BACKGROUND & AIMS Noninvasive tests used in colorectal cancer screening, such as the fecal immunochemical test (FIT), are more acceptable but detect neoplasias with lower levels of sensitivity than colonoscopy. We investigated whether lowering the cut-off concentration of hemoglobin for designation as an abnormal FIT result increased the detection of advanced neoplasia in a mailed outreach program. METHODS We performed a prospective study of 17,017 uninsured patients, age 50 to 64 years, who were not current with screening and enrolled in a safety-net system in Texas. We reduced the cut-off value for an abnormal FIT result from 20 or more to 10 or more μg hemoglobin/g feces a priori. All patients with abnormal FIT results were offered no-cost diagnostic colonoscopy. We compared proportions of patients with abnormal FIT results and neoplasia yield for standard vs lower cut-off values, as well as absolute hemoglobin concentration distribution among 5838 persons who completed the FIT. Our primary aim was to determine the effects of implementing a lower hemoglobin concentration cut-off value on colonoscopy demand and yield, specifically colorectal cancer (CRC) and advanced neoplasia detection, compared with the standard, higher, hemoglobin concentration cut-off value. RESULTS The proportions of patients with abnormal FIT results were 12.3% at the 10 or more μg hemoglobin/g feces and 6.6% at the standard 20 or more μg hemoglobin/g feces cut-off value (P = .0013). Detection rates for the lower vs the standard threshold were 10.2% vs 12.7% for advanced neoplasia (P = .12) and 0.9% vs 1.2% for CRC (P = .718). The positive predictive values were 18.9% for the lower threshold vs 24.4% for the standard threshold for advanced neoplasia (P = .053), and 1.7% vs 2.4% for CRC (P = .659). The number needed to screen to detect 1 case with advanced neoplasia was 45 at the lower threshold compared with 58 at the standard threshold; the number needed to scope to detect 1 case with advanced neoplasia increased from 4 to 5. Most patients with CRC (72.7%) or advanced adenoma (67.3%) had hemoglobin concentrations of 20 or more μg/g feces. In the group with 10 to 19 μg hemoglobin/g feces, there were 3 patients with CRC (3 of 11; 27.3%) and 36 with advanced adenoma (36 of 110; 32.7%) who would not have been detected at the standard positive threshold (advanced neoplasia Pcomparison < .001). The proportion of patients found to have no neoplasia after an abnormal FIT result (false positives) was not significantly higher with the lower cut-off value (44.4%) than the standard cut-off value (39.1%) (P = .1103). CONCLUSIONS In a prospective study of 17,017 uninsured patients, we found that reducing the abnormal FIT result cut-off value (to ≥10 μg hemoglobin/g feces) might increase detection of advanced neoplasia, but doubled the proportion of patients requiring a diagnostic colonoscopy. If colonoscopy capacity permits, health systems that use quantitative FITs should consider lowering the abnormal cut-off value to optimize CRC detection and prevention. (ClinicalTrials.gov no: NCT01946282.).

中文翻译：

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较低的异常粪便免疫化学测试截止值可提高系统级筛查中结直肠癌的检出率。


背景和目的 用于结直肠癌筛查的非侵入性检测，例如粪便免疫化学检测 (FIT)，更容易被接受，但检测肿瘤的敏感性低于结肠镜检查。我们调查了在邮寄外展计划中，降低指定为异常 FIT 结果的血红蛋白截止浓度是否会增加晚期肿瘤的检出率。方法 我们对 17,017 名年龄在 50 至 64 岁之间的未参保患者进行了一项前瞻性研究，这些患者目前尚未接受筛查并加入了德克萨斯州的安全网系统。我们将异常 FIT 结果的截止值从 20 或更高降低到 10 或更高 μg 血红蛋白/g 粪便。所有 FIT 结果异常的患者均接受免费诊断性结肠镜检查。我们比较了完成 FIT 的 5838 名患者中 FIT 结果异常的患者比例、标准与较低截止值的肿瘤发生率以及绝对血红蛋白浓度分布。我们的主要目的是确定与标准的较高血红蛋白浓度截止值相比，实施较低的血红蛋白浓度截止值对结肠镜检查需求和产量的影响，特别是结直肠癌 (CRC) 和晚期肿瘤检测。结果 血红蛋白/克粪便 10 或以上时，FIT 结果异常的患者比例为 12.3%，血红蛋白/克粪便标准值为 20 或以上时，FIT 结果异常的患者比例为 6.6%（P = .0013）。晚期肿瘤的较低阈值与标准阈值的检出率分别为 10.2% 和 12.7% (P = .12)，CRC 的检出率为 0.9% 和 1.2% (P = .718)。晚期肿瘤的阳性预测值为下限阈值的 18.9% 与标准阈值的 24.4% (P = .053)，CRC 的阳性预测值为 1.7% 与 2.4% (P = .053)。659）。在较低阈值下，筛查发现 1 例晚期肿瘤病例所需的人数为 45 例，而标准阈值下为 58 例；检测 1 例晚期肿瘤病例所需的数量从 4 例增加到 5 例。大多数 CRC (72.7%) 或晚期腺瘤 (67.3%) 患者的血红蛋白浓度为 20 μg/g 粪便或更高。在血红蛋白/克粪便为 10 至 19 μg 的组中，有 3 名 CRC 患者（11 名中的 3 名；27.3%）和 36 名晚期腺瘤患者（110 名中的 36 名；32.7%）在标准阳性时不会被检出。阈值（晚期肿瘤 P 比较 < .001）。较低截止值 (44.4%) 的 FIT 结果异常（假阳性）后发现无肿瘤的患者比例并未显着高于标准截止值 (39.1%) (P = .1103) 。结论 在一项针对 17,017 名未投保患者的前瞻性研究中，我们发现降低异常 FIT 结果截止值（至≥10 μg 血红蛋白/g 粪便）可能会增加晚期肿瘤的检出率，但需要诊断性结肠镜检查的患者比例会增加一倍。如果结肠镜检查能力允许，使用定量 FIT 的卫生系统应考虑降低异常截止值，以优化 CRC 检测和预防。 （ClinicalTrials.gov 编号：NCT01946282。）。