Endoscopic Ultrasound in the Diagnosis and Staging of Lung Cancer[1]

Endoscopic Ultrasound in the Diagnosis and Staging of Lung Cancer Klaus Gottlieb, MD FACP, FACG Spokane, WA 1-888-PEG-TUBE 1-888-PEG-TUBE Advantages of EUS • Superior resolution of target organs and structures. • Image not compromised by intervening bowel gas. • Lesions as small as 2-3mm in diameter can be imaged. • Ability to obtain real-time guided biopsies 1-888-PEG-TUBE 1-888-PEG-TUBE 1-888-PEG-TUBE EUS-Traditional Indications • 1. Staging of esophageal, gastric and rectal cancer • 2. Evaluation of abnormalities of the gastrointestinal wall or adjacent structures (submucosal masses, extrinsic compression) • 3. Evaluation of thickened gastric folds • 4. Diagnosis (FNA) and staging of pancreatic cancer • 5. Evaluation of pancreatic abnormalities (suspected masses, cystic lesions including pseudocysts, suspected chronic pancreatitis) 1-888-PEG-TUBE EUS-Traditional Indications • • • • 6. Staging of ampullary neoplasms 7. Diagnosis and staging of cholangiocarcinoma 8. Evaluation of suspected choledocholithiasis 9. Celiac plexus neurolysis for chronic pain due to intra-abdominal malignancy or chronic pancreatitis • 10. Evaluation of fecal incontinence with endoanal ultrasound 1-888-PEG-TUBE The esophagus: a window into the mediastinum 1-888-PEG-TUBE Lung Cancer:A Brief Overview • In the US, lung cancer is the most common cause of cancer deaths among both men and women. • In fact, north Americans have the highest rates of lung cancer in the world. In 1997, some 178,100 new cases were diagnosed and roughly 160,400 deaths occurred from the disease. • Sadly, the 5-year survival rate for patients with lung cancer is only 14%. 1-888-PEG-TUBE Histology • Nonsmall cell lung cancer is more common than small cell lung cancer, and it generally grows and spreads more slowly. There are three main types of non-small cell lung cancer: squamous cell carcinoma (also called epidermoid carcinoma), adenocarcinoma, and large cell carcinoma. • Small cell lung cancer, sometimes called oat cell cancer , is less common than non-small cell lung cancer. This type of lung cancer grows more quickly and is more likely to spread to other organs in the body. 1-888-PEG-TUBE T-Staging • A T1 cancer is less than 3 cm in size and completely surrounded by lung tissue. • A T2 cancer is larger than 3 cm still surrounded by lung tissue • A T3 cancer is a cancer of any size that invades the chest wall or the structures of the chest’s center. • A T4 cancer is a tumor of any size that invades vital structures 1-888-PEG-TUBE N-Staging • N0 absence of any lymph node involvement. • N1 presence of cancer in the hilar lymph nodes. • N2 refers to an involvement of the mediastinal lymph nodes on the cancer side. • N3 cancers involve the lymph nodes on the other side of the chest, or in the supraclavicular area. 1-888-PEG-TUBE 1-888-PEG-TUBE Stage II Non-small Cell Lung Cancer T1, N1, M0 or T2, N1, M0 or T3, N0, M0 • 1. Lobectomy; pneumonectomy; or segmental, wedge, or sleeve resection as appropriate. • 2. Radiation therapy with curative intent (for potentially operable patients who have medical contraindications to surgery). • 3. Clinical trials of adjuvant chemotherapy with or without other modalities following curative surgery. • 4. Clinical trials of radiation therapy following curative surgery. 1-888-PEG-TUBE Stage IIIA Non-small Cell Lung Cancer T1, N2, M0 or T2, N2, M0 or T3, N1, M0 or T3, N2, M0 • 1. Surgery alone in operable patients without bulky lymphadenopathy. • 2. Radiation therapy alone, for patients who are not suitable for neoadjuvant chemotherapy plus surgery. • 3. Chemotherapy combined with other modalities. 1-888-PEG-TUBE Stage IIIB Non-small Cell Lung Cancer • Patients with stage IIIB non-small cell lung cancer (NSCLC) do not benefit from surgery alone and are best managed by initial chemotherapy, chemotherapy plus radiation therapy, or radiation therapy alone, depending on sites of tumor involvement and performance status. 1-888-PEG-TUBE Stage IV Non-small Cell Lung Cancer • 1. External-beam radiation therapy, primarily for palliative relief of local symptomatic tumor growth. • 2. Chemotherapy. The following regimens are associated with similar survival outcomes: • • • • • • cisplatin plus vinblastine plus mitomycin cisplatin plus vinorelbine cisplatin plus paclitaxel cisplatin plus docetaxel cisplatin plus gemcitabine carboplatin plus paclitaxel 1-888-PEG-TUBE Endoscopic Ultrasound guided fine-needle aspiration biopsy (EUS-FNA): • A minimally-invasive complementary tool for diagnosis and staging of lung cancer. 1-888-PEG-TUBE Diagnosis of Lung Cancer (Histology) • In > 70 % of patients the diagnosis of suspected lung cancer and its histology can be confirmed by bronchoscopy, including brushings, washings, and transbronchial biopsy. • Other methods are employed in the remainder of the cases are • CT-guided transthoracic fine needle aspiration (FNA) • Mediastinoscopy • Thoracoscopic biopsy • EUS-FNA 1-888-PEG-TUBE Mediastinal Lymphadenopathy • The mediastinum may be a suitable location to obtain tissue when mediastinal lymphadenopathy is shown by CT or PET scan and a peripheral lesion is relatively inaccessible or the risk of pneumothorax is prohibitive 1-888-PEG-TUBE Modalities • CT-guided transthoracic fine needle aspiration (FNA): Limited by surrounding vascular structures, size of the targeted lesion. Pneumothorax risk. • Mediastinoscopy: Invasive, requires general anesthesia. Subcarinal and subaortic (a-p window) nodes inaccessible. • Thoracoscopic biopsy (video-assisted thoracoscopy) Limited to inferior mediastinum. • EUS-FNA 1-888-PEG-TUBE EUS-FNA Med LN • Endoscopic Ultrasound guided fine needle aspiration biopsy is a safe and accurate method of evaluating lower paratracheal, subcarinal, aortopulmonic and posterior mediastinal lymphadenopathy. 1-888-PEG-TUBE Studies • Role of Transesophageal EndosonographyGuided Fine-Needle Aspiration in the Diagnosis of Lung Cancer Fritscher-Ravens A, Soehendra N, Schirrow L, Sriram PV, Meyer A, Hauber HP, Pforte A. Chest. 2000;117:339-345 1-888-PEG-TUBE Fritscher-Ravens Chest 2000 • This is a prospective study in which 283 consecutive patients with lung cancer underwent bronchoscopy. In 214 a final diagnosis was established by (trans)bronchial biopsies, washings and brushings. In 69 patients routine investigations were inconclusive. Those with a demonstrated lung lesion and mediastinal lymph nodes on CT were enrolled in the study and underwent EUS guided FNA of suspicious lymph nodes. Patients were excluded if there was a prior history of malignancy, an extrathoracic primary, esophageal stenosis or a severe bleeding diathesis (35 patients enrolled). 1-888-PEG-TUBE Fritscher-Ravens Diagnosis Malignancy (n = 25) SCLC Adenocarcinoma Squamous cell cancer Non-Hodgkins lymphoma Benign (n = 9) Inflammatory Sarcoidosis Anthracosis No. 10 11 3 1 5 2 2 1-888-PEG-TUBE 1-888-PEG-TUBE Size of malignant lymph nodes Size, cm 1 1.1–2 Benign (n = 10) 3 2 Malignant (n = 25) 4 4 2.1–3 >3 1 4 1-888-PEG-TUBE 7 10 Conclusions • Suspected lung cancer and/or mediastinal adenopathy: initial thoracic CT followed by bronchoscopy with cytology and biopsy. • If inconclusive, EUS and guided FNA of the mediastinal nodes avoids further tests in patients with SCLC and in those with NSCLC and contralateral metastasis. These patients are usually treated by chemotherapy and/or radiotherapy. • No evidence of lymph nodes on EUS and those with NSCLC and ipsilateral involvement of nodes, further work-up will be mandatory before surgery. 1-888-PEG-TUBE Literature Wiersema MJ, Vazquez-Sequeiros E, Wiersema LM. Evaluation of mediastinal lymphadenopathy with endoscopic USguided fine-needle aspiration biopsy. Radiology 2001 Apr;219(1):252-7 1-888-PEG-TUBE Wiersema Radiology 2001 Eighty-six consecutive patients with mediastinal lymphadenopathy who did not have a primary gastrointestinal neoplasm were examined. In 29 patients, endoscopic US-guided FNAB of mediastinal lymphadenopathy was performed as a component of staging non-small cell lung cancer (NSCLC); in the remaining 57 patients, it was performed to obtain a primary diagnosis. Final diagnosis was based on clinical follow-up, cytologic, and/or surgical results. 1-888-PEG-TUBE Wiersema Radiology 2001 In 82 patients in whom a final diagnosis was available, the sensitivity, specificity, accuracy, negative predictive value, and positive predictive value of endoscopic USguided FNAB in distinguishing benign from malignant mediastinal lymph nodes were 96%, 100%, 98%, 94%, and 100%, respectively. In those patients who underwent staging of NSCLC, endoscopic US-guided FNAB had superior mediastinal lymph node staging accuracy compared with endoscopic US alone (79%) and CT alone (79%) (P =.01). The results of endoscopic US-guided FNAB prompted a change to nonsurgical management in 66 (80%) of 82 patients who underwent the procedure. 1-888-PEG-TUBE But what about PET ? 1-888-PEG-TUBE 1-888-PEG-TUBE • EUS FNA for LN is highly accurate for lower paratracheal (level 4), subcarinal (level 7), aortopulmonic (level 5), and posterior mediastinal (level 8) lymph nodes. 1-888-PEG-TUBE Practical Aspects of FNA Biopsy 1-888-PEG-TUBE Non-Small-Cell Lung Cancer (NSCLC), subcarinal adenopathy • EUS is able to safely access lymph nodes in the posterior mediastinum. Metastatic involvement of a subcarinal node: 25mm in longest axis, discrete borders and hypoechoic echotexture. 1-888-PEG-TUBE NSCLC, Stage IIIA, ipsilateral nodal metastases • EUS-guided FNA is more accurate than CT in identifying mediastinal nodal metastases. A 20mm rounded hypoechoic mediastinal lymph node is identified 35 cm from the incisors in a patient with a right upper lobe primary tumor. EUS-guided FNA biopsy confirmed nodal metastases 1-888-PEG-TUBE NSCLC, aorto-pulmonary window lymphadenopathy • A 15mm discrete rounded hypoechoic lymph node is located in the aortopulmonary window in a patient with a left upper lobe primary tumor (Olympus GFUM30P). 1-888-PEG-TUBE NSCLC, Stage IIIB, contralateral nodal metastases • Identification of contralateral disease selects out patients for nonsurgical therapies. Mediastinal staging in a patient with a left lower lobe primary tumor revealed a small malignant pleural effusion and bilateral mediastinal nodal metastases. 1-888-PEG-TUBE NSCLC, Stage IIIB, contralateral nodal metastases • Mediastinal staging in a patient with a right middle lobe primary tumor revealed a small right pleural effusion (arrow) and a small rounded hypoechoic contralateral lymph node 1-888-PEG-TUBE NSCLC, Stage IIIA, subcarinal nodal metastases • Multiple discrete subcarinal lymph nodes were identified in a patient with a left upper lobe primary tumor. EUS-guided FNA biopsy (Olympus GFUM30P) confirmed nodal metastases. 1-888-PEG-TUBE NSCLC, mediastinal lymph node, FNA biopsy • EUS-guided FNA biopsy (Olympus GFUM30P) was performed on a subcarinal lymph node. Cytology confirmed metastatic disease. The needle tip is clearly seen in the lymph node (arrow). 1-888-PEG-TUBE NSCLC, aortic abutment • Vascular invasion represents nonoperative disease. A hypoechoic mediastinal mass is seen abutting the aortic arch (in crosssection) for a distance of 12mm (arrow). 1-888-PEG-TUBE Mediastinal Mass, venous compression • A rounded hypoechoic mass can be seen compressing the azygous vein (in longitudinal section). EUS-guided FNA biopsy confirmed NSCLC. 1-888-PEG-TUBE NSCLC, T4, aortic invasion • The thoracic aorta is seen to be invaded by a large irregular mediastinal mass. 1-888-PEG-TUBE Small Cell Lung Cancer, pleural mass • The mediastinal pleura is markedly thickened by an irregular, hypoechoic mass (arrows) and an anechoic malignant effusion is also visible. 1-888-PEG-TUBE Bhutani MS. Transesophageal endoscopic ultrasoundguided mediastinal lymph node aspiration: does the end justify the means? Editorial. Chest 2000 Feb;117(2):298-301 1-888-PEG-TUBE Dr. Bhutani concludes that in patients with known or suspected lung cancer with mediastinal lymph nodes or in patients with mediastinal lymphadenopathy of unknown etiology, EUS-guided transesophageal FNA is a safe and minimally invasive method with high accuracy. When EUS is available, it should be used as the next logical step for mediastinal lymph node sampling if transbronchial methods are nondiagnostic, provided the lymph nodes are not located anterior and lateral to the trachea. Locations such as subcarina, aortopulmonary window, and paraesophageal area are especially suited for EUSguided FNA, as these locations are hard to access during mediastinoscopy. Physicians performing EUS-guided transesophageal FNA can play an important role in helping pulmonary and thoracic surgery colleagues in the workup of mediastinal lymphadenopathy. Even with the development of endobronchial ultrasound-guided FNA, certain lymph node locations may be best approached transesophageally. Future research in this area should focus on the cost, complications, and technical feasibility based on the location of the lymph nodes and accuracy of current and evolving techniques for mediastinal lymph node sampling. This will allow physicians to select the most appropriate sequential application of technology on a caseto-case basis. 1-888-PEG-TUBE 1-888-PEG-TUBE