Advanced prostate cancer survival predicted by gene panel

January 1, 2012

Results from testing in an initial patient cohort indicate the potential for a six-gene, whole blood RNA-based expression panel to predict survival in men with progressive metastatic castration-resistant prostate cancer.

Key Points

New York-Results from testing in an initial patient cohort indicate the potential for a six-gene, whole blood RNA-based expression panel to predict survival in men with progressive metastatic castration-resistant prostate cancer (mCRPC), reported researchers from Memorial Sloan-Kettering Cancer Center, New York.

"The ability to differentiate men who will succumb early to their disease and those who will live longer is important in clinical management, where this information can help guide decisions on aggressiveness of therapy, but the ultimate goal is to be able to optimize patient stratification for enrollment into clinical trials where selection of a higher risk population can increase the efficiency and ability of the trial to determine efficacy and safety of interventions. We believe this gene panel holds promise in this regard," said Dr. Subudhi, who worked on the research with Howard I. Scher, MD, and colleagues.

Six genes were found to have prognostic significance and were combined into a biomarker panel that was shown to independently predict survival time in a multivariate analysis.

Panel displays 'moderate' accuracy

A concordance probability estimate (CPE) was used to determine the discriminatory power and predictive accuracy of the six-gene panel, and the six-gene panel was found to have a CPE value of 0.71, which is indicative of moderate accuracy. (A CPE of 0.5 represents a biomarker with no predictive accuracy, ie, a coin toss, whereas a CPE of 1.0 demonstrates a biomarker predicting with 100% accuracy that an event will occur.) Improved prognostic value was achieved by combining the six-gene panel with circulating tumor cell (CTC) enumeration (CellSearch Assay, Veridex, North Raritan, NJ) and lactate dehydrogenase (LDH). The CPE value of the latter biomarker model was 0.76, Dr. Subudhi reported.

"Current biomarkers for predicting survival in patients with metastatic CRPC include CTC enumeration and levels of PSA, LDH, and albumin, but each of these markers has limited clinical utility when used in isolation," Dr. Subudhi told Urology Times.

"Our study also found that the six-gene panel has greater predictive accuracy for predicting survival in patients with progressive mCRPC than the existing biomarkers, which had CPE values ranging from 0.56 to 0.68, and the prognostic value of the combined biomarker model is reasonable enough to suggest a role in clinical practice. However, our findings first need to be validated through testing in an independent population. Such an investigation is currently under way, and if the results are positive, the next step will be to test the ability of the RNA-based gene signature to predict outcomes in a prospective clinical trial," he said.

The six genes comprising the predictive panel are BCL2 (B Cell Lymphoma 2), C1QB (complement component 1, b subcomponent), CAV2 (caveolin 2), CD82 (cluster of differentiation 82), GAS1 (growth arrest-specific protein-1), and NFATC2 (nuclear factor of activated T cells, cytoplasmic 2). They all have different functions that regulate cancer cell growth and metastasis.