Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).
Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).
复制标题
DOI：
10.1783/147118909788707887
复制
发表时间：
2009-04
影响因子：
--
通讯作者：
U. Menon;A. Gentry-Maharaj;Rachel Hallett;Andy Ryan;M. Burnell;Aarti Sharma;S. Lewis;S. Davies-S.-Davi
中科院分区：
文献类型：
--
作者：
U. Menon;A. Gentry-Maharaj;Rachel Hallett;Andy Ryan;M. Burnell;Aarti Sharma;S. Lewis;S. Davies-S.-Davi
背景技术卵巢癌的病死率很高，大多数女性直到疾病晚期才被诊断出来。英国卵巢癌筛查合作试验（UKCTOCS）是一项随机对照试验，旨在评估筛查对死亡率的影响。本报告总结了 UKCTOCS 患病率（初次）筛查的结果。方法 2001 年至 2005 年间，共有 202 638 名 50-74 岁绝经后妇女被随机分配至不接受治疗（对照；n=101 359）；每年进行 CA125 筛查（使用卵巢癌风险算法进行解释），并以经阴道超声扫描作为二线测试（多模式筛查 [MMS]；n=50 640）；或每年使用计算机生成的随机数算法以 2:1:1 的比例单独进行经阴道超声检查（USS；n=50 639）。所有女性在招募时都提供了血液样本。随机分配到 MMS 组的女性接受了 CA125 血液检测，而随机分配到 USS 组的女性则被预约进行经阴道扫描。屏幕异常的女性接受了重复测试。在重复筛查中持续出现异常的女性接受了临床评估，并在适当的情况下进行了手术。该试验在 ClinicalTrials.gov 注册号为 ISRCTN22488978，注册号为 NCT00058032。结果 在患病率筛查中，50 078 名（98.9%）女性接受了 MMS，48 230 名（95.2%）女性接受了 USS。退出的主要原因是死亡（2 例 MMS，28 USS）、非卵巢癌或其他疾病（无 MMS，66 USS）、切除卵巢（5 例 MMS，29 USS）、搬迁（无 MMS，39 USS）、未能参加 3 次筛查预约（72 例 MMS、757 USS）以及参与者改变主意（483 例 MMS、1490 USS）。总体而言，MMS 组中 50 078 名女性中的 4355 名 (8.7%) 女性和 USS 组中 48 230 名女性中 5779 名 (12.0%) 需要重复测试，MMS 组中 167 名 (0.3%) 女性和 USS 组中 1894 名 (3.9%) 女性需要临床评估。 MMS 组的 50 078 名女性中有 97 名 (0.2%) 接受了手术，USS 组的 48 230 名女性中有 845 名 (1.8%) 接受了手术。检测到 42 例 (MMS) 和 45 例 (USS) 原发性卵巢癌和输卵管癌，其中包括 28 例交界性肿瘤（8 例 MMS，20 例 USS）。 58 例（48.3%；95% CI 35.0-61.8）浸润性癌症中有 28 例（16 MMS，12 USS）为 I/II 期，各组之间的分期分布没有差异（p=0.396）。另外 13 名（5 名 MMS，8 名 USS）女性在筛查后一年内患上了原发性卵巢癌。对于所有原发性卵巢癌和输卵管癌，MMS 的敏感性、特异性和阳性预测值分别为 89.4%、99.8% 和 43.3%，USS 的敏感性、特异性和阳性预测值分别为 84.9%、98.2% 和 5.3%。对于原发性浸润性上皮性卵巢癌和输卵管癌，MMS 的敏感性、特异性和阳性预测值分别为 89.5%、99.8% 和 35.1%，USS 的敏感性、特异性和阳性预测值分别为 75.0%、98.2% 和 2.8%。两个筛查组对于原发性卵巢癌和输卵管癌以及原发性上皮浸润性卵巢癌和输卵管癌的特异性存在显着差异（p<0.0001），但敏感性没有显着差异。解释 MMS 和 USS 筛查策略的敏感性令人鼓舞。 MMS 组的特异性高于 USS 组，因此重复测试和手术的比率较低。这在一定程度上反映了 USS 组良性附件异常的高患病率和交界性肿瘤的更频繁检测。患病率筛查已证实筛查策略是可行的。正在等待正在进行的筛查结果，以便确定筛查对死亡率的影响。
BACKGROUND Ovarian cancer has a high case-fatality ratio, with most women not diagnosed until the disease is in its advanced stages. The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is a randomised controlled trial designed to assess the effect of screening on mortality. This report summarises the outcome of the prevalence (initial) screen in UKCTOCS. METHODS Between 2001 and 2005, a total of 202 638 post-menopausal women aged 50-74 years were randomly assigned to no treatment (control; n=101 359); annual CA125 screening (interpreted using a risk of ovarian cancer algorithm) with transvaginal ultrasound scan as a second-line test (multimodal screening [MMS]; n=50 640); or annual screening with transvaginal ultrasound (USS; n=50 639) alone in a 2:1:1 ratio using a computer-generated random number algorithm. All women provided a blood sample at recruitment. Women randomised to the MMS group had their blood tested for CA125 and those randomised to the USS group were sent an appointment to attend for a transvaginal scan. Women with abnormal screens had repeat tests. Women with persistent abnormality on repeat screens underwent clinical evaluation and, where appropriate, surgery. This trial is registered as ISRCTN22488978 and with ClinicalTrials.gov, number NCT00058032. FINDINGS In the prevalence screen, 50 078 (98.9%) women underwent MMS, and 48 230 (95.2%) underwent USS. The main reasons for withdrawal were death (two MMS, 28 USS), non-ovarian cancer or other disease (none MMS, 66 USS), removal of ovaries (five MMS, 29 USS), relocation (none MMS, 39 USS), failure to attend three appointments for the screen (72 MMS, 757 USS), and participant changing their mind (483 MMS, 1490 USS). Overall, 4355 of 50 078 (8.7%) women in the MMS group and 5779 of 48 230 (12.0%) women in the USS group required a repeat test, and 167 (0.3%) women in the MMS group and 1894 (3.9%) women in the USS group required clinical evaluation. 97 of 50 078 (0.2%) women from the MMS group and 845 of 48 230 (1.8%) from the USS group underwent surgery. 42 (MMS) and 45 (USS) primary ovarian and tubal cancers were detected, including 28 borderline tumours (eight MMS, 20 USS). 28 (16 MMS, 12 USS) of 58 (48.3%; 95% CI 35.0-61.8) of the invasive cancers were stage I/II, with no difference (p=0.396) in stage distribution between the groups. A further 13 (five MMS, eight USS) women developed primary ovarian cancer during the year after the screen. The sensitivity, specificity, and positive-predictive values for all primary ovarian and tubal cancers were 89.4%, 99.8%, and 43.3% for MMS, and 84.9%, 98.2%, and 5.3% for USS, respectively. For primary invasive epithelial ovarian and tubal cancers, the sensitivity, specificity, and positive-predictive values were 89.5%, 99.8%, and 35.1% for MMS, and 75.0%, 98.2%, and 2.8% for USS, respectively. There was a significant difference in specificity (p<0.0001) but not sensitivity between the two screening groups for both primary ovarian and tubal cancers as well as primary epithelial invasive ovarian and tubal cancers. INTERPRETATION The sensitivity of the MMS and USS screening strategies is encouraging. Specificity was higher in the MMS than in the USS group, resulting in lower rates of repeat testing and surgery. This in part reflects the high prevalence of benign adnexal abnormalities and the more frequent detection of borderline tumours in the USS group. The prevalence screen has established that the screening strategies are feasible. The results of ongoing screening are awaited so that the effect of screening on mortality can be determined.