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

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.

Association between the Immunophenotype of Peripheral Blood from mCRPC Patients and the Outcomes of Radium-223 Treatment

“…Although the time between diagnosis and collection of the blood sample varies between patients, we saw higher NLR in patients diagnosed at stage IV [ 20 ] and in patients with a high Gleason score [ 21 ]. Even though baseline NLR is considered to be a prognostic factor in Radium-223-treated patients [ 22 , 23 , 24 ], we could not associate NLR values with either PFS or overall survival. Discrepancies with other reports in this regard can be explained by the fact that, in our cohort, only 58% of the patients received five cycles of Radium-223.…”

The DASciS Software for BSI Calculation as a Valuable Prognostic Tool in mCRPC Treated with 223RaCl2: A Multicenter Italian Study

“…According to most of the literature data, the median OS resulted inferior to the 14.9 months reported in the ALSYMPCA study, being of 13 months in our cohort [ 10 , 49 ]. It is worth underlining that in the multivariate analysis, the BSI showed better performance than the ECOG-PS, a well-known reliable tool for prognostic assessment in mCRPC patients undergoing 223 RaCl 2 , according to consistent data from the literature [ 19 , 30 , 35 ]. Based on these considerations and due to its valuable utility in patients’ stratification, independently from treatment choice, baseline BSI could be investigated as an additional variable to be included in a multidimensional approach taking into account different data, such as baseline Hb, tALP and PSA which corroborated their prognostic relevance in the present analysis.…”

“…A three-variable prognostic score taking into account baseline patients’ Hb, ECOG-PS, and PSA has been proposed [ 29 ] and recently further validated in a multicentric study [ 30 ]. Similarly, a composite prognostic score including inflammatory indices from peripheral blood and clinical factors (ECOG-PS, tALP, and the number of bone metastases at the bone scan) has been validated in this clinical setting [ 19 , 20 ]. In such background, the identification of additional reliable prognostic factors, able to select patients most likely to benefit from 223 RaCl 2 , still results of great importance.…”

“…All patients signed a written Informed Consent, which included the use of anonymized data for retrospective research purposes, before each 223 RaCl 2 administration. The present retrospective multicenter study included 370 consecutive mCRPC patients eligible for 223 RaCl 2 therapy according to the criteria in force at the time of enrollment [ 12 , 18 , 19 , 20 ] and treated in six Italian Nuclear Medicine Units between July 2015 to November 2022, time of the analysis. Conforming to the standard selection criteria for 223 RaCl 2 treatment, all enrolled patients had a diagnosis of mCRPC with symptomatic bone metastases, no visceral metastatic involvement except for malignant lymphadenopathies with less than 3 cm in the short-axis diameter assessed through a Computed Tomography (CT) scan and/or a Positron Emission Tomography (PET)-CT scan performed before enrollment, adequate hematological, hepatic and renal function [ 21 ] and absence of inflammatory bowel disease (IBD).…”

Change of the Neutrophil-to-Lymphocyte Ratio during Treatment: A Potential Prognostic Biomarker in Metastatic Prostate Cancer Treated with Radium-223 Dichloride

“…These results are consistent with the available literature regarding 223 Ra-treated patients. Indeed, the fact that the baseline NLR is a prognostic factor in 223 Ra-treated patients is well recognized in most studies on the subject including the post hoc analysis of the ALSYMPCA trial by Meisel et al [ 11 , 15 ] and other trials [ 16 , 17 ]. Our results are unique in finding that not only baseline NLR but also the change of the NLR at 12 weeks is a predictive factor and could help selecting patients who could benefit from changing their systemic treatment.…”