Clinical utility of the exosome based ExoDx Prostate(IntelliScore) EPI test in men presenting for initial Biopsy with a PSA 2-10 ng/mL
Ronald Tutrone, Michael J Donovan, Phillipp Torkler, Vasisht Tadigotla, Tom McLain, Mikkel Noerholm, Johan Skog, James McKiernan, Ronald Tutrone, Michael J Donovan, Phillipp Torkler, Vasisht Tadigotla, Tom McLain, Mikkel Noerholm, Johan Skog, James McKiernan
Abstract
Background: The ExoDx Prostate(IntelliScore) (EPI) test is a non-invasive risk assessment tool for detection of high-grade prostate cancer (HGPC) that informs whether to proceed with prostate biopsy. We sought to assess the impact of EPI on the decision to biopsy in a real-world clinical setting.
Methods: We conducted a prospective, randomized, blinded, two-armed clinical utility study that enrolled 1094 patients with 72 urologists from 24 urology practices. Patients were considered for prostate biopsy at enrollment based on standard clinical criteria. All patients had an EPI test; however, patients were randomized into EPI vs. control arms where only the EPI arm received results for their biopsy decision.
Results: In the EPI arm (N = 458), 93 patients received negative EPI scores of which 63% were recommended to defer biopsy by the urologist and 74% ultimately deferred. In contrast, 87% of patients with positive EPI scores were recommended to undergo biopsy with a 72% compliance rate to the urologist's recommendation. This led to detection of 30% more HGPC compared to the control arm, and we estimate that 49% fewer HGPC were missed due to deferrals compared to standard of care (SOC). Overall, 68% of urologists reported that the EPI test influenced their biopsy decision. The primary reason not to comply with EPI results was rising PSA.
Conclusion: To our knowledge this is the first report on a PC biomarker utility study with a blinded control arm. The study demonstrates that the EPI test influences the overall decision to defer or proceed with a biopsy and improves patient stratification.
Conflict of interest statement
PT, VT, MN and JS are employees of Bio-techne. TM and MJD are consultants for Bio-Techne. ARF: personal relationship with PCAN EIC. Editor recused himself and was not involved in the processing of this manuscript or the editorial decision-making.
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References
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34. doi: 10.3322/caac.21551.
- Potosky AL, Feuer EJ, Levin DL. Impact of screening on incidence and mortality of prostate cancer in the United States. Epidemiol Rev. 2001;23:181–6. doi: 10.1093/oxfordjournals.epirev.a000787.
- Potts JM, Lutz M, Walker E, Modlin C, Klein E. Trends in PSA, age and prostate cancer detection among black and white men from 1990–2006 at a tertiary care center. Cancer. 2010;116:3910–5. doi: 10.1002/cncr.25124.
- Draisma G, Etzioni R, Tsodikov A, Mariotto A, Wever E, Gulati R, et al. Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst. 2009;101:374–83. doi: 10.1093/jnci/djp001.
- Thompson IM, Ankerst DP, Chi C, Lucia MS, Goodman PJ, Crowley JJ, et al. Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower. JAMA. 2005;294:66–70. doi: 10.1001/jama.294.1.66.
- Roddam AW, Duffy MJ, Hamdy FC, Ward AM, Patnick J, Price CP, et al. Use of prostate-specific antigen (PSA) isoforms for the detection of prostate cancer in men with a PSA level of 2-10 ng/ml: systematic review and meta-analysis. Eur Urol. 2005;48:386–99. doi: 10.1016/j.eururo.2005.04.015.
- Barry MJ. Clinical practice. Prostate-specific-antigen testing for early diagnosis of prostate cancer. N. Engl J Med. 2001;344:1373–7. doi: 10.1056/NEJM200105033441806.
- Force USPST, Grossman DC, Curry SJ, Owens DK, Bibbins-Domingo K, Caughey AB, et al. Screening for prostate cancer: US preventive services task force recommendation statement. JAMA. 2018;319:1901–13. doi: 10.1001/jama.2018.3710.
- McKiernan J, Donovan MJ, O’Neill V, Bentink S, Noerholm M, Belzer S, et al. A novel urine exosome gene expression assay to predict high-grade prostate cancer at initial biopsy. JAMA Oncol. 2016;2:882–9. doi: 10.1001/jamaoncol.2016.0097.
- Patel HD, Chalfin HJ, Carter HB. Improving prostate cancer screening and diagnosis: health policy and biomarkers beyond PSA. JAMA Oncol. 2016;2:867–8. doi: 10.1001/jamaoncol.2016.0170.
- Carignan A, Roussy JF, Lapointe V, Valiquette L, Sabbagh R, Pepin J. Increasing risk of infectious complications after transrectal ultrasound-guided prostate biopsies: time to reassess antimicrobial prophylaxis? Eur Urol. 2012;62:453–9. doi: 10.1016/j.eururo.2012.04.044.
- Kim J, Shin W. How to do random allocation (randomization) Clin Orthop Surg. 2014;6:103–9. doi: 10.4055/cios.2014.6.1.103.
- McKiernan J, Donovan MJ, Margolis E, Partin A, Carter B, Brown G, et al. A prospective adaptive utility trial to validate performance of a novel urine exosome gene expression assay to predict high-grade prostate cancer in patients with prostate-specific antigen 2–10ng/ml at initial biopsy. Eur Urol. 2018;74:731–8. doi: 10.1016/j.eururo.2018.08.019.
- Gaines AR, Turner EL, Moorman PG, Freedland SJ, Keto CJ, McPhail ME, et al. The association between race and prostate cancer risk on initial biopsy in an equal access, multiethnic cohort. Cancer Causes Control. 2014;25:1029–35. doi: 10.1007/s10552-014-0402-6.
- Press B, Schulster M, Bjurlin MA. Differentiating molecular risk assessments for prostate cancer. Rev Urol. 2018;20:12–8.
- Pinsky PF, Andriole GL, Kramer BS, Hayes RB, Prorok PC, Gohagan JK, et al. Prostate biopsy following a positive screen in the prostate, lung, colorectal and ovarian cancer screening trial. J Urol. 2005;173:746–50. doi: 10.1097/01.ju.0000152697.25708.71.
- Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017;389:815–22. doi: 10.1016/S0140-6736(16)32401-1.
- El-Shater Bosaily A, Parker C, Brown LC, Gabe R, Hindley RG, Kaplan R, et al. PROMIS-Prostate MR imaging study: a paired validating cohort study evaluating the role of multi-parametric MRI in men with clinical suspicion of prostate cancer. Contemp Clin Trials. 2015;42:26–40. doi: 10.1016/j.cct.2015.02.008.
- White J, Shenoy BV, Tutrone RF, Karsh LI, Saltzstein DR, Harmon WJ, et al. Clinical utility of the prostate health index (phi) for biopsy decision management in a large group urology practice setting. Prostate Cancer Prostatic Dis. 2018;21:78–84. doi: 10.1038/s41391-017-0008-7.
- Konety B, Zappala SM, Parekh DJ, Osterhout D, Schock J, Chudler RM, et al. The 4Kscore(R) test reduces prostate biopsy rates in community and academic urology practices. Rev Urol. 2015;17:231–40.
- Shore NHJ, Langford T, Stein M, DeHart J, Brawer M, Hessels D, et al. Urinary molecular biomarker test impacts prostate biopsy decision making in clinical practice. Urol Pract. 2019;6:256–61. doi: 10.1016/j.urpr.2018.09.002.
Source: PubMed