Centre for Primary Care and Public Health, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, UK.
Health Technol Assess. 2013 Mar;17(12):1-323. doi: 10.3310/hta17120.
BACKGROUND: Cancer of the uterine cervix is a common cause of mortality in women. After initial treatment women may be symptom free, but the cancer may recur within a few years. It is uncertain whether it is more clinically effective to survey asymptomatic women for signs of recurrence or to await symptoms or signs before using imaging. OBJECTIVES: This project compared the diagnostic accuracy of imaging using positron emission tomography/computerised tomography (PET-CT) with that of imaging using CT or magnetic resonance imaging (MRI) alone and evaluated the cost-effectiveness of adding PET-CT as an adjunct to standard practice. DATA SOURCES: Standard systematic review methods were used to obtain and evaluate relevant test accuracy and effectiveness studies. Databases searched included MEDLINE, EMBASE, Science Citation Index and The Cochrane Library. All databases were searched from inception to May 2010. REVIEW METHODS: Study quality was assessed using appropriately modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria. Included were any studies of PET-CT, MRI or CT compared with the reference standard of histopathological findings or clinical follow-up in symptomatic women suspected of having recurrent or persistent cervical cancer and in asymptomatic women a minimum of 3 months after completion of primary treatment. Subjective elicitation of expert opinion was used to supplement diagnostic information needed for the economic evaluation. The effectiveness of treatment with chemotherapy, radiotherapy, chemoradiotherapy, radical hysterectomy and pelvic exenteration was systematically reviewed. Meta-analysis was carried out in RevMan 5.1 (The Cochrane Collaboration, The Nordic Cochrane Centre, Copenhagen, Denmark) and Stata version 11 (StataCorp LP, College Station, Texas, USA). A Markov model was developed to compare the relative cost-effectiveness using TreeAge Pro software version 2011 (TreeAge Software Inc., Evanston, IL, USA). RESULTS: For the diagnostic review, a total of 7524 citations were identified, of which 12 test accuracy studies were included in the review: six studies evaluated PET-CT, two evaluated MRI, three evaluated CT and one evaluated both MRI and CT. All studies were small and the majority evaluated imaging in women in whom recurrence was suspected on the basis of symptoms. The PET-CT studies evaluated local and distant recurrence and most used methods similar to current practice, whereas five of the six CT and MRI studies evaluated local recurrence only and not all employed currently used methods. Meta-analysis of PET-CT studies gave a sensitivity of 92.2% [95% confidence interval (CI) 85.1% to 96.0%] and a specificity of 88.1% (95% CI 77.9% to 93.9%). MRI sensitivities and specificities varied between 82% and 100% and between 78% and 100%, respectively, and CT sensitivities and specificities varied between 78% and 93% and between 0% and 95%, respectively. One small study directly compared PET-CT with older imaging methods and showed more true-positives and fewer false-negatives with PET-CT. The subjective elicitation from 21 clinical experts gave test accuracy results for asymptomatic and symptomatic women and the results for symptomatic women were similar to those from the published literature. Their combined opinions also suggested that the mean elicited increase in accuracy from the addition of PET-CT to MRI and/or CT was less than the elicited minimum important difference in accuracy required to justify the routine addition of PET-CT for the investigation of women after completion of primary treatment. For the effectiveness review, a total of 24,943 citations were identified, of which 62 studies were included (chemotherapy, 19 randomised controlled trials; radiotherapy or chemoradiotherapy, 16 case series; radical hysterectomy and pelvic exenteration, 27 case series). None provided the effectiveness of cisplatin monotherapy, the most commonly used chemotherapeutic agent in the NHS, compared with supportive care in a background of other treatment such as radiotherapy in recurrent and persistent cervical cancer. The model results showed that adding PET-CT to the current treatment strategy of clinical examination, MRI and/or CT scan was significantly more costly with only a minimal increase in effectiveness, with incremental cost-effectiveness ratios for all models being > £1M per quality-adjusted life-year (QALY) and the additional cost per additional case of recurrence being in the region of £600,000. LIMITATIONS: There was considerable uncertainty in many of the parameters used because of a lack of good-quality evidence in recurrent or persistent cervical cancer. The evidence on diagnostic and therapeutic impact incorporated in the economic model was poor and there was little information on surveillance of asymptomatic women. CONCLUSIONS: Given the current evidence available, the addition of PET-CT to standard practice was not found to be cost-effective in the diagnosis of recurrent or persistent cervical cancer. However, although probabilistic sensitivity analysis showed that the main conclusion about cost-ineffectiveness of PET-CT was firm given the range of assumptions made, should more reliable information become available on accuracy, therapeutic impact and effectiveness, and the cost of PET-CT reduce, this conclusion may need revision. Current guidelines recommending imaging for diagnosis using expensive methods such as PET-CT need to be reconsidered in the light of the above. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
背景:宫颈癌是导致女性死亡的常见原因。经过初始治疗,女性可能没有症状,但癌症可能在几年内复发。目前还不确定对无症状女性进行复发迹象的筛查,还是在出现症状或体征之前使用影像学检查,哪种方法在临床上更有效。
目的:本研究旨在比较正电子发射断层扫描/计算机断层扫描(PET-CT)与单独使用计算机断层扫描(CT)或磁共振成像(MRI)的诊断准确性,并评估将 PET-CT 作为标准治疗方法的辅助手段的成本效益。
数据来源:采用标准系统评价方法,获取并评估了相关的检测准确性和有效性研究。检索的数据库包括 MEDLINE、EMBASE、Science Citation Index 和 The Cochrane Library。所有数据库均从建库起至 2010 年 5 月进行检索。
研究方法:使用适当修改的诊断准确性研究质量评估(QUADAS)标准评估研究质量。纳入标准为任何关于 PET-CT、MRI 或 CT 与组织病理学发现或症状性疑似复发性或持续性宫颈癌女性的临床随访,以及在初始治疗后至少 3 个月的无症状女性的参考标准比较的研究。使用主观专家意见补充经济评估所需的诊断信息。系统评价了化疗、放疗、放化疗、根治性子宫切除术和盆腔廓清术的有效性。采用 RevMan 5.1(Cochrane 协作组织,北欧 Cochrane 中心,哥本哈根,丹麦)和 Stata 版本 11(StataCorp LP,德克萨斯州 College Station)进行了荟萃分析。使用 TreeAge Pro 软件版本 2011(TreeAge Software Inc.,伊利诺伊州 Evanston)开发了一个 Markov 模型来比较相对成本效益。
结果:在诊断性综述中,共检索到 7524 条引文,其中纳入了 12 项检测准确性研究:6 项研究评估了 PET-CT,2 项研究评估了 MRI,3 项研究评估了 CT,1 项研究同时评估了 MRI 和 CT。所有研究都较小,且大多数研究评估的是基于症状怀疑复发的女性。PET-CT 研究评估了局部和远处复发,且大多数使用的方法与当前实践相似,而 6 项 CT 和 MRI 研究中的 5 项仅评估了局部复发,且并非所有研究都采用了当前的方法。PET-CT 研究的荟萃分析显示,敏感度为 92.2%(95%置信区间 85.1%至 96.0%),特异度为 88.1%(95%置信区间 77.9%至 93.9%)。MRI 的敏感度和特异度在 82%至 100%之间,CT 的敏感度和特异度在 78%至 93%之间。一项小型研究直接比较了 PET-CT 与较旧的成像方法,结果显示 PET-CT 有更多的真阳性和更少的假阴性。21 位临床专家的主观意见提供了无症状和有症状女性的检测准确性结果,这些结果与已发表文献的结果相似。他们的综合意见还表明,与 MRI 和/或 CT 相比,PET-CT 平均增加的准确性小于在常规添加 PET-CT 以调查初始治疗后女性的情况下所需的最低重要差异的准确性。在有效性综述中,共检索到 24943 条引文,其中纳入了 62 项研究(化疗:19 项随机对照试验;放疗或放化疗:16 项病例系列研究;根治性子宫切除术和盆腔廓清术:27 项病例系列研究)。没有一项研究提供了 NHS 中最常用的化疗药物顺铂单药治疗与其他治疗(如放疗)联合治疗复发性和持续性宫颈癌的有效性比较。模型结果显示,与当前的临床检查、MRI 和/或 CT 扫描的治疗策略相比,将 PET-CT 添加到当前治疗策略中显著增加了成本,且仅增加了微小的效果,所有模型的增量成本效益比均超过 £1M 每质量调整生命年(QALY),每例复发的额外成本约为 £600000。
局限性:由于缺乏复发性或持续性宫颈癌的高质量证据,许多参数的使用存在很大的不确定性。纳入的经济模型中的诊断和治疗影响证据质量较差,且对无症状女性的监测信息较少。
结论:鉴于目前的证据,在诊断复发性或持续性宫颈癌方面,添加 PET-CT 并不能带来成本效益。然而,尽管概率敏感性分析表明,鉴于所做的假设范围,关于 PET-CT 的成本效益的主要结论是可靠的,但如果获得关于准确性、治疗效果和有效性的更可靠信息,以及 PET-CT 的成本降低,这一结论可能需要修改。目前关于使用昂贵的方法(如 PET-CT)进行成像诊断的指南需要根据上述情况进行重新考虑。
资助:英国国家卫生研究院卫生技术评估计划。
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