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AUA 2016: Cell-Cycle Progression Score Provides Significant Prognostic Information in Patients With Gleason Score < 7

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Key Points

  • Prolaris is a novel 46-gene RNA-expression test that directly measures tumor cell growth characteristics for stratifying the risk of disease-specific mortality in patients with prostate cancer.
  • In univariate analysis, both cell-cycle progression and clinical cell-cycle risk (a prognostic model combining cell-cycle progression and cancer of the prostate risk assessment [CAPRA]) were significant predictors of outcome.
  • Cell-cycle progression remained significant after adjusting for CAPRA or after adjusting for a de novo multivariate model including prostate-specific antigen, clinical stage, percent positive cores, and age at diagnosis.

Myriad Genetics announced results from a study of the prognostic information provided by its Prolaris test in patients with prostate cancer and a Gleason score < 7 at the 111th Annual Scientific Meeting of the American Urological Association (AUA) (Abstract MP02-20).

Prolaris is a novel 46-gene RNA-expression test that directly measures tumor cell growth characteristics for stratifying the risk of disease-specific mortality in patients with prostate cancer. The test provides a quantitative measure of the RNA expression levels of genes involved in the progression of tumor growth. Low gene expression is associated with a low risk of disease-specific mortality in men who may be candidates for active surveillance, and high gene expression is associated with a higher risk of disease-specific mortality in patients who may benefit from additional therapy.

Study Objectives 

The Prolaris test focuses on the cell-cycle progression score, which was developed and validated to provide prognostic information to prostate cancer patients in all risk groups. But because previous studies of cell-cycle progression focused on distant oncologic outcomes (eg, biochemical recurrence, metastases, and mortality), any individual study will lack power to demonstrate prognostic utility of the score in low-risk patients due to a low event rate. Researchers presented a meta-analysis of previous studies that evaluated the cell-cycle progression score in men who had Gleason score < 7 disease diagnosed by needle biopsy and were either managed conservatively initially or treated by radical prostatectomy. 

Methods 

The cell-cycle progression score was derived from the biopsy as the mean expression of 31 cell-cycle progression genes normalized by 15 housekeeper genes. The score was evaluated for association with adverse outcome using men with Gleason score ≤ 3+3 in a meta-analysis combining two conservatively managed cohorts (N = 204) and three cohorts after radical prostatectomy (N = 236).

Outcome was either prostate cancer death (in conservatively managed cohorts) or biochemical recurrence (in post–radical prostatectomy cohorts), and association with outcomes was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Analyses were stratified by cohort, and there was no evidence that cell-cycle progression behaved differently by outcome. Hazard ratios (HRs) are given for 1-unit increase in cell-cycle progression score (equivalent to a doubling of gene expression). 

Results 

The cell cycle progression signature was a significant predictor of outcome in the meta-analysis. In univariate analysis, both cell-cycle progression and clinical cell-cycle risk (a prognostic model combining cell-cycle progression score and cancer of the prostate risk assessment [CAPRA]) were significant predictors of outcome (HR = 1.50, = .0099; and HR = 1.83, = .0014).

Cell-cycle progression remained significant after adjusting for CAPRA (HR = 1.46, = .019) or after adjusting for a de novo multivariate model including prostate-specific antigen, clinical stage, percent positive cores, and age at diagnosis (HR = 1.47, = .017). In fact, the only significant variables in the multivariate model were prostate-specific antigen and cell-cycle progression. Both of these variables retained significance in a bivariate model. 

Conclusions 

The cell-cycle progression score, measured by Prolaris, predicts oncologic outcomes in Gleason 6 or less prostate cancer patients. This meta-analysis adds to the evidence that cell-cycle progression score provides significant prognostic discrimination in patients with low-risk localized disease. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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