In people undergoing lung cancer evaluation, does concurrent diagnosis and staging provide greater benefit for patient outcomes compared to sequential testing for diagnosis followed by staging?
In suspected lung cancer, tissue diagnosis may be obtained from the primary mass, or from lymph node or distal metastases. Accurate staging is critical to inform optimum treatment decisions. Timely work up of lung cancer is encouraged to enable patients to receive treatment prior to further disease progression. Staging modalities such as endobronchial and endoscopic ultrasound, have made both diagnosis and staging feasible during the first diagnostic procedure in selected cases..
Systematic Review Evidence
Systematic literature searches did not identify any studies directly comparing concurrent versus sequential diagnosis and staging for improving patient outcomes. The search strategies and inclusion and exclusion criteria are described in detail in the Appendices.
Overview of additional evidence (Non-systematic review)
Timely work up of lung cancer is strongly encouraged or mandated in order to avoid disease progression prior to treatment. In addition, patients report the period during the diagnostic process and waiting for tests in secondary care as the most stressful part off the pathway.
Non-invasive staging of suspected lung cancer is undertaken with staging CT chest and/or CT PET scanning. However, imaging may be insufficiently accurate to obviate the need for tissue sampling, particularly in the mediastinum ; CT size significant or FDG-avid nodes require confirmatory sampling to exclude “false positives”. Endobronchial and/or endoscopic ultrasound guided transbronchial or fine needle aspiration (EBUS-TBNA / EUS-FNA) have allowed nodal sampling to be accurately achieved during a day case procedure with minimal morbidity. Therefore, in selected cases with accessible mediastinal and/or hilar lymph nodes on either CT or CT PET, it is now feasible to achieve staging and diagnosis with EBUS-TBNA/EUS-FNA as the first diagnostic test. If the staging CT shows potentially curable disease, CT PET is recommended. CT PET is more sensitive and specific for mediastinal and hilar nodal metastases, and thus it is best to have CT PET available prior to EBUS-TBNA or EUS-FNA to guide appropriate nodal sampling.
In patients with positive cervical and/or axillary (N3) nodes, pleural disease (M1a) or distal metastases (M1b), percutaneous sampling of such nodes, effusions or deposits to achieve diagnosis and staging may also be considered as the first diagnostic test. This approach may shorten work up times and expedite treatment, and is consistent with guidance issued elsewhere.  Despite this however, direct evidence linking the strategy of concurrent rather than sequential to improved outcomes is lacking.
The size and adequacy of samples obtained via each approach needs to also be factored into the diagnostic algorithm, as does in turn the likely treatment strategy for each individual patient. EBUS-TBNA is usually undertaken with 21G and 22G needles obtaining cytology samples, although 19G needles are in development. There is little specific evidence addressing the adequacy of samples obtained by needles of different gauges. Percutaneous biopsies of metastatic lesions and lung primaries may include both FNA and core biopsies, the latter obtaining samples for histopathological analysis as would endobronchial biopsies of primary lesions. Core biopsies may be associated with a higher complication rate in some patients. Thoracic multidisciplinary meeting discussion may be considered prior to tissue sampling, in order to help select the most appropriate initial modality. Specific guidance with examples has also been published elsewhere in 2011.
Evidence summary and recommendations
Issues requiring more clinical research study
Due to the widespread adoption of minimally invasive staging, it is unlikely that this question will be addressed in prospective, randomised trials. However, the development of standardised lung cancer datasets should be encouraged to promote prospective data capture and subsequent audit at a local, regional and national level. This can drive changes in practice. Comparison of diagnostic and staging data with outcomes would then be informative.
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- Cancer Council Victoria. Optimal care pathway for people with lung cancer.; Available from: http://www.cancer.org.au/content/ocp/health/optimal-care-pathway-for-people-with-lung-cancer-june-2016.pdf.
- W Stevens. Recommendations to Expedite the Diagnosis of Lung Cancer. Final Report of the HRC_DHBNZ Funded Project: “Identification of barriers to the early diagnosis of people with lung cancer and description of best practice solutions”. New Zealand: Northern Cancer Network; Available from: http://www.northerncancernetwork.org.nz/LinkClick.aspx?fileticket=Xgn%2bFhw6HAQ%3d&tabid=101&language=en-US.
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- National Collaborating Centre for Cancer for NICE. The Diagnosis and Treatment of Lung Cancer (Update). 2011 Apr Available from: http://www.nice.org.uk/nicemedia/live/13465/54199/54199.pdf.
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- Evison M, Crosbie P, Martin J, Shah R, Doran H, Borrill Z, et al. EBUS-guided mediastinal lung cancer staging: monitoring of quality standards improves performance. Thorax 2016 Aug;71(8):762-3 Available from: http://www.ncbi.nlm.nih.gov/pubmed/27146201.