Combining functional imaging with circulating biomarker analysis to improve prognostication of metastatic castration-resistant prostate cancer (mCRPC)

Abstract

Background: Biomarkers for treatment personalization in mCRPC could improve patient outcomes. Multiple tests on blood have reported associations with worse outcome, including serum lactate dehydrogenase (LDH), chromogranin A (CgA), neutrophil-lymphocyte ratio (NLR) and more recently AR copy number (CN) in plasma DNA (Conteduca, Ann Oncol 2017). Biological data suggest an association between choline uptake and androgen receptor (AR) expression. We here aimed to integrate 18F-fluorocholine (FCH) uptake on PET/CT with plasma AR CN and other routinely obtained circulating biomarkers and evaluate associations with outcome. Methods: We determined plasma AR DNA by digital PCR and Taqman from 105 CRPC samples collected before abiraterone (n=65) or enzalutamide (n=40). Pretreatment serum LDH, CgA, NLR were also measured. FCH-PET/CT scan was performed at baseline and SUVmax, total lesion activity (TLA) and metabolic tumor volume (MTV) were calculated. Patients (pts) were dichotomized in high and low according to receiver-operating characteristic (ROC) curves. Main endpoints were the correlation of FCH-PET/CT parameters with circulating biomarkers and their impact on progression-free/overall survival (PFS/OS). Results: Plasma AR CN gain was observed in 27 pts (25.7%) and correlated significantly with high SUVmax (p<0.0001), TLA (p<0.0001), MTV (p=0.0006) and greater number of lesions on FCH-PET/CT (p<0.0001). On multivariable analysis, SUVmax, plasma AR, CgA, NLR and LDH were significantly associated with outcome (Table 1). Conclusions: Choline uptake was significantly related to plasma AR CN gain as well as elevated NLR, CgA, and LDH values. This analysis identified independent predictors of survival in mCRPC and more accurate prognostic distinct groups using molecular, laboratory and imaging features. The potential integration of these non-invasive biomarkers could be as a tool for a better treatment selection of CRPC. A larger prospective evaluation is warranted. (Table presented).