PerspectiveNegative Predictive Value of Positron Emission Tomography and Computed Tomography for Stage T1-2N0 Non–Small-Cell Lung Cancer: A Meta-Analysis
Introduction
Lung cancer is the leading cause of cancer deaths worldwide. In 2008 there were an estimated 1.61 million new cases and 1.38 million deaths worldwide,1 among which 85% were non–small-cell lung cancer (NSCLC). Accurate staging, especially nodal staging, is a crucial factor for evaluation of prognosis and determination of treatment strategy in NSCLC.
Intravenous contrast-enhanced computed tomography (CT) is the most commonly used imaging modality for clinical staging. The predictive ability of CT for mediastinal lymph node metastasis has been well documented, with sensitivity and specificity of 57%-68% and 76-82%, respectively.2, 3, 4, 5, 6 Using the fluorine-18 (18F) fluorodeoxyglucose (FDG) tracer, positron emission tomography (PET) has much better performance in identification of nodal disease because abnormal metabolic uptake generally precedes anatomic change, providing a sensitivity of 79%-85% and a specificity of 87%-92%.2, 3, 4, 5, 6 Combined PET and CT (PET-CT), in particular integrated PET-CT, could further improve the accuracy of malignant node detection by combining information on spatial resolution, anatomic localization, and metabolic activity of the suspicious lesion.7, 8
Traditionally, mediastinoscopy and systematic lymph node dissection have been regarded as the gold standard for the identification of mediastinal lymph node metastasis by offering pathologic proof of malignancy. The emerging transesophageal ultrasound-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) may serve as alternatives to mediastinoscopy but have not yet been validated.9, 10, 11 Nevertheless, all these modalities are invasive and highly dependent on operator expertise.
In theory, tumors in the early stage behave less aggressively and may have a lower risk of lymph node involvement. The reported presence of mediastinal lymph node metastasis in patients with stage I NSCLC determined by CT ranged from 6%-21%; this was verified by mediastinoscopy-based or thoracotomy-based lymph node sampling or dissection.12, 13, 14 The relatively low rate of nodal involvement calls into question how much benefit can be gained from routine invasive staging for patients with PET-CT–identified small primary lesions and negative nodal findings. We performed a meta-analysis to evaluate the negative predictive value (NPV) of PET-CT in patients with stage I NSCLC (AJCC 6th edition stage T1-2N0M0) and further investigate the potential risk factors for nodal involvement.
Section snippets
Study Eligibility and Identification
We attempted to identify all studies that investigated the diagnostic performance of combined FDG-PET and CT, either integrated or visually correlated, for nodal staging in patients with stage I (T1-2N0) NSCLC. Computerized search of the MEDLINE database was performed using the following keywords: positron emission tomography, non–small-cell lung cancer, stage I, lymph node. Mediastinoscopy, thoracotomy-based lymph node dissection, or lymph node sampling was required to verify mediastinal
Study Identification and Quality
Sixty-seven English-language articles were retrieved in our initial literature search. After reviewing these articles and corresponding references, 10 studies were identified as eligible for this analysis.24, 25, 26, 27, 28, 29, 30, 31, 32, 33 Results of the methodology quality assessment for all studies are shown in Table 1. Quality scores in the series ranged from 10 to 16, with both mean and median values of 13. The worst described item was technical specifications of imaging, with a total
Discussion
In this meta-analysis of 10 studies including 1122 patients with PET-CT–determined stage I (T1-2N0) NSCLC, the summary estimated NPV was 0.93 for mediastinal metastasis. The NPVs for mediastinal metastases in T1 and T2 subgroups were 0.94 and 0.89, respectively. In terms of the overall nodal metastases, the summary estimated NPV of PET-CT was 0.87 for stage I NSCLC. To our knowledge, this is the first combined study systemically evaluating the diagnostic performance of combined FDG-PET and CT
Conclusions
In summary, combined PET and CT provide a favorable NPV for mediastinal metastases in clinical T1N0 NSCLC, and the presence of occult mediastinal involvement is around 6%, inferring a low yield from routine invasive staging procedures for this group of patients. Patients with T2 disease, adenocarcinoma histology, or high FDG uptake in primary lesions have a higher risk of nodal metastases, and the invasive staging procedures are recommended before the initiation of any active treatment.
Disclosure
All authors report that they have no relevant relationships to disclose.
Acknowledgments
We would like to thank Dr. Morand Piert and Dr. Kirk Frey for their valuable comments. We also thank Matthew Schipper for his comments on statistical analysis. We are appreciative of the efforts of Paul Stanton for editing the manuscript.
This work was funded in part by R21CA127057 and R01 CA142840.
References (50)
- et al.
Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]
(2010) - et al.
Combining independent studies of diagnostic fluorodeoxyglucose positron-emission tomography and computed tomography in mediastinal lymph node staging for non-small cell lung cancer
Tumori
(2006) - et al.
Meta-analysis of positron emission tomographic and computed tomographic imaging in detecting mediastinal lymph node metastases in nonsmall cell lung cancer
Ann Thorac Surg
(2005) - et al.
Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: a meta-analysis
Ann Intern Med
(2003) - et al.
Noninvasive staging of non-small cell lung cancer: a review of the current evidence
Chest
(2003) - et al.
Metastases from non-small cell lung cancer: mediastinal staging in the 1990s—meta-analytic comparison of PET and CT
Radiology
(1999) - et al.
Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography
N Engl J Med
(2003) - et al.
The accuracy of integrated PET-CT compared with dedicated PET alone for the staging of patients with nonsmall cell lung cancer
Ann Thorac Surg
(2004) - et al.
Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial
JAMA
(2010) - et al.
Mediastinoscopy in patients with lung cancer and negative endobronchial ultrasound guided needle aspiration
Ann Thorac Surg
(2010)
The true false negative rates of esophageal and endobronchial ultrasound in the staging of mediastinal lymph nodes in patients with non-small cell lung cancer
Ann Thorac Surg
Mediastinoscopy in patients with clinical stage I non-small cell lung cancer
Ann Thorac Surg
T1 lung cancer: prevalence of mediastinal nodal metastases and diagnostic accuracy of CT
Radiology
N2 disease in T1 non-small cell lung cancer
Ann Thorac Surg
Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative
Fam Pract
The combination of estimates from different experiments
Biometrics
An evaluation of homogeneity tests in meta-analyses in pain using simulations of individual patient data
Pain
Quantifying heterogeneity in a meta-analysis
Stat Med
Measuring inconsistency in meta-analyses
BMJ
Methods for Meta-Analysis in Medical Research
Meta-analysis in clinical trials
Control Clin Trials
Statistical aspects of the analysis of data from retrospective studies of disease
J Natl Cancer Inst
Estimators of the Mantel-Haenszel variance consistent in both sparse data and large-strata limiting models
Biometrics
Non-small cell lung cancer: FDG PET for nodal staging in patients with stage I disease
Radiology
Mediastinal lymph node staging by FDG-PET in patients with non-small cell lung cancer: analysis of false-positive FDG-PET findings
Respiration
Cited by (116)
Video-assisted mediastinoscopic lymphadenectomy (VAMLA): Mature results for staging non–small cell lung cancer with normal mediastinum
2024, Journal of Thoracic and Cardiovascular SurgeryBilan d'extension du cancer bronchique et classification TNM des CBNPC
2023, Revue des Maladies Respiratoires ActualitesLung cancer: Diagnostic techniques
2023, Lung Cancer: an Evidence-Based Approach to Multidisciplinary ManagementBilan du cancer broncho-pulmonaire non à petites cellules : quel bilan anatomique ?
2022, Revue des Maladies Respiratoires Actualites
This study was presented as a Mini oral presentation at the 14th World Conference on Lung Cancer, Amsterdam, Netherland, (July 3-7, 2011).