Background

There is a critical need for improved prognostic discrimination in patients with renal cell carcinoma (RCC) given the increasing awareness that some patients may be managed with active surveillance, while others with higher-risk disease might benefit from adjuvant therapy following surgery.

Objective

To determine whether a multigene proliferation signature predicts long-term oncologic outcomes in surgically resected RCC.

Design, setting, and participants

The cell cycle proliferation (CCP) score was determined after radical nephrectomy for localized clear cell, papillary, or chromophobe RCC in 565 patients.

Outcome measurements and statistical analysis

The primary end point was disease-specific mortality (DSM), and disease recurrence was a secondary end point. Association with outcomes was evaluated by Cox proportional hazards survival analysis. The CCP score was compared with the Karakiewicz nomogram, and a composite (R-CCP) score was developed.

Results and limitations

A total of 68 patients (12%) recurred and 32 (6%) died of disease within 5 yr of nephrectomy. The CCP score was an independent predictor of recurrence (hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.07–2.09) and DSM (HR 2.49, 95% CI 1.53–4.04) after adjusting for clinical variables using the baseline nomogram. The composite R-CCP score gave a Harrell's concordance index of 0.87 and stratified patients into low- (n = 338) and high-risk (n = 202) categories with 99% and 84% cancer-specific survival probabilities, respectively (p < 0.001).

Conclusions

The CCP score is a significant, independent predictor of long-term oncologic outcomes in patients who have undergone nephrectomy for RCC. Combining the molecular classifier with baseline clinical variables allows for accurate, patient-specific risk assessment for use in guiding clinical management.

Patient summary

In this study, we sought to understand how well gene expression information from individual kidney tumors can predict cancer recurrence and death following surgical removal. We found that the combination of the gene expression test and clinical characteristics provides an accurate prognostic assessment to help inform clinical decisions.

中文翻译：

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基于细胞周期增殖的多基因签名改善了肾细胞癌根治性肾切除术在5年内死亡率的预测

背景

迫切需要改善肾细胞癌（RCC）患者的预后判断力，因为人们越来越意识到某些患者可以接受主动监护，而其他高危疾病患者则可能会在术后接受辅助治疗。

客观的

为了确定多基因增殖信号是否可预测手术切除的RCC的长期肿瘤学结局。

设计，设置和参与者

在根治性肾切除术后确定565名患者的局部透明细胞，乳头状或生色性RCC的细胞周期增殖（CCP）评分。

成果测量和统计分析

主要终点是疾病特异性死亡率（DSM），疾病复发是次要终点。与结果的关联性通过Cox比例风险生存分析进行评估。将CCP得分与Karakiewicz诺模图进行比较，并开发出综合（R-CCP）得分。

结果与局限性

在肾切除术的5年内，共有68例患者（12％）复发，32例（6％）死于疾病。在使用基线列线图调整临床变量后，CCP评分是复发率（危险比[HR] 1.50，95％置信区间[CI] 1.07–2.09）和DSM（HR 2.49，95％CI 1.53–4.04）的独立预测指标。 。综合R-CCP评分得出的Harrell一致性指数为0.87，并将患者分为低（n  = 338）和高风险（n  = 202）类别，分别具有99％和84％的癌症特异性生存率（p  < 0.001）。

结论

对于接受RCC肾切除术的患者，CCP评分是长期肿瘤结局的重要独立预测指标。将分子分类器与基线临床变量结合使用，可以进行准确的，针对特定患者的风险评估，以指导临床管理。

病人总结

在这项研究中，我们试图了解来自个体肾脏肿瘤的基因表达信息如何能够很好地预测手术切除后的癌症复发和死亡。我们发现基因表达测试和临床特征的结合提供了准确的预后评估，有助于为临床决策提供依据。