多靶点粪便免疫化学试验用于结直肠癌筛查的临床验证：一项诊断准确性研究。
Clinical Validation of a Multitarget Fecal Immunochemical Test for Colorectal Cancer Screening : A Diagnostic Test Accuracy Study.
机构信息
Netherlands Cancer Institute and Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, the Netherlands (W.d.K.).
Netherlands Cancer Institute, Amsterdam, and Erasmus MC University Medical Center, Rotterdam, the Netherlands (P.H.W.).
出版信息
Ann Intern Med. 2021 Sep;174(9):1224-1231. doi: 10.7326/M20-8270. Epub 2021 Jul 20.
BACKGROUND
The fecal immunochemical test (FIT) is used in colorectal cancer (CRC) screening, yet it leaves room for improvement.
OBJECTIVE
To develop a multitarget FIT (mtFIT) with better diagnostic performance than FIT.
DESIGN
Diagnostic test accuracy study.
SETTING
Colonoscopy-controlled series.
PARTICIPANTS
Persons ( = 1284) from a screening ( = 1038) and referral ( = 246) population were classified by their most advanced lesion (CRC [ = 47], advanced adenoma [ = 135], advanced serrated polyp [ = 30], nonadvanced adenoma [ = 250], and nonadvanced serrated polyp [ = 53]), along with control participants ( = 769).
MEASUREMENTS
Antibody-based assays were developed and applied to leftover FIT material. Classification and regression tree (CART) analysis was applied to biomarker concentrations to identify the optimal combination for detecting advanced neoplasia. Performance of this combination, the mtFIT, was cross-validated using a leave-one-out approach and compared with FIT at equal specificity.
RESULTS
The CART analysis showed a combination of hemoglobin, calprotectin, and serpin family F member 2-the mtFIT-to have a cross-validated sensitivity for advanced neoplasia of 42.9% (95% CI, 36.2% to 49.9%) versus 37.3% (CI, 30.7% to 44.2%) for FIT ( = 0.025), with equal specificity of 96.6%. In particular, cross-validated sensitivity for advanced adenomas increased from 28.1% (CI, 20.8% to 36.5%) to 37.8% (CI, 29.6% to 46.5%) ( = 0.006). On the basis of these results, early health technology assessment indicated that mtFIT-based screening could be cost-effective compared with FIT.
LIMITATION
Study population is enriched with persons from a referral population.
CONCLUSION
Compared with FIT, the mtFIT showed better diagnostic accuracy in detecting advanced neoplasia because of an increased detection of advanced adenomas. Moreover, early health technology assessment indicated that these results provide a sound basis to pursue further development of mtFIT as a future test for population-based CRC screening. A prospective screening trial is in preparation.
PRIMARY FUNDING SOURCE
Stand Up to Cancer/Dutch Cancer Society, Dutch Digestive Foundation, and HealthHolland.
背景
粪便免疫化学检测（FIT）用于结直肠癌（CRC）筛查，但仍有改进空间。
目的
开发一种比 FIT 具有更好诊断性能的多靶标 FIT（mtFIT）。
设计
诊断测试准确性研究。
设置
结肠镜对照系列。
参与者
来自筛查（n=1038）和转诊（n=246）人群的个体（n=1284），根据其最严重的病变进行分类（CRC [=47]、高级腺瘤[=135]、高级锯齿状息肉[=30]、非高级腺瘤[=250]和非高级锯齿状息肉[=53]），以及对照参与者（n=769）。
测量
开发了基于抗体的检测方法，并应用于剩余的 FIT 材料。应用分类和回归树（CART）分析对生物标志物浓度进行分析，以确定检测高级肿瘤的最佳组合。通过使用留一法进行交叉验证来评估这种组合（mtFIT）的性能，并与 FIT 在相等特异性下进行比较。
结果
CART 分析显示血红蛋白、钙卫蛋白和丝氨酸蛋白酶家族 F 成员 2 的组合（mtFIT）检测高级肿瘤的交叉验证敏感性为 42.9%（95%CI，36.2%至 49.9%），而 FIT 为 37.3%（CI，30.7%至 44.2%）（=0.025），特异性均为 96.6%。特别是，交叉验证对高级腺瘤的敏感性从 28.1%（CI，20.8%至 36.5%）增加到 37.8%（CI，29.6%至 46.5%）（=0.006）。基于这些结果，早期卫生技术评估表明，与 FIT 相比，基于 mtFIT 的筛查可能具有成本效益。
局限性
研究人群中富含来自转诊人群的个体。
结论
与 FIT 相比，mtFIT 在检测高级肿瘤方面具有更好的诊断准确性，因为增加了对高级腺瘤的检测。此外，早期卫生技术评估表明，这些结果为进一步开发 mtFIT 作为基于人群的 CRC 筛查的未来检测方法提供了合理依据。一项前瞻性筛查试验正在筹备中。
主要资金来源
Stand Up to Cancer/Dutch Cancer Society、Dutch Digestive Foundation 和 HealthHolland。
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