Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer.
Publication/Presentation Date
2-20-2018
Abstract
Purpose It is clinically challenging to integrate genomic-classifier results that report a numeric risk of recurrence into treatment recommendations for localized prostate cancer, which are founded in the framework of risk groups. We aimed to develop a novel clinical-genomic risk grouping system that can readily be incorporated into treatment guidelines for localized prostate cancer. Materials and Methods Two multicenter cohorts (n = 991) were used for training and validation of the clinical-genomic risk groups, and two additional cohorts (n = 5,937) were used for reclassification analyses. Competing risks analysis was used to estimate the risk of distant metastasis. Time-dependent c-indices were constructed to compare clinicopathologic risk models with the clinical-genomic risk groups. Results With a median follow-up of 8 years for patients in the training cohort, 10-year distant metastasis rates for National Comprehensive Cancer Network (NCCN) low, favorable-intermediate, unfavorable-intermediate, and high-risk were 7.3%, 9.2%, 38.0%, and 39.5%, respectively. In contrast, the three-tier clinical-genomic risk groups had 10-year distant metastasis rates of 3.5%, 29.4%, and 54.6%, for low-, intermediate-, and high-risk, respectively, which were consistent in the validation cohort (0%, 25.9%, and 55.2%, respectively). C-indices for the clinical-genomic risk grouping system (0.84; 95% CI, 0.61 to 0.93) were improved over NCCN (0.73; 95% CI, 0.60 to 0.86) and Cancer of the Prostate Risk Assessment (0.74; 95% CI, 0.65 to 0.84), and 30% of patients using NCCN low/intermediate/high would be reclassified by the new three-tier system and 67% of patients would be reclassified from NCCN six-tier (very-low- to very-high-risk) by the new six-tier system. Conclusion A commercially available genomic classifier in combination with standard clinicopathologic variables can generate a simple-to-use clinical-genomic risk grouping that more accurately identifies patients at low, intermediate, and high risk for metastasis and can be easily incorporated into current guidelines to better risk-stratify patients.
Volume
36
Issue
6
First Page
581
Last Page
590
ISSN
1527-7755
Published In/Presented At
Spratt, D. E., Zhang, J., Santiago-Jiménez, M., Dess, R. T., Davis, J. W., Den, R. B., Dicker, A. P., Kane, C. J., Pollack, A., Stoyanova, R., Abdollah, F., Ross, A. E., Cole, A., Uchio, E., Randall, J. M., Nguyen, H., Zhao, S. G., Mehra, R., Glass, A. G., Lam, L. L. C., … Nguyen, P. L. (2018). Development and Validation of a Novel Integrated Clinical-Genomic Risk Group Classification for Localized Prostate Cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 36(6), 581–590. https://doi.org/10.1200/JCO.2017.74.2940
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
29185869
Department(s)
Administration and Leadership
Document Type
Article