Development, Evaluation, and Comparison of Prognostic Biomarkers in Prostate Cancer

Detection, diagnosis and risk stratification in prostate cancer

Histological grading to determine aggressiveness

Tissue-based Biomarkers for risk stratification

Tissue-based molecular biomarkers may facilitate accurate risk stratification for appropriate treatment in the clinical continuum of PCa:

  • identify patients with favorable risk disease, candidates for active surveillance
  • determining the optimal treatment approach for men with high-risk disease
  • identifying patients for additional treatment following initial therapy

Decipher: Main points

  • insurance reimbursed test included in NCCN and ASCO guideline statements
  • microarray-based expression of 22 genes involved in androgen receptor signaling, cell proliferation differentiation, motility, and immune modulation
  • test can be performed on either a positive biopsy specimen or a post-RP specimen
  • provides percentage risk of distant metastasis in 5- and 10-years, 15-year disease specific mortality, and the risk of adverse pathology at RP
  • Decipher is the most broadly validated of all the tissue-based biomarkers
  • costs: ~$4.000

Decipher: Sample report

Oncotype Dx: Main points

  • mentioned in both the ASCO and NCCN guidelines
  • quantitative RT-PCR assay, expression of 17 genes (12 cancer specific and 5 housekeeping genes)
  • Oncotype score is combined with NCCN risk groupings on the test report to provide a comprehensive risk score
  • provides a percentage risk of PCa death within 10 years, metastasis within 10 years, and risk of adverse pathology on RP
  • Costs: ~$4.520

Oncotype Dx: Sample report

Oncotype Dx: Sample report

Prolaris: Main points

  • is mentioned in the NCCN and ASCO guidelines
  • 46 genes, comprising 31 genes involved in cell cycle progression and 15 housekeeping genes by RT-PCR
  • gives the score percentile within the patient’s NCCN risk group
  • also provides a percentage risk of 10-year disease specific mortality and distant metastasis
  • costs: ~$3.400

Prolaris: Sample report

Prolaris: Sample report

Workflow

Summary of datasets

ID event n_max event_and_n alias First_author Last_author technology Sample_type
GSE16560 OS 281 OS (281) Swedish Watchful Waiting cohort Sboner microarray TURP samples
TCGA-PRAD PFS; DFS 497 PFS (491); DFS (337) TCGA_PRAD RNA-seq prostatectomy
GSE70768 RFS 111 RFS (111) Cambridge Ross-Adams microarray prostatectomy
GSE70769 RFS 92 RFS (92) Stockolm Ross-Adams microarray prostatectomy
GSE116918 RFS; MFS 248 RFS (248); MFS (248) Belfast Jain microarray diagnostic biopsies
SU2C-Capture OS 71 OS (71) SU2C-PCF-2019-Capture RNA-seq biopsy of metastasis
SU2C-PolyA OS 81 OS (81) SU2C-PCF-2019-PolyA RNA-seq biopsy of metastasis
GSE54460 RFS 106 RFS (106) Moreno RNA-seq prostatectomy
GSE94767 RFS 233 RFS (233) CancerMap microarray prostatectomy
GSE21034 RFS; OS 140 RFS (140); OS (140) MSKCC2010 Taylor microarray prostatectomy
GSE107299 RFS 65 RFS (65) CPC-Gene microarray prostatectomy

Risk score

Signature evaluation on multiple data sets

DFS: Disease-free survival, MFS: Metastasis-free survival, OS: Overall survival, PFS: Progression-free survival, RFS: Relapse-free survival

Performance comparison

Concordance-index

DFS: Disease-free survival, MFS: Metastasis-free survival, OS: Overall survival, PFS: Progression-free survival, RFS: Relapse-free survival

The concordance index evaluates how well a survival model classifies or predicts the order of survival of different subjects in a data set.

Performance comparison

Hazard Ratio

DFS: Disease-free survival, MFS: Metastasis-free survival, OS: Overall survival, PFS: Progression-free survival, RFS: Relapse-free survival

Next steps

Extended view