Characterization of a solitary pulmonary nodule was, along with initial staging of non-small cell lung cancer, the first indication for PET imaging approved by CMS in 1998. However, when to obtain a PET/CT in the evaluation a specific patient with a pulmonary nodule is not always a simple question.
This is a discussion of how PET/CT imaging with 18-fluorodeoxyglucose (FDG) fits into the evaluation of a pulmonary nodule, including guidelines from thoracic and radiological societies.
A key question is “how large must a nodule be to display suspicious FDG uptake on PET/CT imaging?”
Unfortunately much of the data on PET for this indication comes from earlier studies. The more recent PET/CT studies cited in current guidelines are at this point nearly 10 years old. Suspicious uptake is often defined as greater than mediastinal blood pool, although a lower threshold may be more appropriate for small nodules. Fletcher JW, et al. A comparison of the diagnostic accuracy of 18F-FDG PET and CT in the characterization of solitary pulmonary nodules. J Nucl Med 2008;49:179-85. Veronesi G, et al. Role of positron emission tomography scanning in the management of lung nodules detected at baseline computed tomography screening. Ann Thorac Surg 2007;84:959-65. Yet PET/CT technology has continued to evolve, with 3-D and time-of-flight systems offering improved signal-to-noise ratio, while using similar or deceased clinical scan times / radiotracer doses. Other factors such as the intensity of uptake (FDG avidity) in a particular type of malignancy certainly play a role, as well as blurring artifact caused by respiratory motion (greater at the lung bases).
In fact the nodule size needed to detect suspicious uptake is not one number, but probably a gradient based on these different factors. Here is conceptual table illustrating this gradient (note: specific numbers not based on published data).
(Of course even this conceptual table has limitations. For example, despite the intense FDG uptake seen in most melanoma lesions, a proportion of melanoma lung metastases are non-FDG avid. Smyth EC, et al. Histology and outcomes of newly diagnosed lung lesions in melanoma patients. Ann Oncol 2012;23:577-582. Also note that PET/CT is currently only recommended in solid nodules greater than 8 mm, discussed below.)
Multiple composite prediction models have been published using clinical information and CT parameters to estimate the probability of malignancy in a pulmonary nodule. Some of the more commonly cited examples are described below:
Mayo Clinic Model: 419 nodules, single center, 23% of nodules were malignant; independent predictors: age, smoking status, history of cancer, nodule diameter, spiculation, upper lobe location. Swensen SJ, et al. The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules. Arch Intern Med 1997;157:849-55.
VA Model: 375 patients, multiple centers, 54% of nodules were malignant; independent predictors: smoking history, age, nodule diameter, shorter time since quitting smoking. Gould MK, et al. A clinical model to estimate the pretest probability of lung cancer in patients with solitary pulmonary nodules. Chest 2007;131:383-8.
Brock Model: 1871 subjects undergoing low-dose CT screening, multiple centers, 5.5% of subjects had malignant nodules; independent predictors: age, female gender, family history of lung CA, emphysema, nodule size, upper lobe location, partly solid nodule, spiculation, fewer # of nodules. McWilliams A, et al. Probability of cancer in pulmonary nodules detected on first screening CT. N Engl J Med 2013;369;910-9.
FDG PET/CT imaging has been shown to significantly increase diagnostic accuracy when incorporated into the Mayo Clinic model. Herder GJ, et al. Clinical prediction model to characterize pulmonary nodules: validation and added value of 18F-fluorodeoxyglucose positron emission tomography. Chest 2005;128:2490-6. Additional improvement in risk stratification provided by PET/CT has been demonstrated in patients with history of cancer but nodules classified as low or intermediate risk by the Mayo Clinic and VA models. Evangelista L, et al. Indeterminate lung nodules in cancer patients: pretest probability of malignancy and the role of 18F-FDG PET/CT. AJR 2014;202:507-14.
Increase in nodule size on serial CT studies is an important risk factor for malignancy. The largest longitudinal study demonstrated that a nodule with a volume-doubling time of >600 days was associated with no increased risk of lung cancer compared to absence of nodules (0.8%). Higher rates of malignancy were seen in nodules with volume-doubling times of 400-600 days (4.0%) and <400 days (9.9%). Horweg N, et al. Detection of lung cancer through low-dose CT screening (NELSON): a prespecified analysis of screening test performance and interval cancers. Lancet Oncol 2014;15:1342-50.
Thoracic Society Recommendations
American College of Chest Physicians Guidelines:
- A solid nodule > 8 mm in diameter with low or moderate pretest probability of malignancy should be evaluated with functional imaging (PET/CT).
- A solid nodule > 8 mm in diameter with high pretest probability of malignancy should not be evaluated with functional imaging.
Gould MK, et al. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence=based clinical practice guidelines. Chest 2013;143:e93S-120S.
British Thoracic Society Guidelines:
- PET/CT should be offered to patients with a pulmonary nodule with an initial risk of malignancy > 10% using the Brock Model, where the nodule size is above the local PET/CT detection threshold.
- Reassess the risk of malignancy after PET/CT using the prediction model described by Herder et al (referenced above).
Callister MEJ, et al. British Thoracic Society guidelines for the investigation and management of pulmonary nodules: accredited by NICE. Thorax 2015;70:ii1-ii54.
Radiology Society Recommendations
(UPDATED JUNE 2019)
Fleischner Society 2017 Guidelines for Incidental Pulmonary Nodules (subjects >35 years of age, without known or suspected malignancy, without immunosuppression)
- Consider PET/CT for solid nodules > 8 mm
- Consider PET/CT for part-solid nodules with solid component > 8 mm
MacMahon H, et al. Guidelines for management of incidental pulmonary nodules detected on CT images: from the Fleischner Society 2017. Radiology 2017;epub Feb 23.
Prior Fleischner Society Recommendations:
MacMahon H, et al. Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. Radiology 2005;237:395-400.
Naidich DP, et al. Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society. Radiology 2013;266:304-17.
ACR Lung-RADS (lung cancer screening population, 55-80 years of age, at least 30 pack-year smoking history)
- PET/CT suggested for Category 4 (Suspicious) nodules with solid component equal or greater than 8 mm
http://www.acr.org/~/media/ACR/Documents/PDF/QualitySafety/Resources/LungRADS/AssessmentCategories.pdf
McKee BJ, et al. Performance of ACR Lung-RADS in a clinical CT lung screening program. JACR 2015;12:273-6.
Change in Management
Like other imaging tests, PET/CT in the evaluation of pulmonary nodule should only be performed if the results will affect patient management. PET/CT is recommended in the 2016 NCCN Guidelines (for solid nodules > 8 mm and for initial staging of non-small cell lung cancer; NCCN Guidelines) in part because prior studies have shown decreased number of “futile” thoracic surgeries in patients whose initial evaluation included PET/CT. Fischer B, et al. Preoperative staging of lung cancer with combined PET-CT. N Engl J Med 2009;361:32-39.