This issue of Grand Rounds in Urology provides a thorough review of available biomarkers and genomic tests for diagnosing clinically significant prostate cancer. It also discusses the challenges, implementation, and costs associated with these tests, and offers an algorithm incorporating the latest data for clinical use.

prostate carcinoma, biomarkers, PSA screening, antiandrogens, biopsy, aggressive prostate cancer




Medical Editor:

E. David Crawford, MD
Professor of Surgery, Urology, and Radiation Oncology Head, Urologic Oncology
E. David Crawford Endowed Chair in Urologic Oncology
University of Colorado, Denver
Aurora, Colorado


Paul Arangua
Research Assistant
University of Colorado, Denver
Aurora, CO

Salvatore P. Catarinicchia, MD
Surgery/Urology Resident
University of Colorado, Denver
Aurora, Colorado

John Hoenemeyer, MD
Urologic Oncology Research Fellow
University of Colorado, Denver
Aurora, CO

Robert E. Donohue, MD
Professor, Department of Surgery
University of Colorado, Denver
Aurora, CO

L. Michael Glode, MD
Professor, Division of Medical Oncology
Robert Rifkin Chair for Prostate Cancer Research
University of Colorado, Denver
Aurora, CO

Michael Maccini, MD
Urology Resident
University of Colorado, Denver
Aurora, CO

Priya N. Werahera, PhD
Research Assistant Professor
University of Colorado, Denver
Aurora, CO

Nick Westfall, MD
Urology Resident
University of Colorado, Denver
Aurora, CO

Cole Wiedel, MD
General Surgeon
Aurora, CO



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24. Parekh DJ, Punnen S, Sjoberg DD, Asroff SW, Bailen JL, Cochran JS, et al. A multiinstitutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer. Eur Urol. 2015 Sep;68(3):464–70.

25. Chevli KK, Duff M, Walter P, Yu C, Capuder B, Elshafei A, et al. Urinary PCA3 as a predictor of prostate cancer in a cohort of 3,073 men undergoing initial prostate biopsy. J Urol. 2014 Jun;191(6):1743–8.

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32. Marks LS, Fradet Y, Deras IL, Blase A, Mathis J, Aubin SMJ, et al. PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy. Urology. 2007 Mar;69(3):532–5.

33. Okcelik S, Soydan H, Ates F, Berber U, Saygin H, Sonmez G, et al. Evaluation of PCA3 and multiparametric MRI’s: collective benefits before deciding initial prostate biopsy for patients with PSA level between 3-10ng/mL. Int Braz J Urol Off J Braz Soc Urol. 2016 Jun;42(3):449–55.

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37. Van Neste L, Herman JG, Otto G, Bigley JW, Epstein JI, Van Criekinge W. The epigenetic promise for prostate cancer diagnosis. The Prostate. 2012 Aug 1;72(11):1248–61.

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41. Partin AW, Van Neste L, Klein EA, Marks LS, Gee JR, Troyer DA, et al. Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies. J Urol. 2014 Oct;192(4):1081–7.

42. Van Neste L, Partin AW, Stewart GD, Epstein JI, Harrison DJ, Van Criekinge W. Risk score predicts high-grade prostate cancer in DNA-methylation positive, histopathologically negative biopsies. The Prostate. 2016 Sep 1;76(12):1078–87. 12

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44. Crawford ED, Ventii K, Shore ND. New biomarkers in prostate cancer. Oncol Williston Park N. 2014 Feb;28(2):135–42.

45. Falzarano SM, Ferro M, Bollito E, Klein EA, Carrieri G, Magi-Galluzzi C. Novel biomarkers and genomic tests in prostate cancer: a critical analysis. Minerva Urol E Nefrol Ital J Urol Nephrol. 2015 Sep;67(3):211–31.

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48. Yoshimoto M, Joshua AM, Cunha IW, Coudry RA, Fonseca FP, Ludkovski O, et al. Absence of TMPRSS2:ERG fusions and PTEN losses in prostate cancer is associated with a favorable outcome. Mod Pathol Off J U S Can Acad Pathol Inc. 2008 Dec;21(12):1451–60.

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50. Wojno K, Hornberger J, Schellhammer P, Dai M, Morgan T. The clinical and economic implications of specimen provenance complications in diagnostic prostate biopsies. J Urol. 2015 Apr;193(4):1170–7.

51. Knezevic D, Goddard AD, Natraj N, Cherbavaz DB, Clark-Langone KM, Snable J, et al. Analytical validation of the Oncotype DX prostate cancer assay – a clinical RT-PCR assay optimized for prostate needle biopsies. BMC Genomics. 2013;14:690.

52. Klein EA, Cooperberg MR, Magi-Galluzzi C, Simko JP, Falzarano SM, Maddala T, et al. A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol. 2014 Sep;66(3):550–60.

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56. Blume-Jensen P, Berman DM, Rimm DL, Shipitsin M, Putzi M, Nifong TP, et al. Development and Clinical Validation of an In Situ Biopsy-Based Multimarker Assay for Risk Stratification in Prostate Cancer. Am Assoc Cancer Res [Internet]. 2015 Mar 2 [cited 2016 Sep 8]; Available from: http:// 2015/04/22/1078-0432.CCR-14-2603

57. Shipitsin M, Small C, Giladi E, Siddiqui S, Choudhury S, Hussain S, et al. Automated quantitative multiplex immunofluorescence in situ imaging identifies phospho-S6 and phospho-PRAS40 as predictive protein biomarkers for prostate cancer lethality. Proteome Sci. 2014;12:40.

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65. Klein EA, Haddad Z, Yousefi K, Lam LLC, Wang Q, Choeurng V, et al. Decipher Genomic Classifier Measured on Prostate Biopsy Predicts Metastasis Risk. Urology. 2016 Apr;90:148–52.

66. Simon R. Development and validation of therapeutically relevant multi-gene biomarker classifiers. J Natl Cancer Inst. 2005 Jun 15;97(12):866–7.

67. Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, et al. AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer. N Engl J Med. 2014 Sep 11;371(11):1028–38.

68. Scher HI, Lu D, Schreiber NA, et al. ASsociation of ar-v7 on circulating tumor cells as a treatment-specific biomarker with outcomes and survival in castration-resistant prostate cancer. JAMA Oncol [Internet]. 2016 Jun 4 [cited 2016 Sep 8]; Available from: http://

69. Sarwar M, Semenas J, Miftakhova R, Simoulis A, Robinson B, Wingren AG, et al. Targeted suppression of AR-V7 using PIP5K1α inhibitor overcomes enzalutamide resistance in prostate cancer cells. Oncotarget. 2016 Aug 31;

70. Hearn JWD, AbuAli G, Reichard CA, Reddy CA, Magi-Galluzzi C, Chang K-H, et al. HSD3B1 and resistance to androgen-deprivation therapy in prostate cancer: a retrospective, multicohort study. Lancet Oncol [Internet]. 2016 Aug [cited 2016 Sep 8]; Available from: http://linkinghub.elsevier. com/retrieve/pii/S1470204516302273

71. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017;67:7-30.

72. Sakr WA, Grignon DJ, Crissman JD, Heilbrun LK, Cassin BJ, Pontes JJ, et al. High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases. In Vivo 1994;8:439-43.

73. Lubeck DP, Grossfeld GD, Carroll PR. A review of measurement of patient preferences for treatment outcomes after prostate cancer. Urology 2002;60:72-7.

74. Meng MV, Elkin EP, Harlan SR, Mehta SS, Lubeck DP, Carroll PR. Predictors of treatment after initial surveillance in men with prostate cancer: results from CaPSURE. J Urol 2003;170:2279-83.

75. Crawford ED, Rosenberg MT, Partin AW, Cooperberg MR, Maccini M, Loeb S, et al. An Approach Using PSA Levels of 1.5 ng/mL as the Cutoff for Prostate Cancer Screening in Primary Care. Urology 2016;96:116-20.

76. Crawford ED, Moul JW, Rove KO, Pettaway CA, Lamerato LE, Hughes A. Prostate- specific antigen 1.5-4.0 ng/mL: a diagnostic challenge and danger zone. BJU Int 2011;108:1743-9.

77. Van NL, Hendriks RJ, Dijkstra S, Trooskens G, Cornel EB, Jannink SA, et al. Detection of High-grade Prostate Cancer Using a Urinary Molecular Biomarker-Based Risk Score. Eur Urol 2016;70:740-8.

78. Crawford ED, KO Rove, AB Barqawi, PD Maroni, et al., Clinical-pathologic correlation between transperineal mapping biopsies of the prostate and three-dimensional reconstruction of prostatectomy specimens. Prostate, 2013 May;73(7):778-87. doi: 10.1002/pros.22622. Epub 2012 Nov 20.


Researcher-physician E. David Crawford, MD, Jack A. Vickers Director of Prostate Research and Professor of Urology at the University of California, San Diego, has devoted his career in medicine to educating the public about men's health issues and finding effective techniques and procedures to address prostate cancer, the most common malignancy affecting men in the United States.