全球结直肠癌疾病自然史转归参数的Meta分析

Natural history of colorectal cancer:a Meta-analysis on global prospective cohort studies

目的汇总全球结直肠癌疾病自然史随访研究,了解结直肠癌疾病自然史转归参数可获得性及1年转归概率。方法基于PubMed、Embase、Cochrane和中国生物医学文献数据库(CBM)开展文献检索(截至2017年3月);摘录研究基本信息,确认结局健康状态分类体系和各健康状态人群转归参数可获得性,对研究数量>3篇的转归参数进行Meta分析和敏感性分析。使用1年转归概率(95%CI)表示结果大小,采用随机效应模型进行Meta分析、NOS量表进行文献质量评价。结果最终纳入29项队列研究,平均随访时间5.7年。研究多关注经典“腺瘤-癌”路径参数(28项),均报告了不同风险腺瘤转归参数(28项),部分同时报告不同大小腺瘤转归参数(6项)。健康人群(基线内镜结果阴性)可获得6组转归参数,对应研究数量、样本量及1年转归概率Meta结果分别为低风险腺瘤[16项,58 235,0.030(0.024~0.037)]和高风险腺瘤[17项,62 089,0.003(0.002~0.004)],到微小腺瘤[<5 mm,4项,1 277,0.021(0.013~0.029)]、小腺瘤[6~9 mm,4项,1 277,0.006(0.001~0.010)]和大腺瘤[≥10 mm,7项,3 531,0.002(0.000~0.003)],到癌症[19项,104 836,0.000 3(0.000 2~0.000 5)]。低风险腺瘤切除后人群可获得3组转归参数,研究数量、样本量及1年转归概率Meta结果依次为复发[9项,4 788,0.109(0.062~0.157)],到高风险腺瘤[10项,5 736,0.009(0.004~0.013)]和到癌症[12项,11 347,0.000 6(0.000 4~0.000 8)]。高风险腺瘤切除后人群转归可获得3组转归参数,研究数量、样本量及1年转归概率Meta结果依次为复发[12项,7 030,0.038(0.028~0.048)],到低风险腺瘤[8项,2 489,0.133(0.081~0.185)]和到癌症[14项,14 899,0.002(0.001~0.003)]。除健康到低风险腺瘤外,其他8组转归参数敏感性分析结果稳定。仅2项研究报告不同临床分期结直肠癌发病数据,2项关注锯齿状病变路径参数。结论全球可获得结直肠癌自然史转归参数的随访研究文献较为有限。相比“腺瘤-癌”路径,锯齿状病变路径的自然史转归参数可获得性更有限。研究结果为全球以基线内镜结果为发病风险依据的结直肠癌筛查人群监测策略提供高质量证据;也为我国人群特异性结直肠癌干预模型优化提供数据支持。

Objective To acknowledge the availability and rates of annual transition of outcomes during the progression and regression stages of colorectal cancer (CRC) and related diseases, by pooling global follow-up studies on the natural history of CRC. Methods Till March, 2017, data was collected through systematic literature review over multiple databases, including PubMed, Embase, Cochrane and Chinese Biology Medicine (CBM) disc. Information regarding the characteristics, classification system of health states, related outcomes and incidence rates on CRC or high-risk adenoma for the surveillance cohorts of the studies, were extracted and summarized. Both Meta and sensitivity analyses were performed on those outcomes if they appeared in more than 3 studies, using the random effects model. Annual transition rate with 95%CI was used to estimate each of the outcomes, Quality of the studies was assessed, using the Newcastle-Ottawa Scale. Results A total of 29 cohort studies were included, with the mean follow-up period as 5.7 years. All studies except one, focused on adenoma-carcinoma pathway and reported the outcome parameters of adenomas by different risk, and some reported the findings on different sizes (n=6) of adenomas. These cohorts were divided into three groups (normal status, with low-risk or high-risk adenoma) according to the status of baseline endoscopic pathologic findings. Their available outcome parameters, corresponding number of involved articles, aggregated sample size and pooled annual transition rates were presented. Six parameters were obtained in the normal cohorts, including those from normal to low-risk adenoma (16 articles, 58 235, 0.030:0.024-0.037), to high-risk adenoma (17 articles, 62 089, 0.003:0.002-0.004), to diminutive adenoma (< 5 mm, 4 articles, 1 277, 0.021:0.013-0.029), to small adenoma (6-9 mm, 4 articles, 1 277, 0.006:0.001-0.010), to large adenoma (≥ 10 mm, 7 articles, 3 531, 0.002:0.000-0.003) and to CRC (19 articles, 104 836, 0.000 3:0.000 2-0.000 5). Three parameters were obtained in low-risk adenoma in cohorts with polypectomy findings, including recurrence (9 articles, 4 788, 0.109:0.062-0.157) from low-risk adenoma after polypectomy to high-risk adenoma (10 articles, 5 736, 0.009:0.004-0.013) and to CRC (12 articles, 11 347, 0.000 6:0.000 4-0.000 8). Three parameters were obtained on high-risk adenoma from cohorts with polypectomy findings, including recurrence (12 articles, 7 030, 0.038:0.028-0.048) from high-risk adenoma after polypectomy to low-risk adenoma (8 articles, 2 489, 0.133:0.081-0.185) and CRC (14 articles, 14 899, 0.002:0.001-0.003). Except for normal to low-risk adenomas, results from the sensitivity analysis for the other parameters showed stable. Of the included studies, two presented incidence rates of CRC in different clinical stages and the another two were focusing on the parameters related to serrated pathway. Conclusions Globally, follow-up studies reported data on natural history of colorectal cancer is of paucity. Compared to the "adenoma-carcinoma" pathway, transition parameters of the serrated lesion pathway are more limited. This Meta-analysis provided convincing evidence for optimizing the strategies regarding follow-up program on the disease, using the baseline endoscopic findings from global CRC Screening Program. These results also offered strong data-related support for Chinese population- specific interventional model on colorectal cancer.