{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T08:30:28Z","timestamp":1787041828009,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2019s 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 &lt; 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.<\/jats:p>","DOI":"10.3390\/cancers18162660","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T08:08:41Z","timestamp":1787040521000},"page":"2660","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Incorporating Metastatic Disease Burden into Prognostic Assessment in Metastatic Castration-Resistant Prostate Cancer: The MIRA Score"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0741-1668","authenticated-orcid":false,"given":"Mario","family":"Uccello","sequence":"first","affiliation":[{"name":"Royal United Hospitals Bath NHS Foundation Trust, Bath BA1 3NG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1704-1517","authenticated-orcid":false,"given":"Panagiotis J.","family":"Vlachostergios","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, IASO Thessalias Hospital, 41500 Larissa, Greece"},{"name":"Department of Medical Oncology, Ioannina University Hospital, 45500 Ioannina, Greece"},{"name":"Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece"},{"name":"Division of Hematology & Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruni","family":"Ghose","sequence":"additional","affiliation":[{"name":"Cancer Division, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK"},{"name":"Department of Research and Innovation, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2512-6131","authenticated-orcid":false,"given":"Stergios","family":"Boussios","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Ioannina University Hospital, 45500 Ioannina, Greece"},{"name":"Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece"},{"name":"Department of Research and Innovation, Medway NHS Foundation Trust, Gillingham ME7 5NY, UK"},{"name":"School of Cancer and Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, King\u2019s College London, London SE1 1UL, UK"},{"name":"Faculty of Medicine, Health and Social Care, Canterbury Christ Church University, Canterbury CT1 1QU, UK"},{"name":"AELIA Organisation, 9Th Km Thessaloniki-Thermi, 57001 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1200\/JCO.2013.52.3696","article-title":"Updated prognostic model for predicting overall survival in first-line chemotherapy for patients with metastatic castration-resistant prostate cancer","volume":"32","author":"Halabi","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.1093\/annonc\/mdy406","article-title":"Development and validation of a prognostic model for overall survival in chemotherapy-na\u00efve men with metastatic castration-resistant prostate cancer","volume":"29","author":"Armstrong","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3972","DOI":"10.1200\/JCO.2002.11.021","article-title":"Nomogram for overall survival of patients with progressive metastatic prostate cancer after castration","volume":"20","author":"Smaletz","year":"2002","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6396","DOI":"10.1158\/1078-0432.CCR-07-1036","article-title":"A Contemporary prognostic nomogram for men with hormone-refractory metastatic prostate cancer: A TAX327 study analysis","volume":"13","author":"Armstrong","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1200\/JCO.2003.06.100","article-title":"Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer","volume":"21","author":"Halabi","year":"2003","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1093\/jnci\/djt280","article-title":"Prognostic model predicting metastatic castration-resistant prostate cancer survival in men treated with second-line chemotherapy","volume":"105","author":"Halabi","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3346","DOI":"10.1002\/cncr.28890","article-title":"Simple prognostic score for metastatic castration-resistant prostate cancer with incorporation of neutrophil-to-lymphocyte ratio","volume":"120","author":"Templeton","year":"2014","journal-title":"Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1093\/annonc\/mdv594","article-title":"A prognostic index model for predicting overall survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate after docetaxel","volume":"27","author":"Chi","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/S1470-2045(16)30560-5","article-title":"Prediction of overall survival for patients with metastatic castration-resistant prostate cancer: Development of a prognostic model through a crowdsourced challenge with open clinical trial data","volume":"18","author":"Guinney","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Santorsola, M., Di Lauro, V., Nasti, G., Caraglia, M., Capuozzo, M., Perri, F., Cascella, M., Misso, G., and Ottaiano, A. (2022). Tumour Burden Reporting in Phase III Clinical Trials of Metastatic Lung, Breast, and Colorectal Cancers: A Systematic Review. Cancers, 14.","DOI":"10.3390\/cancers14133262"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5709","DOI":"10.1002\/cncr.27674","article-title":"Phase 3, randomized, placebo-controlled study of zibotentan (ZD4054) in patients with castration-resistant prostate cancer metastatic to bone","volume":"118","author":"Nelson","year":"2012","journal-title":"Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"464-e20","DOI":"10.1634\/theoncologist.2014-0431","article-title":"The project data sphere initiative: Accelerating cancer research by sharing data","volume":"20","author":"Green","year":"2015","journal-title":"Oncologist"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/sim.6370","article-title":"Comparing two correlated C indices with right-censored survival outcome: A one-shot nonparametric approach","volume":"34","author":"Kang","year":"2015","journal-title":"Stat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Uccello, M., Gee, A.L., Bennett, J.A., Hazell, H.L., Ruiz-Echarri Rueda, M., and Beresford, M.J. (2026). Metastatic Tumour Burden as Prognostic Factor in Nivolumab-Treated Metastatic Renal Cell Carcinoma: An Exploratory Study. Curr. Oncol., 33.","DOI":"10.3390\/curroncol33060320"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1056\/NEJMoa1503747","article-title":"Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer","volume":"373","author":"Sweeney","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1056\/NEJMoa1704174","article-title":"Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer","volume":"377","author":"Fizazi","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_17","first-page":"1475","article-title":"Time to castration resistance is an independent predictor of castration-resistant prostate cancer survival","volume":"31","author":"Bournakis","year":"2011","journal-title":"Anticancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1056\/NEJMoa1209096","article-title":"Abiraterone in metastatic prostate cancer without previous chemotherapy","volume":"368","author":"Ryan","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1056\/NEJMoa1405095","article-title":"Enzalutamide in metastatic prostate cancer before chemotherapy","volume":"371","author":"Beer","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1506824","DOI":"10.1155\/2017\/1506824","article-title":"Dynamics of Neutrophils-to-Lymphocyte Ratio Predict Outcomes of PD-1\/PD-L1 Blockade","volume":"2017","author":"Moschetta","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lolli, C., Caffo, O., Scarpi, E., Aieta, M., Conteduca, V., Maines, F., Bianchi, E., Massari, F., Veccia, A., and Chiuri, V.E. (2016). Systemic Immune-Inflammation Index Predicts the Clinical Outcome in Patients with mCRPC Treated with Abiraterone. Front. Pharmacol., 7.","DOI":"10.3389\/fphar.2016.00376"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"15387","DOI":"10.1038\/s41598-017-15673-2","article-title":"The Prognostic Value of Platelet-to-Lymphocyte Ratio in Urological Cancers: A Meta-Analysis","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nieder, C., Haukland, E., Pawinski, A., and Dalhaug, A. (2010). Anaemia and thrombocytopenia in patients with prostate cancer and bone metastases. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-284"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Giannakeas, V., Kotsopoulos, J., Brooks, J.D., Cheung, M.C., Rosella, L., Lipscombe, L., Akbari, M.R., Austin, P.C., and Narod, S.A. (2022). Platelet Count and Survival after Cancer. Cancers, 14.","DOI":"10.3390\/cancers14030549"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1200\/JCO.2018.78.8687","article-title":"Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology","volume":"36","author":"Mohile","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e658","DOI":"10.1016\/j.clgc.2019.03.012","article-title":"Assessing Outcomes and Prognostic Factors for First-Line Therapy in Elderly Patients With Metastatic Renal Cell Carcinoma: Real-Life Data From a Single United Kingdom Institution","volume":"17","author":"Uccello","year":"2019","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1093\/annonc\/mdr587","article-title":"Screening older cancer patients: First evaluation of the G-8 geriatric screening tool","volume":"23","author":"Bellera","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Beltran, H., Calais, J., Emmett, L., Kuo, P.H., and Logothetis, C.J. (2025). Biomarkers to optimize PSMA-targeted radioligand therapy for metastatic castration-resistant prostate cancer. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1583168"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bang, S., Ahn, Y.J., and Koo, K.C. (2025). Harnessing machine learning to predict prostate cancer survival: A review. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1502629"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Malerba, S., Vladimirov, M., Goyal, A., Dulskas, A., Bau\u0161ys, A., Cwalinski, T., Girnyi, S., Skokowski, J., Duka, R., and Molchanov, R. (2026). Artificial Intelligence Applications in Gastric Cancer Surgery: Bridging Early Diagnosis and Responsible Precision Medicine. J. Clin. Med., 15.","DOI":"10.3390\/jcm15062208"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/16\/2660\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T08:16:26Z","timestamp":1787040986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/16\/2660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":30,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cancers18162660"],"URL":"https:\/\/doi.org\/10.3390\/cancers18162660","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]}}}