Opportunistic skeletal muscle metrics as prognostic tools in metastatic castration-resistant prostate cancer patients candidates to receive Radium-223

Abstract

Objective Androgen deprivation therapy alters body composition promoting a significant loss in skeletal muscle (SM) mass through inflammation and oxidative damage. We verified whether SM anthropometric composition and metabolism are associated with unfavourable overall survival (OS) in a retrospective cohort of metastatic castration-resistant prostate cancer (mCRPC) patients submitted to 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) imaging before receiving Radium-223. Patients and methods Low-dose CT were opportunistically analysed using a cross-sectional approach to calculate SM and adipose tissue areas at the third lumbar vertebra level. Moreover, a 3D computational method was used to extract psoas muscles to evaluate their volume, Hounsfield Units (HU) and FDG retention estimated by the standardized uptake value (SUV). Baseline established clinical, lab and imaging prognosticators were also recorded. Results SM area predicted OS at univariate analysis. However, this capability was not additive to the power of mean HU and maximum SUV of psoas muscles volume. These factors were thus combined in the Attenuation Metabolic Index (AMI) whose power was tested in a novel uni- and multivariable model. While Prostate-Specific Antigen (PSA), Alkaline Phosphatase (ALP), Lactate Dehydrogenase and Hemoglobin, Metabolic Tumor Volume, Total Lesion Glycolysis and AMI were associated with long-term OS at the univariate analyses, only PSA, ALP and AMI resulted in independent prognosticator at the multivariate analysis. Conclusion The present data suggest that assessing individual 'patients' SM metrics through an opportunistic operator-independent computational analysis of FDG PET/CT imaging provides prognostic insights in mCRPC patients candidates to receive Radium-223. Graphical abstract

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

“…Beyond the enrollment procedure for 223 RaCl 2 therapy, a simple count of the number of bone metastases turns out to be extremely reductive. Indeed, a number of studies focused on the use of imaging semi-quantification as a tool to assess tumor spread in mCRPC candidates to receive 223 RaCl 2 therapy [ 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. The BSI, a measure expressing the fraction of the skeleton involved by the tumor as a percentage value of the whole body mass [ 14 ], has been proposed for determining the extent of disease, monitoring disease progression, and assessing treatment response in different malignancies.…”

The impact of sarcopenia on clinical outcomes in men with metastatic castrate-resistant prostate cancer

“…Previous studies in men with PC have assessed sarcopenia based on CT scans using the entire cross-sectional skeletal muscle area at the level of the 3 rd lumbar vertebra, or of the psoas muscle [ 8 – 12 , 30 ]. Although this opportunistic method provides accurate estimates of muscle mass and density, it omits other important elements of sarcopenia, such as measures of muscle function that have been included in the updated definition per expert study groups on sarcopenia [ 2 , 14 , 19 , 31 ].…”

“…Several studies in men with mCRPC have demonstrated that CT-based low skeletal muscle quantity/mass or muscle quality at the level of the 3 rd lumbar vertebra, notably also of the psoas muscle, are associated with a higher risk of grade I-II neutropenia during chemotherapy [ 8 ], disease progression [ 9 , 10 ], and overall mortality [ 9 , 11 , 12 ]. Although these studies provided promising evidence of the role of sarcopenia in predicting clinical and disease outcomes in men with mCRPC, there was no consensus on the skeletal muscle measure (e.g., mass versus quality) that could best predict outcomes.…”

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

“…In a precision medicine perspective, the addition of molecular biomarkers to the BIO-Ra score might further improve its capability for selecting the best drug for the right patient. A similar consideration applies to next-generation imaging, particularly with positron emission tomography (PET), whose functional nature may at the same time provide an accurate staging of the disease extent [ 30 ] and display tumour heterogeneity in vivo [ 13 , 17 , 18 , 31 , 32 , 33 , 34 , 35 ], potentially improving the patient selection process. Unfortunately, given the study’s retrospective nature, we built the BIO-Ra score exclusively using widely available clinical and lab data.…”

“…Several studies previously investigated many parameters potentially able to improve patient’s selection since baseline [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. However, most of them remained inconclusive since none of the identified clinical or biochemical biomarkers has been validated as a unique and reliable selection tool.…”