For patients undergoing workup for known or suspected lung cancer, what is the optimal timing of PET/CT? Before or after tissue biopsy confirmation?
The use of PET/CT scanning in the diagnostic and staging workup for lung cancer varies according to local availability and practice. International guidelines vary in their detailed recommendations but generally include PET/CT in diagnostic and staging algorithms for lung cancer.  International guidelines for evaluation of pulmonary nodules also include PET/CT in the diagnostic workup. However, this guideline will focus on the role and optimal timing of PET/CT in the evaluation of patients with more than a pulmonary nodule, where lung cancer has been either confirmed on tissue biopsy or where lung cancer is suspected and where the clinical effort underway aims to confirm this suspicion and to correctly ascertain the disease stage. This guideline restricts its recommendations to the use of PET/CT in the diagnosis and work up of non-small cell lung cancer (NSCLC). The term PET/CT refers to FDG-PET/CT throughout.
Non-systematic Review Evidence
Ideally, guideline recommendations on this question would draw upon high-level evidence that specifically investigated the best timing for PET/CT in the work up of NSCLC. However, extensive literature searches have not identified such evidence so a combination of published recommendations and clinical expertise inform this content.
Even though this section of the guidelines will focus particularly on PET/CT for workup of lung cancer, there exists some overlap with the use of PET/CT for the assessment of pulmonary nodules. Two publications give relatively clear recommendations for the use of PET/CT in the evaluation of pulmonary nodules where lung cancer is suspected. Both papers concentrate on evaluation of pulmonary nodules per se, but pertinent recommendations for lesions suspicious for malignancy are summarized in Table 1. Levels of evidence are given where available.
Table 1. Summarised recommendations for PET/CT in the evaluation of pulmonary nodules suspicious for lung cancer
|Gould 2013||Callister 2015|
|PET/CT is recommended for solid, indeterminate nodules >8mm with low-moderate pre-test probability of malignancy (estimated by clinical judgement or by using a validated model. (Grade 2C)*
*Where factors contributing to a pre-test likelihood of malignancy include age, smoking history, extra-thoracic cancer diagnosis > 5 years prior, size of lesion, spiculation and upper lobe location.
**In practice this would be a common point at which PET/CT would be used, whatever the intent of the clinician.
***The Brock model comprises four smoking variables (smoking intensity, smoking duration, quit time in former smokers, and current smoking status [current versus former]) and seven non-smoking variables (age, race/ethnicity, socioeconomic circumstance estimated by education level, body mass index, personal history of cancer, chronic obstructive pulmonary disease, family history of lung cancer).
PET/CT for staging of known or suspected NSCLC
The other significant use of PET/CT is for non-invasive staging of NSCLC. Again, little data exist to inform us on optimal timing. However, recommendations from published guidelines are summarized in Table 2. Levels of evidence are given where available.
Table 2. Summarised recommendations for PET/CT from published lung cancer guidelines (with key references included)
|NICE 2011||Silvestri 2013||SIGN 2014||NCCN 2016|
|Offer PET/CT as a first test for patients with low to intermediate probability of mediastinal malignancy potentially suitable for curative treatment.
||In patients with clinical (and CT) early stage disease considered for curative intent treatment, PET/CT is recommended to evaluate for metastases (except the brain). (Grade 1B)
||After FDG PET/CT scanning of solitary lung lesions pathological confirmation of results is still required. (Grade C) 
||PET/CT imaging is frequently best performed before biopsy. (Grade 2A)
Evidence summary and recommendations
Of four major international guidelines, only one comments on the timing of PET/CT in the work up of lung cancer , observing that PET/CT is often best performed before biopsy. In patients potentially suitable for curative therapy, UK guidelines  recommend PET/CT as (i) the first test with low likelihood of mediastinal involvement and as (ii) an early test (along with EBUS TBNA) for patients with possible mediastinal involvement. In patients potentially suitable for curative therapy, the Chest guidelines include PET/CT as an early test for patients without extra thoracic involvement on CT and acknowledge the multiple roles of PET/CT including guiding biopsy and staging. The Scottish national guidelines recommend PET/CT for patients potentially suitable for curative therapy and discuss the utility of a negative PET/CT in the exclusion of adrenal metastases. The NCCN guidelines  give detailed recommendations for the use of PET/CT across all stages of NSCLC; these guidelines note that PET/CT may be best performed prior to biopsy. The recommendations are based on a range of studies (details in Table 2) evaluating the sensitivity and specificity of PET/CT compared with other imaging modalities and with tissue sampling.
Investigators have explored the use of PET/CT early in the diagnostic algorithm, performed directly after suspicious CXR without the use of interventing diagnostic CT and indicate the potential for greater efficiency without major increases in cost.
Issues requiring more clinical research study
- Does the use of PET/CT prior to biopsy improve the efficiency and accuracy of diagnosis and staging?
- What factors weigh against the use of PET/CT in the workup of known or suspected NSCLC?
- What are the potential benefits of early PET/CT, following CXR without intervening diagnostic CT? What is the cost-benefit analysis of this approach?
Approach to Content Development
The development of the content addressing this question was based on a non-systematic approach to the literature. There is a relative lack of papers that specifically address the question of optimal timing of PET/CT in the diagnosis and workup of lung cancer. This guideline has therefore explored available international recommendations as well as, appropriate papers that address aspects of the question and has combined these findings with practical clinical expertise.
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