The clinical behavior and course of prostate cancer is highly variable, reflecting the heterogeneity of disease. Although most men currently diagnosed with prostate cancer have low-risk, favorable disease characteristics, some may harbor aggressive features and progress despite definitive treatment. Thus, initial risk stratification is important but has been traditionally based on the conventional serum biomarker PSA as well as biopsy Gleason score and clinical stage.
The desire for personalized and precision medicine combined with the elucidation of the pathogenesis of prostate cancer have led to the development of a new generation of genomic biomarkers and tissue-based gene expression tests (table) (Curr Oncol Rep 2016; 18:30; Eur Urol 2015; 68:1033-44). These novel approaches, as explained in this article, may provide additional information to assist and improve clinical decision-making at several junctures for men with localized prostate cancer.
Prognostic vs. predictive markers
It is important to distinguish between prognostic and predictive markers (J Clin Oncol 2005; 23:9067-72). Prognostic markers are those that are related to a prespecified clinical outcome, usually a time-to-event outcome such as overall or recurrence-free survival. They can be used for clinical management by informing on disease aggressiveness and potential candidacy for disparate strategies like active surveillance for indolent disease and multimodal therapy for more virulent disease.
Predictive markers are those that provide information on the likely benefit from a specific treatment, and can be used to help determine which modality may be best for that individual patient. Thus, prognostic markers reflect the effects of tumor and/or patient characteristic on outcome, while predictive markers reflect the effects of treatment on outcome.
This article focuses on contemporary, commercially available molecular tests for clinically localized prostate cancer after diagnosis (figure). Several other tests are available to aid in the diagnosis of prostate cancer, including the PCA3 assay (non-coding RNA [Progensa]) and assessment of epigenetic changes (methylation [ConfirmMDx]), but are beyond the scope of our discussion. Despite the development, study, and availability of these tools, clinical decisions are often still made based only on stage, grade, and serum PSA, possibly enhanced with the incorporation of more sophisticated nomograms and models. Nevertheless, there remains a need for more refined prognostic and predictive biomarkers in prostate cancer.