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Prostate Cancer Prostatic Dis. 2017 Jun;20(2):186-192. doi: 10.1038/pcan.2016.58. Epub 2017 Jan 24.

Utilization of biopsy-based genomic classifier to predict distant metastasis after definitive radiation and short-course ADT for intermediate and high-risk prostate cancer.

Author information

1
Department of Radiation Oncology, Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, MA, USA.
2
GenomeDx Biosciences, Vancouver, BC, Canada.
3
Department of Radiation Oncology, University of California at San Francisco, San Francisco, CA, USA.

Abstract

BACKGROUND:

We examined the ability of a biopsy-based 22-marker genomic classifier (GC) to predict for distant metastases after radiation and a median of 6 months of androgen deprivation therapy (ADT).

METHODS:

We studied 100 patients with intermediate-risk (55%) and high-risk (45%) prostate cancer who received definitive radiation plus a median of 6 months of ADT (range 3-39 months) from 2001-2013 at a single center and had available biopsy tissue. Six to ten 4 micron sections of the needle biopsy core with the highest Gleason score and percentage of tumor involvement were macrodissected for RNA extraction. GC scores (range, 0.04-0.92) were determined. The primary end point of the study was time to distant metastasis. Median follow-up was 5.1 years. There were 18 metastases during the study period.

RESULTS:

On univariable analysis (UVA), each 0.1 unit increase in GC score was significantly associated with time to distant metastasis (hazard ratio: 1.40 (1.10-1.84), P=0.006) and remained significant after adjusting for clinical variables on multivariable analysis (MVA) (adjusted hazard ratio: 1.36 (1.04-1.83), P=0.024). The c-index for 5-year distant metastasis was 0.45 (95% confidence interval: 0.27-0.64) for Cancer of the Prostate Risk Assessment score, 0.63 (0.40-0.78) for National Comprehensive Cancer Network (NCCN) risk groups, and 0.76 (0.57-0.89) for the GC score. Using pre-specified GC risk categories, the cumulative incidence of metastasis for GC>0.6 reached 20% at 5 years after radiation (P=0.02).

CONCLUSIONS:

We believe this is the first demonstration of the ability of the biopsy-based GC score to predict for distant metastases after definitive radiation and ADT for intermediate- and high-risk prostate cancer. Patients with the highest GC risk (GC>0.6) had high rates of metastasis despite multi-modal therapy suggesting that they could potentially be candidates for treatment intensification and/or enrollment in clinical trials of novel therapy.

PMID:
28117383
PMCID:
PMC5435968
DOI:
10.1038/pcan.2016.58
[Indexed for MEDLINE]
Free PMC Article

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