Background The incidence rate and mortality rate of liver cancer were 11.6 (ranked 8th among cancers) and 10.7 (4th) per 100,000 individuals respectively globally in 2020, whereas in Korea, they were higher at 29.5 (7th) and 20.6 (2nd) per 100,000 individuals. The National Cancer Screening Program (NCSP) in Korea conducts biannual concurrent liver ultrasound and serum alpha-fetoprotein (AFP) measurement for hepatocellular carcinoma (HCC) surveillance in high-risk groups, including those with chronic hepatitis B and C, and liver cirrhosis. The effectiveness of surveillance is impacted by varying AFP cutoffs; however, within the NCSP, different cutoffs are being used, and it is not clear which cutoffs are being employed. Harmonization of AFP test results by major reagent manufacturers have been achieved, enabling the adoption of a uniform threshold. This study aims to assess the variation of AFP cutoffs among institutions within the NCSP and suggest a unified and optimal AFP threshold. Methods This study examined HCC screening results from the NCSP between 2018 and 2020, investigating unit and cutoff usage for AFP test across institutions each year (number of institutions were 4452 for 2018, 4754 for 2019, and 4847 for 2020). To determine the optimal AFP cutoff for HCC screening, datasets comprised unique patient results from 2018 to 2020 (number of patients = 819,644). Receiver operating characteristic (ROC) curve analyses were conducted for determine best AFP cutoffs. Cancer diagnosis was defined by billing records indicating HCC within one year post-screening. Results More than 96% of institutions used ng/mL as a unit of AFP test. Among institutions using ng/mL, the most frequently used AFP cutoff was 7 ng/mL, with frequency percentages of 75.7%, 72.2%, and 62.2% in 2018, 2019, 2020, respectively. The percentiles (1st, 10th, 90th, 99th) of AFP cutoff usage for the years 2018, 2019, and 2020 were (7, 7, 8.8, 15), (7, 7, 8.9, 15), and (7, 7, 9, 15) respectively. The AUC of ROC was 0.824 and some cut-off points with their sensitivity and specificity values were as follows: 5 ng/mL (0.648, 0.874); 10 (0.457, 0.976); 20 (0.327, 0.993); 40 (0.246, 0.997); 100 (0.169, 0.998); 200 (0.123, 0.999); 400 (0.084, 1). Conclusions Different cutoffs observed across institutions in NCSP. Our study cautiously suggests that the optimal AFP value for screening HCC in NCSP may range from 10 to 20 ng/mL, considering sensitivity and specificity when AFP is combined with ultrasound in regions with a high prevalence of HCC. For a more suitable AFP cutoff recommendation, additional analyses based on ultrasound findings and underlying diseases should be considered.

中文翻译：

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B-333 优化肝细胞癌筛查的 AFP 截止值：来自韩国国家癌症筛查计划的见解


背景 2020年，全球肝癌发病率和死亡率分别为每10万人11.6例（排名癌症第8位）和10.7例（第4位），而韩国则更高，为每10万人29.5例（第7位）和20.6例（第2位）个人。韩国国家癌症筛查计划 (NCSP) 每两年进行一次肝脏超声检查和血清甲胎蛋白 (AFP) 测量，以监测高危人群（包括慢性乙型肝炎、丙型肝炎和肝硬化患者）的肝细胞癌 (HCC)。监测的有效性受到不同的 AFP 截止值的影响；然而，在 NCSP 内部，正在使用不同的截止值，并且尚不清楚正在使用哪些截止值。主要试剂制造商已实现 AFP 检测结果的统一，从而能够采用统一的阈值。本研究旨在评估 NCSP 内机构之间 AFP 截止值的差异，并提出统一且最佳的 AFP 阈值。方法本研究检查了 2018 年至 2020 年 NCSP 的 HCC 筛查结果，每年调查各机构 AFP 检测的单位和截止使用情况（机构数量为 2018 年 4452 个、2019 年 4754 个、2020 年 4847 个）。为了确定 HCC 筛查的最佳 AFP 截止值，数据集包含 2018 年至 2020 年的独特患者结果（患者数量 = 819,644）。进行受试者工作特征 (ROC) 曲线分析以确定最佳 AFP 截止值。癌症诊断是根据筛查后一年内显示 HCC 的账单记录来定义的。结果 96%以上的机构采用ng/mL作为AFP检测单位。在使用 ng/mL 的机构中，最常用的 AFP 临界值是 7 ng/mL，频率百分比分别为 75.7%、72.2% 和 62。2018年、2019年、2020年分别为2%。 2018 年、2019 年和 2020 年 AFP 截止使用率的百分位数（第 1、10、90、99）分别为（7、7、8.8、15）、（7、7、8.9、15）和（7、7） 、 9、 15）分别。 ROC 的 AUC 为 0.824，一些临界点及其敏感性和特异性值如下：5 ng/mL（0.648，0.874）； 10（0.457，0.976）； 20（0.327，0.993）； 40（0.246，0.997）； 100（0.169，0.998）； 200（0.123，0.999）； 400（0.084，1）。结论 NCSP 各机构观察到不同的截止值。我们的研究谨慎地表明，考虑到在 HCC 高发地区 AFP 与超声结合时的敏感性和特异性，NCSP 中筛查 HCC 的最佳 AFP 值可能为 10 至 20 ng/mL。为了获得更合适的 AFP 截止值建议，应考虑基于超声检查结果和基础疾病的额外分析。