Dataset Information

Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort.

ABSTRACT:

Background

The natural history of prostate cancer is highly variable and difficult to predict accurately. Better markers are needed to guide management and avoid unnecessary treatment. In this study, we validate the prognostic value of a cell cycle progression score (CCP score) independently and in a prespecified linear combination with standard clinical variables, that is, a clinical-cell-cycle-risk (CCR) score.

Methods

Paraffin sections from 761 men with clinically localized prostate cancer diagnosed by needle biopsy and managed conservatively in the United Kingdom, mostly between 2000 and 2003. The primary end point was prostate cancer death. Clinical variables consisted of centrally reviewed Gleason score, baseline PSA level, age, clinical stage, and extent of disease; these were combined into a single predefined risk assessment (CAPRA) score. Full data were available for 585 men who formed a fully independent validation cohort.

Results

In univariate analysis, the CCP score hazard ratio was 2.08 (95% CI (1.76, 2.46), P<10(-13)) for one unit change of the score. In multivariate analysis including CAPRA, the CCP score hazard ratio was 1.76 (95% CI (1.44, 2.14), P<10(-6)). The predefined CCR score was highly predictive, hazard ratio 2.17 (95% CI (1.83, 2.57), ?(2)=89.0, P<10(-20)) and captured virtually all available prognostic information.

Conclusions

The CCP score provides significant pretreatment prognostic information that cannot be provided by clinical variables and is useful for determining which patients can be safely managed conservatively, avoiding radical treatment.

SUBMITTER: Cuzick J

PROVIDER: S-EPMC4522632 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Publications

Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort.

Cuzick J J Stone S S Fisher G G Yang Z H ZH North B V BV Berney D M DM Beltran L L Greenberg D D Møller H H Reid J E JE Gutin A A Lanchbury J S JS Brawer M M Scardino P P

British journal of cancer 20150623 3

<h4>Background</h4>The natural history of prostate cancer is highly variable and difficult to predict accurately. Better markers are needed to guide management and avoid unnecessary treatment. In this study, we validate the prognostic value of a cell cycle progression score (CCP score) independently and in a prespecified linear combination with standard clinical variables, that is, a clinical-cell-cycle-risk (CCR) score.<h4>Methods</h4>Paraffin sections from 761 men with clinically localized pro ...[more]

PMID: 26103570

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Project description:Standard clinical parameters fail to accurately differentiate indolent from aggressive prostate cancer. Our previous studies showed that immunohistochemical testing for Ki-67 improved prediction of prostate cancer death in a previous cohort of conservatively treated clinically localized prostate cancer. However there is a need for validation of usage with whole biopsy sections rather than tissue micro-arrays for use in routine diagnostics. Prostate cancer biopsy cases were identified in the UK, between 1990 and 2003, treated conservatively. Tumor extent and prostate-specific antigen (PSA) serum measurements were available. Biopsy cases were centrally reviewed by three uropathologists and Gleason conformed to contemporary ISUP 2014 criteria. Follow-up was through cancer registries up until 2012. Deaths were divided into those from prostate cancer and those from other causes. The percentage of Ki-67 in tumor cells was evaluated by immunohistochemistry on whole biopsy sections and was available for 756 patients. This percentage was used in analysis of cancer specific survival using a Cox proportional hazards model. In univariate analysis, the interquartile hazard ratio (HR) (95% confidence intervals) for continuous Ki-67 was 1.68 (1.49, 1.89), χ12 = 47.975, P < 0.001. In grade groups 1 and 2, continuous Ki-67 was a statistically significant predictor of time to death from prostate cancer, HR (95% CI) = 1.97 (1.34, 2.88), χ12 = 9.017, p = 0.003. In multivariate analysis, continuous Ki-67 added significant predictive information to that provided by grade groups, extent of disease and serum PSA, HR (95% CI) = 1.34 (1.16, 1.54), Δχ12 = 13.703, P < 0.001. We now advocate the introduction of Ki-67 as a viable and practicable prognostic biomarker in clinical practice. The association of Ki-67 with mortality was highest in grade groups 1 and 2, showing that Ki-67 can be used as a routine biomarker in patients being considered for active surveillance.

Project description:BackgroundAccurate risk stratification can help guide appropriate treatment decisions in men with localized prostate cancer. Here, we evaluated the independent ability of the molecular cell cycle progression (CCP) score and the combined cell-cycle clinical risk (CCR) score to predict 10-year risk of progression to metastatic disease in a large, pooled analysis of men with definitively treated prostate cancer.MethodsThe pooled analysis included 1,062 patients from four institutions (Martini Clinic, Durham VA Medical Center, Intermountain Healthcare, Ochsner Clinic) treated definitively for localized prostate cancer by either radical prostatectomy or radiotherapy (brachytherapy or external beam radiotherapy ± hormone therapy). The CCP score was determined using the RNA expression of 46 genes from archival formalin-fixed paraffin-embedded biopsy tissue. The CCR score was calculated using a predefined linear combination of the CCP score and the Cancer of the Prostate Risk Assessment (CAPRA) score. The scores were evaluated for association with 10-year risk of metastatic disease following definitive therapy after adjusting for other clinical variables.ResultsThe CCP score was strongly associated with 10-year risk of metastatic disease in multivariable analysis [Hazard Ratio per unit score = 2.21; 95% confidence interval (CI) 1.64, 2.98; p = 1.9 × 10-6] after adjusting for CAPRA, treatment type, and cohort. CCR was also highly prognostic (Hazard Ratio per unit score = 4.00; 95% CI 2.95, 5.42; p = 6.3 × 10-21). There was no evidence of interaction between CCP or CCR and cohort (p = 0.79 and p = 0.86, respectively) or treatment type (p = 0.55 and p = 0.78, respectively). Observed patient CCR-based predicted risks for metastatic disease by 10 years ranged from 0.1 to 99.4%, (IQR 0.7%, 4.6%).ConclusionsBoth CCP and CCR scores provided independent prognostic information for predicting progression to metastatic disease after both surgery and radiation. These results further demonstrate their potential use as a risk stratification tool in patients with newly-diagnosed prostate cancer.

Dataset Information

Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort.

Background

Methods

Results

Conclusions

Publications

Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort.

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