The value of FDG positron emission tomography/computerised tomograph (PET/CT) in pre-operative staging of colorectal cancer: a systematic review and economic evaluation
The value of FDG positron emission tomography/computerised tomograph (PET/CT) in pre-operative staging of colorectal cancer: a systematic review and economic evaluation
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DOI：
10.3310/hta15350
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发表时间：
2011-09-01
影响因子：
3.6
通讯作者：
Dunlop, M.
中科院分区：
文献类型：
--
作者：
Brush, J.;Boyd, K.;Dunlop, M.
目的：在英国，结直肠癌 (CRC) 是第三大常见恶性肿瘤（仅次于肺癌和乳腺癌），2006 年登记了 37,514 例结直肠癌：约三分之二 (23,384) 发生在结肠，三分之一 (14,130) 发生在直肠。结肠癌的治疗方法可能有很大差异，但手术切除是达到治愈目的的主要治疗方法。手术切除后，对肿瘤、其侵袭特征和扩散进行全面评估（肿瘤分期）。 CRC 术前分期采用多种成像方式，包括：计算机断层扫描（CT）、磁共振成像、超声成像和正电子发射断层扫描（PET）。本报告探讨了 CT 与 PET 扫描（PET/CT“混合”扫描）相结合的作用。研究目标是：使用系统评价方法评估氟-18-脱氧葡萄糖（FDG）PET/CT对原发性、复发性和转移性癌症术前分期的诊断准确性和治疗效果；进行概率决策分析建模（使用蒙特卡罗模拟）；并进行信息价值分析，以帮助判断是否有进行进一步研究的潜在价值。 数据来源：对于研究的每个方面，系统评价、手工检索研究和经济评估，通过对已发表和未发表研究的全面检索而形成数据库，其中包括数据库检索、参考文献列表检索和与专家的联系。在系统评价中，前瞻性和回顾性患者系列（诊断队列）和随机对照试验（RCT）均符合纳入条件。包括连续系列和未明确报告为连续的系列。审查方法：两名审查员提取所有数据并独立应用标准，并通过讨论解决分歧。提取了使用研究自己的定义填充 2 x 2 列联表的数据，其中包括真阳性、真阴性、假阳性和假阴性的数量，以及与管理变化相关的数据。诊断准确性研究质量评估清单中的 14 项用于评估纳入研究的方法学质量。患者水平数据用于计算敏感性和特异性以及置信区间 (CI)。数据以森林图的形式绘制。为了进行经济评估，针对每种疾病状态设计了经济模型：原发性、复发性和转移性。这些数据是根据各种信息源（特别是已发表的数据源）和文献，并咨询临床专家而开发和填充的。结果：审查发现 30 项研究符合资格标准。只有两项小型研究评估了 FDG PET/CT 在原发性 CRC 中的应用，目前没有足够的证据支持其常规使用。使用 FDG PET/CT 检测复发性疾病确定了来自五项回顾性研究的数据，观察到的汇总敏感性为 91%（95% Cl 0.87% 至 0.95%），特异性为 91%（95% Cl 0.85% 至 0.95%）。来自接受疑似转移性疾病分期的患者的汇总准确性数据显示，FDG PET/CT 的汇总敏感性为 91%（95% Cl 87% 至 94%），特异性为 76%（95% Cl 58% 至 88%），但研究质量较差意味着数据的有效性可能会受到多种偏差的影响。单独的手工检索研究没有产生任何与 FDG PET/CT 相关的其他独特研究。复发性疾病模型显示，直肠癌每质量调整生命年 (QALY) 的增量成本效益比为 21,409 磅，结肠癌每质量调整生命年 6189 磅，转移性疾病每质量调整生命年 21,434 磅。手动检索以确定定义或报告不明确的诊断测试的研究的价值仍有待调查。结论：系统评价发现没有足够的证据支持在原发性 CRC 中常规使用 FDG PET/CT，只有少量证据支持其在复发性和转移性 CRC 的术前分期中使用，而且，尽管 FDG PET/CT 被证明可以改变患者管理，但数据存在分歧，研究质量普遍较差。手工检索以确定不太明确定义或报告的诊断测试的研究，但没有发现其他研究。经济评估的主要局限性是由于五个模型中每个模型的关键参数的系统评价的不确定性和缺乏可用证据。为了解决这个问题，在选择模型参数的 DTA 估计值时采用了保守的方法。对每个模型都进行了概率分析，纳入了广泛的不确定性，特别是 DTA 估计的不确定性。没有一个经济模型报告了成本节约，但由于缺乏当前信息，为了确定更可靠的结果，所采用的方法是保守的。经济评估得出的结论是，FDG PET/CT 作为附加成像设备在复发性结肠癌、复发性直肠癌和转移性疾病的术前分期中具有成本效益，但在原发性结肠癌或直肠癌中则不然。进行随机对照试验并同时进行经济评估，以评估 FDG PET/CT 与传统成像（无 PET）相比对复发性和转移性 CRC 术前分期的治疗影响和成本效益是有价值的。
Objectives: In the UK, colorectal cancer (CRC) is the third most common malignancy (behind lung and breast cancer) with 37,514 cases registered in 2006: around two-thirds (23,384) in the colon and one-third (14,130) in the rectum. Treatment of cancers of the colon can vary considerably, but surgical resection is the mainstay of treatment for curative intent. Following surgical resection, there is a comprehensive assessment of the tumour, it's invasion characteristics and spread (tumour staging). A number of imaging modalities are used in the pre-operative staging of CRCs including; computerised tomography (CT), magnetic resonance imaging, ultrasound imaging and positron emission tomography (PET). This report examines the role of CT in combination with PET scanning (PET/CT 'hybrid' scan). The research objectives are: to evaluate the diagnostic accuracy and therapeutic impact of fluorine-18-deoxyglucose (FDG) PET/CT for the pre-operative staging of primary, recurrent and metastatic cancer using systematic review methods; undertake probabilistic decision-analytic modelling (using Monte Carlo simulation); and conduct a value of information analysis to help inform whether or not there is potential worth in undertaking further research.Data sources: For each aspect of the research the systematic review, the handsearch study and the economic evaluation a database was assembled from a comprehensive search for published and unpublished studies, which included database searches, reference lists search and contact with experts. In the systematic review prospective and retrospective patient series (diagnostic cohort) and randomised controlled trials (RCTs) were eligible for inclusion. Both consecutive series and series that are not explicitly reported as consecutive were included.Review methods: Two reviewers extracted all data and applied the criteria independently and resolved disagreements by discussion. Data to populate 2 x 2 contingency tables consisting of the number of true positives, true negatives, false positives and false negatives using the studies' own definitions were extracted, as were data relating to changes in management. Fourteen items from the Quality Assessment of Diagnostic Accuracy Studies checklist were used to assess the methodological quality of the included studies. Patient-level data were used to calculate sensitivity and specificity with confidence intervals (CIs). Data were plotted graphically in forest plots. For the economic evaluation, economic models were designed for each of the disease states: primary, recurrent and metastatic. These were developed and populated based on a variety of information sources (in particular from published data sources) and literature, and in consultation with clinical experts.Results: The review found 30 studies that met the eligibility criteria. Only two small studies evaluated the use of FDG PET/CT in primary CRC, and there is insufficient evidence to support its routine use at this time. The use of FDG PET/CT for the detection of recurrent disease identified data from five retrospective studies from which a pooled sensitivity of 91% (95% Cl 0.87% to 0.95%) and specificity of 91% (95% Cl 0.85% to 0.95%) were observed. Pooled accuracy data from patients undergoing staging for suspected metastatic disease showed FDG PET/CT to have a pooled sensitivity of 91% (95% Cl 87% to 94%) and a specificity of 76% (95% Cl 58% to 88%), but the poor quality of the studies means the validity of the data may be compromised by several biases. The separate handsearch study did not yield any additional unique studies relevant to FDG PET/CT. Models for recurrent disease demonstrated an incremental cost-effectiveness ratio of 21,409 pound per quality-adjusted life-year (QALY) for rectal cancer, 6189 pound per QALY for colon cancer and 21,434 pound per QALY for metastatic disease. The value of handsearching to identify studies of less clearly defined or reported diagnostic tests is still to be investigated.Conclusions: The systematic review found insufficient evidence to support the routine use of FDG PET/CT in primary CRC and only a small amount of evidence supporting its use in the pre-operative staging of recurrent and metastatic CRC, and, although FDG PET/CT was shown to change patient management, the data are divergent and the quality of research is generally poor. The handsearch to identify studies of less clearly defined or reported diagnostic tests did not find additional studies. The primary limitations in the economic evaluations were due to uncertainty and lack of available evidence from the systematic reviews for key parameters in each of the five models. In order to address this, a conservative approach was adopted in choosing DTA estimates for the model parameters. Probabilistic analyses were undertaken for each of the models, incorporating wide levels of uncertainty particularly for the DTA estimates. None of the economic models reported cost-savings, but the approach adopted was conservative in order to determine more reliable results given the lack of current information. The economic evaluations conclude that FDG PET/CT as an add-on imaging device is cost-effective in the pre-operative staging of recurrent colon, recurrent rectal and metastatic disease but not in primary colon or rectal cancers. There would be value in undertaking an RCT with a concurrent economic evaluation to evaluate the therapeutic impact and cost-effectiveness of FDG PET/CT compared with conventional imaging (without PET) for the pre-operative staging of recurrent and metastatic CRC.