DOI: https://doi.org/10.26641/2307-5279.23.4.2019.187195

Diagnostic value of the prostate health index in the early detection of prostate cancer (literature review)

G.V. Bachurin, M.Y. Bohun, S.S. Lomaka

Abstract


Introduction. Prostate cancer (PC) is the second most common cause of cancer death in men. The prevalence of prostate cancer increases with age. Since the detection of serum prostate-specific antigen (PSA), it has become a major molecular marker used in the diagnosis of prostate cancer. The purpose of PSA screening is to test asymptomatic men and improve long-term treatment outcomes by diagnosing early-stage cancer. Today, tPSA screening is controversial because of its many limitations. Although higher levels of tPSA indicate an increased risk of prostate cancer, nevertheless tPSA is sensitive but not specific to cancer. P2PSA is a proPSA isoform, and it is considered to be the most cancerous-specific form of free PSA. As a result of the detection of the proPSA isoform - p2PSA, it became possible to determine the prostate health index.

Purpose. To establish the diagnostic value of the prostate health index in the early detection of prostate cancer, based on the results of relevant scientific studies.

Materials and Methods. Foreign Research on Prostate Health Index.

Results. The prostate health index (phi) is a combination of three different isoforms of PSA: total PSA, free PSA and p2PSA, combined in the mathematical formula: Phi = (p2PSA / fPSA) ґ Ц tPSA.

Phi is a simple blood test, but it is superior to any single component of it for identifying clinically relevant prostate cancer. The prostate health index (phi) can be used to determine the likelihood of prostate cancer on biopsy in men 50 years of age and older with a general prostate-specific antigen (tPSA) level in the range of 4 to 10 ng/ml. Low phi is associated with a low probability of detecting prostate cancer on biopsy, while high phi is associated with a high probability of detecting prostate cancer on biopsy. Phi to be used in clinical practice, but is individual to each patient and at the same time may depend on other clinical factors or family history.

Recently, there is a growing body of research showing the possibility of phi as a collateral for unnecessary biopsy. Catalona WJ, Partin AW, Sanda MG conducted a large prospective multicenter phi study in the United States from 2003 to 2009, which showed that men with high phi scores compared to the lowest phi score (mean score 0-24.9) > 55) had a significantly higher risk of detecting prostate cancer and a Gleason score і7. A further study found that among 658 men in the prospective study who underwent a primary or repeated prostate biopsy for a PSA level of 4-10 ng/ml, phi had a more accurate prediction of clinically relevant prostate cancer on biopsy.

Phi has also been evaluated prospectively in several European populations. Guazzoni G, Nava L, Lazzeri M, et al. reported a study that included 268 men with a tPSA level of 2-10 ng/ml and no cancer-specific signs of prostate cancer in a finger rectal study. It showed that phi has greater sensitivity and accuracy in predicting the outcome of a biopsy compared to the total and free PSA, PSA density.

According to Supon Sriplakich, Bannakij Lojanapiwat et al. phi increases the specificity in the detection of prostate cancer in men with PSA 4-10 ng / ml and in the absence of signs of prostate cancer when conducting a finger rectal examination. The prostate health index also increases the rate of detection of highly differentiated cancer. This test is a very useful and effective tool for discriminating between men with or without prostate cancer in clinical practice to avoid unnecessary prostate biopsy.

Findings. Numerous large prospective studies from geographically different regions constantly demonstrate that phi is a more specific marker for prostate cancer than existing standard reference tests, such as total PSA, free PSA, PSA density, PSA doubling time. The prostate health index can serve as a new biomarker in the detection of prostate cancer. Also, phi can serve as the key to an unnecessary prostate biopsy, and can also be used to predict the level of Gleason that will be determined after a prostate biopsy. Despite the above evidence of the effectiveness of using phi, there are currently some technical difficulties in determining the level of p2PSA. We consider it necessary to improve laboratory capabilities for the impregnation of this indicator in the routine of a urologist, because it can reduce the level of detection of prostate cancer in advanced stages of the disease, prolong cancer-specific survival and reduce the number of unnecessary biopsies.

Keywords


prostate health index; prostate cancer; prostate-specific antigen; p2PSA

References


Heidenreich A., Bellmunt J., Bolla M., Joniau S., Mason M., Matveev V. et al. EAU guidelines on prostate cancer. Part I: screening, diagnosis, and treatment of clinically localized disease. Eur Urol. 2011. Vol. 59. P. 61–71.

Nadler R.B., Humphrey P.A., Smith D.S., Catalona W.J., Ratliff T.L. Effect of inflammation and benign prostatic hyperplasia on elevated serum prostate specific antigen levels. J Urol. 1995. Vol. 154. P. 407–413. URL: https://www.ncbi.nlm.nih.gov/pubmed/7541857.

Cabarkapa S., Perera M., McGrath S., Lawrentschuk N. Prostate cancer screening with prostate-specific antigen: a guide to the guidelines. Prostate Int. 2016. Vol. 4. P. 125–129.

McGrath S., Christidis D., Perera M., Hong S.K., Manning T., Vela I. et al. Prostate cancer biomarkers: are we hitting the mark? Prostate Int. 2016. Vol. 4. P. 130–135.

Loeb S., Bjurlin M.A., Nicholson J. et al. Overdiagnosis and overtreatment of prostate cancer. European urology. 2014. Vol. 65, No. 6. P. 1046–1055. URL: https://www.ncbi.nlm.nih.gov/pubmed/24439788.

Mikolajczyk S.D., Rittenhouse, Pro H.G. PSA: a more cancer specific form of prostate specific antigen for the early detection of prostate cancer. Keio J Med. 2003. Vol. 52. P. 86–91.

Catalona W.J., Partin A.W., Sanda M.G., Wei J.T., Klee G.G., Bangma C.H., Slawin K.M., Marks L.S., Loeb S., Broyles D.L., Shin S.S., Crus A.B., Chan D.W., Sokoll L.J., Roberts W.L., van Schaik R.H.N., Mizrahi I.A. A Multicenter Study of (-2)Pro-Prostate Specific Antigen Combined With Prostate Specific Antigen and Free Prostate Specific Antigen for Prostate Cancer Detection in the 2.0 to 10.0 ng/ml Prostate Specific Antigen Range. J Urol. 2011. Vol. 185. P. 1650–1655. URL: https://www.ncbi.nlm.nih.gov/pubmed/21419439.

de la Calle C., Patil D., Wei J.T. et al. Multicenter Evaluation of the Prostate Health Index (PHI) for Detection of Aggressive Prostate Cancer in Biopsy-Naive Men. J Urol. 2015.

Loeb S., Sanda M.G., Broyles D.L. et al. The Prostate Health Index Selectively Identifies Clinically Significant Prostate Cancer. J Urol. 2014.

Catalona W.J., Partin A.W., Sanda M.G. et al. A multicenter study of (-2)pro-prostate-specific antigen combined with prostate-specific antigen and free prostate-specific antigen for prostate cancer detection in the 2.0 to 10.0 ng/mL prostate-specific antigen range. J Urology. 2011. Vol. 185. P. 1650–1655.

Pecoraro V., Roli L., Plebani M. el al. Clinical utility of the (-2)proPSA and evaluation of the evidence: a systematic review. Clin Chem Lab Med. 2015. Vol. 54. P. 1123–1132. doi: 10.1515/cclm-2015-0876.

Loeb S., Catalona W.J. The Prostate Health Index: a new test for the detection of prostate cancer. Ther Adv Urol. 2014. Vol. 6, No. 2. P. 74–77. doi: 10.1177/1756287213513488.

Guazzoni G., Nava L., Lazzeri M. et al. Prostate-specific antigen (PSA) isoform p2PSA significantly improves the prediction of prostate cancer at initial extended prostate biopsies in patients with total PSA between 2.0 and 10 ng/ml: results of a prospective study in a clinical setting. European urology. 2011. Vol. 60, No. 2. P. 214–222. URL: https://www.ncbi.nlm.nih.gov/pubmed/21482022.

Supon Sriplakich, Bannakij Lojanapiwat, Wilaiwan Chongruksut, Siwat Phuriyaphan, Pruit Kitirattakarn, Jakrit Jun-Ou, Akara Amantakul. Prospective performance of the Prostate Health Index in prostate cancer detection in the first prostate biopsy of men with a total prostatic specific antigen of 4–10 ng/mL and negative digital rectal examination.