scholarly journals MP60-16 CELL CYCLE PROGRESSION SCORE AND PTEN AS PROGNOSTIC FACTORS FOR METASTASIS IN INTERMEDIATE AND HIGH RISK PROSTATE CANCER OVERALL, AND IN THOSE WHO RECEIVED SALVAGE RADIOTHERAPY

2021 ◽  
Vol 206 (Supplement 3) ◽  
Author(s):  
Bruce Trock ◽  
Brent Mabey ◽  
Igor Vidal ◽  
Stephanie Glavaris ◽  
Tracy Jones ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Prognostic Factors ◽  
High Risk ◽  
Cell Cycle Progression ◽  
Salvage Radiotherapy ◽  
Cycle Progression ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer

Cell cycle progression score and PTEN as prognostic factors for metastasis in intermediate- and high-risk prostate cancer overall, and in those who also received salvage radiotherapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 247-247
Author(s):  
Bruce J. Trock ◽  
Saradha Rajamani ◽  
Igor Vidal ◽  
Stephanie Glavaris ◽  
Tracy Jones ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
High Risk ◽  
Cell Cycle Progression ◽  
Lymph Node Involvement ◽  
Cycle Progression ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Myriad Genetics ◽  
Node Involvement

247 Background: The cell cycle progression (CCP) score and PTEN have never been evaluated together as prognostic markers for risk of metastasis in a radical prostatectomy (RP) cohort of men with National Comprehensive Cancer Network intermediate- and high-risk prostate cancer (PCa), nor in such patients who also received salvage radiation (SRT) alone or with androgen deprivation (SRT+ADT). This study evaluated CCP score and PTEN in both settings. Methods: Participants were treated with RP at Johns Hopkins from 2007-2015. Paraffin-embedded RP tissue was analyzed blind to clinical outcome at Myriad Genetics, for CCP score using qRT-PCR, and PTEN by immunohistochemistry. For overall evaluation of CCP and PTEN in intermediate- and high-risk men a case-cohort sample was selected. Intermediate- and high-risk men with biochemical recurrence who received SRT or SRT+ADT were also sampled to provide a population at particularly high risk. Metastasis-free survival (MFS) was analyzed with the proportional hazards model, weighted for case-cohort design for the overall analysis, and adjusted for CAPRA-S. The clinical cell-cycle risk (CCR) score, a fixed algorithm combining CCP and CAPRA-S was also analyzed in both contexts. Data were analyzed independently by Johns Hopkins and Myriad Genetics. Results: The case-cohort consisted of 209 men, including 47% with Gleason score >4+3, 48% extra-prostatic extension, and 18% with seminal vesicle or lymph node involvement; 42 (20%) developed metastasis. In univariate analyses CCP, CAPRA-S, and PTEN were all highly significant. In multivariable analysis, only CCP and CAPRA-S retained significance (Table section A). CCR was also strongly prognostic, HR=7.9 (95% CI 4.4, 14.5) per unit change, p<0.00001. SRT (56%) or SRT+ADT (44%) were received by 172 men, of whom 78% had Gleason >4+3, 48% extra-prostatic extension, and 34% seminal vesicle or lymph node involvement; 19 (11%) developed metastases. Again, CCP and CAPRA-S, but not PTEN, were statistically significant (Table section B). CCR was also statistically significant, HR=1.7 (95% CI 1.2, 2.4), p=0.002. Conclusions: This is the first comparison, in a recent cohort of intermediate- and high-risk men, of CCP score and PTEN as risk factors for metastasis, and first evaluation in such men receiving SRT. In both multivariable settings, CCP score, but not PTEN, was significantly associated with MFS, adjusted for CAPRA-S. CCR, a fixed algorithm that combines CCP and CAPRA-S was also significant in both settings. [Table: see text]

Cell cycle progression score and PTEN as prognostic factors for metastasis in intermediate and high-risk prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16575-e16575
Author(s):  
Bruce J. Trock ◽  
Saradha Rajamani ◽  
Igor Vidal ◽  
Stephanie Glavaris ◽  
Tracy Jones ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
High Risk ◽  
Cell Cycle Progression ◽  
Multivariable Analysis ◽  
Cycle Progression ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
Myriad Genetics ◽  
Univariate Analyses

e16575 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. [Table: see text]

Ability of the combined clinical cell-cycle risk score to identify patients that benefit from multi versus single modality therapy in NCCN intermediate and high-risk prostate cancer.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 346-346
Author(s):  
Jonathan David Tward ◽  
Thorsten Schlomm ◽  
Stephen Bardot ◽  
Stephen J. Freedland ◽  
Lauren Lenz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
High Risk ◽  
Risk Score ◽  
Cell Cycle Progression ◽  
Full Cohort ◽  
Treatment Benefit ◽  
High Risk Prostate Cancer ◽  
Kaplan Meier ◽  
Risk Prostate Cancer ◽  
The Difference

346 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.[Table: see text]

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