Ochsner Clinic, Department of Urology, New Orleans, LA, USA.
Queensland School of Medicine, Queensland, Australia.
Prostate Cancer Prostatic Dis. 2020 Mar;23(1):102-107. doi: 10.1038/s41391-019-0159-9. Epub 2019 Jun 27.
Accurate risk stratification can help guide appropriate treatment decisions in men with localized prostate cancer. Here, we evaluated the independent ability of the molecular cell cycle progression (CCP) score and the combined cell-cycle clinical risk (CCR) score to predict 10-year risk of progression to metastatic disease in a large, pooled analysis of men with definitively treated prostate cancer.
The pooled analysis included 1,062 patients from four institutions (Martini Clinic, Durham VA Medical Center, Intermountain Healthcare, Ochsner Clinic) treated definitively for localized prostate cancer by either radical prostatectomy or radiotherapy (brachytherapy or external beam radiotherapy ± hormone therapy). The CCP score was determined using the RNA expression of 46 genes from archival formalin-fixed paraffin-embedded biopsy tissue. The CCR score was calculated using a predefined linear combination of the CCP score and the Cancer of the Prostate Risk Assessment (CAPRA) score. The scores were evaluated for association with 10-year risk of metastatic disease following definitive therapy after adjusting for other clinical variables.
The CCP score was strongly associated with 10-year risk of metastatic disease in multivariable analysis [Hazard Ratio per unit score = 2.21; 95% confidence interval (CI) 1.64, 2.98; p = 1.9 × 10] after adjusting for CAPRA, treatment type, and cohort. CCR was also highly prognostic (Hazard Ratio per unit score = 4.00; 95% CI 2.95, 5.42; p = 6.3 × 10). There was no evidence of interaction between CCP or CCR and cohort (p = 0.79 and p = 0.86, respectively) or treatment type (p = 0.55 and p = 0.78, respectively). Observed patient CCR-based predicted risks for metastatic disease by 10 years ranged from 0.1 to 99.4%, (IQR 0.7%, 4.6%).
Both CCP and CCR scores provided independent prognostic information for predicting progression to metastatic disease after both surgery and radiation. These results further demonstrate their potential use as a risk stratification tool in patients with newly-diagnosed prostate cancer.
准确的风险分层有助于指导局限性前列腺癌患者的适当治疗决策。在这里，我们评估了分子细胞周期进展（CCP）评分和联合细胞周期临床风险（CCR）评分在一项大型、局限性前列腺癌患者荟萃分析中的独立能力，以预测 10 年转移疾病进展风险。
该荟萃分析包括来自四个机构（马蒂尼诊所、达勒姆退伍军人事务医疗中心、山间医疗保健公司、奥克斯纳诊所）的 1062 名患者，他们通过根治性前列腺切除术或放疗（近距离放疗或外照射放疗+激素治疗）治疗局限性前列腺癌。CCP 评分是通过对存档福尔马林固定石蜡包埋活检组织中的 46 个基因的 RNA 表达进行测定。CCR 评分是通过预先定义的 CCP 评分和前列腺癌风险评估（CAPRA）评分的线性组合计算得出。在调整其他临床变量后，评估这些评分与根治性治疗后 10 年转移疾病风险的相关性。
多变量分析显示，CCP 评分与 10 年转移疾病风险密切相关[每单位评分的危险比=2.21；95%置信区间（CI）1.64，2.98；p=1.9×10]，调整 CAPRA、治疗类型和队列后。CCR 也具有高度预后价值（每单位评分的危险比=4.00；95%CI 2.95，5.42；p=6.3×10）。CCP 或 CCR 与队列（p=0.79 和 p=0.86）或治疗类型（p=0.55 和 p=0.78）之间没有证据表明存在交互作用。观察到的患者基于 CCR 的 10 年转移疾病预测风险范围为 0.1%至 99.4%（IQR 0.7%，4.6%）。
CCP 和 CCR 评分均为手术和放疗后预测转移疾病进展的独立预后因素。这些结果进一步证明了它们在新诊断前列腺癌患者中作为风险分层工具的潜在用途。
