Review – Prostate Cancer Screening for Prostate Cancer in 2008 II: The Importance of Molecular Subforms of Prostate-Specific Antigen and Tissue Kallikreins Flip H. Jansen *, Monique Roobol, Guido Jenster, Fritz H. Schro ¨ der, Chris H. Bangma Department of Urology, Erasmus MC, Rotterdam, The Netherlands european urology 55 (2009) 563–574 available at www.sciencedirect.com journal homepage: www.europeanurology.com Article info Article history: Accepted November 21, 2008 Published online ahead of print on November 29, 2008 Keywords: BPSA Prostate cancer screening PSA-isoforms Tissue kallikreins Please visit www.eu-acme.org/ europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically. Abstract Context: Over the past decades, prostate-specific antigen (PSA), its isoforms, and other members of the tissue kallikrein family have been of continuous interest with regard to early detection and screening for prostate cancer (PCa). Objective: This review strives to give an overview of the possible clinical utilities of these markers, focused on early diagnostics and PCa screening. Evidence acquisition: Using the Medline database, a literature search was performed on the role of molecular subforms of PSA and other members of the tissue kallikrein family in PCa detection. Evidence synthesis: With respect to PSA isoforms, only the combination of the various truncated forms (pPSA) shows additional value over total PSA (tPSA) and free PSA (fPSA) in PCa detection within the range of 2–10 ng/ml tPSA. At a high sensitivity for PCa, the specificity of the ratio of pPSA to fPSA (%pPSA) is, in general, better than that of the ratio of fPSA to tPSA (%fPSA), with a gain of 5–11%. The (2)pPSA, (4)pPSA, (5)pPSA, (7)pPSA, and benign PSA (BPSA) isoforms generally show no additional value over either pPSA or the existing parameters of tPSA and fPSA. Of the other members of the tissue kallikrein family, most studies on human kallikrein 2 (hK2) show an additional value of the ratio of hK2 to fPSA (%hK2) over %fPSA alone in PCa prediction. Other tissue kallikreins cannot be recommended for diagnosing PCa, due to the lack of additional value over tPSA or fPSA or to insufficient research. Regarding a prognostic role, the value of PSA subforms as well as of other members of the tissue kallikrein family is limited with regard to existing parameters. Conclusions: pPSA and hK2 are able to improve PCa diagnosis in the range of 4–10 ng/ml tPSA over the existing variables tPSA and fPSA. # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, Josephine Nefkens Institute, Erasmus MC, room Be331, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Tel. +31 10 7043381; Fax: +31 10 704 4661. E-mail address: f.h.jansen@erasmusmc.nl (F.H. Jansen). 0302-2838/$ – see back matter # 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2008.11.040