Development and validation of a quantitative reactive stroma biomarker (qRS) for prostate cancer prognosis

Samuel Ruder, Yan Gao, Yi Ding, Ping Bu, Brian Miles, Angelo De Marzo, Thomas Wheeler, Jesse K. McKenney, Heidi Auman, Ladan Fazli, Jeff Simko, Antonio Hurtado-Coll, Dean A. Troyer, Peter R. Carroll, Martin Gleave, Elizabeth Platz, Bruce Trock, Misop Han, Mohammad Sayeeduddin, Lawrence D. TrueDavid Rowley, Daniel W. Lin, Peter S. Nelson, Ian M. Thompson, Ziding Feng, Wei Wei, James D. Brooks, Michael Ittmann, Min Jae Lee, Gustavo Ayala

Research output: Contribution to journalArticlepeer-review

Abstract

To develop and validate a new tissue-based biomarker that improves prediction of outcomes in localized prostate cancer by quantifying the host response to tumor. We use digital image analysis and machine learning to develop a biomarker of the prostate stroma called quantitative reactive stroma (qRS). qRS is a measure of percentage tumor area with a distinct, reactive stromal architecture. Kaplan Meier analysis was used to determine survival in a large retrospective cohort of radical prostatectomy samples. qRS was validated in two additional, distinct cohorts that include international cases and tissue from both radical prostatectomy and biopsy specimens. In the developmental cohort (Baylor College of Medicine, n = 482), patients whose tumor had qRS > 34% had increased risk of prostate cancer-specific death (HR 2.94; p = 0.039). This result was replicated in two validation cohorts, where patients with qRS > 34% had increased risk of prostate cancer-specific death (MEDVAMC; n = 332; HR 2.64; p = 0.02) and also biochemical recurrence (Canary; n = 988; HR 1.51; p = 0.001). By multivariate analysis, these associations were shown to hold independent predictive value when compared to currently used clinicopathologic factors including Gleason score and PSA. qRS is a new, validated biomarker that predicts prostate cancer death and biochemical recurrence across three distinct cohorts. It measures host-response rather than tumor-based characteristics, and provides information not represented by standard prognostic measurements.

Original languageEnglish (US)
Pages (from-to)84-91
Number of pages8
JournalHuman Pathology
Volume122
DOIs
StatePublished - Apr 2022
Externally publishedYes

Keywords

  • Biomarker
  • Cancer
  • Host response
  • Prostate
  • Stroma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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