AUA 2018: Biomarker Debate: Adopt, Expand, Trust (CON)

San Francisco, CA (UroToday.com) Ben Davies, MD from the University of Pittsburgh provided the rebuttal to Matt Cooperberg’s argument for prostate cancer biomarkers. Davies started with a case of a 51-year-old healthy man with a PSA of 6 and one core of Gleason 3+4 prostate cancer. A Decipher test score of <0.45 would place this gentleman in the low genomic classifier group, and coupled with being NCCN low-favorable intermediate risk, this would give this patient a 6-tier clinical-genomic risk group score of 1 (low risk). More to come from this case…

Davies posed the question “are urologists using biomarkers”? In a Twitter survey of 240 respondents, 75% reported that biomarkers were not needed, 7% used Decipher, 8% used Prolaris, and 10% used ConfirmDx. Davies notes that indeed, it appears that urologists are not using biomarkers, showing the fiscal first-quarter 2018 Revenue By Product stats that YoY growth from 1Q17 to 1Q18 was 0% for Prolaris.

Davies highlights that over the last year we have two studies (PRECISION1 and PROMIS2) that suggest that men with an increased PSA should have an mpMRI prior to prostate biopsy. As deftly highlighted, in the PROMIS study, there were 0 cases of Gleason ≥4+3 prostate cancer missed by mpMRI. Long-term active surveillance outcomes suggest that 15-year prostate cancer specific mortality (PCSM) incidence for strict criteria (no Gleason 3+4) is 0.1% and 5.7% for expanded criteria (some Gleason 3+4). Metastasis incidence for strict AS criteria is 0.1% and 2.8% for expanded criteria. So even when patients are enrolled in active surveillance programs, Davies asks “do we really need to biomarkers” when mortality and PCSM outcomes in these patients are so low?

Davies highlights that there are four components that should encompass the perfect biomarker:
  • Developed in active surveillance patients
  • Validated in active surveillance patients
  • Improve prostate mortality
  • Decreases metastatic rate
Unfortunately, no biomarker to date fulfills these criteria. According to Davies, there are several flaws with biomarkers:

  • Prognostic flaws – GPS has a minor improvement in stratification, but in a low-risk cohort, the AUC only improved to 0.67 from 0.63 (clinical only). Furthermore, Prolaris fails to improve prognostication without clinical input.
  • Imaging flaws – in a study evaluating the association between GPS and mpMRI, mean GPS results differed between mpMRI categories (p=0.001), however, a broad range was observed for all categories, particularly for Gleason 3+4 disease3.
  • Basic science flaws – in data provided to Davies by colleagues at the University of Michigan, there is a demonstration of clonal independence among biopsy sampled prostates.
When Davies performed a radical prostatectomy on the 51-year-old healthy male with a single core of Gleason 3+4 disease and PSA of 6, the final pathology was Gleason 4+5, pT3aN0Mx despite a Decipher score of < 0.45. Davies concluded his rebuttal to Cooperberg by leaving the audience with a final slide and take-home message:

biomarkers in prostate cancer

Presented by: Ben Davies, MD, University of Pittsburgh

Read the Opposing Debate: Biomarker Debate: Adopt, Expand, Trust (PRO)

References:
  1. Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): A paired validating confirmatory study. Lancet 2017;389(10071):815-822.
  2. Kasivisvanathan V, Rannikko AS, Borghi M, et al. MRI-targeted or standard biopsy for prostate cancer diagnosis. N Engl J Med 2018;378(19):1767-1777.
  3. Leapman MS, Westphalen AC, Ameli N, et al. Association between a 17-gene genomic prostate score and multi-parametric prostate MRI in men with low and intermediate risk prostate cancer (PCa). PLoS One 2017;12(10):e0185535.
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA
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