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多聚酶链反应(PCR)和 mt-sDNA 检测、粪便免疫化学检测(FIT)、CT 结肠成像用于高级别瘤变的检测率:非侵入性结直肠筛查试验的分层贝叶斯荟萃分析。

PPV and Detection Rate of mt-sDNA Testing, FIT, and CT Colonography for Advanced Neoplasia: A Hierarchic Bayesian Meta-Analysis of the Noninvasive Colorectal Screening Tests.

机构信息

Department of Radiology, University of Wisconsin School of Medicine & Public Health, E3/311 Clinical Science Center, 600 Highland Ave, Madison, WI 53792-3252.

Digestive Endoscopy Unit, Nuovo Regina Margherita Hospital, Rome, Italy.

出版信息

AJR Am J Roentgenol. 2021 Oct;217(4):817-830. doi: 10.2214/AJR.20.25416. Epub 2021 Mar 11.

DOI:10.2214/AJR.20.25416
PMID:33703913
Abstract

Noninvasive tests for colorectal cancer (CRC) screening and prevention limit the need for invasive colonoscopy to follow up positive test results. However, the relative performance characteristics of available noninvasive tests have not yet been adequately compared. We performed a systematic review and meta-analysis to compare the diagnostic performance of the available noninvasive CRC screening tests, including multitarget stool DNA (mt-sDNA) testing, fecal immunochemical testing (FIT), and CT colonography (CTC), with an emphasis on comparison of PPV and detection rate (DR) for advanced neoplasia (AN; encompassing cases of advanced adenomas and CRC). After systematic searches of MEDLINE and Google Scholar databases, 10 mt-sDNA, 27 CTC, and 88 FIT published screening studies involving 25,132, 33,493, and 2,355,958 asymptomatic adults, respectively, were included. Meta-analysis with hierarchic Bayesian modeling was conducted in accordance with Cochrane Collaboration and PRISMA guidelines to determine test positivity rates (TPRs) leading to optical colonoscopy, as well as PPVs and DRs for both AN and CRC. Different positivity thresholds were considered for FIT and CTC. Point estimates (with 95% credible intervals) from pooled Bayesian meta-analysis combining all thresholds for FIT and stratifying CTC results by a polyp size threshold of 6 mm or larger (CTC6) and 10 mm or larger (CTC10) were calculated. TPR was 13.5% (10.9-16.6%) for mt-sDNA testing, 6.4% (5.8-7.2%) for FIT, 13.4% (11.4-15.6%) for CTC6, and 6.6% (5.2-7.7%) for CTC10. AN PPV was 26.9% (95% credible interval, 21.8-33.2%) for mt-sDNA testing, 31.8% (29.3-34.5%) for FIT, 34.4% (27.2-41.0%) for CTC6, and 61.0% (54.0-70.0%) for CTC10. CRC PPV was 2.4% (1.5-3.9%) for mt-sDNA testing, 4.9% (4.3-5.3%) for FIT, 3.5% (2.5-4.8%) for CTC6, and 6.0% (4.3-8.0%) for CTC10. The DR for AN was 3.4% (95% credible interval, 2.5-4.8%) for mt-SDNA, 2.0% (1.8-2.3%) for FIT, 4.8% (4.0-6.5%) for CTC6, and 4.0% (3.0-4.6%) for CTC10. When FIT is restricted to a lower threshold (< 10 μg Hb/g feces), its performance profile is similar to that of mt-sDNA testing, although available data are limited. AN PPV odds ratios (relative to CTC10 as the reference) were 0.24 (95% credible interval, 0.17-0.33) for mt-sDNA testing, 0.30 (0.24-0.45) for FIT, and 0.33 (0.25-0.47) for CTC6. Among noninvasive CRC screening tests, CTC with a polyp size threshold of 10 mm or larger most effectively targets AN, preserving detection while also decreasing unnecessary colonoscopies compared with mt-sDNA testing and FIT. CTC performed with a polyp size threshold for colonoscopy referral set at 10 mm or larger represents the most effective and efficient noninvasive screening test for CRC prevention and detection.

摘要

用于结直肠癌(CRC)筛查和预防的非侵入性检测方法限制了需要进行侵入性结肠镜检查来跟进阳性检测结果。然而,尚未充分比较现有非侵入性检测方法的相对性能特征。我们进行了系统评价和荟萃分析,以比较现有的非侵入性 CRC 筛查检测方法的诊断性能,包括多靶点粪便 DNA(mt-sDNA)检测、粪便免疫化学检测(FIT)和 CT 结肠成像(CTC),重点比较高级别肿瘤(AN;包括高级腺瘤和 CRC 病例)的阳性预测值(PPV)和检出率(DR)。在系统搜索 MEDLINE 和 Google Scholar 数据库后,纳入了 10 项 mt-sDNA、27 项 CTC 和 88 项 FIT 发表的筛查研究,分别涉及 25132、33493 和 2355958 名无症状成年人。根据 Cochrane 协作和 PRISMA 指南进行荟萃分析,使用层次贝叶斯建模来确定导致光学结肠镜检查的检测阳性率(TPR),以及针对 AN 和 CRC 的 PPV 和 DR。对于 FIT 和 CTC,考虑了不同的阳性阈值。对于 FIT,结合所有阈值的点估计值(置信区间为 95%),并对 CTC 结果进行分层,根据息肉大小阈值为 6 毫米或更大(CTC6)和 10 毫米或更大(CTC10)进行分层。对于 mt-sDNA 检测,TPR 为 13.5%(10.9-16.6%),FIT 为 6.4%(5.8-7.2%),CTC6 为 13.4%(11.4-15.6%),CTC10 为 6.6%(5.2-7.7%)。对于 mt-sDNA 检测,AN 的 PPV 为 26.9%(95%置信区间为 21.8-33.2%),FIT 为 31.8%(29.3-34.5%),CTC6 为 34.4%(27.2-41.0%),CTC10 为 61.0%(54.0-70.0%)。对于 CRC,mt-sDNA 检测的 PPV 为 2.4%(1.5-3.9%),FIT 为 4.9%(4.3-5.3%),CTC6 为 3.5%(2.5-4.8%),CTC10 为 6.0%(4.3-8.0%)。对于 mt-SDNA,AN 的 DR 为 3.4%(95%置信区间为 2.5-4.8%),FIT 为 2.0%(1.8-2.3%),CTC6 为 4.8%(4.0-6.5%),CTC10 为 4.0%(3.0-4.6%)。当将 FIT 限制在较低的阈值(<10 μg Hb/g 粪便)时,其性能特征与 mt-sDNA 检测相似,尽管可用数据有限。与 CTC10 相比,AN 的 PPV 比值(相对于 CTC10)为 mt-sDNA 检测 0.24(95%置信区间为 0.17-0.33),FIT 为 0.30(0.24-0.45),CTC6 为 0.33(0.25-0.47)。在非侵入性 CRC 筛查检测中,对于息肉大小阈值为 10 毫米或更大的 CTC 最有效地针对 AN,与 mt-sDNA 检测和 FIT 相比,在保留检测的同时还减少了不必要的结肠镜检查。对于结直肠癌预防和检测,以 10 毫米或更大的息肉大小作为结肠镜检查转诊阈值的 CTC 代表了最有效和最有效的非侵入性筛查检测方法。

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