BACKGROUND: We aimed to explore the utility of prostate specific antigen (PSA) isoform [- 2] proPSA and its derivatives for prediction of pathological outcome after radical prostatectomy (RP). METHODS: Preoperative blood samples were prospectively and consecutivelyanalyzed from 472 patients treated with RP for clinically localized prostate cancerat four medical centers. Measured parameters were PSA, free PSA (fPSA), fPSA/PSA ratio, [- 2] proPSA (p2PSA), p2PSA/fPSA ratio and Prostate Health Index (PHI)(p2PSA/fPSA)*√PSA]. Logistic regression models were fitted to determine the accuracy of markers for prediction of pathological Gleason score (GS) ≥7, Gleason score upgrading, extracapsular extension of the tumor (pT3) and the presence of positive surgical margin (PSM). The accuracy of predictive models was compared using area under the receiver operating curve (AUC). RESULTS: Of 472 patients undergoing RP, 339 (72%) were found to have pathologic GS ≥ 7, out of them 178 (53%) experienced an upgrade from their preoperative GS = 6. The findings of pT3 and PSM were present in 132 (28%) and 133 (28%) cases, respectively. At univariable analysis of all the preoperative parameters, PHI was the most accurate predictor of pathological GS ≥7 (OR 1.02, 95% CI 1.01-1.03, p<0.001), GS upgrading (OR 1.02, 95% CI 1.01-1.03, p<0.003), pT3 disease (OR 1.01, 95% CI 1.00-1.02, p<0.007) and the presence of PSM (OR 1.01, 95% CI 1.00-1.02, p<0.002). Adding of PHI into the base multivariable model increased significantly the accuracy for prediction of pathological GS by 4.4% to AUC = 66.6 (p = 0.015) and GS upgrading by 5.0% to AUC = 65.9 (p = 0.025), respectively. CONCLUSIONS: Preoperative PHI levels may contribute significantly to prediction of prostate cancer aggressiveness and expansion of the tumor detected at final pathology.

Department of Immunochemistry University Hospital and Faculty of Medicine in Pilsen Pilsen Czech Republic

Department of Medical Chemistry and Clinical Biochemistry Charles University 2nd Faculty of Medicine University Hospital Motol Prague Czech Republic

Department of Urology and 1st and 3rd Medical Faculty Thomayer Hospital Charles University Prague Czech Republic

Department of Urology Charles University 2nd Faculty of Medicine University Hospital Motol Prague Czech Republic

Department of Urology General University Hospital and 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Urology University Hospital and Faculty of Medicine in Pilsen Pilsen Czech Republic

Medical University of Vienna Vienna Austria

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Zhou CK, Check DP, Lortet-Tieulent J, et al. Prostate cancer incidence in 43 populations worldwide: an analysis of time trends overall and by age group. Int J Cancer. 2016;138:1388–1400. doi: 10.1002/ijc.29894. PubMed DOI PMC

Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate cancer mortality: results of the European randomised study of screening for prostate Cancer (ERSPC) at 13 years of followup. Lancet. 2014;384:2027–2035. doi: 10.1016/S0140-6736(14)60525-0. PubMed DOI PMC

Beauval JB, Ploussard G, Soulié M, et al. Pathologic findings in radical prostatectomy specimens from patients eligible for active surveillance with highly selective criteria: a multicenter study. Urology. 2012;80(3):656–660. doi: 10.1016/j.urology.2012.04.051. PubMed DOI

Jansen FH, van Schaik RH, Kurstjens J, et al. Prostate-specific antigen (PSA) isoform p2PSA in combination with total PSA and free PSA improves diagnostic accuracy in prostate cancer detection. Eur Urol. 2010;57:921–927. doi: 10.1016/j.eururo.2010.02.003. PubMed DOI

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. Eur Urol. 2011;60:214–222. doi: 10.1016/j.eururo.2011.03.052. PubMed DOI

Lazzeri M, Haese A, Abrate A, et al. Clinical performance of serum prostate-specific antigen isoform [−2]proPSA (p2PSA) and its derivatives, %p2PSA and the prostate health index (PHI), in men with a family history of prostate cancer: results from a multicentre European study, the PROMEtheuS project. BJU Int. 2013;112(3):313–321. doi: 10.1111/bju.12217. PubMed DOI

Guazzoni G, Lazzeri M, Nava L, 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. Eur Urol. 2012;61(3):455–466. doi: 10.1016/j.eururo.2011.10.038. PubMed DOI

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. 2015;68(1):132–138. doi: 10.1016/j.eururo.2014.07.034. PubMed DOI

Maxeiner A, Kilic E, Matalon J, et al. The prostate health index PHI predicts oncological outcome and biochemical recurrence after radical prostatectomy - analysis in 437 patients. Oncotarget. 2017;8(45):79279–79288. doi: 10.18632/oncotarget.17476. PubMed DOI PMC

Epstein JI, Allsbrook WC, Jr, Amin MB, Egevad LL. The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol. 2005;29:1228–1242. doi: 10.1097/01.pas.0000173646.99337.b1. PubMed DOI

Van der Kwast TH, Amin MB, Billis A, et al. International Socienty of urological pathology (ISUP) consensus conference on handling and staging of radical prostatectomy Speciments. Working group 2: T2 substaging and prostate cancer volume. Mod Pathol. 2011;24:16–25. doi: 10.1038/modpathol.2010.156. PubMed DOI

Semjonow A, Köpke T, Eltze E, et al. Pre-analytical in-vitro stability of [−2] pro PSA in blood and serum. Clin Biochem. 2010;43:496–498. doi: 10.1016/j.clinbiochem.2010.04.062. PubMed DOI

DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–845. doi: 10.2307/2531595. PubMed DOI

Ferlay J, Shin H-R, Bray F, et al. Estimates of worldwide burden of cancer in2008:GLOBOCAN2008. Int J Cancer. 2010;127:2893–2917. doi: 10.1002/ijc.25516. PubMed DOI

Miyake H, Fujisawa M. Prognosticpredictionfollowingradicalprostatectomy for prostatecancer using conventional as well as molecularbiologicalapproaches. Int J Urol. 2013;20(3):301–311. doi: 10.1111/j.1442-2042.2012.03175.x. PubMed DOI

Dolejsova O, Kucera R, Fuchsova R, et al. The Ability of Prostate Health Index (PHI) to Predict Gleason Score in Patients With Prostate Cancer and Discriminate Patients Between Gleason Score 6 and Gleason Score Higher Than 6-A Study on 320 Patients After Radical Prostatectomy. Technol Cancer Res Treat. 2018;17 1533033818787377. PubMed PMC

Hashimoto T, Yoshioka K, Horiguchi Y, et al. Clinical effect of a positive surgical margin without extraprostatic extension after robot-assisted radical prostatectomy. Urol Oncol. 2015;33(12):503.e1–503.e6. doi: 10.1016/j.urolonc.2015.07.009. PubMed DOI

Sooriakumaran P, Haendler L, Nyberg T, et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-Centre cohort with a minimum follow-up time of 5 years. Eur Urol. 2012;62(5):768–774. doi: 10.1016/j.eururo.2012.05.024. PubMed DOI

Prostate Cancer Diagnostic Algorithm as a "Road Map" from the First Stratification of the Patient to the Final Treatment Decision