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.

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.47 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 47-47 ◽

Cited By ~ 5

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.

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

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.127 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 127-127 ◽

Cited By ~ 2

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]

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