Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort

Abstract

Background:The natural history of prostate cancer is highly variable and it is difficult to predict. We showed previously that a cell cycle progression (CCP) score was a robust predictor of outcome in a conservatively managed cohort diagnosed by transurethral resection of the prostate. A greater need is to predict outcome in patients diagnosed by needle biopsy.Methods:Total RNA was extracted from paraffin specimens. A CCP score was calculated from expression levels of 31 genes. Clinical variables consisted of centrally re-reviewed Gleason score, baseline prostate-specific antigen level, age, clinical stage, and extent of disease. The primary endpoint was death from prostate cancer.Results:In univariate analysis (n=349), the hazard ratio (HR) for death from prostate cancer was 2.02 (95% CI (1.62, 2.53), P<10−9) for a one-unit increase in CCP score. The CCP score was only weakly correlated with standard prognostic factors and in a multivariate analysis, CCP score dominated (HR for one-unit increase=1.65, 95% CI (1.31, 2.09), P=3 × 10−5), with Gleason score (P=5 × 10−4) and prostate-specific antigen (PSA) (P=0.017) providing significant additional contributions.Conclusion:For conservatively managed patients, the CCP score is the strongest independent predictor of cancer death outcome yet described and may prove valuable in managing clinically localised prostate cancer.

A 17-gene Assay to Predict Prostate Cancer Aggressiveness in the Context of Gleason Grade Heterogeneity, Tumor Multifocality, and Biopsy Undersampling

“…Although multiple prior studies have related genomic markers to PCa clinical outcomes [17][18][19][20]51], the development of GPS specifically addresses the impact of tumor sampling in predicting aggressive PCa and included central pathology review and a large number of clinical recurrence events providing robust statistical power. By adding independent molecular information to established risk parameters, the GPS improves risk stratification at time of diagnosis and may favorably shift the balance of risks and benefits for men who are candidates for AS and facing challenging decisions regarding optimal management of localized PCa.…”

“…Although many groups have demonstrated the potential of gene expression analysis to predict outcome in localized PCa [17][18][19][20], frequent genetic differences between regions of individual tumors and limited tumor sampling by needle biopsy pose challenges to molecular-based assays in PCa [21,22]. With these challenges in mind, we conducted two studies to identify genes for which expression in both prostatectomy and biopsy tissues consistently correlates with tumor aggressiveness regardless of multifocality, heterogeneity, or technical challenges associated with limited tumor obtained through biopsy.…”

Active Surveillance of Prostate Cancer: Use, Outcomes, Imaging, and Diagnostic Tools

“…CCP scores were retrospectively assessed for 349 men conservatively managed within the Transatlantic Prostate Group. 71 Ten-year rates of prostate cancer death associated with CCP score groups <0, 0-1, 1-2, 2-3, and >3 were 19.3%, 19.8%, 21.1%, 48.2%, and 74.9%, respectively. In multivariable analysis, the CCP score (HR for one-unit change: 1.65; 95% CI, 1.31-2.09), Gleason score >7 (HR 1.90; 95% CI, 1.18-3.07), and PSA (HR 1.37; 95% CI, 1.05-1.79) significantly predicted prostate cancer death.…”

Active surveillance for men with low‐risk prostate cancer

“…A recent study reported that the measurement of the expression level of 31 genes involved with CCP from biopsy tissue provides the strongest independent predictor of cancer death outcome yet described ( Figure 1). 8 …”