CCP score and risk stratification for prostate cancer patients at biopsy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 47-47 ◽  
Author(s):  
E. David Crawford ◽  
Neal Shore ◽  
Peter T. Scardino ◽  
John W. Davis ◽  
Jonathan D. Tward ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Risk Stratification ◽  
Gleason Score ◽  
Cell Cycle Progression ◽  
Specific Antigen ◽  
Risk Category ◽  
Cycle Progression ◽  
Aggressive Cancer ◽  
Cancer Aggressiveness

47 Background: New prognostic markers for prostate cancer play an important role in addressing the controversies of over diagnosis and treatment. The cell cycle progression score (CCP) (Prolaris, Myriad Genetic Laboratories, Inc.) is a new RNA-based marker, which improved the prediction of prostate cancer aggressiveness in eight separate cohorts. Each one-unit increase in CCP score corresponds with approximately a doubling of the risk of the studied event (recurrence or death from prostate cancer). In this analysis, we characterized the CCP score distribution from our initial CCP signature commercial testing. Methods: Our current laboratory database was evaluated for patients whose biopsy was analyzed with the CCP test and whose clinicopathologic data was collected by the ordering physician. Formalin fixed, prostate biopsy tissue from 1,648 patients diagnosed with adenocarcinoma ordered by more than 300 physicians were analyzed. The CCP score was calculated by measuring the RNA expression of 31 cell cycle progression genes normalized to 15 housekeeping genes. Results: Of the 1,648 samples that contained sufficient carcinoma (more than 0.5mm linear extent), 1,604 (97.3%) provided quality RNA for analysis. This retrospective analysis showed a normal distribution for the CCP score ranging from −2.9 to 3.1. Correlation with Gleason score was r=0.35. A relative classification of cancer aggressiveness based on CCP of approximately1,200 patients from multiple cohorts was developed to interpret how the patient’s CCP score compared to that of patients within the same AUA risk category. The thresholds between each of the five intervals are one unit of CCP score apart, with the "consistent" interval centered at the median CCP score. Based on the CCP score, 27.9% of men had a less aggressive cancer compared to the clinicopathologic prediction and were assigned to a lower risk group while 27.6% of patients had a more aggressive cancer. Conclusions: The CCP signature test is a novel assay that can improve risk stratification for men with prostate adenocarcinoma independent of the Gleason score and prostate-specific antigen level. Over 50% of men initially tested in the commercial assay were assigned to a different risk category than predicted by clinicopathologic features alone.

Performance of CCP assay in an updated series of biopsy samples obtained from commercial testing.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 64-64 ◽  
Author(s):  
E. David Crawford ◽  
Neal Shore ◽  
Peter T. Scardino ◽  
John W. Davis ◽  
Jonathan D. Tward ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Housekeeping Genes ◽  
Risk Category ◽  
Score Distribution ◽  
Cycle Progression ◽  
Improve Risk Stratification ◽  
Aggressive Cancer ◽  
Cancer Aggressiveness ◽  
Commercial Testing

64 Background: The cell cycle progression (CCP) score is an RNA-based expression assay which has improved the prediction of prostate cancer aggressiveness in nine separate retrospective cohorts. In this analysis, we characterized the patient population and CCP score performance in commercial testing. Methods: Formalin-fixed prostate biopsy samples from 4,261 patients were submitted by 930 physicians to Myriad Genetic Laboratories for CCP test analysis. Patient clinicopathologic data was obtained from the test request form. The CCP score was calculated based on RNA expression of 31 cell cycle progression genes normalized to 15 housekeeping genes. Patients were sorted in to AUA risk categories and assigned a relative classification of cancer aggressiveness based on the CCP score. Results: Of the 4,261 samples that contained sufficient carcinoma (>0.5mm linear extent), 4,218 (99.0%) provided quality RNA for analysis. The CCP score distribution ranged from -2.9 to 3.4. Correlation with Gleason score was r=0.35 and the correlation with PSA was r=0.16. Based on the CCP score, 36.8% of men had a less aggressive cancer and 21.2% of patients had a more aggressive cancer than expected based on clinicopathologic prediction. Conclusions: The CCP test can improve risk stratification for men with prostate adenocarcinoma independent of other clinicopathologic variables. Fifty-eight percent of men tested in the commercial assay were assigned to a different risk category than predicted by their clinicopathologic features.

Predicting radical prostatectomy outcome: Cell cycle progression (CCP) score compared with primary Gleason grade among men with clinical Gleason less than 7 who are upgraded to Gleason 7.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 13-13 ◽  
Author(s):  
Matthew R. Cooperberg ◽  
Stephen J. Freedland ◽  
Thorsten Schlomm ◽  
Julia E. Reid ◽  
Steven Stone ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Risk Assessment ◽  
Radical Prostatectomy ◽  
Cell Cycle Progression ◽  
Specific Antigen ◽  
Gleason Grade ◽  
Cycle Progression ◽  
Major Barrier ◽  
Cancer Aggressiveness

13 Background: Improved prognostic markers for prostate cancer are an important part of addressing the issue of over- and under-treatment in prostate cancer. Gleason score (GS), prostate-specific antigen and clinical stage work well for population risk assessment but lack precision for individual patients. Concern over undergrading on biopsy is felt to be a major barrier to increasing use of active surveillance. Molecular analysis can further refine risk assessment as demonstrated by the cell cycle progression (CCP) score (Prolaris) which has been shown to predict prostate cancer aggressiveness in eight separate cohorts. In these studies, CCP scores typically ranged from −2 to +3 with each one−unit increase in CCP score corresponding to approximately a doubling of the risk of the studied event (recurrence or death from prostate cancer). In the present investigation, we sought to assess how upgrading compared with CCP in predicting failure after radical prostatectomy (RP). Methods: In this study, we examined men from three cohorts (UCSF, Martini Clinic, and Durham VAMC) with clinical GS (cGS) less than 7 who had pathologic GS (pGS) 3+4 or 4+3. The CCP assay was performed using RP specimen from UCSF and biopsy material from the other cohorts. We compared the rates of biochemical recurrence (BCR) as predicted by pGS, CAPRA, or CCP score alone versus CAPRA combined with CCP score using a Cox proportional hazards model stratified by cohort. Results: Among the 230 men with cGS less than 7 and pGS equal to 7 included in this analysis, 207 had pGS 3+4 and 57 had BCR; 23 had pGS 4+3; and eight had BCR. There was no difference in BCR based on GS (p=0.8) or CAPRA (p=0.4). In contrast, CCP score alone and a pre-defined score combining the CCP score and CAPRA were prognostic of BCR (HR=1.82 [95 % CI 1.32-2.52; p<0.001]; HR=1.84 [95 % CI 1.10-3.05; p=0.021] respectively). Conclusions: These data indicate that the risk of BCR is indistinguishable in men with cGS less than 7 who have pGS 3+4 or 4+3. However, the CCP assay does provide stratification of this risk. Tests that can predict BCR on biopsy will aid in initial therapeutic decision making.

Stratification of risk for patients with prostate cancer at biopsy using CCP score.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 127-127 ◽  
Author(s):  
Neal D. Shore ◽  
Brian Abbott ◽  
Raoul S. Concepcion ◽  
Daniel Saltzstein ◽  
Rajesh R. Kaldate ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Risk Assessment ◽  
Gleason Score ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Clinical Stage ◽  
Cycle Progression ◽  
Cancer Aggressiveness ◽  
Prostate Cancers

127 Background: In the US, most prostate cancers are treated with surgery or radiation, despite many having low malignant potential. If low cancer progression risk can be established, some men can be spared treatment. PSA, Gleason score and clinical stage work well for population risk assessment but lack precision for individuals. Molecular analysis can refine risk assessment as demonstrated by a cell cycle progression score (CCP) predictive of prostate cancer aggressiveness in 4 separate cohorts. In these studies, CCP typically ranged from −2 to +3 with each 1−unit increase corresponding to approximately a doubling of risk. We characterized the CCP distribution using recent samples from a typical US urology multi−centered clinical setting and determined the analytic success rate of the assay. Methods: Formalin fixed, prostate biopsy tissue from 300 patients diagnosed with adenocarcinoma within the last 12 months was analyzed. CCP is calculated by measuring the relative RNA expression of 31 cell cycle progression genes. Patients were recruited from 15 geographically diverse community urology practices. Results: CCP could be measured for 98% of samples (294/300). This study showed a normal distribution for the CCP ranging from −2 to 3.2 (median = −0.3, SD=0.92). There was little correlation of CCP with PSA, age, or body mass index. Correlation with Gleason score was similar to those in prior studies (r=0.494). A relative classification of cancer aggressiveness based on CCP of ~ 1200 patients from multiple cohorts has been developed. The 294 evaluable patients were cross−classified by AUA risk and cancer aggressiveness (see table). CCP further stratified patients within each AUA risk classification. Conclusions: CCP is a novel assay that can facilitate risk stratification for men with prostate adenocarcinoma. [Table: see text]

scholarly journals Validation of a Cell-Cycle Progression Gene Panel to Improve Risk Stratification in a Contemporary Prostatectomy Cohort

2013 ◽  
Vol 31 (11) ◽  
pp. 1428-1434 ◽  
Author(s):  
Matthew R. Cooperberg ◽  
Jeffry P. Simko ◽  
Janet E. Cowan ◽  
Julia E. Reid ◽  
Azita Djalilvand ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Risk Assessment ◽  
Risk Stratification ◽  
Cell Cycle Progression ◽  
Genetic Risk Score ◽  
Specific Antigen ◽  
Low Risk ◽  
Partial Likelihood ◽  
Cycle Progression ◽  
Clinical Risk

Purpose We aimed to validate a previously described genetic risk score, denoted the cell-cycle progression (CCP) score, in predicting contemporary radical prostatectomy (RP) outcomes. Methods RNA was quantified from paraffin-embedded RP specimens. The CCP score was calculated as average expression of 31 CCP genes, normalized to 15 housekeeper genes. Recurrence was defined as two prostate-specific antigen levels ≥ 0.2 ng/mL or any salvage treatment. Associations between CCP score and recurrence were examined, with adjustment for clinical and pathologic variables using Cox proportional hazards regression and partial likelihood ratio tests. The CCP score was assessed for independent prognostic utility beyond a standard postoperative risk assessment (Cancer of the Prostate Risk Assessment post-Surgical [CAPRA-S] score), and a score combining CAPRA-S and CCP was validated. Results Eighty-two (19.9%) of 413 men experienced recurrence. The hazard ratio (HR) for each unit increase in CCP score (range, −1.62 to 2.16) was 2.1 (95% CI, 1.6 to 2.9); with adjustment for CAPRA-S, the HR was 1.7 (95% CI, 1.3 to 2.4). The score was able to substratify patients with low clinical risk as defined by CAPRA-S ≤ 2 (HR, 2.3; 95% CI, 1.4 to 3.7). Combining the CCP and CAPRA-S improved the concordance index for both the overall cohort and low-risk subset; the combined CAPRA-S + CCP score consistently predicted outcomes across the range of clinical risk. This combined score outperformed both individual scores on decision curve analysis. Conclusion The CCP score was validated to have significant prognostic accuracy after controlling for all available clinical and pathologic data. The score may improve accuracy of risk stratification for men with clinically localized prostate cancer, including those with low-risk disease.

1955-P: GLP-1R Activation Attenuates Prostate Cancer Growth via Inhibiting Cell Cycle Progression

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1955-P
Author(s):  
TORU SHIGEOKA ◽  
TAKASHI NOMIYAMA ◽  
TAKAKO KAWANAMI ◽  
YURIKO HAMAGUCHI ◽  
TOMOKO TANAKA ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cancer Growth ◽  
Cycle Progression

scholarly journals Pre-treatment risk stratification of prostate cancer patients:A critical review

2012 ◽  
Vol 6 (2) ◽  
Author(s):  
George Rodrigues ◽  
Padraig Warde ◽  
Tom Pickles ◽  
Juanita Crook ◽  
Michael Brundage ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factors ◽  
Cancer Risk ◽  
Risk Stratification ◽  
Gleason Score ◽  
Critical Review ◽  
Specific Antigen ◽  
Prostate Cancer Risk ◽  
Original Research ◽  
Pre Treatment

Introduction:  The use of accepted prostate cancer risk stratification groups based on prostate-specific antigen, T stage and Gleason score assists in therapeutic treatment decision-making, clinical trial design and outcome reporting. The utility of integrating novel prognostic factors into an updated risk stratification schema is an area of current debate. The purpose of this work is to critically review the available literature on novel pre-treatment prognostic factors and alternative prostate cancer risk stratification schema to assess the feasibility and need for changes to existing risk stratification systems. Methods:  A systematic literature search was conducted to identify original research publications and review articles on prognostic factors and risk stratification in prostate cancer. Search terms included risk stratification, risk assessment, prostate cancer or neoplasms, and prognostic factors. Abstracted information was assessed to draw conclusions regarding the potential utility of changes to existing risk stratification schema. Results:  The critical review identified three specific clinically relevant potential changes to the most commonly used three-group risk stratification system: (1) the creation of a very-low risk category; (2) the splitting of intermediate-risk into a low- and highintermediate risk groups; and (3) the clarification of the interface between intermediate- and high-risk disease. Novel pathological factors regarding high-grade cancer, subtypes of Gleason score 7 and percentage biopsy cores positive were also identified as potentially important risk-stratification factors. Conclusions:  Multiple studies of prognostic factors have been performed to create currently utilized prostate cancer risk stratification systems. We propose potential changes to existing systems.

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