Prostate specific antigen (PSA) is the current gold standard in prostate cancer detection. Prostate specific antigen is distinct from virtually all other cancer biomarkers because it is almost exclusively specific to the prostate, allowing for the direct assessment of physiological conditions and anatomical changes in the gland with a simple blood test. PSA is however tissue specific but not cancer specific thus many pathologies and biological processes unrelated to cancer i.e prostatitis and benign cellular hyperplasia in the prostate gland may lead to elevated total and free PSA in serum. Over diagnosis and over treatment of PSA-detected, biologically insignificant cancers are recognized as key limitations in the clinical utility of PSA. 1,3 

Diseases modify the structure of proteins produced by affected cell in addition to changing the level of proteins. Genetic modification associated with cancer leads to changes in the 3D conformation of proteins produced by the affected cells. Structural changes in proteins directly relate to cancer mutations since cells become cancer cells largely because of mutation in their genes leading to changes in amino acid sequences and proteins. This provides direct information about the onset or progression of disease.1

A biomarker is a measurable protein whose altered expression indicates that an individual has a disease. A specific protein may be underexpressed or overexpressed under certain physiological conditions such as stress of disease. Current prostate cancer diagnostic test are based on the overexpression of Prostate Specific Antigen which is not specific for prostate cancer since other conditions i.e benign prostatic hyperplasia and inflammation of the prostate also leads to increased production of prostate specific antigen.

Cleveland Diagnostics, Inc., is a biotechnology company focused on developing next-generation diagnostics technology for the detection of cancers. Cleveland Diagnostics was formed in October 2013in association with Cleveland Clinic Foundation. Cleveland Diagnostics, Inc. (Cleveland DX) is developing technology that focuses on protein biomarker structural changes that correlate with the presence of a disease. The company’s portfolio of non-invasive cancer diagnostic tests includes blood-based tests to screen for prostate, breast and ovarian cancer. The tests are designed to enable early detection of cancer cells, allowing for early treatment and increased survival rates. 4

Cleveland Diagnostics is currently involved in a multi-centre prospective pilot study of the IsoPSA assay utilizing the IsoPSATM reagent and a Solvent Interaction Analysis platform. Quest Laboratories Limited was selected as the centre for analysis of both Kenyan samples and those from other African countries including Nigeria.

IsoPSATM is a structure-based (rather than concentration-based) reagent. It utilizes Cleveland Diagnostics’ Solvent Interaction Analysis platform to separate prostate specific antigen, with an aqueous two phase solution, into two layers consisting different protein isoforms correlating with prostate cancer. Analysis of total and free PSA concentration in the two phases and calculation of complex PSA is essential in identifying those with prostate cancer and determining the relative risk of developing an aggressive form of the disease. PSA isoform testing capitalizes on the structural changes to PSA that result from dysregulated cellular processes in prostate cancer, an improvement over the existing PSA tests that are prostate-specific but not prostate cancer specific. According to a preliminary analysis of a study published in the European Urology Journal, the new IsoPSA test outperformed standard PSA at both detecting those with or without cancer and at differentiating a high-grade from a low-grade cancer. IsoPSATM returns highly relevant for healthcare providers and patients by changing the focus from PSA concentration to PSA variants and structures.1,4

IsoPSA approach not only reduces the number of false positives, but also allows providers a window into the cancer grade before deciding on whether a biopsy is indicated. Results of a study published in the European Urology Journal suggests that if validated and adopted clinically, IsoPSA could significantly reduce the number of unnecessary biopsies while preserving both positive and negative predictive values for cancer detection and staging.


  1. Pinsky PF, Crawford ED, Kramer BS, Andriole GL, Gelmann EP, Grubb R, Greenlee R, Gohagan JK. Repeat prostate biopsy in the prostate, lung, colorectal and ovarian cancer screening trial. BJU International. 2017; 99(4):775-9.
  2. Klein, E.A., Chait, A., Hafron, J.M. et al. The single-parameter, structure-based IsoPSA assay demonstrates improved diagnostic accuracy for detection of any prostate cancer and high-grade prostate cancer compared to a concentration-based assay of total prostate-specific antigen: a preliminary report. Eur Urol. 2017; 72: 942–949
  3. Heidenreich, A., Bellmunt, J., Bolla, M…., and European Association of Urology. EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and treatment of clinically localised disease. Eur Urol. 2011; 59: 61–71