Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Prognostic association of plasma cell-free DNA-based androgen receptor amplification and circulating tumor cells in pre-chemotherapy metastatic castration-resistant prostate cancer patients. Prostate Cancer Prostatic Dis 2018 09;21(3):411-418 PMID: 29858592 PMCID: PMC6126974

Pubmed ID

29858592

DOI

10.1038/s41391-018-0043-z

Abstract

BACKGROUND: The prognostic significance of plasma cell-free DNA (cfDNA) androgen receptor amplification (ARamp) in metastatic castration-resistant prostate cancer (mCRPC) compared with circulating tumor cell (CTC) counts is not known.

METHODS: As part of correlative aims of a prospective study in mCRPC, concurrent and serial collections of plasma and CTCs were performed. Specimen collections were performed at baseline after progression on androgen deprivation therapy and then 12 weeks later. QuantStudio3D digital PCR system was used to determine plasma cfDNA AR copy number variations and Cell search assay for enumerating CTC counts. Association of baseline cfDNA ARamp status/CTC counts with overall survival (OS) (primary goal) was evaluated using Kaplan-Meier method and log-rank test (p ≤ 0.05 for significance) and receiver operator curves (ROCs) for ARamp status and CTC counts ≥5. A multivariate analysis was performed using Cox regression models that included ARamp, CTC counts, and other clinical factors.

RESULTS: ARamp was detected in 19/70 patients at baseline. At the time of analysis, 28/70 patients had died (median follow-up 806 days; interquartile range: 535-966). ARamp was associated with poor OS (2-year OS of 35% in ARamp vs. 71% in non-ARamp; log-rank p value ≤0.0001). Baseline CTC counts ≥5 (vs. <5) was also associated with poor survival (2-year OS of 44 vs. 74%; log-rank p = 0.001). ROC analysis demonstrated area under the curve of 0.66 for ARamp-based prognosis and 0.68 for CTC count-based prognosis (p = 0.84 for difference). The best two variables included for multivariable analysis were ARamp and CTC counts ≥5; however, the two-factor model was not significantly better than using ARamp alone for predicting survival (hazard ratio = 5.25; p = 0.0002).

CONCLUSIONS: CTCs and plasma cfDNA ARamp were observed to have equal prognostic value in mCRPC. Larger cohorts that incorporate molecular and clinical factors are needed to further refine prognosis in CRPC.

Author List

Kohli M, Li J, Du M, Hillman DW, Dehm SM, Tan W, Carlson R, Campion MB, Wang L, Wang L, Zhang H, Zhang P, Kilari D, Huang CC, Wang L

Authors

Deepak Kilari MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Liang Wang MD, PhD Professor in the Pathology department at Medical College of Wisconsin




Scopus

2-s2.0-85047928806   1 Citations

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Androgen Antagonists
Biomarkers, Tumor
Cell Count
Circulating Tumor DNA
DNA Copy Number Variations
Disease Progression
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Neoplastic Cells, Circulating
Predictive Value of Tests
Prognosis
Prospective Studies
Prostatic Neoplasms, Castration-Resistant
Receptors, Androgen
Treatment Outcome
jenkins-FCD Prod-336 69ef4a6b262d135130251597d5d39873903802b5