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Background Biomarkers based on detecting prostate cancer (PCa)-specific transcripts in blood are associated with inferior outcomes, but their validation in a clinical context is lacking. Objective To determine whether detecting enhanced transcripts for PCa in whole blood using an analytically valid assay has prognostic significance relative to circulating tumor cell (CTC) enumeration. Design, setting, and participants The detection of KLK3, KLK2, HOXB13, GRHL2, and FOXA1 in whole blood by reverse transcription polymerase chain reaction (RT-PCR) was studied in 97 men with metastatic castration-resistant PCa (mCRPC) as a prognostic factor for overall survival. Intervention The 2.5 ml of blood was collected in PAXgene tubes for total RNA extraction and 7.5 ml for CTC enumeration from patients with progressive mCRPC. Outcome measurements and statistical analysis PCa-enriched genes were detected using a sensitive RT-PCR assay in whole blood from patients with mCRPC. Analytical validity of the assay was established in a clinical laboratory environment. The frequency of detecting transcripts was compared to CTC enumeration using CellSearch in an independent data set and survival associations were explored by concordance probability estimate (CPE). Results and limitations Two or more genes were detected by PCR in 53% of patients (51 of 97; 95% confidence interval [CI], 43-63%), and unfavorable CTC counts (five of more cells) were seen in 46% (45 of 97; 95% CI, 36-56%). Importantly, transcripts were detectable in 11 of 52 patients with favorable CTC counts (21%; 95% CI, 8-35%). Transcript detection predicted overall survival in a proportional hazards model. Significantly, the predictive accuracy of RT-PCR detection in combination with CTC enumeration had a CPE of 0.752 (standard error: 0.038), although this was limited by the number of patients evaluated. Conclusions This validated RT-PCR assay detecting prostate-specific RNA in whole blood is prognostic for survival and may assess patient risk in tandem with CellSearch CTC enumeration. Its clinical utility is being prospectively explored. © 2013 European Association of Urology.

Original publication

DOI

10.1016/j.eururo.2013.07.006

Type

Journal article

Journal

European Urology

Publication Date

01/01/2014

Volume

65

Pages

1191 - 1197