2006

2006 Role of endoscopic ultrasound in the staging and management of lung cancer --- a literature review

Dr. Kin-chung Ng, Department of Medicine and Geriatrics, Caritas Medical Center

Lung Cancer is a leading cause of death among all diseases in developed countries, including Hong Kong. In 2000, there were 41.5 new cases of lung cancer per 100,000 population.1 Tumours with similar clinical outcomes are grouped under the same TMN stage, and each of these stages carries different prognosis and survival, and has different treatment strategies. As mediastinal lymph nodes are the most common site of metastases (75%) for regionally-advanced non-small cell lung cancer (NSCLC)2, a correct mediastinal nodal staging with histological diagnosis is crucial in our management of lung cancer.

Mediastinotomy and mediastinoscopy are well adopted as the “gold standard” for lung cancer staging as they can get a tissue diagnosis for pathological staging. Yet, they have the disadvantages of being invasive and require general anaesthesia. Computed tomography (CT) and positron emission tomography (PET) are alternatives for nodal staging, but they have their own limitations. Endoscopic ultrasound (EUS) has well-established values in the diagnosis and management of various gastrointestinal diseases. Since early 1980s, gastroenterologists have been exploring the role of EUS in nodal staging of lung cancers. For chest physicians, Kondo et al were the pioneers, with their first published series of 132 cases in 1990.3

Transoesophageal EUS can readily identify lymph nodes in the subcarinal, para-oesophageal and paratracheal regions, with pretracheal and intrapulmonary regions being the blind spots as ultrasound cannot penetrate through air-filled structures. Moreover, it can assess lymph nodes as small as 5mm4, and is superior to CT which can only visualize structures more than 1cm. Furthermore, EUS can obtain a tissue diagnosis rather than only an image by CT and PET scan. Only conscious sedation is required and is non-invasive as compared with thoracotomy. Overall, EUS-fine needle aspiration (FNA) has a sensitivity and specificity of 88 to 96% and 80 to 100% respectively.5 Varadarajulu et al also explored the role of transoesophageal EUS in staging of T4 lung cancer, with sensitivity and specificity of 87.5% and 98% in their study.6 In addition, as the negative predictive value of CT was 82%7, CT will miss 18% lung cancer patients with mediastinal diseases. Yet, using EUS, LeBlanc and Wallace could upstage the CT lung cancer staging and altered management in 25% of patients, avoiding them from unnecessary surgeries.8,9

On the other hand, high costs of the equipment involved, special training requirements and inaccessibility to anterior mediastinum are the potential limitations of transoesophageal EUS.

The invention of endobronchial ultrasound (EBUS) and exploration of its role on lung cancer staging by Hurter and Hanrath in 1990 is an important breakthrough.10 EBUS-transbronchial needle aspiration (TBNA) allows real-time targeting of either mediastinal lymph nodes or lung lesions as compared with “blind” biopsy of traditional TBNA. The use of small-gauze needles minimizes risks of procedure-related bleeding. Puncturing blood vessel between bronchial wall and the lesion can be avoided by pre-biopsy Doppler examination. EBUS is particularly useful for evaluation of anterior mediastinal lymph nodes, and can access lymph nodes as small as 5mm in short axis in close proximity to major vessels.11 In addition, it is a safe procedure and can be done on out-patient basis without need of general anaesthesia.

Anatomically, transoesophageal EUS and EBUS-TBNA are complimentary to each other, so both anterior and posterior mediastinal lymph nodes can be assessed together. Rintoul el al and Vilmann’s group showed that accuracy of mediastinal nodal staging could be improved to 100% if both procedures were performed.12,13

EUS-FNA also allows us to get minimal tissue for detection of micrometastases in mediastinal lymph nodes. Such molecular staging by detecting tumour markers such as Muc 1, lunx and telomerase has important implications in terms of tumour prognosis and choice of treatment.

In conclusion, EUS-FNA and EBUS-TBNA are well proven to have high sensitivity and specificity in lung cancer mediastinal staging. Still, most endoscopists doing EUS and EBUS are on their learning curves, and such technology has not been widely adopted as initial step of lung cancer staging. The availability of resources is another important issue. With the publications of more large-scale prospective studies on EUS and EBUS, we hope that these 2 technologies can play an early and essential step in lung cancer staging in the near future.

References:

1. Hong Kong Cancer Registry 2000.
2. Ries LA, Eisner MP, Kosary CL, et al. SEER Cancer Statistics Review, 1975-2001. Bethesda, National Caner Institute, 2001.
3. Kondo D, Imaizumi M, Abe T, Naruke T, Suemasu K. Endoscopic ultrasound examination for mediastinal lymph node metastases of lung cancer. Chest 1990; 98: 586-593.
4. Vilmann P. Endoscopic ultrasonography-guided fine-needle aspiration biopsy of lymph nodes. Gastrointest Endosc 1996; 43: S24-29.
5. Savoy AD, Ravenel JG, Joffman BJ, et al. Endoscopic ultrasound for thoracic malignancy: a review. Curr Probl Diagn Radiol 2005; 34: 106-115.
6. Varadarajulu S, Schmulewitz N, Wildi SM, et al. Accuracy of EUS in staging of T4 lung cancer. Gastrointest Endosc 2004; 59: 345-348.
7. Toloza EM, Harpole L, McCrory DC. Noninvasive staging of non-small cell lung cancer: a review of the current evidence. Chest 2003; 123: 137S-146S.
8. LeBlanc JK, Devereaux BM, Imperiale TF, et al. Endoscopic ultrasound in non-small cell lung cancer and negative mediastinum on computed tomography. Am J Respir Crit Care Med 2005; 171: 177-182.
9. Wallace MB, Ravenel J, Block MI, et al. Endoscopic ultrasound in lung cancer patients with a normal mediastinum on computed tomography. Ann Thorac Surg 2004; 77: 1763-1768.
10. Hurter T, Hanrath P. Endobronchial sonography in the diagnosis of pulmonary and mediastinal tumours. Dtsch Med Wochenschr. 1990; 115(50): 1899-1905.
11. Yasufuku K, Chiyo M, Koh E, et al. Endobronchial ultrasound guided transbronchial needle aspiration for staging of lung cancer. Lung Cancer 2005; 50: 347-354.
12. Rintoul RC, Skwarski KM, Murchison JT, et al. Endobronchial and endoscopic ultrasound-guided real-time fine-needle aspiration for mediastinal staging. Eur Respir J 2005; 25: 416-421.
13. Vilmann P, Krasnik M, Larsen SS, et al. Transoesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy: a combined approach in the evaluation of mediastinal lesions. Endoscopy 2005; 37: 833-839.