主题：漫谈体检策略－统计相关的故事（一） -- xtqntd

今年asco年会有一个口头报告，是关于卵巢癌筛查的，想请专家看看，这个策略是否有操作性、有无缺陷。如果在技术上没有问题，我们想在我们做的ASCO专门报道上介绍一下，希望有助于国内医生参考。

A prospective U.S. ovarian cancer screening study using the risk of ovarian cancer algorithm (ROCA).

Background: There are currently no effective screening tools for the early detection of ovarian cancer in women at average population risk. We evaluated a screening strategy that incorporates change of CA-125 over time and age of the participant to estimate risk of ovarian cancer, referring a small fraction (~2%) of apparently healthy individuals annually to transvaginal sonography (TVS). Methods: A single arm, prospective, multicenter screening study enrolled postmenopausal women age 50 to 74 with no significant family history of breast or ovarian cancer. Participants underwent a CA-125 blood test annually. Based on the Risk of Ovarian Cancer Algorithm (ROCA) result, women were triaged to the next annual CA-125 (low risk), repeat CA-125 in 3 months (intermediate risk), or TVS and referral to a gynecologic oncologist (high risk). Based on clinical findings and TVS, the gyn onc made the decision whether to proceed with surgery. Results: 3238 women participated over an eight year period. The average annual rate of referral to 3 monthly CA125 was 6.8%, and the average annual rate of TVS and gyn onc referral was 0.9%. Cumulatively 85 women (2.6%) received TVS and referral to a gyn onc. Eight women subsequently underwent surgery based on the TVS and referral, with 3 invasive ovarian cancers, 2 borderline ovarian tumors and 3 benign ovarian tumors, providing a positive predictive value of 37.5% (95% CI 8.5%,75.5%).The combined specificity of ROCA followed by TVS for referral to surgery is 99.7% (95% CI 99.5%, 99.9%). The 3 invasive ovarian cancers were high-grade epithelial tumors that were all early stage (two stage 1C and stage IIB). All 3 women with invasive ovarian cancer had at least 3 years with low risk, annual CA-125 values prior to a rising CA-125. Conclusions: In this prospective, single arm study, the ROCA followed by TVS demonstrated excellent specificity and PPV in a population of U.S. women at average risk for ovarian cancer. As expected, less than 1% of participants annually required a TVS. In addition, the invasive high-grade ovarian cancers that were detected were early stage. This study provides early evidence that ROCA followed by TVS is a feasible strategy for screening women over 50 years of age.

这个ROCA的出处是这样（J Clin Oncol 23:7919-7926.）：英国一项卵巢癌筛查使用的是CA125（fixed cutoff of 30 U/mL），异常者查B超。获得了比较好的结果：high specificity

(99.9%) and positive predictive value (PPV; 26.8%)。但是研究者发现其实真正的卵巢癌患者的ＣＡ１２５水平实际表现为在某个变化点(change-point)后持续上升。如果对这一特征采用longitudinal statistical models进行回顾分析，单纯CA125的敏感性就可以从70%提高到86%，特异性仍有98%。

利用这个结合了年龄因素、CA125动态变化模式的模型，可以把首次进行CA125检查的妇女分为3档，高中低危（分别是风险<1/2000、〉1/500和之间），再给予不同的建议（查B超、3月后复查CA125和1年后复查）。

ASCO这项报道应该是把这个模型直接在美国人群中使用。不知道对于中国妇女来说，直接使用是否合适（CA125基值和动态变化模式估计不会完全一样）?