Comparison of the Prognostic Utility of the Cell Cycle Progression Score for Predicting Clinical Outcomes in African American and Non-African American Men with Localized Prostate Cancer

Abstract

Background: Better prostate cancer risk stratification is necessary to inform medical management, especially for African American (AA) men, for whom outcomes are particularly uncertain. Objective: To evaluate the utility of[ 5 _ T D $ D I F F ] both a cell cycle progression (CCP) score and a clinical cell-cycle risk (CCR) score to predict clinical outcomes in a large cohort of men with prostate cancer highly enriched in an AA patient population. Design, setting, and participants: Patients were diagnosed with clinically localized adenocarcinoma of the prostate and treated at The Ochsner Clinic (New Orleans, LA, USA) from January 2006 to December 2011. [ 6 _ T D $ D I F F ] CCP[ 3 _ T D $ D I F F ] scores were derived from archival formalin-fixed, paraffin-embedded biopsy tissue. CCR scores were calculated as the combination of molecular (CCP score) and clinical (Cancer of the Prostate Risk Assessment [CAPRA] score) components. Intervention: Active treatment (radical prostatectomy, radiation therapy alone, or radiation and hormone therapy) or watchful waiting. Outcome measurements and statistical analysis: The primary outcome was progression to metastatic disease. Association with outcomes was evaluated via Cox proportional hazards survival analysis and likelihood ratio tests. Results and limitations: The final cohort included 767 men, of whom 281 (36.6%) were AA. After accounting for ancestry, treatment, and CAPRA in multivariable analysis, the CCP score remained a significant predictor of metastatic disease (hazard ratio [HR] 2.04; p < 0.001)[ 7 _ T D $ D I F F ] , and there was no interaction with ancestry (p = 0.20) or treatment (p = 0.09). The CCR score was highly prognostic (HR 3.86; p < 0.001), and as with the CCP score, there was no interaction with ancestry (p = 0.24) or treatment (p = 0.32). Limitations include the retrospective study design and the use of self-reported ancestry information. Conclusions: A CCR score provided significant prognostic information regardless of ancestry. The findings demonstrate that AA men in this study cohort appear to have similar prostate cancer outcomes to non-AA patients after accounting for all available molecular and clinicopathologic variables.

Cell‐cycle risk score more accurately determines the risk for metastases and death in prostatectomy patients compared with clinical features alone

“…The hope was that molecular markers would add significant prognostic information beyond what was provided by clinicopathologic variables. Indeed, the ability of the CCP score to improve risk discrimination by itself or in combination with other factors has been well documented 9,11–15,22–24 . It has also been included in several professional guidelines (i.e., ASCO, NCCN) as an important tool for improving risk discrimination in patients with newly diagnosed localized disease 25–27 .…”

“…Indeed, the ability of the CCP score to improve risk discrimination by itself or in combination with other factors has been well documented. 9,[11][12][13][14][15][22][23][24] It has also been included in several professional guidelines (i.e., ASCO, NCCN) as an important tool for improving risk discrimination in patients with newly diagnosed localized disease. [25][26][27] We previously evaluated the CCP in the present study cohort, and with a median of 9.4 years of follow-up were able to show that the CCP score was prognostic of BCR.…”

“…When CCP gene expression was added to other clinicopathologic features, the combined model was a significantly better predictor of recurrence than clinicopathologic features alone 9 . This observation has subsequently been validated in many independent cohorts, 10–14 including in patients following radical prostatectomy 15,16 . In fact, Cooperberg et al 15 validated a predefined model (clinical cell‐cycle risk [CCR] score) that combines the CCP score and the postsurgical Cancer of the Prostate Cancer Risk Assessment (CAPRA‐S) for determining patient prognosis post‐prostatectomy 15 .…”

The Clinical Applications of Tissue Biomarkers in Prostate Cancer

“…Risk stratification is often more challenging in certain cohorts such as African American men, for whom non-clinical social determinants of health may influence receipt of treatment and ultimate oncologic outcomes [26]. In a retrospective cohort of 767 men of whom 281 (37%) were African American, the CCP score was a significant predictor of metastatic disease on multivariable analysis including clinical parameters; however, there was no interaction with ancestry or treatment [27]. Of note, ancestry was self-reported, and this may have introduced error thereby limiting the generalizability of the conclusions, as population-based genetic heterogeneity was not addressed.…”

Analysis of the prognostic utility of the cell cycle progression (CCP) score generated from needle biopsy in men treated with definitive therapy

“…The Intermountain Healthcare cohort was treated with RP at Intermountain Healthcare (Salt Lake City, UT) between 1997 and 2004. The Ochsner Clinic cohort has also been previously described in detail and included a consecutive series of men treated at the Ochsner Clinic (New Orleans, LA) between 2006 and 2011 [15]. Institutional review board approval was obtained at all study sites.…”