Discipline of Genetics, Faculty of Medicine, Memorial University, 300 Prince Philip Drive, New Medical Education Building, St. John's, NL, A1B 3V6, Canada.
Discipline of Surgery, Faculty of Medicine, Memorial University, St. John's, NL, Canada.
BMC Med. 2019 Jul 29;17(1):150. doi: 10.1186/s12916-019-1379-5.
Colorectal cancer is the third most common cancer in the world. In this study, we assessed the long-term survival characteristics and prognostic associations and potential time-varying effects of clinico-demographic variables and two molecular markers (microsatellite instability (MSI) and BRAF Val600Glu mutation) in a population-based patient cohort followed up to ~ 19 years.
The patient cohort included 738 incident cases diagnosed between 1999 and 2003. Cox models were used to analyze the association between the variables and a set of survival outcome measures (overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), metastasis-free survival (MFS), recurrence/metastasis-free survival (RMFS), and event-free survival (EFS)). Cox proportional hazard (PH) assumption was tested for all variables, and Cox models with time-varying effects were used if any departure from the PH assumption was detected.
During the follow-up, ~ 61% patients died from any cause, ~ 26% died from colorectal cancer, and ~ 10% and ~ 20% experienced recurrences and distant metastases, respectively. Stage IV disease and post-diagnostic recurrence or metastasis were strongly linked to risk of death from colorectal cancer. If a patient had survived the first 6 years without any disease-related event (i.e., recurrence, metastasis, or death from colorectal cancer), their risks became very minimal after this time period. Distinct sets of markers were associated with different outcome measures. In some cases, the effects by variables were constant throughout the follow-up. For example, MSI-high tumor phenotype and older age at diagnosis predicted longer MFS times consistently over the follow-up. However, in some other cases, the effects of the variables varied with time. For example, adjuvant radiotherapy treatment was associated with increased risk of metastasis in patients who received this treatment after 5.5 years post-diagnosis, but not before that.
This study describes the long-term survival characteristics of a prospective cohort of colorectal cancer patients, relationships between baseline variables and a detailed set of patient outcomes over a long time, and time-varying effects of a group of variables. The results presented advance our understanding of the long-term prognostic characteristics in colorectal cancer and are expected to inspire future studies and clinical care strategies.
结直肠癌是世界上第三大常见癌症。在这项研究中，我们评估了临床人口统计学变量和两个分子标志物（微卫星不稳定性（MSI）和 BRAF Val600Glu 突变）在基于人群的患者队列中的长期生存特征和预后相关性以及潜在的时变效应，这些患者队列随访时间长达~19 年。
患者队列包括 1999 年至 2003 年间诊断的 738 例新发病例。使用 Cox 模型分析变量与一组生存结局测量（总生存（OS）、疾病特异性生存（DSS）、无复发生存（RFS）、无转移生存（MFS）、无复发/转移生存（RMFS）和无事件生存（EFS））之间的关联。对所有变量进行 Cox 比例风险（PH）假设检验，如果检测到任何偏离 PH 假设的情况，则使用具有时变效应的 Cox 模型。
在随访期间，约 61%的患者因任何原因死亡，约 26%的患者死于结直肠癌，约 10%和 20%的患者分别经历复发和远处转移。IV 期疾病和诊断后复发或转移与结直肠癌死亡风险密切相关。如果患者在无疾病相关事件（即复发、转移或死于结直肠癌）的情况下存活了前 6 年，那么在此时间后，他们的风险就非常低。不同的标志物与不同的结局测量相关。在某些情况下，变量的影响在整个随访期间是恒定的。例如，MSI 高肿瘤表型和诊断时年龄较大一致预测 MFS 时间更长。然而，在其他情况下，变量的影响随时间而变化。例如，辅助放疗治疗与诊断后 5.5 年后接受此治疗的患者的转移风险增加相关，但在此之前则不然。
本研究描述了前瞻性结直肠癌患者队列的长期生存特征、基线变量与长期详细患者结局之间的关系，以及一组变量的时变效应。所呈现的结果增进了我们对结直肠癌长期预后特征的理解，并有望激发未来的研究和临床护理策略。
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