Endoscopic Ultrasound in the Diagnosis and Staging of Lung Cancer

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Endoscopic Ultrasound in the Diagnosis and
Staging of Lung Cancer

• Klaus Gottlieb, MD
• FACP, FACG
• Spokane, WA
• 1-888-PEG-TUBE

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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

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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)

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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
  endo-anal ultrasound

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The esophagus a window into the mediastinum
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Lung CancerA 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.

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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.

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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 chests
  center.
• A T4 cancer is a tumor of any size that invades
  vital structures

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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.

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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.

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Stage IIIA Non-small Cell Lung CancerT1, 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.

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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.

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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

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Endoscopic Ultrasound guided fine-needle
aspiration biopsy (EUS-FNA)

• A minimally-invasive complementary tool for
  diagnosis and staging of lung cancer.

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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

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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

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Modalities

• CT-guided transthoracic fine needle aspiration
  (FNA)Limited by surrounding vascular
  structures, size of the targeted lesion.
  Pneumothorax risk.
• MediastinoscopyInvasive, requires general
  anesthesia. Subcarinal  and subaortic (a-p
  window) nodes inaccessible.
• Thoracoscopic biopsy (video-assisted
  thoracoscopy)Limited to inferior mediastinum.
• EUS-FNA

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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.

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Studies

• Role of Transesophageal Endosonography-Guided
  Fine-Needle Aspiration in the Diagnosis of Lung
  CancerFritscher-Ravens A, Soehendra N, Schirrow
  L, Sriram PV, Meyer A, Hauber HP, Pforte
  A.Chest. 2000117339-345

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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).

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Fritscher-Ravens
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Size of malignant lymph nodes
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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.

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Literature
Wiersema MJ, Vazquez-Sequeiros E, Wiersema
LM.Evaluation of mediastinal lymphadenopathy
with endoscopic US-guided fine-needle aspiration
biopsy.Radiology 2001 Apr219(1)252-7
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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.
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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 US-guided 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.
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But what about PET ?
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• 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.

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Practical Aspects of FNA Biopsy
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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.

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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

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NSCLC, aorto-pulmonary window lymphadenopathy

• A 15mm discrete rounded hypoechoic lymph node is
  located in the aorto-pulmonary window in a
  patient with a left upper lobe primary tumor
  (Olympus GF-UM30P).

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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.

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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

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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
  GF-UM30P) confirmed nodal metastases.

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NSCLC, mediastinal lymph node, FNA biopsy

• EUS-guided FNA biopsy (Olympus GF-UM30P) was
  performed on a subcarinal lymph node. Cytology
  confirmed metastatic disease. The needle tip is
  clearly seen in the lymph node (arrow).

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NSCLC, aortic abutment

• Vascular invasion represents nonoperative
  disease. A hypoechoic mediastinal mass is seen
  abutting the aortic arch (in cross-section) for a
  distance of 12mm (arrow).

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Mediastinal Mass, venous compression

• A rounded hypoechoic mass can be seen compressing
  the azygous vein (in longitudinal section).
  EUS-guided FNA biopsy confirmed NSCLC.

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NSCLC, T4, aortic invasion

• The thoracic aorta is seen to be invaded by a
  large irregular mediastinal mass.

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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.

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Bhutani MS.Transesophageal endoscopic
ultrasound-guided mediastinal lymph node
aspiration does the end justify the means?
Editorial.Chest 2000 Feb117(2)298-301
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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
EUS-guided 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 case-to-case
basis.
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