MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK.
MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK.
Lancet. 2021 Jun 5;397(10290):2182-2193. doi: 10.1016/S0140-6736(21)00731-5. Epub 2021 May 12.
Ovarian cancer continues to have a poor prognosis with the majority of women diagnosed with advanced disease. Therefore, we undertook the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) to determine if population screening can reduce deaths due to the disease. We report on ovarian cancer mortality after long-term follow-up in UKCTOCS.
In this randomised controlled trial, postmenopausal women aged 50-74 years were recruited from 13 centres in National Health Service trusts in England, Wales, and Northern Ireland. Exclusion criteria were bilateral oophorectomy, previous ovarian or active non-ovarian malignancy, or increased familial ovarian cancer risk. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer generated random numbers to annual multimodal screening (MMS), annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. Follow-up was through national registries. The primary outcome was death due to ovarian or tubal cancer (WHO 2014 criteria) by June 30, 2020. Analyses were by intention to screen, comparing MMS and USS separately with no screening using the versatile test. Investigators and participants were aware of screening type, whereas the outcomes review committee were masked to randomisation group. This study is registered with ISRCTN, 22488978, and ClinicalTrials.gov, NCT00058032.
Between April 17, 2001, and Sept 29, 2005, of 1 243 282 women invited, 202 638 were recruited and randomly assigned, and 202 562 were included in the analysis: 50 625 (25·0%) in the MMS group, 50 623 (25·0%) in the USS group, and 101 314 (50·0%) in the no screening group. At a median follow-up of 16·3 years (IQR 15·1-17·3), 2055 women were diagnosed with tubal or ovarian cancer: 522 (1·0%) of 50 625 in the MMS group, 517 (1·0%) of 50 623 in the USS group, and 1016 (1·0%) of 101 314 in the no screening group. Compared with no screening, there was a 47·2% (95% CI 19·7 to 81·1) increase in stage I and 24·5% (-41·8 to -2·0) decrease in stage IV disease incidence in the MMS group. Overall the incidence of stage I or II disease was 39·2% (95% CI 16·1 to 66·9) higher in the MMS group than in the no screening group, whereas the incidence of stage III or IV disease was 10·2% (-21·3 to 2·4) lower. 1206 women died of the disease: 296 (0·6%) of 50 625 in the MMS group, 291 (0·6%) of 50 623 in the USS group, and 619 (0·6%) of 101 314 in the no screening group. No significant reduction in ovarian and tubal cancer deaths was observed in the MMS (p=0·58) or USS (p=0·36) groups compared with the no screening group.
The reduction in stage III or IV disease incidence in the MMS group was not sufficient to translate into lives saved, illustrating the importance of specifying cancer mortality as the primary outcome in screening trials. Given that screening did not significantly reduce ovarian and tubal cancer deaths, general population screening cannot be recommended.
National Institute for Health Research, Cancer Research UK, and The Eve Appeal.
卵巢癌的预后仍然较差，大多数被诊断为晚期疾病的女性。因此，我们进行了英国卵巢癌筛查协作试验（UKCTOCS），以确定人群筛查是否可以降低疾病死亡率。我们报告了 UKCTOCS 长期随访后的卵巢癌死亡率。
在这项随机对照试验中，从英格兰、威尔士和北爱尔兰的国家卫生服务信托的 13 个中心招募了绝经后年龄在 50-74 岁的女性。排除标准为双侧卵巢切除术、既往卵巢或活动性非卵巢恶性肿瘤或增加的家族性卵巢癌风险。试验管理系统确认了合格性，并使用计算机生成的随机数以 32 人为一组随机分配参与者，以 1:1:2 的比例接受年度多模态筛查（MMS）、年度经阴道超声筛查（USS）或不筛查。随访通过国家登记处进行。主要结局是 2020 年 6 月 30 日前由卵巢或输卵管癌引起的死亡（2014 年世卫组织标准）。分析采用意向性筛查，分别比较 MMS 和 USS 与不筛查，使用多功能测试。调查人员和参与者了解筛查类型，而结果审查委员会对随机分组不知情。本研究在 ISRCTN 注册，编号为 22488978，在 ClinicalTrials.gov 注册，编号为 NCT00058032。
2001 年 4 月 17 日至 2005 年 9 月 29 日，邀请了 1243282 名女性，招募了 202638 名参与者，并进行了随机分配，其中 202562 名被纳入分析：MMS 组 50625 名（25.0%），USS 组 50623 名（25.0%），无筛查组 101314 名（50.0%）。在中位随访 16.3 年（IQR 15.1-17.3）期间，2055 名女性被诊断为输卵管或卵巢癌：MMS 组 522 名（1.0%），USS 组 517 名（1.0%），无筛查组 1016 名（1.0%）。与不筛查相比，MMS 组的 I 期和 IV 期疾病发病率分别增加了 47.2%（95%CI 19.7-81.1），IV 期疾病发病率降低了 24.5%（-41.8-2.0）。MMS 组整体 I 期或 II 期疾病发病率比不筛查组高 39.2%（95%CI 16.1-66.9），而 III 期或 IV 期疾病发病率低 10.2%（-21.3-2.4）。1206 名女性死于该疾病：MMS 组 296 名（0.6%），USS 组 291 名（0.6%），无筛查组 619 名（0.6%）。与不筛查组相比，MMS 组（p=0.58）或 USS 组（p=0.36）卵巢和输卵管癌死亡人数没有显著减少。
MMS 组 III 期或 IV 期疾病发病率的降低不足以转化为挽救生命，这说明了在筛查试验中指定癌症死亡率为主要结局的重要性。鉴于筛查并未显著降低卵巢和输卵管癌的死亡率，因此不能推荐对普通人群进行筛查。
英国国家卫生研究院、英国癌症研究中心和 Eve 呼吁。
