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), χ2=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.

Clinical Utility of Biomarkers in Localized Prostate Cancer

“…The association between CCP score derived from biopsy specimens and adverse outcomes after treatment was also seen in a radical prostatectomy cohort [33]. In the pre-treatment setting, the test provides a prediction of PCSM in untreated patients, a probability derived from an observational cohort of men undergoing conservative management [34].…”

New developments in prostate cancer biomarkers

“…In this population, low CCP scores were associated with an approximate 20% risk of prostate cancer death at 10 years whereas those with scores greater than 2 had a rate more than 70%. In another similarly diagnosed and managed cohort of 761 men, the estimated 10-year rates of prostate cancer mortality were 59%, 36%, 15%, and 7% for CCP scores of more than 2, more than 1 to 2 or less, more than 0 to 1 or less, and 0 or less, respectively [25]. Although none of these studies address specifically the question of who to start on active surveillance, the supposition is that if you are at a low risk of dying of prostate cancer without treatment for 10 years, a program of close observation may be reasonable.…”

What Can Be Expected from Prostate Cancer Biomarkers A Clinical Perspective

“…After observing an encouraging outcome of combining CCP with clinicopathological markers in this and similar studies [62,63], previously mentioned team validated clinical-cell-cycle-risk score in the group of 585 men. Clinical-cell-cycle-risk score was developed as a linear combination of the CCP score and clinical variables included in the CAPRA score [64]. Initial experience suggests that CCP might be even more accurate when combined with 3D-documented biopsy-mapping technology [65].…”