Tumour markers in prostate cancer III: biomarkers in urine

The serum PSA test still is the most important biomarker for the detection and follow-up of prostate cancer. PSA-based screening can reduce disease specific mortality but coinciding unnecessary testing and overdiagnosis warrant further research for more specific biomarkers. Numerous studies of both serum and urine-based prostate cancer biomarker candidates have been presented the last ten years. However, biomarkers for identifying the most aggressive subsets of this malignancy are still missing. Being non-invasive, urine-based tests might be suitable for both clinical and (mass) screening purposes, but also for prediction and to gain prognostic information. Protein-based, DNA-based and RNA-based urine biomarkers have been developed and tested.

Data on protein-based urine biomarkers (i.e. Annexin A3, matrix metalloproteinases and the urinary:serum PSA ratio) show up to now contradictory results and further studies are warranted to be able to assess their clinical value in which the cost aspect should not be overlooked. DNA markers in urine. Studies on DNA-based urine biomarkers focus on hypermethylation of gene panels with GSTP1 hypermethylation being the most promising individual marker. Larger prospective clinical studies of single markers and gene panels are however needed to validate their clinical utility.

RNA-based urine biomarkers are by far the most developed. The PCA3 test, the TMPRSS2-ERG fusion gene, transcript expression levels of GOLPH2, SPINK1 and their combination have been subject of many studies showing encouraging results.

Up to now urine-based biomarkers represent a promising alternative or addition to serum-based biomarkers. Prospective studies in a multivariate setting, including larger sample sizes and avoiding attribution bias caused by preselection on the basis of serum PSA are however required.