Metastatic colorectal cancer (mCRC) remains a lethal disease. Survival, however, is increasing due to a growing number of treatment options. Yet due to the number of prognostic factors and their interactions, prediction of mortality is difficult. The aim of this study is to provide a clinical model supporting prognostication of mCRC mortality in daily practice. Data from 1104 patients with mCRC in three prospective cancer datasets were used to construct and validate Cox models. Input factors for stepwise backward method variable selection were sex, RAS/BRAF-status, microsatellite status, treatment type (no treatment, systemic treatment with or without resection of metastasis), tumor load, location of primary tumor, metastatic patterns and synchronous or metachronous disease. The final prognostic model for prediction of survival at two and 3 years was validated via bootstrapping to obtain calibration and discrimination C-indices and dynamic time dependent AUC. Age, sidedness, number of organs with metastases, lung as only site of metastasis, BRAF mutation status and treatment type were selected for the model. Treatment type had the most prominent influence on survival (resection of metastasis HR 0.26, CI 0.21–0.32; any treatment vs no treatment HR 0.31, CI 0.21–0.32), followed by BRAF mutational status (HR 2.58, CI 1.19–1.59). Validation showed high accuracy with C-indices of 72.2 and 71.4%, and dynamic time dependent AUC’s of 76.7 ± 1.53% (both at 2 or 3 years), respectively. The mCRC mortality prediction model is well calibrated and internally valid. It has the potential to support both, clinical prognostication for treatment decisions and patient communication.

中文翻译：

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现实生活人群中转移性结直肠癌死亡率的预测：多中心探索性分析

转移性结直肠癌（mCRC）仍然是一种致命疾病。然而，由于治疗选择的增加，生存率正在增加。然而，由于预后因素的数量及其相互作用，预测死亡率很困难。本研究的目的是提供一个临床模型，支持日常实践中 mCRC 死亡率的预测。使用来自三个前瞻性癌症数据集中 1104 名 mCRC 患者的数据来构建和验证 Cox 模型。逐步向后方法变量选择的输入因素是性别、RAS/BRAF状态、微卫星状态、治疗类型（不治疗、全身治疗伴或不伴切除转移）、肿瘤负荷、原发肿瘤位置、转移模式和同步或异时疾病。通过自举法验证了预测 2 年和 3 年生存率的最终预后模型，以获得校准和区分 C 指数以及动态时间依赖性 AUC。模型选择年龄、单侧性、转移器官数量、肺作为唯一转移部位、BRAF突变状态和治疗类型。治疗类型对生存的影响最为显着（转移灶切除 HR 0.26，CI 0.21–0.32；任何治疗与不治疗 HR 0.31，CI 0.21–0.32），其次是 BRAF 突变状态（HR 2.58，CI 1.19–1.59）。验证显示准确性较高，C 指数分别为 72.2 和 71.4%，动态时间依赖性 AUC 为 76.7 ± 1.53%（均为 2 年或 3 年）。mCRC 死亡率预测模型经过良好校准且内部有效。它有可能支持治疗决策的临床预测和患者沟通。