Genome classifiers may aid prostate cancer risk stratification and treatment

1. In this systematic review, ten studies reported risk reclassification of prostate cancer with genome classifier testing, with wide variation across different genome classifier tests.

2. Treatment decisions tended to either remain unchanged or slightly favor conservative management following genome classifier testing.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Prostate cancer is the most prevalent cancer among men. While it often carries an excellent long-term prognosis, prostate cancer can range from indolent to more aggressive forms, the latter which often require surgery and radiation therapy. However, it is not always clear which cases require active surveillance versus intensive therapy, and histopathological features seen on biopsy are not specific predictors of metastatic disease. Hence, reliable risk stratification for patients diagnosed with prostate cancer is imperative. Current risk assessment tools use a combination of tumor staging, serum prostate-specific antigen (PSA), and Gleason score to stratify risk, but they exhibit limited accuracy in predicting disease progression and treatment response. Tissue-based genomic classifiers, which evaluate the expression of genes involved in tumor motility and proliferation, have shown considerable promise in risk assessment, including ability to provide information on biochemical recurrence, metastatic spread, and mortality. However, the use of genomic classifier tests remains controversial; the American Urological Association recommends against the use of such testing while the National Comprehensive Cancer Network supports their use in initial risk stratification for patients with low or favorable intermediate-risk disease. Thus, this systematic review aimed to summarize the data on the impact of using genomic classifiers on risk stratification and treatment decisions in men with localized prostate cancer. Among studies which reported risk reclassification of prostate cancer with genome classifier testing, most patients with low or very-low risk were not reclassified to a higher risk category. However, there was much greater variation in reclassification among those at intermediate risk, ranging from less than two percent to over two-thirds of patients depending on the study. Most studies that investigated treatment decisions after genome classifier testing reported either no change in management or a higher likelihood for conservative management. These results were limited by variations in screening patterns, risk determination cutoffs, and clinical practices. In summary, genome classifier testing was shown to influence the intensity of care for patients with prostate cancer, but further research is needed to inform optimal usage.

Click to read the study in AIM

Relevant Reading: Discovery and validation of a prostate cancer genomic classifier that predicts early metastases following radical prostatectomy

In-Depth [systematic review]: This systematic review investigated the impact of tissue-based genomic classifiers on risk stratification and treatment of patients with localized prostate cancer. Decipher by Veracyte, Polaris by Myriad Genetics, and Oncotype DX Genomic Prostate Score (GPS) were primarily studied given their prevalent use in clinical practice. Of 3,117 total articles describing risk stratification and treatment of patients with localized prostate cancer, 170 were retained for full-text review and 19 were included in the analysis. The included studies encompassed 17 observational cohorts and 2 reports from the randomized controlled trial, ENACT (Engaging Newly Diagnosed Men About Cancer Treatment Options). Reclassification was determined by comparing risk assessment from clinical risk models and genome classifier tests or by incorporating genome classifier results into risk models with clinical features. Ten studies reported risk reclassification with genome classifier testing. Most observational studies found that patients with low or very-low baseline risk were not reclassified to a higher risk category. A total of 0% to 11.9% of these patients in GPS-based studies, 12.8% to 17.1% of patients in Decipher-based studies, and 21.8% to 23.1% of patients in the Polaris-based observational studies were reclassified as higher risk. In the ENACT trial, however, GPS reclassified 34.5% of very-low risk and 29.4% or low risk patients to a higher risk category. Similarly, 10 studies reported risk reclassification among patients with intermediate baseline risk, with 0% to 1.7% of these patients being reclassified as higher risk and 3.8% to 28.8% being reclassified to lower risk in GPS-based studies; and 69.2% being reclassified to higher risk and 15.4% to lower risk in the ENACT trial. Decipher-based and Prolaris-based trials showed similar numbers of intermediate risk patients reclassified to higher and lower risk categories. Out of 14 studies which assessed the impact of genome classifiers on treatment decisions, 12 observational studies found that treatment remained unchanged or slightly favored active surveillance with genome classifier testing, whereas the ENACT trial showed GPS testing shifted more patients away from active surveillance. In summary, this systematic review showed the increasing role of genome classifiers on risk stratification and treatment of patients with localized prostate cancer.

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