These exploratory findings support metastatic tumour burden as a relevant prognostic factor in mCRPC and suggest that a simple combined measure of skeletal and measurable soft-tissue disease may have value for risk stratification. Refinement and independent external validation of MIRA are required before clinical use.