Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial.
Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial.
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DOI：
10.1016/s0140-6736(15)01224-6
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发表时间：
2016-03-05
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影响因子：
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通讯作者：
Skates SJ
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作者：
Jacobs IJ;Menon U;Ryan A;Gentry-Maharaj A;Burnell M;Kalsi JK;Amso NN;Apostolidou S;Benjamin E;Cruickshank D;Crump DN;Davies SK;Dawnay A;Dobbs S;Fletcher G;Ford J;Godfrey K;Gunu R;Habib M;Hallett R;Herod J;Jenkins H;Karpinskyj C;Leeson S;Lewis SJ;Liston WR;Lopes A;Mould T;Murdoch J;Oram D;Rabideau DJ;Reynolds K;Scott I;Seif MW;Sharma A;Singh N;Taylor J;Warburton F;Widschwendter M;Williamson K;Woolas R;Fallowfield L;McGuire AJ;Campbell S;Parmar M;Skates SJ
卵巢癌预后差，只有40%的患者存活5年。我们设计了这项试验，以确定通过筛查早期发现对卵巢癌死亡率的影响。在这项随机对照试验中，我们从英格兰、威尔士和北方爱尔兰的13个国家卫生服务信托中心招募了50-74岁的绝经后妇女。排除标准为既往双侧卵巢切除术或卵巢恶性肿瘤、家族性卵巢癌风险增加和活动性非卵巢恶性肿瘤。试验管理系统确认了合格性，并使用计算机生成的随机数将32名受试者随机分配到年度多模式筛查（MMS），血清CA 125使用卵巢癌风险算法进行解释，年度经阴道超声筛查（USS）或无筛查，比例为1：1：2。主要结局是截至2014年12月31日因卵巢癌死亡，分别比较MMS和USS，无筛选，由对随机分组不知情的结局委员会确定。所有分析均通过改良的意向筛选进行，排除了我们在随机化后发现的少数女性，这些女性患有双侧卵巢切除术、卵巢癌或在招募前退出登记研究。研究者和参与者了解筛选类型。本试验在ClinicalTrials.gov注册，编号为NCT 00058032。在2001年6月1日至2005年10月21日期间，我们随机分配了202638名妇女：50640名（25.0%）接受MMS，50639名（25.0%）接受USS，101359名（50.0%）不接受筛查。 202546名（> 99.9%）妇女有资格进行分析：MMS组50624名（> 99.9%）妇女，USS组50623名（> 99.9%）妇女，无筛查组101299名（> 99.9%）妇女。 放映于2011年12月31日结束，包括345570 MMS和327775 USS年度放映集。 中位随访时间为11.1年（IQR 10.0 - 12.0），我们在1282名（0.6%）妇女中诊断出卵巢癌：MMS组338名（0.7%），USS组314名（0.6%），无筛查组630名（0.6%）。在这些妇女中，MMS组有148名（0.29%）妇女死于卵巢癌，USS组有154名（0.30%）妇女死于卵巢癌，无筛查组有347名（0.34%）妇女死于卵巢癌。使用考克斯比例风险模型进行的主要分析显示，MMS组0-14年死亡率降低15%（95% CI −3 - 30; p= 0.10），USS组降低11%（95% CI −7 - 27; p= 0.21）。Royston-Parmar灵活参数模型显示，在MMS组中，这种死亡率效应在0-7岁为8%（-20至31），在7-14岁为23%（1-46），在USS组中，0-7岁为2%（-27至26），在7-14岁为21%（-2至42）。一项预先设定的对卵巢癌死亡的分析显示，MMS与未筛查的卵巢癌死亡率存在显著差异（p= 0.021），总体平均死亡率降低20%（-2至40），0-7岁降低8%（-27至43），7-14岁降低28%（-3至49）。虽然在初步分析中死亡率的降低并不显著，但我们注意到当排除流行病例时，MMS的死亡率显著降低。我们注意到7-14岁死亡率降低的令人鼓舞的证据，但在卵巢癌筛查的有效性和成本效益得出确切结论之前，需要进一步随访。医学研究理事会，英国癌症研究，卫生部，前夕呼吁。
Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. In this randomised controlled trial, we recruited postmenopausal women aged 50–74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202 638 women: 50 640 (25·0%) to MMS, 50 639 (25·0%) to USS, and 101 359 (50·0%) to no screening. 202 546 (>99·9%) women were eligible for analysis: 50 624 (>99·9%) women in the MMS group, 50 623 (>99·9%) in the USS group, and 101 299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345 570 MMS and 327 775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0–12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0–14 of 15% (95% CI −3 to 30; p=0·10) with MMS and 11% (−7 to 27; p=0·21) with USS. The Royston-Parmar flexible parametric model showed that in the MMS group, this mortality effect was made up of 8% (−20 to 31) in years 0–7 and 23% (1–46) in years 7–14, and in the USS group, of 2% (−27 to 26) in years 0–7 and 21% (−2 to 42) in years 7–14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p=0·021), with an overall average mortality reduction of 20% (−2 to 40) and a reduction of 8% (−27 to 43) in years 0–7 and 28% (−3 to 49) in years 7–14 in favour of MMS. Although the mortality reduction was not significant in the primary analysis, we noted a significant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7–14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-effectiveness of ovarian cancer screening. Medical Research Council, Cancer Research UK, Department of Health, The Eve Appeal.