• Toni Krstev Department of Urology, City General Hospital 8th of September, Skopje North Macedonia
  • Ivica Stojanoski Department of Urology, City General Hospital 8th of September Skopje, North Macedonia, Faculty of Medicine, Goce Delchev University, Shtip, Republic of North Macedonia
  • Lazar Ilievski Department of Urology, City General Hospital 8th of September Skopje, North Macedonia
  • Nerhim Tufekchioski Department of Urology, City General Hospital 8th of September Skopje, North Macedonia
  • Olivera Stojcheva-Taneva Clinic of Nephrology, Skopje, North Macedonia
  • Jasmina Trojacanec Institute for Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss.Cyril and Methodius University in Skopje, North Macedonia
  • Cvetanka Volkanovska Ilijevska University Clinic for Endocrinology, Diabetes and Metabolic Disorders, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia


The Prostate Health Index (PHI) is a new test combining total, free and (-2)proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. Our aim is to investigate whether PHI improves specificity for detecting clinically significant prostate cancer and can help to reduce prostate cancer biopsies. We examined 100 men age 50 years or older with prostate specific antigen 4 to 10 ng/ml („gray zone„) and normal digital rectal examination with suspected prostate cancer who had undergone biopsies and were divided into a benign and malignant group.  In this population we compared the performance of prostate specific antigen, % free prostate specific antigen, (-2)proPSA and PHI to predict biopsy results and, specifically, the presence of clinically significant prostate cancer using multiple criteria. We found statistically significantly increased levels of −2proPSA, PHI and PSA and decreased levels of %freePSA in patients diagnosed with prostate cancer by prostate biopsy vs. patients with benign prostatic conditions (median values: −2proPSA: 28.3 vs. 20.11 ng/l, PHI: 73.04 vs. 30.5, total PSA: 7.3 vs. 6.48 ng/ml and %free PSA: 17.06 vs. 25.62%). On receiver operating characteristic analysis PHI had the highest AUC for overall prostate cancer (AUCs PHI 0.954, percent free prostate specific antigen 0.345, (-2)proPSA 0.753 and prostate specific antigen 0.656). The optimal cut-off for PHI in the study population was 42.8 with sensitivity of 85.7% (95% CI: 54.8-90.6) and specificity of 86.1% (CI 95%, 0.913-0.995). Whereas, in the tPSA for cut-off 6.54 sensitivity is 61.9 and specificity 59.5, respectively.  The Prostate Health Index was significantly higher in men with Gleason 7 or greater. In our study for the PHI levels (36-54.99) only 23.08% of patients had Gleason score ≥ 7.In patients with  PHI levels >55, 76.92% of patients had Gleason score ≥ 7. The new PHI test outperforms its individual components of total, free and (-2)proPSA for the identification of clinically significant prostate cancer. PHI may be useful as part of a multivariable approach to reduce prostate biopsies and overdiagnosis.

Keywords: PHI; prostate cancer, early detection, prostate biopsy.


1. Chen R, Ren S, Yiu MK, et al. Prostate cancer in Asia: A collaborative report. Asian J Urol. 2014; 1(1): 15-29.
2. https://www.worldlifeexpectancy.com/macedonia-prostate-cancer (авторот, насловот, годината, волуменот
3. Fuchsova R, Topolcan O, Windrichova J, et al. PHI in the early detection of prostate cancer. Anticancer Res. 2015; 35(9):4855-4857.
4. Wilt TJ, Jones KM, Barry MJ, et al. Follow-up of prostatectomy versus observation for early prostate cancer. N Enql J Med. 2017; 377(2):132-142. doi:10.1056/NEJMoa1615869.
5. Adhyam M, Gupta AK. A Review on the Clinical Utility of PSA in Cancer Prostate. Indian J Surg Oncol. 2012; 3(2): 120-9.
6. Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of Prostate Cancer among Men with a Prostate-Specific Antigen Level ≤4.0 ng per Milliliter. N Engl J Med. 2004; 350(22): 2239-46.
7. Mikolajczyk, S., Catalona, W., Evans, C., Linton, H., Millar, L., Marker, K. et al. Proenzyme forms of prostate-specific antigen in serum improve the detection of prostate cancer. Clin Chem 2004; 50: 1017–1025.
8. Sokoll, L., Sanda, M., Feng, Z., Kagan, J., Mizrahi, I., Broyles, D. et al. A prospective, multicenter, National Cancer Institute Early Detection Research Network study of [-2]proPSA: improving prostate cancer detection and correlating with cancer aggressiveness. Cancer Epidemiol Biomarkers Prev 2010; 19: 1193–1200.
9. Catalona, W., Partin, A., Sanda, M., Wei, J., Klee, G., Bangma, C. 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 Urol 2011; 185: 1650–1655.
10. Lazzeri M, Haese A, de la Taille A, et al. Serum isoform [-2]proPSA derivatives significantly improve prediction of prostate cancer at initial biopsy in a total PSA range of 2-10 ng/ml: a multicentric European study. Eur Urol. 2013; 63:986. [PubMed] [Google Scholar.
11. Hatakeyama S, Yoneyama T, Tobisawa Y, Ohyama C. Recent progress and perspectives on prostate cancer biomarkers. Int J Clin Oncol. 2017;22(2):214–21.
12. Borghesi M, Ahmed H, Nam R, Schaeffer E, Schiavina R, Taneja S, Weidner W, Loeb S. Complications after systematic, random, and image-guided prostate biopsy. Eur Urol. 2017;71(3):353–65.
13. Heijnsdijk EA, Wever EM, Auvinen A, Hugosson J, Ciatto S, Nelen V, Kwiatkowski M, Villers A, Paez A, Moss SM, et al. Quality-of-life effects of prostate-specific antigen screening. N Engl J Med. 2012;367(7):595–605.
14. Lughezzani G, Lazzeri M, Larcher A, Lista G, Scattoni V, Cestari A, Buffi NM, Bini V and Guazzoni G: Development and internal validation of a prostate health index-based nomogram for predicting prostate cancer at extended biopsy. J Urol 2012; 188: 1144-1150.
15. Filella X and Giménez N: Evaluation of [−2] pro PSA and Prostate Health Index (phi) for the detection of prostate cancer:a systematic review and meta-analysis. Clin Chem Lab Med 2013; 51(4): 729-739
16. Boegemann M, Stephan C, Cammann H, Vincendeau S, Houlgatte A, Jung K, et al. The percentage of prostatespecific antigen (PSA) isoform [-2]proPSA and the Prostate Health Index improve the diagnostic accuracy for clinically relevant prostate cancer at initial and repeat biopsy compared with total PSA and percentage free PSA in men aged ≤65 years. BJU Int 2016 Jan;117(1):72-79.
17. Loeb S, Sanda MG, Broyles DL, et al. The prostate health index selectively identifies clinically significant prostate cancer. J Urol 2015;193:1163-9. 10.1016/j.juro.2014.10.121 [PMC free article] [PubMed] [CrossRef] [Google Scholar.
18. Catalona WJ, Partin AW, Sanda MG, Wei JT, Klee GG, Bangma CH, Slawin KM, Marks LS, Loeb S, Broyles DL, Shin SS, Cruz AB, Chan DW, Sokoll LJ, Roberts WL, van Schaik RH and Mizrahi IA: 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; 185: 1650-165
19. Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur Urol 2017;71:618e29.
20. Wang W, Wang M, Wang L, Adams TS, Tian Y, Xu J. Diagnostic ability of %p2PSA and prostate health index for aggressive prostate cancer: a meta-analysis. Sci Rep 2014 May;4:5012.
21. Abrate A, Lughezzani G, Gadda GM, Lista G, Kinzikeeva E, Fossati N, et al. Clinical use of [-2]proPSA (p2PSA) and its derivatives (%p2PSA and Prostate Health Index) for the detection of prostate cancer: a review of the literature. Korean J Urol 2014 Jul;55(7):436-445.
22. Filella X, Foj L, Augé JM, Molina R, Alcover J. Clinical utility of %p2PSA and prostate health index in the detection of prostate cancer. Clin Chem Lab Med 2014 Sep;52(9):1347-1355.
23. Tosoian JJ, Druskin SC, Andreas D, Mullane P, Chappidi M, Joo S, et al. Use of the Prostate Health Index for detection of prostate cancer: results from a large academic practice. Prostate Cancer Prostatic Dis. 2017;20:228–33.
24. Sanda M, Wei J, Broyles D, et al. Evaluation of the Prostate Health Index (PHI) for improving prostate cancer detection and identification of clinically significant prostate cancer in the 4 to 10 ng/mL PSA range. In: Proceedings of American Urological Association Annual Meeting San Diego, Rev Urol.2013; 02:2474.
25. Fossati N, Buffi NM, Haese A, et al. Preoperative prostate-specific antigen isoform p2PSA and its derivatives, %p2PSA and prostate health index, predict pathologic outcomes in patients undergoing radical prostatectomy for prostate cancer: results from a Multicentric European Prospective Study. Eur Urol. 2016; 68(1):132–138. [PubMed] [Google Scholar].
26. Ito K, Miyakubo M, Sekine Y, et al. Diagnostic significance of [-2]pro-PSA and prostate dimension adjusted PSA-related indices in men with total PSA in the 2.0-10.0ng/mL range. World J Urol. 2013; 31(2): 305-11.
27. Tan LG, Tan YK, Tai BC, et al. Prospective validation of %p2PSA and the Prostate Health Index, in prostate cancer detection in initial prostate biopsies of Asian men, with total PSA 4-10 ng ml1. Asian J Androl. 2017; 19(3): 286-90.
28. Ng CF, Chiu PKF, Lam NY, Lam HC, Lee KWM, Hou SSM. The Prostate Health Index in predicting initial prostate biopsy outcomes in Asian men with prostate-specific antigen levels of 4-10ng/mL. Int Urol Nephrol. 2014; 46(4): 711-7.
29. Na R, Ye D, Liu F, et al. Performance of serum prostate-specific antigen isoform [-2]proPSA (p2PSA) and the prostate health index (PHI) in a Chinese hospital-based biopsy population. Prostate. 2014; 74(15): 1569-75.
How to Cite
KRSTEV, Toni et al. DIAGNOSTIC PERFORMANCE OF PROSTATE HEALTH INDEX (PHI) IN PREDICTING PROSTATE CANCER ON PROSTATE BIOPSY; A SINGLE CENTER STUDY. Journal of Morphological Sciences, [S.l.], v. 6, n. 3, p. 222-233, dec. 2023. ISSN 2545-4706. Available at: <https://jms.mk/jms/article/view/vol6no3-29>. Date accessed: 20 july 2024.