Prognostic Value of the BIO-Ra Score in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Radium-223 after the European Medicines Agency Restricted Use: Secondary Investigations of the Multicentric BIO-Ra Study

SIMPLE SUMMARY: Radium-223 prolongs overall survival in metastatic castration-resistant prostate cancer patients with bone metastases. However, prognosis after Radium-223 administration varies among patients. One possible reason for this heterogeneity could rely on the suboptimal selection of patients with unfavourable prognostic factors. Moreover, in 2018, the European Medicines Agency limited the Radium-223 prescription to patients pre-treated with at least two systemic therapies or ineligible for any systemic treatment and more than six bone lesions. This moved Radium-223 treatment to the later stages of the disease, making the patient selection process even more challenging. In the BIO-Ra study, we previously combined peripheral inflammatory indices and clinical factors in a composite score able to stratify the prognosis of these patients since baseline. In the present study, the BIO-Ra score was also a reliable prognostic tool in the current clinical scenario, with a potential added value in the patient’s selection for Radium-223 treatment. ABSTRACT: The multicentric retrospective BIO-Ra study combined inflammatory indices from peripheral blood and clinical factors in a composite prognostic score for metastatic castration-resistant prostate cancer patients receiving Radium-223 (Ra-223). In the present study, we evaluated (i) the prognostic power of the BIO-Ra score in the framework of the restricted use of Ra-223 promoted by the European Medicines Agency in 2018; (ii) the treatment completion prediction of the BIO-Ra score. Four hundred ninety-four patients from the BIO-Ra cohort were divided into three risk classes according to the BIO-Ra score to predict the treatment completion rate (p < 0.001 among all the three groups). Patients receiving Ra-223 after restriction (89/494) were at later stages of the disease compared with the pre-restriction cohort (405/494), as a higher percentage of BIO-Ra high-risk classes (46.1% vs. 34.6%) and lower median Overall survival (12.4 vs. 23.7 months, p < 0.001) was observed. Despite this clinically relevant difference, BIO-Ra classes still predicted divergent treatment completion rates in the post-restriction subgroup (72%, 52.2%, and 46.3% of patients belonging to low-, intermediate-, and high-risk classes, respectively). Although the restricted use has increased patients at higher risk with unfavourable outcome after Ra-223 treatment, the BIO-Ra score maintains its prognostic value.