Performance of the Genomic Evaluators of Metastatic Prostate Cancer (GEMCaP) Tumor Biomarker for Identifying Recurrent Disease in African American Patients

Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 06/2014; 23(8). DOI: 10.1158/1055-9965.EPI-13-1124
Source: PubMed


Evaluation of prostate cancer prognosis after surgery is increasingly relying upon genomic analyses of tumor DNA. We assessed the ability of the biomarker panel Genomic Evaluators of Metastatic Prostate Cancer (GEMCaP) to predict biochemical recurrence in 33 European American and 28 African American prostate cancer cases using genome-wide copy number data from a previous study. "Biomarker positive" was defined as ≥20% of the 38 constituent copy number gain/ loss GEMCaP loci affected in a given tumor; based on this threshold, the frequency of a positive biomarker was significantly lower in African Americans (n=2; 7%) than European Americans (n=11; 33%; p=0.013). GEMCaP positivity was associated with risk of recurrence (HR=5.92; 95%CI=2.32-15.11; p=3*10-4) in the full sample and among European Americans (HR=3.45; 95%CI=1.13-10.51; p=0.032) but was not estimable in African Americans due to the low rate of GEMCaP positivity. Overall, the GEMCaP recurrence positive predictive value (PPV) was 85%; in African Americans, PPV was 100%. When we expanded the definition of loss to include copy-neutral loss of heterozygosity (i.e. loss of one allele with concomitant duplication of the other), recurrence PPV was 83% for European American subjects. Under this definition, five African American subjects had a positive GEMCaP test value; four went on to develop biochemical recurrence (PPV=80%). Our results suggest that the GEMCaP biomarker set could be an effective predictor for both European American and African American men diagnosed with localized prostate cancer who may benefit from immediate aggressive therapy after radical prostatectomy.

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    ABSTRACT: Over the past several years, multiple biomarkers designed to improve prostate cancer risk stratification have become commercially available, while others are still being developed. In this review, we focus on the evidence supporting recently reported biomarkers, with a focus on gene expression signatures. Many recently developed biomarkers are able to improve upon traditional risk assessment at nearly all stages of disease. Prominent examples are reviewed in this article. ConfirmMDx uses gene methylation patterns to improve detection of clinically significant cancer following negative biopsy. Both the Prolaris and Oncotype DX Genomic Prostate Score tests can improve risk stratification following biopsy, especially among men who are eligible for active surveillance. Prolaris and the Decipher genomic classifier have been associated with risk of adverse outcome following prostatectomy, while Oncotype DX is being studied in this setting. Finally, recent reports of the association of androgen receptor-V7 in circulating tumor cells with resistance to enzalutamide and abiraterone raise the possibility of extending the use of genetic biomarkers to advanced disease. With the development of multiple genetic expression panels in prostate cancer, careful study and validation of these tests and integration into clinical practice will be critical to realizing the potential of these tools.
    No preview · Article · Jan 2015 · Current Opinion in Urology