Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Jonathan David Tward , Thorsten Schlomm , Stephen Bardot , Stephen J. Freedland , Lauren Lenz , Todd Cohen , Steven Stone , Jay Bishoff
Background: Prolaris combines RNA expression analysis of cell cycle progression genes with clinicopathologic information to create a combined clinical cell-cycle risk score (CCR). We evaluated the ability of CCR to predict metastasis (mets) in men for whom guidelines indicate that multimodality therapy (MTx) should be considered. Methods: A commercial cohort (N=15669) of National Comprehensive Cancer Network unfavorable intermediate-risk (UFI) and high-risk (HR) men revealed a distribution of 70.5% and 29.5% respectively. A CCR threshold of 2.112 was selected so that 29.5% of these men were above the threshold. MTx was defined as combined use of androgen deprivation therapy with radiation (RT) or surgery, or with adjuvant RT. Associations were evaluated in a 718-person retrospective, multi-institutional database of Prolaris-tested UFI and HR men. Kaplan-Meier (KM) analyses and Cox regressions were used to estimate the effects of prognostic covariates. Results: Median follow-up was 5.13 years. CCR predicted mets in the full cohort (HR =3.8 [2.7,5.2], p<10−15) and after accounting for CAPRA (HR=4.3 [2.7,7.0], p< 10−7). CCR also was a significant predictor of mets in patients who received STx, as a continuous predictor (HR=4.0 [2.6,6.1], p<10−9) and when dichotomized at the threshold (HR=15.9 [5.4,46.5], p< 10−9). The KM probability of mets by 10 years for those below and above the threshold was 4.3% and 20.4% respectively. MTx reduced patients’ risk of mets (HR=0.46 [0.22,0.97], p=0.04), and treatment benefit can be evaluated as a function of CCR score (Table). Conclusions: The CCR score prognosticates a clinically meaningful different risk of metastasis for those receiving MTx versus STx. Approximately 27% and 73% of people with HR or UFI risk cancer have CCR scores below the risk threshold and may consider STx after considering the difference in risk of mets.
CCR | STx Risk | MTx Risk | Risk Reduction for MTx |
---|---|---|---|
0 | 0.4% (0.1%, 1.2%) | 0.2% (0.04%, 0.7%) | -0.2% |
1 | 1.6% (0.7%, 3.8%) | 0.7% (0.2%, 2.4%) | -0.9% |
2 | 6.8% (3.6%, 12.9%) | 3.2% (1.3%, 7.9%) | -3.6% |
3 | 26.9% (15.5%, 43.9%) | 13.5% (6.6%, 26.5%) | -13.4% |
4 | 74.9% (47.5%, 94.8%) | 47.4% (26.4%, 73.8%) | -27.5% |
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Abstract Disclosures
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