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EDITORIAL |
United Kingdom
Recently the use of positron-emission tomography (PET) or PET/computed tomography (PET/CT) has become invaluable in the investigation and staging of lung cancers. Currently in the United Kingdom, there are guidelines from both the National Institute for Health and Clinical Excellence and the Scottish Intercollegiate Guidelines Network regarding the use of PET scanning in lung cancer.1,2 The key points of both guidelines are:
The practice in our unit varies somewhat from these guidelines, thus we looked at the evidence behind some of these guidelines and developed a protocol for the use of PET and PET/CT based on the current literature.
The first point we looked at was the use of in the evaluation of solitary pulmonary nodules (SPNs), as we felt that PET may be unnecessary for peripheral SPNs. Solitary pulmonary nodules are a common problem seen on up to 0.2% of chest radiographs. The prevalence of malignancy in SPNs has a large range, reported as 10% 68%, depending on the definition used (1 6 cm), selection criteria, and prevalence in the population.3 A meta-analysis of 40 studies by Gould and colleagues4 demonstrated PET sensitivity and specificity for malignancy of approximately 96.8% and 77.8%, respectively. They explained how these data need to be interpreted in the light of the pre-test probability of malignancy: "if we assume that the pretest probability of malignancy is 20% for a hypothetical low-risk patient with a pulmonary nodule, the post-test probability is about 1% when the FDG-PET result is negative. In contrast, for a high-risk patient (e.g., pre-test probability = 80%) with negative findings on FDG-PET, the post-test probability of malignancy is 14%. Thus, the negative predictive value depends on the pre-test probability of disease." Therefore, in patients with a high pre-test probability of malignancy (e.g., heavy smokers with a spiculated mass on CT), a negative PET may still leave a relatively high post-test probability of malignancy. In view of this, it is appropriate to offer such patients surgery even after a negative PET scan.
A second concern regarding the use of PET in SPN imaging is the ability to accurately show activity in small nodules. Current PET scanners have a spatial resolution in the order of 5 8 mm, therefore, they may miss lesions below 1 cm in size. Certain malignancies, such as bronchoalveolar carcinomas, adenocarcinoma, or carcinoid tumors may show little or no activity on PET scanning, giving a false-negative result.5 A relatively small Japanese study comprising 57 patients looked at the role of video-assisted thoracoscopic surgery for diagnosis SPNs.6 It concluded that video-assisted thoracoscopic excision of SPNs was safe, PET scanning with sensitivity and specificity of almost 100%; all 57 patients obtained a histological diagnosis, with 57% being malignant. In light of this evidence, our current policy on SPNs is that for a peripheral nodule < 3 cm in a patient fit for surgery, excisional biopsy (preferably by video-assisted thoracoscopic surgery) is the procedure of choice. In patients who have comorbidities making them high risk for surgery, PET and interval CT may be useful.
The second area we looked at was the use of PET in detecting N2/N3 lung cancer. Both sets of United Kingdom guidelines agree that if mediastinal nodes are PET-negative, no biopsy is needed, but that PET-positive nodes need histological confirmation. However, there is evidence to suggest that there may be exceptions to this. The current guidelines published by the European Society of Thoracic Surgeons for 2007 suggest that a PET-negative result may still require histological staging. They state that invasive procedures can be omitted in patients with peripheral tumors and a negative mediastinal PET, but invasive staging remains indicated in cases of central tumors, PET hilar N1 disease, low FDG uptake of the primary tumor, and mediastinal lymph nodes 
16 mm on CT scan. The report agrees that PET-positive nodes need histological confirmation. A recent meta-analysis demonstrated that in patients with lymph nodes > 16 mm on CT and a negative FDG-PET scan, the post-test probability of N2 disease was 21%.7 This suggests that such patients should have histological staging prior to thoracotomy, to prevent unnecessary thoracotomies in this subgroup.
Lastly we looked at the evidence regarding PET vs PET/CT. PET/CT offers the advantage of giving both metabolic and anatomical information. Currently, there are few comparative trials of PET/CT vs PET. PET/CT is especially useful in patients with advanced tumors and extrathoracic disease. One study concluded that PET/CT was significantly more accurate for T staging of NSCLC compared to CT or PET alone, and that all modalities tended to under-stage the tumor; however, equivocal findings were reduced by PET/CT.8 There is some evidence that PET/CT increases the number of patients needing invasive staging compared to PET alone.9 This is explained by the fact that although integrated PET/CT has increased sensitivity (61.1% vs 85.7%) compared to PET, specificity is decreased (94.3%vs 80.6%). This gives fewer false negatives but an increase in false positives, as all false positives then require histological diagnosis, this increases the need for invasive staging. There are some concerns about PET/CT missing small nodules that would be seen on breath-hold CT alone, due to the fact that PET/CT is acquired during shallow breathing and lesions can be missed due to respiratory motion. Currently this is not a real problem as CT is much more available than PET/CT, meaning that almost all patients have had thorax CT prior to PET/CT. However, as PET/ CT becomes more available and cheaper, this may be a concern if used instead of breath-hold CT.10
In conclusion, PET and PET/CT are increasingly useful investigations in the evaluation and staging of lung lesions. They allow us to stage patients more accurately and select the most appropriate candidates for surgery. Nevertheless, any clinician involved in using these imaging techniques must be aware of their strengths and weaknesses. Our current policy, based on the literature, is that all patients who are candidates for surgery or radical radiotherapy should undergo PET, except those with small (< 3 cm) peripheral SPNs. We suggest excisional biopsy for such lesions. PET and PET/CT are useful for evaluating mediastinal disease and metastatic spread, they are most useful for picking up patients with advanced-stage disease or extrathoracic spread. Most reports agree that PET-positive mediastinal nodes require histological confirmation, but in contrast to some guidelines, it appears that a negative PET result for mediastinal lymphadenopathy may still need further evaluation prior to thoracotomy.
REFERENCES
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