Abstract
PurposeTo combine peripheral blood indices and clinical factors in a prognostic score for metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223 dichloride ([223Ra]RaCl2).Patients and methodsBaseline neutrophil-to-lymphocyte ratio (NLR), derived NLR (donor), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason score (GS) group, number of bone metastases, prostate-specific antigen (PSA), alkaline phosphatase (ALP), line of therapy, previous chemotherapy, and the presence of lymphadenopathies were collected from seven Italian centers between 2013 and 2020. Lab and clinical data were assessed in correlation with the overall survival (OS). Inflammatory indices were then included separately in the multivariable analyses with the prognostic clinical factors. The model with the highest discriminative ability (c-index) was chosen to develop the BIO-Ra score.ResultsFive hundred and nineteen mCRPC patients (median OS: 19.9 months) were enrolled. Higher NLR, dNLR, PLR, and SII and lower LMR predicted worse OS (all with a p < 0.001). The multivariable model including NLR, ECOG PS, number of bone metastases, ALP, and PSA (c-index: 0.724) was chosen to develop the BIO-Ra score. Using the Schneeweiss scoring system, the BIO-Ra score identified three prognostic groups (36%, 27.3%, and 36.6% patients, respectively) with distinct median OS (31, 26.6, and 9.6 months, respectively; hazard ratio: 1.62, p = 0.008 for group 2 vs. 1 and 5.77, p < 0.001 for group 3 vs. 1).ConclusionsThe BIO-Ra score represents an easy and widely applicable tool for the prognostic stratification of mCRPC patients treated with [223Ra]RaCl2 with no additional costs.
Highlights
Bone metastases represent the leading cause of poor quality of life and increased mortality in patients with metastatic castration-resistant prostate cancer [1, 2]
From the complete blood count, we calculated the following ratios: neutrophil-to-lymphocyte ratio (NLR), derived NLR, lymphocyteto-monocyte ratio (LMR), platelets-to-lymphocyte ratio (PLR), and systemic inflammation index (SII). dNLR was calculated as ANC/(WBC-ANC) and SII as NLRxPLT
As many thresholds have been explored, but none validated in metastatic castration-resistant prostate cancer (mCRPC) patients, the cut-off values of inflammatory indices were determined using time-dependent ROC curves with the Liu approach, maximizing the concordance probability function [20,21,22,23]
Summary
Bone metastases represent the leading cause of poor quality of life and increased mortality in patients with metastatic castration-resistant prostate cancer (mCRPC) [1, 2]. The phase III Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) study demonstrated a significantly prolonged overall survival (OS) and time to first symptomatic skeletal event in mCRPC patients with bone metastasis and no visceral metastatic involvement receiving [223Ra] RaCl2 compared to placebo [4]. According to these results, [223Ra]RaCl2 was approved by the Food and Drug Administration in 2013 [5]. From the complete blood count, we calculated the following ratios: NLR, derived NLR (dNLR), lymphocyteto-monocyte ratio (LMR), platelets-to-lymphocyte ratio (PLR), and systemic inflammation index (SII). dNLR was calculated as ANC/(WBC-ANC) and SII as NLRxPLT
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