The Prognostic Role of Baseline Metabolic Tumor Burden and Systemic Inflammation Biomarkers in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Radium-223: A Proof of Concept Study

Abstract

Over the last years has emerged the urgent need for the identification of reliable prognostic biomarkers able to potentially identify metastatic castration-resistant prostate cancer (mCRPC) patients most likely to benefit from Radium-223 (Ra-223) since baseline. In the present monocentric retrospective study, we analyzed the prognostic power of systemic inflammation biomarkers and 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET)-derived parameters and their potential interplay in this clinical setting. The following baseline laboratory parameters were collected in 59 mCRPC patients treated with Ra-223: neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelets-to-lymphocyte ratio (PLR), and systemic inflammation index (SII), while maximum Standardized Uptake Value, Metabolic Tumor Volume (MTV), and Total Lesion Glycolysis (TLG) were calculated in the 48 of them submitted to baseline FDG-PET. At the univariate analysis, NLR, dNLR, MTV, and TLG were able to predict the overall survival (OS). However, only NLR and MTV were independent predictors of OS at the multivariate analysis. Additionally, the occurrence of both increased NLR and MTV at baseline identified mCRPC patients at higher risk for lower long-term survival after treatment with Ra-223. In conclusion, the degree of systemic inflammation, the quantification of the metabolically active tumor burden and their combination might represent potentially valuable tools for identifying mCRPC patients who are most likely to benefit from Ra-223. However, further studies are needed to reproduce these findings in larger settings.

The prognostic power of inflammatory indices and clinical factors in metastatic castration-resistant prostate cancer patients treated with radium-223 (BIO-Ra study)

“…In the last years, a few studies showed the predictive value of NLR in mCRPC patients treated with [ 223 Ra]RaCl 2 , related to the prediction of PFS and OS [6,35]. A recent monocentric study analyzed many inflammatory indices as prognostic factors in this clinical setting, confirming that NLR is the most accurate survival predictor among inflammatory indices [18]. However, most of the studies mentioned above remained inconclusive since none of these clinical or biochemical parameters has been validated as a unique and reliable selection tool.…”

Radium-223 Treatment of Patients with Metastatic Castration Resistant Prostate Cancer: Biomarkers for Stratification and Response Evaluation

“…Peripheral blood mediators of inflammation hold promise as biomarkers of therapeutic efficacy in various cancers [80]. Of these, neutrophil-to-lymphocyte ratio (NLR) is the most studied cellular inflammation marker, with higher levels being predictive of poor OS.…”

“…[81] This biomarker has been evaluated in relation to multiple mCRPC treatments, where it showed prognostic value [105]. In one study in 59 patients with mCRPC and treated with Ra-223, a low baseline NLR was independently associated with longer OS [80]. Cytokines and chemokines are important soluble mediators of inflammation, and can be detected in the serum.…”

“…For instance, the reaction of the tumor microenvironment of the bone metastases to Ra-223 treatment and subsequent immune response have not been extensively explored. Assessments of serum levels of mediators of inflammation and infection, such as chemokines and cytokines, in relation to Ra-223 treatment, could be an interesting means by which to understand the mechanism of action of Ra-223, and could be explored as a biomarker [80,104].…”

Neuroendocrine Differentiation of Prostate Cancer Is Not Systematically Associated with Increased 18F-FDG Uptake

“…After three cycles of Cabazitaxel administration, the patient underwent 18F-FDG PET/CT for prognostic purposes. Indeed, while FDG-avidity is low in naïve prostate cancer, it is increased in advanced and heavily pretreated metastatic castration-resistant prostate cancer (mCRPC), providing relevant prognostic insights [ 1 , 2 , 3 ]. 18F-FDG-PET/CT images of the patient showed low tracer avidity in both lymph nodes and bone lesions, suggesting low glycolytic activity and disease aggressiveness.…”