The faecal immunochemical test (FIT) is the most used colorectal cancer (CRC) screening test worldwide [1]. FIT is a family of tests, the performance of which varies by brand, positivity threshold and testing interval [2, 3]. Despite myriad studies, the optimal FIT threshold and interval remain elusive. Countries and large health care systems that screen primarily with FIT must decide on the threshold for a positive test, knowing that there are trade-offs.

The novel cross-sectional study [4] of 47,265 Norwegians who were first participants in a biennial FIT screening program in which the FIT threshold for positivity (and diagnostic colonoscopy) was 15 μg/g, was designed to quantify colonoscopies performed, yield for CRC, advanced adenomas (AA) and advanced serrated lesions (ASLs), and adverse events at different thresholds. The > 15 μg/g threshold was compared to thresholds of > 20, > 47, > 80, > 120 and > 150 μg/g. Outcomes include positivity rate, detection rates of CRC, AA and ASLs, positive predictive value (PPV) and severe adverse events. All outcomes were reported relative to the > 15 μg/g threshold.

As expected, as the threshold increased from 15 to 150 μg/g, the positivity (i.e. detection) rate and colonoscopy demand decreased, as did the yield for CRCs, AAs and ASLs, while the PPVs increased for CRCs and AAs, but not for ASLs. There was a small CRC stage shift, with detection of a lower proportion of Stage I CRCs and a higher proportion of advanced CRCs. Adverse events fell as the threshold increased, but the proportion of significant bleeding events increased due to a higher proportion of polypectomies for advanced polyps.

These data provide a quantitative framework for understanding the trade-offs among the various thresholds. Countries and large health care systems screening primarily with FIT—especially those with fixed or limited colonoscopy resources—need to know this to optimise those resources. Notably, the detection and PPV of advanced SSLs, both overall and by anatomical site, were unchanged at different thresholds, suggesting that detection may have been serendipitous, supporting the non-bleeding biology of these lesions. Trends by FIT threshold did not differ by age or sex.

Despite their public health utility, these data do not provide estimates of sensitivity and specificity because colonoscopy was not performed for a FIT value of ≤ 15 μg/g. Further, they do not tell us the ‘optimal’ threshold, as this determination requires judgement and because FIT screening is a longitudinal rather than one-time process. Lastly, these results may not generalise to other brands of FIT or to other populations.

Greater attention should be given to studying FIT's quantitative value, which may be useful for prioritising who requires colonoscopy sooner and for tailoring the re-testing interval. The Netherlands is conducting an observational study in which the re-testing interval among FIT-‘negative’ persons depends on the quantitative value. Several studies have used FIT's quantitative value along with other factors to stratify patient risk for advanced neoplasia [5-7]. There is likely untapped potential of FIT to improve the efficiency and cost-effectiveness of CRC screening.

粪便免疫化学检测 （FIT） 是全球最常用的结直肠癌 （CRC） 筛查检测 [1]。FIT 是一系列测试，其性能因品牌、阳性阈值和测试间隔而异 [2， 3]。尽管有无数的研究，但最佳 FIT 阈值和间隔仍然难以捉摸。主要使用 FIT 进行筛查的国家和大型医疗保健系统必须决定检测呈阳性的阈值，因为要知道需要权衡取舍。

这项新颖的横断面研究 [4] 对 47,265 名挪威人进行了首次参与者两年一次的 FIT 筛查计划，其中阳性（和诊断性结肠镜检查）的 FIT 阈值为 15 μg/g，旨在量化进行的结肠镜检查、CRC 的检出率、晚期腺瘤 （AA） 和晚期锯齿状病变 （ASL） 以及不同阈值下的不良事件。将 > 15 μg/g 阈值与 > 20、> 47、> 80、> 120 和 > 150 μg/g 阈值进行比较。结果包括阳性率、CRC 、 AA 和 ASLs 检出率、阳性预测值 （PPV） 和严重不良事件。所有结局均相对于 > 15 μg/g 阈值报告。

正如预期的那样，随着阈值从 15 μg/g 增加到 150 μg/g，阳性率（即检测）率和结肠镜检查需求下降，CRCs、AAs 和 ASLs 的检出率也下降，而 CRCs 和 AAs 的 PPV 增加，但 ASL 没有。CRC 分期变化很小，检测到 I 期 CRC 的比例较低，而晚期 CRC 的比例较高。不良事件随着阈值的增加而减少，但由于晚期息肉切除术的比例较高，显着出血事件的比例增加。

这些数据为理解各种阈值之间的权衡提供了一个定量框架。主要使用 FIT 进行筛查的国家和大型医疗保健系统（尤其是那些结肠镜检查资源固定或有限的国家）需要了解这一点以优化这些资源。值得注意的是，高级 SSL 的检测和 PPV，无论是总体还是按解剖部位，在不同阈值下都没有变化，这表明检测可能是偶然的，支持了这些病变的非出血生物学。FIT 阈值的趋势不因年龄或性别而异。

尽管它们对公共卫生有用，但这些数据并不能提供敏感性和特异性的估计值，因为 FIT 值为 ≤ 15 μg/g 时未进行结肠镜检查。此外，它们没有告诉我们“最佳”阈值，因为这个决定需要判断，而且 FIT 筛查是一个纵向而不是一次性的过程。最后，这些结果可能无法推广到其他品牌的 FIT 或其他人群。

应更加注意研究 FIT 的定量值，这可能有助于优先考虑需要更早结肠镜检查的患者以及调整复查间隔。荷兰正在进行一项观察性研究，其中 FIT“阴性”人群的复测间隔取决于定量值。一些研究使用 FIT 的定量值和其他因素对患者晚期肿瘤风险进行分层 [5-7]。FIT 在提高 CRC 筛查的效率和成本效益方面可能存在尚未开发的潜力。