Staging Work-up for Early Lung Cancer: The More the Better?

Article information

Tuberc Respir Dis. 2017;80(4):403-404
Publication date (electronic) : 2017 September 08
doi :
1Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
2Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Address for correspondence: Jae Cheol Lee, M.D., Ph.D. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. Phone: 82-2-3010-3208, Fax: 82-2-3010-6961,
Received 2017 August 22; Revised 2017 August 29; Accepted 2017 August 31.

The initial staging work-up is a crucial step in patients with newly diagnosed non-small cell lung cancer (NSCLC) to provide the appropriate treatment and assess the prognosis. The stage of NSCLC is determined by TNM system which is based on the location and extent of the primary tumor (T), the status of lymph nodes (N), and the distant metastasis (M). To apply local treatment of surgery or radiotherapy which has the potential opportunity of cure, it is very important to exclude metastasis. At the time of first presentation, occult metastases can be present in up to 30% of NSCLC patients, especially in adrenal gland and liver1. Because the positron emission tomography/computed tomography (PET/CT) has been proven to be very useful to detect these unsuspected distant and lymph node metastases and to improve the diagnostic accuracy since its introduction, it becomes one of the essential diagnostic modalities in initial staging for lung cancer. PET/CT is currently recommended in pretreatment evaluation of lung cancer regardless of its stage by National Comprehensive Cancer Network (NCCN) guidelines.

In the article of this issue of the Tuberculosis and Respiratory Diseases (TRD), Song et al.2 addressed the necessity of PET/CT and brain magnetic resonance imaging (MRI) in the staging of ground-glass nodular lung adenocarcinoma. They found that the chest computed tomography (CT) did not differ from the combined modality of PET/CT and brain MRI for 403determination of overall stage (94.6% vs. 90.5%; kappa value, 0.712) in the analysis of 74 ground-glass nodules of less than 3 cm in diameter in 72 patients.

Actually, the addition of PET/CT to the conventional methods could alter the treatment in 20%–30% of patients with NSCLC, mostly by upstaging3. According to the PLUS multi-center randomized trial, additional PET/CT prevented unnecessary surgery in almost half of patients4. Two more randomized trials also showed that the use of PET/CT for preoperative staging significantly reduced the unnecessary thoracotomy56. Notably, Maziak et al.6 found that PET/CT was superior to conventional staging for disease at all stages although the greatest benefit was seen at higher stages. Even in stage IA, 5 of 81 patients (6%) were correctly upstaged by PET/CT6. Although we could not see detailed data according to stage in the study by Fischer et al.5, PET/CT reduced the frequency of futile thoracotomy in stage IA–IIB. Based on these, NCCN guidelines recommend PET/CT for initial staging work-up even in stage I. Therefore, it is too early to accept the conclusion of study by Song et al.2 as it is. The problem is that the numbers of enrolled patients in all studies mentioned above do not seem to be enough to draw a clear conclusion, especially in stage IA.

In changing a viewpoint, why does the use of PET/CT in stage IA matter? Aside from the high cost of PET/CT, the incorrect upstaging by PET/CT requires additional investigation, often invasive procedures. Maziak et al.6 showed eight false-positive cases by PET/CT of which the abnormal sites were adrenals, pituitary, tonsils, contralateral lung, and mediastinal nodes. Confirmatory imaging or biopsy was needed as expected. In the study of Song et al.2, incidental fluoro-2-deoxy-D-glucose uptake on PET/CT was found in seven thyroid glands, two adrenal glands, one colon, and one 4R lymph node. None of them was related to lung cancer although it required more tests. The relatively high false positivity and the low risk of missing metastasis may warrant the advocate of no need of PET/CT, particularly in stage IA NSCLC.

Taken together, it is true to say that it's not conclusive at present. We should wait for results of larger, well-designed, randomized, prospective studies to have a correct answer.

Brain is one of the most frequent sites of metastasis from lung cancer. Brain MRI is the diagnostic choice to detect brain metastasis because of its better performance than cranial CT7. The prognosis of patients with brain metastasis is generally poor8 even though patients with oligo-metastasis to brain and otherwise operable stage lung cancer would benefit from aggressive treatment of both lesions9. The detection of multiple brain metastases before treatment enables to avoid unnecessary local therapy to primary site such as surgery or definitive radiotherapy. Therefore, it is important to know the exact status of brain metastasis before making a decision on how to treat.

However, the necessity of brain MRI in preoperative work-up in asymptomatic patients with early stage (especially stage I) lung cancer has been a long debate because of the low incidence of brain metastasis in those patients10 and the high cost of imaging. Actually, silent brain metastasis could be detected preoperatively by brain MRI in 2%–5% of patients with potentially operable NSCLC710. But, the actual incidence of brain metastasis seems to be much lower in stag I NSCLC. Among 643 patients with stage IA in the National Lung Screening Trial, 77 patients (12%) received at least one brain imaging study. There was no intracranial metastasis11. In addition, Yohena et al.10 could not detect any metastatic brain lesion in 80 patients with stage I NSCLC. Hence, the routine use of brain MRI is not recommended in stage IA and optional in stage IB by NCCN guidelines. Accordingly, Song et al.2 also could not find out brain metastasis in all of enrolled patients by brain MRI. At present, it seems like there is no argument over the needlessness of brain MRI during work-up for stage IA NSCLC.

Song et al.2 in this issue of TRD addressed one of unsolved questions in the diagnosis of NSCLC. Although the conclusion suggested by authors should be regarded with caution because of the limitations of the study and the previous contradictory results of others, we expect that more clear answers will come out in the near future through this kind of efforts.


Conflicts of Interest: No potential conflict of interest relevant to this article was reported.


1. Sider L, Horejs D. Frequency of extrathoracic metastases from bronchogenic carcinoma in patients with normal-sized hilar and mediastinal lymph nodes on CT. AJR Am J Roentgenol 1988;151:893–895. 2845761.
2. Song JU, Song J, Lee KJ, Kim H, Kwon OJ, Choi JY, et al. Are there any additional benefits to performing positron emission tomography/computed tomography scans and brain magnetic resonance imaging on patients with ground-glass nodules prior to surgery? Tuberc Respir Dis 2017;8. [Epub]. 10.4046/trd.2017.0050.
3. Changlai SP, Tsai SC, Chou MC, Ho YJ, Kao CH. Whole body 18F-2-deoxyglucose positron emission tomography to restage non-small cell lung cancer. Oncol Rep 2001;8:337–339. 11182051.
4. van Tinteren H, Hoekstra OS, Smit EF, van den Bergh JH, Schreurs AJ, Stallaert RA, et al. Effectiveness of positron emission tomography in the preoperative assessment of patients with suspected non-small-cell lung cancer: the PLUS multicentre randomised trial. Lancet 2002;359:1388–1393. 11978336.
5. Fischer B, Lassen U, Mortensen J, Larsen S, Loft A, Bertelsen A, et al. Preoperative staging of lung cancer with combined PET-CT. N Engl J Med 2009;361:32–39. 19571281.
6. Maziak DE, Darling GE, Inculet RI, Gulenchyn KY, Driedger AA, Ung YC, et al. Positron emission tomography in staging early lung cancer: a randomized trial. Ann Intern Med 2009;151:221–228. 19581636.
7. Yokoi K, Kamiya N, Matsuguma H, Machida S, Hirose T, Mori K, et al. Detection of brain metastasis in potentially operable non-small cell lung cancer: a comparison of CT and MRI. Chest 1999;115:714–719. 10084481.
8. Penel N, Brichet A, Prevost B, Duhamel A, Assaker R, Dubois F, et al. Pronostic factors of synchronous brain metastases from lung cancer. Lung Cancer 2001;33:143–154. 11551409.
9. Griffioen GH, Toguri D, Dahele M, Warner A, de Haan PF, Rodrigues GB, et al. Radical treatment of synchronous oligometastatic nonsmall cell lung carcinoma (NSCLC): patient outcomes and prognostic factors. Lung Cancer 2013;82:95–102. 23973202.
10. Yohena T, Yoshino I, Kitajima M, Uehara T, Kanematsu T, Teruya T, et al. Necessity of preoperative screening for brain metastasis in non-small cell lung cancer patients without lymph node metastasis. Ann Thorac Cardiovasc Surg 2004;10:347–349. 15658906.
11. Balekian AA, Fisher JM, Gould MK. Brain imaging for staging of patients with clinical stage IA non-small cell lung cancer in the national lung screening trial: adherence with recommendations from the choosing wisely campaign. Chest 2016;149:943–950. 26356134.

Article information Continued