Characterizing population-wide genomic risk distribution for development of a novel clinical-genomic risk system for prognostication in patients with clinically localized prostate cancer

Abstract

Abstract Purpose Genomic classifiers are endorsed by guidelines and commonly used to inform prognosis in prostate cancer. We aimed to understand the distribution of genomic risk within the validated staging collaboration for cancer of the prostate (STAR-CAP) and propose a system integrating genomic and clinicopathologic risk. We hypothesized that genomic heterogeneity would have implications on risk estimates and may inform treatment decisions. Materials and methods Genomic risk was assessed using the Decipher genomic classifier in two separate multi-institutional, prospectively collected population-based registries: (1) Decipher Genomics Resource for Intelligent Discovery (GRID) [ n = 50,891] and (2) Michigan Urological Surgery Improvement Collaborative (MUSIC-Decipher) [ n = 1602]. The primary endpoint was estimated prostate cancer-specific mortality (PCSM), and secondary endpoint was distant metastasis (DM). Marginal risk estimates provided by STAR-CAP were combined with hazard ratios of Decipher to calculate integrated risk estimates. Results Median age and PSA was 68 years and 6.2 ng/mL in GRID, and 66 years and 10.5 ng/mL in MUSIC. The GRID population had 50.2%, 18.5%, and 31.4% with low-, intermediate-, and high-Decipher risk, compared to 48.0%, 16.2%, and 35.8% in MUSIC. Decipher-based genomic risk varied across STAR-CAP stages in both registries. Estimates of 10-year PCSM (0.1% to 48.8%) and DM (0.3%-72.9%) varied widely after integration of clinical-genomic risk. Use of an integrated Decipher-STAR-CAP system led to significant stage reclassification, including 23.4% upstaging and 45.6% downstaging at least one stage. Conclusions These findings suggest integration of genomic and clinicopathologic risk may lead to more nuanced risk assessment in prostate cancer and may help individualize treatment consideration.

Affiliated Institutions

• University of California, Los Angeles US
• Durham VA Medical Center US
• University of Michigan US
• University Hospitals Seidman Cancer Center US
• University of Toronto CA
• Case Western Reserve University US
• Veracyte (United States) US
• New York University US
• Queen's University CA
• Los Angeles Medical Center US
• Johns Hopkins University US
• University of California San Francisco Medical Center US
• Mayo Clinic in Arizona US
• Cedars-Sinai Medical Center US
• Augusta University US
• Kingston General Hospital CA

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