Clinical validity of detecting circulating tumor cells by AdnaTest assay compared to direct detection of tumor mRNA in stabilized whole blood as a biomarker predicting overall survival for metastatic castration-resistant prostate cancer patients

摘要

Circulating tumor cell (CTC) number measured with the CellSearch^® assay is prognostic for survival in metastatic castration-resistant prostate cancer (mCRPC) pre- and post-therapy. Using a standard operating protocol for sample collection, processing, and analysis, we compared detection rates of CellSearch^® performed using FDA-cleared methodology with a second positive selection assay, AdnaTest^®, and a non-selection polymerase chain reaction (PCR)-based (DDPCR) assay in 55 blood samples from 47 men with progressive mCRPC. AdnaTest requires processing within 4 hours of the draw and detects KLK3, PSMA, and EGFR transcripts in cells captured on magnetic beads. The DDPCR assay can be processed up to 7 days after a draw and detects KLK2, KLK3, HOXB13, GRHL2, and FOXA1 genes. AdnaTest and DDPCR were considered positive if at least 1 transcript was detected. AdnaTest detected CTCs in 34 samples (62%, 95% confidence interval [CI] 48%–75%), of which 23 (68%) had unfavorable CTC counts by CellSearch. A positive DDPCR result was seen in 38 cases (69%, 95% CI 55%–81%), including 24 (63%) with unfavorable CellSearch CTC counts. CellSearch found unfavorable CTC counts in 25 samples (45%, 95% CI 33%–58%). Sensitivities were similar between the AdnaTest and DDPCR assays, and both were more sensitive than CellSearch. Concordance probability estimates (possible values 0.5–1.0) associating the biomarker result with survival were similar: 0.77 (standard error [SE] = 0.07) for AdnaTest, 0.72 (SE = 0.08) for DDPCR, and 0.76 (SE = 0.06) for CellSearch. Overall detection rates between the AdnaTest and DDPCR assays were similar and both were superior to CellSearch. The DDPCR assay required the lowest blood volume, least on-site processing and longest stability for batch processing.