Faculty Collaboration Database

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 Sep;21(3):411-418

Date

06/03/2018

Pubmed ID

29858592

Pubmed Central ID

PMC6126974

DOI

10.1038/s41391-018-0043-z

Scopus ID

2-s2.0-85047928806 (requires institutional sign-in at Scopus site)   29 Citations

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

Author

Deepak Kilari MD Associate Professor in the Medicine department at Medical College of Wisconsin

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