title: Evaluating the clinical impact of a genomic classifier in prostate cancer using individualized decision analysis.
abstract: BACKGROUND
  Currently there is controversy surrounding the optimal way to treat patients with prostate cancer in the post-prostatectomy setting. Adjuvant therapies carry possible benefits of improved curative results, but there is uncertainty in which patients should receive adjuvant therapy. There are concerns about giving toxicity to a whole population for the benefit of only a subset. We hypothesized that making post-prostatectomy treatment decisions using genomics-based risk prediction estimates would improve cancer and quality of life outcomes.
  
  
  METHODS
  We developed a state-transition model to simulate outcomes over a 10 year horizon for a cohort of post-prostatectomy patients. Outcomes included cancer progression rates at 5 and 10 years, overall survival, and quality-adjusted survival with reductions for treatment, side effects, and cancer stage. We compared outcomes using population-level versus individual-level risk of cancer progression, and for genomics-based care versus usual care treatment recommendations.
  
  
  RESULTS
  Cancer progression outcomes, expected life-years (LYs), and expected quality-adjusted life-years (QALYs) were significantly different when individual genomics-based cancer progression risk estimates were used in place of population-level risk estimates. Use of the genomic classifier to guide treatment decisions provided small, but statistically significant, improvements in model outcomes. We observed an additional 0.03 LYs and 0.07 QALYs, a 12% relative increase in the 5-year recurrence-free survival probability, and a 4% relative reduction in the 5-year probability of metastatic disease or death.
  
  
  CONCLUSIONS
  The use of genomics-based risk prediction to guide treatment decisions may improve outcomes for prostate cancer patients. This study offers a framework for individualized decision analysis, and can be extended to incorporate a wide range of personal attributes to enable delivery of patient-centered tools for informed decision-making.
authors.affiliation: Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, United States of America.
authors.forename: Jennifer Mason
authors.initials: JM
authors.lastname: Lobo
authors.affiliation: Department of Radiation Oncology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States of America.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Dicker
authors.affiliation: GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Buerki
authors.affiliation: GenomeDx Biosciences, Vancouver, British Columbia, Canada.
authors.forename: Elai
authors.initials: E
authors.lastname: Daviconi
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, United States of America.
authors.forename: R Jeffrey
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.affiliation: Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, VA, United States of America.
authors.forename: Nirav
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Radiation Oncology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, United States of America.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Den
authors.affiliation: Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, VA, United States of America.
authors.forename: Timothy N
authors.initials: TN
authors.lastname: Showalter
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003661:Decision Support Techniques; D023281:Genomics; D006801:Humans; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D057285:Precision Medicine; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D016019:Survival Analysis
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