lunes, 19 de mayo de 2014

Gene Expression Analysis for Prostate Cancer Management

Gene Expression Analysis for Prostate Cancer Management

BlueCross BlueShield Association



Gene Expression Analysis for Prostate Cancer Management

Executive Summary
Background
Prostate cancer is the second most common cancer diagnosed among men in the U.S. According to the National Cancer Institute, nearly 240,000 new cases are expected to be diagnosed in the U.S. in 2013, and associated with around 30,000 deaths. Localized prostate cancers may appear clinically very similar at diagnosis. However, they often exhibit diverse risk of progression that may not be captured by accepted clinical risk categories (e.g., D’Amico criteria) or prognostic tools that are based on clinical findings, including prostate-specific antigen (PSA) titers, Gleason grade, or tumor stage. This creates uncertainty whether or not to treat immediately. A patient may choose definitive treatment comprising radiotherapy, surgery, chemotherapy, or androgen deprivation. Alternatively, the patient may forgo immediate therapy and continue regular monitoring until signs or symptoms of disease progression are evident, at which point curative treatment is instituted. This approach is referred to as “active surveillance.”
Given the unpredictable behavior of early prostate cancer, additional prognostic tests are under investigation. These include gene expression profiling using RTPCR-based technology. Gene expression profiling refers to analysis of mRNA expression levels of many genes simultaneously in a tumor specimen.
Two gene expression profiling tests are now offered, intended to biologically stratify prostate cancers: Prolaris® (Myriad Genetics, Salt Lake City, UT) and Oncotype Dx® Prostate Cancer Assay (Genomic Health, Redwood City, CA). Both use archived tumor specimens as the mRNA source, reverse transcriptase polymerase chain reaction amplification, and a low density RTPCR array platform. Prolaris® is used to quantify expression levels of 31 cell cycle progression (CCP) genes and 15 housekeeper genes to generate a CCP score. Oncotype Dx® Prostate is used to quantify expression levels of 12 cancer-related and 5 reference genes to generate a Genomic Prostate Score (GPS). In the final analysis, the CCP score (median 1.03, interquartile range 0.41–1.74) and GPS (range 0–100) are combined in proprietary algorithms with clinical risk criteria (PSA, Gleason grade, tumor stage) to generate new risk categories (i.e., reclassification) intended to reflect biological indolence or aggressiveness of individual lesions, and thus inform management decisions.

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