New Genetic Markers for Prostate Cancer

Prostate cancer risk stratification based on conventional clinical and pathologic characteristics alone may misclassify a proportion of men at various stages of the disease process. Many gene-based assays have emerged in recent years that seek to improve the predictive accuracy in the prediagnostic and postdiagnostic settings. Following primary treatment failure, gene expression tests may offer improved stratification of individuals at risk for disease progression and inform refinements in the necessity of additional treatment. Unifying limitations among all novel gene-based tests are include clinical validation derived from historical cohorts and a dearth of empirical clinical effectiveness data.

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Tissue-based gene expression tests have been developed to predict the occurrence of subsequent PCa events, including adverse characteristics, biochemical recurrence, metastatic progression, and PCa mortality.

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On the heels of insights gained into PCa biology and technological advancements affording accessible, high throughput sequencing, assays have emerged that evaluate numerous junctures within the PCa disease process. Spanning the prediagnostic, initial detection and posttreatment settings, this expanding battery of risk-stratification tools seek to offer improved assessment of outcome and gain widespread implementation in clinical practice. In light of the novelty of such developments, the authors aim to critically review the current body of tools that have appeared in recent years and the details of their supporting evidence and offer a contextualization of the pipeline of emerging tests under development.

Most PCa detected worldwide are the result of biopsy undertaken in the setting of elevated PSA. Owing to the well-recognized deficiencies in specificity of PSA for the identification of clinically significant disease, a considerable number of individuals will undergo screening and biopsy to detect a single high-risk cancer. The development of accurate markers to better select those at greatest risk for harboring significant and actionable disease would, therefore, be impactful for men who may be spared unneeded biopsy or detection of low-grade tumors in whom treatment may offer little benefit to longevity or quality of life. In this setting, new markers have emerged that seek to offer improvements in the selection for initial or repeat biopsy.

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