Multigene panels in prostate cancer risk assessment: a systematic review

Single-nucleotide polymorphism (SNP) panel tests have been proposed for use in the detection of, and prediction of risk for, prostate cancer and as prognostic indicator in affected men. A systematic review was undertaken to address three research questions to evaluate the analytic validity, clinical validity, clinical utility, and prognostic validity of SNP-based panels.

Data sources comprised MEDLINE, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, and EMBASE; these were searched from inception to April 2013. The gray-literature searches included contact with manufacturers. Eligible studies included English-language studies evaluating commercially available SNP panels. Study selection and risk of bias assessment were undertaken by two independent reviewers.

Twenty-one studies met eligibility criteria. All focused on clinical validity and evaluated 18 individual panels with 2 to 35 SNPs. All had poor discriminative ability (overall area under receiver-operator characteristic curves, 58-74%; incremental gain resulting from inclusion of SNP data, 2.5-11%) for predicting risk of prostate cancer and/or distinguishing between aggressive and asymptomatic/latent disease. The risk of bias of the studies, as assessed by the Newcastle Ottawa Scale (NOS) and Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tools, was moderate.

The evidence on currently available SNP panels is insufficient to assess analytic validity, and at best the panels assessed would add a small and clinically unimportant improvement to factors such as age and family history in risk stratification (clinical validity). No evidence on the clinical utility of current panels is available.Genet Med 18 6, 535-544.