ASCO Abstract
Saturday June 4, 2:00 PM to 6:00 PM
Prognostic value of a 46-gene cell cycle progression (CCP) RNA signature for prostate cancer death in a conservatively managed watchful waiting needle biopsy cohort
Sub-category:
Prostate Cancer
Category:
Genitourinary Cancer
Meeting:
2011 ASCO Annual Meeting
Abstract No:
4542
Citation:
J Clin Oncol 29: 2011 (suppl; abstr 4542)
Author(s): J. M. Cuzick, G. Fisher, D. Berney, D. Mesher, H. Møller, J. E. Reid, A. Gutin, J. S. Lanchbury, S. Stone; EMS, Wolfson Institute of Preventive Medicine, London, United Kingdom; Wolfson Institute of Preventive Medicine, London, United Kingdom; Department of Histopathology, St. Bartholomew's Hospital, London, United Kingdom; King's College London, Thames Cancer Registry, London, United Kingdom; Myriad Genetics Inc., Salt Lake City, UT
Abstract Disclosures
Abstract:
Background: The natural history of newly diagnosed prostate cancer is highly variable and difficult to predict accurately. Improved tools are needed to more appropriately match treatment to a patient’s risk of progression. We previously showed that a 46 gene cell cycle progression (CCP) RNA signature is a robust predictor of biochemical recurrence after radical prostatectomy and of prostate cancer-specific death in a conservatively managed cohort diagnosed by transurethral resection of the prostate. However, the greatest need exists for predicting outcome in patients diagnosed by needle biopsy. Here we report the utility of the CCP score obtained from a needle biopsy in a cohort of conservatively managed watchful waiting patients.
Methods: mRNA was extracted from paraffin embedded needle biopsies from UK men diagnosed with clinically localized prostate cancer between 1990 and 1996. RNA levels of 46 genes were determined and a mean composite score calculated (CCP score) for each patient. Clinical variables consisted of centrally re-reviewed Gleason score, baseline PSA, age, clinical stage, and extent of disease (proportion of positive cores). The primary endpoint was death from prostate cancer after a mean follow up of 9.8 yrs.
Results: In univariate analysis (n=352), The hazard ratio (HR) for death for prostate cancer was 2.67 (95% CI (1.99,3.58), P =10-10) for a change from the 25th to 75th percentile of the CCP score. In a multivariate analysis (n=333) which included Gleason and PSA, CCP dominated (HR for change from 25th to 75th percentile = 2.07, 95% CI(1.50, 2.85) ?2 = 20.8, , P = 5 x 10-6) with only Gleason score providing a significant, additional contribution (?2 = 15, 1df, P = 0.0001) and baseline PSA was nonsignificant (?2 = 1.6).
Conclusions: For patients managed by active surveillance, the CCP score is the strongest predictor of cancer death outcome yet described. The additional independent prognostic information offered by this RNA assay may be valuable in the management of prostate cancer.
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