Introduction: To assess whether [-2]pro-prostate-specific antigen (p2PSA) meets the criteria to justify its inclusion in a predictive model of prostate cancer (PCa) diagnosis and in the clinical decision-making process. Materials and Methods: A total 172 men with total prostate-specific antigen of 2–10 ng/mL underwent measurement of free PSA and p2PSA before prostate biopsy in an observational and prospective study. From these measurements, the Prostate Health Index (PHI) was calculated. Clinical and analytical predictive models were created incorporating PHI. Results: Of 172 men, 72 (42%) were diagnosed with PCa, 33 (46%) of whom were found to be with high-grade disease. PHI score was the most predictive of biopsy outcomes in terms of discriminative ability (area under the curve = 0.79), with an added gain in predictive accuracy of 17%. All the models that incorporated PHI worked better in terms of calibration close to 45° on the slope. In the decision curve analysis, at a threshold probability of 40% we could prevent 82 biopsies, missing only 16 tumors and 5 high-grade tumors. Conclusions: PHI score is a more discriminant biomarker, has superior calibration and superior net benefit, and provides a higher rate of avoided biopsies; thus, it can be useful for aiding in making a more informed decision for each patient.

Keywords:
Prostatic neoplasms, Prostate-specific antigen, [-2]pro-prostate specific antigen, Prostate Health Index, Clinical decision-making
1.
Choi H, Cho S, Bae JH, Lee SE, Hong SK, Moon DG, et al: Characteristics of Prostate Cancer by opportunistic screening in Korean men with a prostate-specific antigen level less than 4.0 ng per milliliter. Urol Int 2017; 99: 143–148.
2.
Gershman B, Van Houten HK, Herrin J, Moreira DM, Kim SP, Shah ND, et al: Impact of Prostate-specific antigen (PSA) screening trials and revised PSA screening guidelines on rates of prostate biopsy and postbiopsy complications. Eur Urol 2017; 71: 55–65.
3.
Pinsky PF, Prorok PC, Yu K, Kramer BS, Black A, Gohagan JK, et al: Extended mortality results for prostate cancer screening in the PLCO trial with median follow-up of 15 years. Cancer 2017; 123: 592–599.
4.
Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Zappa M, Nelen V, et al: Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; 384: 2027–2035.
5.
Hull D, Ma J, Singh H, Hossain D, Qian J, Bostwick DG: Precursor of prostate-specific antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 90 cases. BJU Int 2009; 104: 915–918.
6.
Mikolajczyk SD, Catalona WJ, Evans CL, Linton HJ, Millar LS, Marker KM, et al: Proenzyme forms of prostate-specific antigen in serum improve the detection of prostate cancer. Clin Cem 2004; 50: 1017–1025.
7.
Lazzeri M, Haese A, de la Taille A, Palou J, Mc Nicholas T, Lughezzani G, et al: Serum isoform [-2]proPSA derivates 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: 986–994.
8.
Loeb S, Shin SS, Broyles DL, Wei JT, Sanda M, Klee G, et al: Prostate Health Index improves multivariable risk prediction of aggressive prostate cancer. BJU Int 2017; 120: 61–68.
9.
Foley RW, Gorman L, Sharifi N, Murphy K, Moore H, Tuzova AV, et al: Improving multivariable prostate cancer risk assessment using the Prostate Health Index. BJU Int 2016; 117: 409–417.
10.
Zhu Y, Han CT, Zhang GM, Liu F, Ding Q, Xu JF, et al: Development and external validation of a prostate health index-based nomogram for predicting prostate cancer. Sci Rep. 2015; 5: 15341.
11.
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.
12.
Semjonow A, Köpke T, Eltze E, Pepping-Schefers B, Bürgel H, Darte C: Pre-analytical in-vitro stability of [-2]proPSA in blood and serum. Clin Biochem 2010; 47: 926–928
13.
Epstein JI, Allsbrook WC, Amin MB, Egevad LL: The 2005 International society of urological pathology (ISUP) consensus conference on gleason grading of prostate carcinoma. Am J Surg Pathol 2005; 29: 1228–1242.
14.
Hanley JA, McNeil BJ: The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982; 143: 29–36.
15.
DeLong ER, DeLong DM, Clarke-Pearson DL: Comparing the areas under two or more correlated receiver operating characteristics curves: a nonparametric approach. Biometrics 1988; 44: 837–845.
16.
Vickers AJ, Elkin EB: Decision curve analysis: a novel method for evaluating prediction models. Med Dec Making 2006; 26: 565–574.
17.
Vickers AJ, Van Calster B, Steyerberg EW: Net benefit approaches to the evaluation of predictions models, molecular markers, and diagnostic tests. BMJ 2016; 352:i6.
18.
Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S, et al: Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012; 367: 203–213.
19.
Lazzeri M, Briganti A, Scattoni V, Lughezzani G, Larcher A, Gadda GM, et al: Serum index test %[-2]proPSA and Prostate Health Index are more accurate than prostate specific antigen and %fPSA in predicting a positive repeat prostate biopsy. J Urol 2012; 188: 1137–1143.
20.
Loeb S, Sokoll LJ, Broyles DL, Bangma CH, van Schaik RH, Klee GG, et al: Prospective multicenter evaluation of the Beckman Coulter Prostate Health Index using WHO calibration. J Urol 2013; 189: 1702–1706.
21.
Lughezzani G, Lazzeri M, Larcher A, Lista G, Scattoni V, Cestari A et al. Development and internal validation of a Prostate Health Index based nomogram for predicting prostate cancer at extended biopsy. J Urol 2012; 188: 1144–50
22.
Maeda Y, Kawahara T, Kumano Y, Ohtaka M, Kondo T, Mochizuki T, et al: The neutrophil-to-lymphocyte ratio before repeat prostate needle biopsy for predicting prostate cancer. Urol Int 2016; 96: 123–124.
23.
Rosenkrantz AB, Lepor H, Huang WC, Taneja SS: Practical barriers to obtaining pre-biopsy prostate MRI: assessment in over 1,500 consecutive men undergoing prostate biopsy in a single urologic practice. Urol Int 2016; 97: 247–248.
24.
Umbehr MH, Lüscher M, Hunziker R, Falkner F, Wild PJ, Poyet C, et al: Influence of varying assessment parameters on the diagnostic accuracy of magnetic resonance imaging in the local staging of prostate cancer. Urol Int 2016; 96: 309–314.
25.
Roemeling S, Schröder FH: Words of Wisdom. Re: needle biopsies on autopsy prostates: sensitivity of cancer detection based on true prevalence. Eur Urol 2008; 53: 663–664.
© 2018 S. Karger AG, Basel
2018
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.