Next generation screening tests

Abstract

Prostate cancer (PrCa) is a major health care problem. Not all criteria are met for diseases for which population-based screening is advised. Yet many medical organizations have endorsed PrCa screening for the well-informed patient. Currently, PrCa screening is based on the serum PSA test. The conditional recommendation for screening is due to the main limitations of the PSA test, that is, the low specificity, and the fact that the test does not discriminate indolent from clinically significant PrCa. High specificity is a priority requirement for a screening test. Other criteria for PrCa screening tests are easy obtainable sample, simple and cost-effectiveness, able to discriminate significant from indolent PrCa, and to detect early PrCa. Advancement in biotechnology, such as molecular profiling using microarrays, has given more opportunities to discover new biomarkers that are better than PSA. Many steps and a long period of time are needed to identify a novel marker as an alternative to PSA and to clinically implement it. Many markers are being identified but until now only two markers, PCA3 and ETS gene fusions, are clinically available or close to implementation. These markers are candidates to evaluate in a screening setting. These two biomarkers still need more validation, cost-effectiveness, and prospective studies. Meanwhile, there are several ways to increase PSA specificity and sensitivity. Targeting high-risk population by stratification based on SNPs identified by genome-wide association studies (GWAS) has been suggested. GWAS has found at least 40 relevant SNPs, but if this can be translated to the entire population remains to be shown. Recently, gene variants are also found to correlate with serum PSA levels, so one should anticipate to individualize PSA cutoff levels. Another gene that was widely studied is BRCA. Men carrying BRCA2 mutations have a high chance to develop aggressive PrCa. There is one international study to explore PSA-based screening effect to this BRCA2-positive population (the IMPACT study). Risk calculators have been developed to increase PSA specificity and sensitivity since PSA was considered as range of risk. Risk calculators were developed based on certain population so the utility of these calculators may be limited to a similar patient population. Nevertheless, risk calculators provide an excellent tool to integrate the effect of various available clinical, pathological, and molecular parameters.