Lung Cancer: Diagnosis, Staging, and Treatment

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Lung CancerDiagnosis, Staging, and Treatment

• Eric D. Anderson, MD, FCCP
• Director, Interventional Pulmonology
• Associate Professor of Medicine
• Division of Pulmonary, Critical Care, Sleep
  Medicine

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Question 1

• Which of the following statements about lung
  cancer in the United States is correct?

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Question 1

• A) There are more new cases of lung cancer each
  year than breast or prostate CA.
• B) Survival of patients diagnosed with lung
  cancer has improved significantly in the past 20
  years.
• C) There are more deaths each year from lung
  cancer than colorectal, breast, prostate
  pancreatic cancers combined.
• D) More women die from breast cancer than lung
  cancer.

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Answer 1

• A) There are more new cases of lung cancer each
  year than breast or prostate CA.
• B) Survival of patients diagnosed with lung
  cancer has improved significantly in the past 20
  years.
• C) There are more deaths each year from lung
  cancer than colorectal, breast, prostate
  pancreatic cancers combined.
• D) More women die from breast cancer than lung
  cancer.

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Lung Cancer

• Most common cause of cancer death in US
• Overall 5 year survival of 15
• More deaths by lung cancer than the next four
  most common cancers combined (Colorectal, Breast,
  Prostate, Pancreas)

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Cancer Deaths in U.S.2007
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Lung Cancer in the U.S.

• Number of patients in the U.S. with lung cancer
  continues to rise
• In 2007 estimated
• 213,380 new cases
• 160,390 deaths
• American Cancer Society 2007.

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Lung Cancer Risk Factors

• Gender
• Smoking history
• Older age
• Presence of airflow obstruction
• Genetic predisposition
• Occupational exposures

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Lung Cancer and Gender

• Male predilection, but changing rapidly
• Increase in women smokers
• In 2007
• 55 Men
• 45 Women

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Age-Adjusted Cancer Death Rates (1930
-1988)Males Females
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LUNG CANCER
Relationship to Smoking
Etiology
Tobacco Percent active 85-87 passive
3-5
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Lung Cancer and Smoking

• 90 of lung cancers attributed to smoking
• However, only 20 smokers will develop lung
  cancer in their lifetime.
• ? Death from other causes ie. CAD, COPD
• Genetic predisposition
• Risk decreases when stop smoking
• Yet, 50 of new cases are former smokers

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Occupational Exposures Linked to 3 - 15 of Lung
CancersProven Suspected

• Arsenic
• Asbestos
• Bischloromethyl ether
• Chromium
• Mustard gas
• Nickel
• Polycyclic aromatic hydrocarbons
• Ionizing radiation

• Acrylonitrile
• Beryllium
• Vinyl chloride
• Silica
• Iron ore
• Wood dust

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Asbestosis Lung Cancer

• Prolonged heavy exposure has relative risk
  between 2 - 10 of causing lung cancer.
• Peak incidence 15 - 24 years after exposure.
• Fiber type is important
• Crocidolite amosite gt chrysotile
  anthophyllite.

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Asbestosis Lung Cancer

• Risk of smoking asbestos exposure is
  multiplied.
• Mortality ratio
• Nonsmoking asbestos worker 5.17
• Smoker 10.85
• Smoker asbestos worker 53.24

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Relative Risk of Developing Lung Cancer
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Lung CancerSymptoms at Presentation

• Due to primary tumor
• Cough, hemoptysis, chest pain, wheezing, dyspnea,
  fever.
• Thoracic extension of tumor
• Chest pain, SVC syndrome, hoarseness, dysphagia.

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Lung CancerSymptoms at Presentation

• Metastases
• Lymph node enlargement, bone pain, neurologic
  deficits, skin subcutaneous lesions.
• Systemic symptoms
• Anorexia, weight loss, weakness, paraneoplastic
  syndromes
• Patients often present with advanced disease due
  to lack of symptoms at early stages.

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Question 2

• A 65 year old male presents with a complaint of
  fevers, chills, a productive cough and scant
  hemoptysis. A CXR is obtained. What diagnostic
  test do you order next?

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Question 2

• A) CT scan of the thorax with IV contrast.
• B) Sputum cytology.
• C) Flexible bronchoscopy.
• D) CT-guided transthoracic needle biopsy.
• E) Surgical resection.

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Answer 2

• A) CT scan of the thorax with IV contrast.
• B) Sputum cytology.
• C) Flexible bronchoscopy.
• D) CT-guided transthoracic needle biopsy.
• E) Surgical resection.

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Lung CancerFindings on Chest X-ray

• Nodule (lt 3cm) vs. Mass (gt 3cm).
• Location
• Peripheral (Adenocarcinoma) vs.
• Central (Squamous).
• Single or multiple (metastases).
• Endobronchial obstruction.
• Atelectasis of lobe or lung.
• Pneumonia.

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Lung CancerThe Chest X-ray

• Hilar and mediastinal adenopathy.
• Pleural effusions.
• Elevated hemidiaphragm.

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Lung CancerCT Scan of Thorax

• Nodule details
• Calcification, spiculation etc..
• Evaluate extension into adjacent structures
• Endobronchial, great vessels, pericardium etc..
• Evaluation of adenopathy.
• Upper abdominal pathology
• Metastatic lesions in liver, adrenals, kidneys.

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Lung CancerSputum Cytology

• Helpful for central lesions.
• With three samples
• 80 detection rate of centrally located tumors.
• 50 detection rate of peripheral lesions.

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Lung CancerVideo Flexible Bronchoscopy

• Excellent to evaluate endobronchial disease.
• Brushings and bronchial biopsies are high yield
  for visible lesions.
• Transbronchial biopsies of large peripheral
  lesions /- fluoroscopic guidance.
• Evaluation of obstruction for stent placement
  brachytherapy.

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Lung CancerTransbronchial Needle Aspiration
(TBNA)

• Allows biopsy of subcarinal paratracheal lymph
  nodes during flexible bronchoscopy.
• Helpful for staging.
• Minimal risk to patient.

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Lung CancerCT - Guided Transthoracic Needle
Biopsy

• Peripheral lesions away from diaphragm.
• 25 pneumothorax risk.
• May be beneficial for poor operative candidates.
• Remember
• Negative needle biopsy result may be false
  negative.

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Question 3

• Patient is a 65 year old smoker with following
  CXR and CT scan of chest

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Question 3

• What test do we order next?
• A. CT-guided lung biopsy.
• B. Video Assisted Thoracic Surgical open lung
  biopsy with possible lobectomy.
• C. PET scan.
• D. PFTs.
• E. CT scan of head.

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Answer 3

• What test do we order next?
• A. CT-guided lung biopsy.
• B. Video Assisted Thoracic Surgical open lung
  biopsy.
• C. PET scan.
• D. PFTs.
• E. CT scan of head.

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Answer 3

• Mediastinoscopy or Transbronchial Needle
  Aspiration (TBNA)
• would also have been an appropriate method of
  staging mediastinum.

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Lung CancerPET Scan

• Marker of active glucose metabolism.
• Can detect lesions to 0.8cm.
• 90 sensitivity 85 specificity.
• Indications
• Staging lung cancer.
• Solitary pulmonary nodule.

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PET Case

• 85 yo male with h/o COPD and s/p LLL lobectomy in
  2003 for stage IA adenocarcinoma.
• Follow up CT chest

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PET/CT
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Lung CancerOther Diagnostic Tests

• Thoracentesis.
• Surgical resection
• Thoracotomy vs. VATS.

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Staging of the Mediastinum

• Mediastinoscopy
• Mediastinal lymphadenopathy staging.
• Central lesions.
• Large peripheral lesions.
• Gold Standard.

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Newer Technologies

• Endobronchial Ultrasound (EBUS)
• Endoscopic Ultrasound (EUS)

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Histology of Lung Cancers in U.S.
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Adenocarcinoma

• Most common cell type in US.
• Peripheral location.
• Glandular formation.
• Mucin production.

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Bronchoalveolar Cell Carcinoma

• Subtype of adenocarcinoma.
• Preservation of alveolar architecture.
• Spread through the airways.
• May present as unresolving pneumonia.

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Squamous Cell Carcinoma

• Cavitation.
• Centrally located along airways.
• Intravascular invasion.
• Intercellular bridging.
• Keratinization.

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Squamous Cell Carcinoma

• Keratin pearls.
• Nests of cells.

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Large Cell Carcinoma

• A poorly differentiated carcinoma.
• Diagnosis of exclusion.
• Large cells.
• Abundant cytoplasm.
• Large nuclei with prominent or vesicular nucleoli.

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NonSmall Cell CancerT Stage

• T1 lt 3cm in diameter, contained within
  visceral pleura.
• T2 gt 3cm in diameter, gt 2cm away from carina,
  invading into visceral pleura, or lobar
  atelectasis
• T3 any size, extension into chest wall,
  diaphragm, mediastinum, (but not great vessels)
  or lt2cm from carina or atelectasis of entire lung

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NonSmall Cell CancerT Stage

• T4 any size invading into great vessels, heart,
  trachea, esophagus, vertebrae, main carina or
  malignant pleural effusion.

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NonSmall Cell CancerN Stage

• N0 No nodes.
• N1 Ipsilateral hilar or peribronchial.
• N2 Ipsilateral mediastinal, subcarinal.
• N3 Contralateral hilar, contralateral
  mediastinal or supraclavicular/scalene.

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Non Small Cell Carcinoma Staging
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Non Small Cell CASurvival Months after Treatment
CF Mountain. Chest. 1997 111(6).
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Non Small Cell CASurvival Months after Treatment
CF Mountain. Chest. 1997 111(6).
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Upcoming Changes

• Satellite nodules ?T3
• Malignant effusions. ?stageIV
• Nodules in same lung but different lobe. StageIV?

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Neuroendocrine Lung Tumors

• Small cell carcinoma.
• Atypical carcinoid.
• Typical carcinoid.

• Malignant
• Intermediate
• Benign

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Small Cell Carcinoma

• Aggressive tumor.
• Smokers.
• Centrally located.
• Bulky adenopathy is common.
• Distant metastases common on presentation.

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Small Cell Carcinoma

• Small cells.
• Fine chromatin pattern.
• Abundant mitosis.
• Scant cytoplasm.
• Tends to smudge on microscopy.
• Synaptophysin chromogranin.

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Carcinoid

• Typical carcinoid
• Usually endobrochial.
• Present with postobstructive pneumonia.
• Surgical resection is curative.
• Atypical carcinoid
• More aggressive.
• May require surgery with chemotherapy.

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Small Cell Lung CancerStaging

• Limited
• 30-40 of small cell lung cancers.
• Confined to the hemithorax, mediastinum, and
  ipsilateral supraclavicular lymph node.
• Within the confines of radiation port.
• Extensive
• 60-70 of small cell lung cancers.
• Any distant spread.

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Lung CancerWhy the Poor Prognosis?

• Survival statistics reveal the advanced stage at
  time of diagnosis
• Presentation is often after the patient becomes
  symptomatic
• Usually Stages IIIA/B or IV
• These stages have poor long term survival
  lt 10 at 5 years

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Lung CancerWhy the Poor Prognosis?

• Successful surgical resection and cure are only
  possible at early stages
• In U.S. only 20-25 of newly detected lung cancer
  is Stage I

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Question 4

• 60 yo male smoker with 4.1 cm solitary
  adenocarcinoma. What is the best option for
  treatment/survival?
• Wedge resection.
• Lobectomy.
• Lobectomy with adjuvant chemotherapy.
• Lobectomy with adjuvant radiation.
• Lobectomy with adjuvant chemotherapy and
  radiation.

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Answer 4

• 60 yo male smoker with 4.1 cm solitary
  adenocarcinoma. What is the best option for
  treatment/survival?
• Wedge resection.
• Lobectomy.
• Lobectomy with adjuvant chemotherapy.
• Lobectomy with adjuvant radiation.
• Lobectomy with adjuvant chemotherapy and
  radiation.

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Non Small Cell Lung CancerTreatment

• Stage IA
• Lobectomy is treatment of choice.
• T1N0, lobectomy has 70 5 year recurrence free
  survival.
• If inoperable
• 30 cure rate with XRT alone.
• Stereotactic radiosurgery (CyberKnife).
• Radiofrequency ablation.

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Non Small Cell Lung CancerTreatment

• Stage 1B
• Lobectomy.
• Adjuvant chemotherapy adds a 4-12 survival
  benefit. Best in tumors gt 4 cm.
• NEJM 2004.
• ASCO 2004.

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Non Small Cell Lung CancerTreatment

• Stage II
• Lobectomy is treatment of choice.
• Adjuvant chemotherapy now standard.
• Consider adjuvant XRT to mediastinum

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Non Small Cell Lung CancerTreatment

• Stage III
• Combination chemotherapy with XRT is treatment of
  choice.
• Surgery has yet to be established consistently as
  benefit in randomized trials.
• Neoadjuvant therapy followed by surgical
  resection is option in IIIA.

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Non Small Cell Lung CancerTreatment

• Stage IV
• Chemotherapy.

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Non Small Cell Lung CancerContraindications to
Surgical Resection

• Stage IIIB or IV.
• Extensive invasion into surrounding structures
• Vena cava or atrium involvement.
• Recurrent laryngeal or phrenic nerve involvement.
• SVC obstruction, malignant effusion, pericardial
  tamponade.
• Contralateral lymph nodes.

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Non Small Cell Lung CancerContraindications to
Surgical Resection

• Medically unfit
• Poor cardiac or pulmonary status.
• Predicted postoperative FEV1 lt 40.
• Predicted postoperative DLCO lt 40.
• Exercise studies for marginal candidates.

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Chemotherapy Drugs

• Non small cell
• Two drug regimen.
• Cis/Carbo platin 1 other (Taxol/Taxotere/Gemcita
  bine)
• Small cell
• Cisplatin / Etoposide

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Biologic Agents

• Avastin
• Angiogenesis inhibitor.
• Added to chemo.
• Bleeding risk.
• Contraindicated in squamous cell carcinoma.

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Biologic Agents

• Tarceva
• Epidermal growth factor inhibitor.
• Second line therapy.
• Asian, never smoking, women, adenocarcinoma /
  bronchoalveolar cell CA.
• PO.
• Rash, diarrhea.

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Small Cell Lung Cancer Treatment

• Untreated 1.5 - 3 month median survival
• Limited Chemotherapy with XRT.
• 10-20 month median survival.
• 5 year survival 10
• Extensive Chemotherapy.
• 7-11 month median survival.
• 5 year survival lt 1.

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Small Cell Lung Cancer Brain Irradiation

• For known metastatic lesions.
• Prophylaxis in both Limited Extensive disease.
• Decreases the risk of developing brain
  metastases.
• Improved survival.

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Question 5

• A 60 year old white male smoker without symptoms
  presents for a routine annual physical and a CXR
  is performed. What test do you order next?

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Question 5

• A) CT chest with IV contrast.
• B) CT-guided transthoracic needle biopsy.
• C) Review prior chest X-rays.
• D) Full body PET scan.
• E) Surgical resection.

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Answer 5

• A) CT chest with IV contrast.
• B) CT-guided transthoracic needle biopsy.
• C) Review prior chest X-rays.
• D) Full body PET scan.
• E) Surgical resection.

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Evaluation of the Solitary Pulmonary Nodule

• 25 have symptoms of cough, chest pain, or
  hemoptysis.
• 75 asymptomatic.
• Benign nodules
• 23 Tubercular lesions
• 14 Benign tumors (Hamartoma, neurogenic
  tumors, bronchial adenoma, mesothelioma)
• 13 Others (Chronic pneumonia, echinoccoccal
  cyst, bronchogenic cyst, aspergilloma etc.)

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Evaluation of the Solitary Pulmonary Nodule

• Malignant nodules 49 of all SPNs
• Primary lung cancer 38, metastatic cancer 9
• Incidence of malignancy increases with age
• Ages 35-39 3 are malignant.
• Ages 40-49 15
• Ages 50-59 42
• Ages 60 50

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Evaluation of the Solitary Pulmonary Nodule

• Malignant Characteristics
• Spiculations.
• Irregular contour.
• Eccentric calcifications.
• gt 3 cm.

• Benign Characteristics
• Smooth round.
• Well circumscribed.
• Central, densely calcified, laminated, or
  popcorn.
• lt 3 cm.

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Evaluation of the Solitary Pulmonary Nodule

• Comparison to prior films
• New? Enlarging? Change in shape?
• Likely benign if no change in 2 years.
• CT scan for better detail.
• Removal if new, bigger, or changing.
• CT-guided biopsy if not surgical candidate.
• Sampling error may require surgical biopsy.

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Evaluation of the Solitary Pulmonary Nodule

• Close follow up (3 months) if benign appearance
  may be an option.
• Consider PET scan.
• Risk of waiting - may spread if malignant
  decrease survival.
• Future? Superdimension 3D electromagnetic
  tracking/ virtual bronch

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Solitary Nodule

• Follow up CTs
• 3, 6, 12, 24 months.
• If stable at 2 years, no further follow up.

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Common Paraneoplastic SyndromesSyndrome Freque
nt Histology

• Hypercalcemia
• SIADH
• Cushings Syndrome
• Eaton-Lambert

• Squamous Cell
• Small Cell
• Small Cell
• Small Cell

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Question 6

• A 55 year old former smoker is concerned about
  his risk for lung cancer and seeks your advice.
  Which of the following screening tests is
  recommended?

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Question 6

• A) Annual chest x-ray.
• B) Sputum for cytology.
• C) Spiral CT scan.
• D) Flexible bronchoscopy /- flourescence.
• E) None of the above.

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Answer 6

• A) Annual chest x-ray.
• B) Sputum for cytology.
• C) Spiral CT scan.
• D) Flexible bronchoscopy /- flourescence.
• E) None of the above.

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NCI Cooperative StudyResults Mortality
Rates/1,000/year

• No significant change in mortality was noted
• Screening should not be offered to general
  population
• However, CXR may be of benefit in an individual
  high risk patient

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Lung Cancer ScreeningSpiral CT Scan

• In preliminary studies, spiral CT detected higher
  numbers of Stage I lung cancers in patients at
  high risk.
• However, many benign nodules were also discovered
  and required close follow up.
• Some patients had surgery for benign disease as a
  result.
• Three large studies look promising!

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Lung Cancer and Smoking

• In North America
• 50 million current tobacco smokers
• 50 million former smokers
• Primary prevention is key especially among the
  youth

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