Introduction: Recent data has demonstrated the utility of baseline plasma cell-free DNA (cfDNA) concentration as an independent prognostic indicator for metastatic castration-resistant prostate cancer (mCRPC) patients receiving systemic chemotherapy. However, the clinical utility of this biomarker is still unknown in the androgen receptor signalling inhibitor (ARSI)-treated population.
Aims: Our objective was to correlate baseline cfDNA concentration and clinical outcomes in patients commencing ARSI for mCRPC.
Methods: Blood for cfDNA analysis was prospectively collected from 42 mCRPC patients prior to commencing abiraterone or enzalutamide. Evaluable patients were required to have a minimum of 12 weeks follow-up. cfDNA was extracted from plasma using the QIAamp circulating nucleic acid kit as per the manufacturer’s protocol, then quantified using fluorescence spectrometry (Qubit). Univariable analyses was conducted using logistic regression to determine if there was an association between baseline cfDNA concentration (expressed as log10 concentration) and prostate-specific antigen (PSA) response. In addition, Cox proportional hazard models tested for associations between cfDNA concentration (plus other baseline prognostic variables) and the composite endpoint of clinical/radiological progression-free survival (clin/rPFS). All p-values <0.05 were considered significant.
Results: The median baseline cfDNA concentration in this cohort was 8.2ng/ml (IQR 4.7 -14.9ng/ml). Median follow-up was 9.2 months. Baseline log10 cfDNA concentration was not associated with a confirmed PSA response (odds ratio [OR] = 0.4; p=0.2). Median clin/rPFS was not reached. In univariate analyses, baseline log10 cfDNA concentration significantly correlated with shorter clin/rPFS (hazard ratio [HR] = 3.1; 95% CI: 1.2-7.7; p=0.02). Other baseline prognostic factors correlating with shorter clinical/rPFS included log10 LDH concentration (p=0.002) and log10 neutrophil-lymphocyte ratio (p=0.008).
Conclusions: In mCRPC patients commencing ARSI, higher baseline cfDNA concentration was associated with shorter clinical/rPFS, and a non-significant trend towards lower PSA response rates. Baseline cfDNA may be a potential independent prognostic biomarker for patients commencing ARSI, but validation will require greater patient numbers and ongoing data maturation. Future directions include cohort expansion, and analysis of on-progression samples.