Evaluating the clinical impact of a genomic classifier in prostate cancer using individualized decision analysis

PLoS One. 2015 Apr 2;10(3):e0116866. doi: 10.1371/journal.pone.0116866. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Decision Support Techniques
  • Genomics
  • Humans
  • Male
  • Middle Aged
  • Patient Outcome Assessment*
  • Precision Medicine
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / surgery
  • Quality of Life
  • Quality-Adjusted Life Years
  • Survival Analysis

Grants and funding

This work was supported by a research grant from GenomeDx Biosciences (genomedx.com/), as well as by a 2011 Prostate Cancer Foundation Young Investigator Award (T.N.S.; www.pcf.org/) and an American Society for Radiation Oncology Comparative Effectiveness Research Award (T.N.S.; www.astro.org). GenomeDx Biosciences provided support in the form of salaries for authors CB and ED, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.