OBJECTIVES Fecal immunochemical tests (FITs) for hemoglobin are increasingly used in colorectal cancer (CRC) screening. The use of uniform positivity thresholds (cutoffs) within screening populations is expected to imply lower positive predictive values (PPVs) and higher numbers of colonoscopies needed (numbers needed to scope [NNSs]) to detect advanced neoplasms among screening participants at lower risk compared with those at higher risk. We aimed to assess such variation and its potential implications in a large screening cohort. METHODS A quantitative FIT (FOB Gold; Sentinel Diagnostics, Milan, Italy) was conducted in fecal samples collected by 4,332 participants of screening colonoscopy before bowel preparation. Participants were classified into 3 risk groups (low, medium, and high) by tertiles of a previously derived risk-factor-based risk score. We determined the variation of PPVs and NNSs for detecting advanced neoplasms (i.e., CRC or advanced adenoma) when using the same FIT cutoffs and variation of FIT cutoffs that would yield uniform PPVs across risk groups. RESULTS When a fixed FIT cutoff of 10 μg/g was used, the PPV increased from 23.3% to 41.8% from the low- to the high-risk group, with NNS decreasing from 4.3 to 2.4 (P < 0.001). Similar variations of PPVs and NNSs across risk groups were observed at higher FIT cutoffs. When risk group-specific cutoffs were defined to achieve fixed PPVs of 25%, 30%, and 35% across all risk groups, cutoffs varied from 5.3 to 11.4, 6.5 to 18.7, and 7.5 to 31.0 μg hemoglobin/g feces, respectively, between high- and low-risk groups (P < 0.05 for all differences). DISCUSSION Using risk-adapted cutoffs may help to achieve target levels of PPV and NNS and might be an option to consider for personalized FIT-based CRC screening.

中文翻译：

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通过粪便免疫化学测试进行结直肠癌筛查的风险适应截止值。


目的 粪便血红蛋白免疫化学检测 (FIT) 越来越多地用于结直肠癌 (CRC) 筛查。在筛查人群中使用统一的阳性阈值（截止值）预计意味着较低的阳性预测值（PPV）和需要更多的结肠镜检查次数（范围[NNS]所需的次数）来检测风险较低的筛查参与者中的晚期肿瘤那些风险较高的人。我们的目的是在大型筛查队列中评估这种变异及其潜在影响。方法 对 4,332 名在肠道准备前进行结肠镜检查的参与者收集的粪便样本进行定量 FIT（FOB Gold；Sentinel Diagnostics，米兰，意大利）。根据先前得出的基于风险因素的风险评分的三分位数，将参与者分为 3 个风险组（低、中和高）。当使用相同的 FIT 截止值时，我们确定了用于检测晚期肿瘤（即 CRC 或晚期腺瘤）的 PPV 和 NNS 的变化，以及 FIT 截止值的变化，这将在不同风险组中产生统一的 PPV。结果 当使用 10 μg/g 的固定 FIT 截止值时，从低风险组到高风险组，PPV 从 23.3% 增加到 41.8%，NNS 从 4.3 下降到 2.4（P < 0.001）。在较高的 FIT 截止值下，观察到不同风险组的 PPV 和 NNS 具有类似的变化。当确定特定风险组的临界值以在所有风险组中实现 25%、30% 和 35% 的固定 PPV 时，临界值分别为 5.3 至 11.4、6.5 至 18.7 和 7.5 至 31.0 μg 血红蛋白/g 粪便，高风险组和低风险组之间的差异（所有差异 P < 0.05）。讨论 使用风险适应截止值可能有助于实现 PPV 和 NNS 的目标水平，并且可能是基于 FIT 的个性化 CRC 筛查的一种选择。