James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD
Bruce J. Trock , Saradha Rajamani , Igor Vidal , Stephanie Glavaris , Tracy Jones , Misop Han , Alan W. Partin , Todd Cohen , Steven Stone , Angelo M De Marzo
Background: To evaluate the cell cycle progression (CCP) score and PTEN as prognostic markers for risk of metastasis in a radical prostatectomy (RP) cohort of NCCN intermediate and high risk prostate cancer. Methods: This IRB-approved case-cohort study included men treated with RP at Johns Hopkins from 2007-2015. Paraffin-embedded RP tissue was analyzed blind to study outcome at Myriad Genetics, for CCP score using qRT-PCR, and PTEN by immunohistochemistry. Metastasis-free survival (MFS) was analyzed with the Cox proportional hazards model, weighted for case-cohort design. CCP and PTEN were analyzed independently, and adjusted for CAPRA-S. The CCR score, which combines CCP and CAPRA-S, was also analyzed. Data were analyzed independently by Johns Hopkins and Myriad Genetics. Results: There were 209 patients, of whom 42 were cases (metastasis). Median age was 59 years, 47% had Gleason 4+3 or higher, 48% had non-organ confined tumor, and 18% had seminal vesicle or lymph node involvement. NCCN risk was intermediate in 77% and high in 23%. Median follow-up was 4 years. Both CCP and PTEN, as well as CCR score, were statistically significant in univariate analyses, but only CCP retained statistical significance in a multivariable model of CCP, PTEN, and CAPRA-S (Table). Conclusions: This is the first comparison of the CCP score and PTEN as risk factors for metastasis in a recent RP cohort of patients at NCCN intermediate or high risk. Both CCP score and PTEN were strongly associated with MFS in univariate analyses, but only CCP score retained significance in a multivariable analysis with both biomarkers adjusted for CAPRA-S.
Variables | Univariate | Multivariable | ||
---|---|---|---|---|
HR (95% CI) | p-value | HR (95% CI) | p-value | |
CCP (per unit) | 4.7 (2.6, 8.7) | <0.00001 | 3.1 (1.6, 6.1) | 0.001 |
CAPRA-S (per unit) | 2.4 (1.9, 3.0) | <0.00001 | 2.2 (1.7, 2.9) | <0.00001 |
PTEN (loss vs. intact) | 4.3 (1.8, 10.2) | 0.00088 | 1.9 (0.6, 5.7) | 0.28 |
CCR (per unit) | 7.94 (4.6, 14.5) | <0.00001 | NA* |
* CCR score not included because it already incorporates CAPRA-S
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Abstract Disclosures
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