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

J. Cuzick*, S. Stone, G. Fisher, Z. H. Yang, B. V. North, D. M. Berney, L. Beltran, David Greenberg, H. Møller, J. E. Reid, A. Gutin, J. S. Lanchbury, M. Brawer, P. Scardino

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

93 Citations (Scopus)

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), χ 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.

Original languageEnglish
Pages (from-to)382-389
Number of pages8
JournalBritish Journal of Cancer
Volume113
Issue number3
DOIs
Publication statusPublished - 28 Jul 2015

Bibliographical note

Funding Information:
We thank investigators and staff in the cancer registries and participating hospitals (Supplementary Appendix) for their support. We thank also Dr Kathryn Kolquist (Myriad Genetics) for pathology support. We gratefully acknowledge support from Cancer Research UK, ORCHID, National Institutes of Health (SPORE), the Koch Foundation and Myriad Genetics. This work was supported by Cancer Research UK, Queen Mary University of London, Orchid Appeal, US National Institutes of Health, and Koch Foundation.

Publisher Copyright:
© 2015 Cancer Research UK. All rights reserved.

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