不同年龄组人群CA125筛查卵巢癌最佳切点值探讨及验证

Optimal Cut-Off Values of CA125 in Screening of Ovarian Cancer Among Subjects in Different Age Groups

[目的]探索并验证不同年龄组人群CA125筛查卵巢癌的最佳切点值。[方法]基于天津市常见恶性肿瘤联合筛查项目人群及同期天津市常见恶性肿瘤病例队列人群,选取2017年以来基线未患癌且接受CA125检测的女性,通过多渠道随访匹配获得卵巢癌结局。采用Logistic回归的ROC曲线和曲线下面积(AUC)评价CA125筛查卵巢癌的总体准确性及最佳切点值。同时分别探讨<60岁、60~69岁和≥70岁不同年龄组的CA125筛查准确性及最佳切点值,以及相应年龄别特异性CA125筛查切点值下,卵巢癌筛查的灵敏度和特异度。采用Bootstrap重抽样方法进行内部验证,并采用PLCO试验人群进行外部验证。[结果]本研究纳入女性共41620名,中位随访1.22年后,共计发现413例卵巢癌病例。CA125筛查卵巢癌的总体AUC为83.0%,最佳切点值为26.8 U/mL。根据年龄分组后,<60岁、60~69岁和≥70岁女性CA125筛查卵巢癌的AUC分别为78.8%、88.6%和89.1%,最佳切点值分别为26.8 U/mL、20.3 U/mL和28.0 U/mL。基于年龄别特异性的CA125筛查切点值,阳性人群相比较于阴性人群,卵巢癌风险的OR(95%CI)分别为11.18(8.54~14.63)、39.26(23.85~64.62)和25.00(12.85~48.61),相应灵敏度分别为67.1%、82.9%和81.4%,特异度分别为84.6%、89.0%和85.1%。内部及外部验证均得到类似的结果及趋势。[结论]为提高筛查效果,减少卵巢癌漏诊,推荐采用年龄别特异性的CA125筛查切点值在一般风险人群中进行卵巢癌筛查。

[Purpose]To investigate and validate the optimal cut-off values of CA125 in screening for ovarian cancer among subjects in different age groups.[Methods]Based on the Chinese colo-rectal,breast,lung,liver and stomach cancer screening trial and the Tianjin common cancer case cohort,women who received CA125 tests for screening of ovarian cancer since 2017 were selected,and ovarian cancer cases were identified based on screening,clinical diagnosis and follow-up.The overall accuracy and the optimal cut-off values of CA125 for screening of ovarian cancer were evaluated with ROC curve;and also evaluated in age groups of<60,60~69 and≥70 year old,respectively.Bootstrap resampling was used to internally validate these age-specific cut-off values,and the PLCO cancer screening trial was used for external validation.[Results]A total of 41620 women were finally enrolled in this study.After a median follow-up of 1.22 years,a total of 413 cases of ovarian cancer were identified.The overall area under ROC curve(AUC)of CA125 in screening for ovarian cancer was 83.0%,and the optimal cut-off point was 26.8 U/mL.The AUCs of CA125 in screening for ovarian cancer in age groups of<60,60~69 and≥70 years old were 78.8%,88.6%and 89.1%,respectively,and the optimal cut-off values were 26.8 U/mL,20.3 U/mL and 28.0 U/mL,respectively.The age-specific OR(95%CI)of positive CA125 for risk of ovarian cancer in women with<60,60~69 and≥70 years old were 11.18(8.54~14.63),39.26(23.85~64.62)and 25.00(12.85~48.61)compared to those with negative CA125;the corresponding sensitivities were 67.1%,82.9%and 81.4%,and the specificities were 84.6%,89.0%and 85.1%,respectively.Both internal and external validation yielded similar results and trends.[Conclusion]To improve the screening effect and reduce the missed diagnosis of ovarian cancer,the age-specific CA125 optimal cut-off values are recommended in this study for screening of ovarian cancer.