Fast Five Quiz: Prostate Cancer Molecular and Biomarker Analysis

Chad R. Tracy, MD


August 11, 2023

Along with ConfirmMDX, PCA3 is a type of molecular testing that is used when repeat biopsy is a consideration. Nearly one quarter of PCas are missed on initial biopsy, with many patients requiring second, third and fourth biopsies to get a positive result. The PCA3 gene is a noncoding mRNA that is 60-100 times higher in cancerous tissue (than in benign). It is measured using the first 20-30 ml of post-DRE urine and provides the ratio of PCA3 mRNA transcripts in the sample to serum PSA.

Polaris, Oncotype DX, and Decipher are tissue-based molecular biomarkers that might provide accurate risk stratification for appropriate treatment of PCa. According to American Society of Clinical Oncology (ASCO) guidelines, these tests should be offered to patients who would benefit from active surveillance or some type of definitive therapy.

Polaris consists of measurement of mRNA levels of 46 genes, comprising 31 genes involved in cell cycle progression and 15 housekeeping genes by reverse transcription polymerase chain reaction (RT-PCR), that is scored on a 10-point scale and gives the score percentile within the patient's NCCN risk profile. It also provides a percentage risk for 10-year disease-specific mortality and distant metastasis. The test is part of both the NCCN and ASCO guidelines.

Oncotype DX is a quantitative RT-PCR assay that measures the expression of 17 genes (12 cancer-specific and five housekeeping genes). The numeric score, which is on a scale of 0-100, is combined with NCCN risk groupings to provide a comprehensive risk score. The report provides a percentage risk for PCa death within 10 years, metastasis within 10 years, and risk for adverse pathology (defined as Gleason ⩾ 4 + 3 or pT3 +) on radical prostatectomy(RP). It is mentioned in the PCa workup in both the NCCN and ASCO guidelines.

Decipher is the most broadly validated tissue-based gene expression classifier. The score is based on the microarray-based expression of 22 genes involved in androgen receptor signaling, cell proliferation, differentiation, motility, and immune modulation. It is reported using a score of 0-1, independent of clinical or demographic data. Scores ⩽ 0.6 are classified as low risk, while scores > 0.6 are classified as high risk. The test can be performed on either a positive biopsy specimen or a post-RP specimen. Additionally, this test provides several prognostic variables, including percentage risk for distant metastasis in 5 and 10 years, 15-year disease-specific mortality, and the risk for adverse pathology at RP. Per ASCO guidelines, Decipher results should help to guide post-prostatectomy adjuvant or salvage radiation.

Learn more about molecular and biomarker analysis in PCa.

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