Lung Cancer: Diagnosis, Staging, and Treatment

Lung Cancer:Diagnosis, Staging, and Treatment

Dene W. Daugherty, DODepartment of Surgery

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)

Cancer Deaths in U.S.(2007 American Cancer Society Data)

Lung 160,390

Colorectal 52,180

Breast 40,910

Prostate 27,050

Lung Cancer in the U.S.(2007 American Cancer Society Data)

• Number of patients in the U.S. with lung cancer continues to rise

• In 2007 estimated:– 213,380 new cases– 160,390 deaths

Lung Cancer Risk Factors (2007 American Cancer Society Data)

• Gender

• Smoking history

• Older age

• Presence of airflow obstruction

• Genetic predisposition

• Occupational exposures

Lung Cancer and Gender(2007 American Cancer Society Data)

• Male predilection, but changing rapidly

• Increase in women smokers– 55% Men– 45% Women

LUNG CANCERLUNG CANCER(2007 American Cancer Society Data)

Tobacco Percentactive 85-87passive 3-5

Etiology

Relationship to Smoking

Lung Cancer and Smoking(2007 American Cancer Society Data)

• ~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

Occupational Exposures Linked to 3 - 15% of Lung Cancers

(2007 American Cancer Society Data)

Proven Suspected• Arsenic• Asbestos• Bischloromethyl ether• Chromium• Mustard gas• Nickel• Polycyclic aromatic

hydrocarbons• Ionizing radiation

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

Asbestosis & Lung Cancer(2007 American Cancer Society Data)

• 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 > chrysotile &

anthophyllite.

Asbestosis & Lung Cancer (2007 American Cancer Society Data)

• Risk of smoking & asbestos exposure is multiplied.

• Mortality ratio:– Nonsmoking asbestos worker: 5.17– Smoker: 10.85– Smoker & asbestos worker: 53.24

Relative Risk of Developing Lung Cancer (2007 American Cancer Society Data)

Lung Cancer:Symptoms at Presentation

• Due to primary tumor:• Cough, hemoptysis, chest pain, wheezing, dyspnea,

& fever.

• Thoracic extension of tumor:• Chest pain, SVC syndrome, hoarseness, &

dysphagia.

Lung Cancer:Symptoms 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.

Question

• 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?

Question

• A) CT scan of the thorax with IV contrast.

• B) Sputum cytology.

• C) Flexible bronchoscopy.

• D) CT-guided transthoracic needle biopsy.

• E) Surgical resection.

Answer

• A) CT scan of the thorax with IV contrast.

• B) Sputum cytology.

• C) Flexible bronchoscopy.

• D) CT-guided transthoracic needle biopsy.

• E) Surgical resection.

Lung Cancer:Findings on Chest X-ray

• Nodule (< 3cm) vs. Mass (>= 3cm).– Location:

• Peripheral (Adenocarcinoma) vs. • Central (Squamous).

– Single or multiple (metastases).

• Endobronchial obstruction.– Atelectasis of lobe or lung.– Pneumonia.

Lung Cancer:The Chest X-ray

• Hilar and mediastinal adenopathy.

• Pleural effusions.

• Elevated hemidiaphragm.

Lung Cancer:CT 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.

Lung Cancer:Sputum Cytology

• Helpful for central lesions.

• With three samples:– 80% detection rate of centrally located tumors.– 50% detection rate of peripheral lesions.

Lung Cancer:Video 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.

Lung Cancer:Transbronchial Needle Aspiration (TBNA)

• Allows biopsy of subcarinal & paratracheal lymph nodes during flexible bronchoscopy.

• Helpful for staging.

• Minimal risk to patient.

Lung Cancer:CT - 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.

Question

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

Question

• 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. PFT’s.

• E. CT scan of head.

• What test do we order next?• A. CT-guided lung biopsy.

• B. Video Assisted Thoracic Surgical open lung biopsy.

• C. PET scan.

• D. PFT’s.

• E. CT scan of head.

Answer

Alternative Answer

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

staging mediastinum.

Lung Cancer:PET Scan

• Marker of active glucose metabolism.

• Can detect lesions to 0.8cm.

• ~90% sensitivity & ~85% specificity.

• Indications:– Staging lung cancer.– Solitary pulmonary nodule.

Lung Cancer:Other Diagnostic Tests

• Thoracentesis.

• Surgical resection:– Thoracotomy vs. VATS.

Staging of the Mediastinum

• Mediastinoscopy:– Mediastinal lymphadenopathy staging.– Central lesions.– Large peripheral lesions.– “Gold Standard.”

Newer Technologies

• Endobronchial Ultrasound (EBUS)

• Endoscopic Ultrasound (EUS)

Histology of Lung Cancers in U.S. (2007 American Cancer Society Data)

0

5

10

15

20

25

30

35

40

Percent of New Cases of Lung Cancer

AdenocarcinomaSquamousLarge CellBronchoalveolarSmall Cell

Adenocarcinoma

• Most common cell type in US.

• Peripheral location.• Glandular formation.• Mucin production.

Bronchoalveolar Cell Carcinoma

• Subtype of adenocarcinoma.

• Preservation of alveolar architecture.

• Spread through the airways.

• May present as unresolving pneumonia.

Squamous Cell Carcinoma

• Cavitation.• Centrally located

along airways.• Intravascular invasion.• Intercellular bridging.• Keratinization.

Squamous Cell Carcinoma

• Keratin pearls.• Nests of cells.

Large Cell Carcinoma

• A poorly differentiated carcinoma.

• Diagnosis of exclusion.

• Large cells.• Abundant cytoplasm.• Large nuclei with

prominent or vesicular nucleoli.

NonSmall Cell CancerT Stage

• T1: < 3cm in diameter, contained within visceral pleura.

• T2: > 3cm in diameter, >= 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 <2cm from carina or atelectasis of entire lung

NonSmall Cell CancerT Stage

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

NonSmall Cell CancerN Stage

• N0: No nodes.• N1: Ipsilateral hilar or

peribronchial. • N2: Ipsilateral

mediastinal, subcarinal.• N3: Contralateral hilar,

contralateral mediastinal or supraclavicular/scalene.

Non Small Cell Carcinoma Staging

N0 N1 N2 N3

T1 IA IIA IIIA IIIBT2 IB IIB IIIA IIIBT3 IIB IIIA IIIA IIIBT4 IIIB IIIB IIIB IIIBM1 IV

Clinical Stage

12 24 36 48 60

IA 91 79 71 67 61

IB 72 54 46 41 38

IIA 79 49 38 34 34

IIB 59 41 33 26 24

IIIA 50 25 18 14 13

IIIB 34 13 7 6 5

IV 19 6 2 2 1

CF Mountain. Chest. 1997; 111(6).

Non Small Cell CASurvival Months after Treatment

Non Small Cell CASurvival Months after Treatment

Pathologic Stage

12 24 36 48 60

IA 94 86 80 73 67

IB 87 76 67 62 57

IIA 89 70 66 61 55

IIB 73 56 46 42 39

IIIA 64 40 32 26 23

CF Mountain. Chest. 1997; 111(6).

Current AJCC Changes

• Satellite nodules: T3

• Malignant effusions: StageIV

• Nodules in same lung but different lobe: StageIV

Neuroendocrine Lung Tumors

• Small cell carcinoma.

• Atypical carcinoid.

• Typical carcinoid.

• Malignant

• Intermediate

• Benign

Small Cell Carcinoma

• Aggressive tumor.• Smokers.• Centrally located.• Bulky adenopathy is

common.• Distant metastases

common on presentation.

Small Cell Carcinoma

• Small cells.• Fine chromatin

pattern.• Abundant mitosis.• Scant cytoplasm.• Tends to smudge

on microscopy.• Synaptophysin

& chromogranin.

Carcinoid• Typical carcinoid:

– Usually endobrochial.– Present with

postobstructive pneumonia.

– Surgical resection is curative.

• Atypical carcinoid:– More aggressive.– May require surgery

with chemotherapy.

Small Cell Lung Cancer:Staging

• 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.

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

< 10% at 5 years

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

Question

• 60 yo male smoker with 4.1 cm solitary adenocarcinoma. What is the best option for treatment/survival?

A) Wedge resection.

B) Lobectomy.

C) Lobectomy with adjuvant chemotherapy.

D) Lobectomy with adjuvant radiation.

E) Lobectomy with adjuvant chemotherapy and radiation.

Answer

• 60 yo male smoker with 4.1 cm solitary adenocarcinoma. What is the best option for treatment/survival?

A) Wedge resection.

B) Lobectomy.

C) Lobectomy with adjuvant chemotherapy.

D) Lobectomy with adjuvant radiation.

E) Lobectomy with adjuvant chemotherapy and radiation.

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.

Non Small Cell Lung CancerTreatment

• Stage 1B:– Lobectomy.– Adjuvant chemotherapy adds a 4-12% survival

benefit. Best in tumors > 4 cm.» NEJM 2004.» ASCO 2004.

Non Small Cell Lung CancerTreatment

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

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.

Non Small Cell Lung CancerTreatment

• Stage IV:– Chemotherapy.

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.

Non Small Cell Lung CancerContraindications to Surgical Resection

• Medically unfit:– Poor cardiac or pulmonary status.– Predicted postoperative FEV1% < 40%.– Predicted postoperative DLCO% < 40%.– Exercise studies for marginal candidates.

Chemotherapy Drugs

• Non small cell:– Two drug regimen.– Cis/Carbo platin + 1 other

(Taxol/Taxotere/Gemcitabine)

• Small cell:– Cisplatin / Etoposide

Biologic Agents

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

Biologic Agents

• Tarceva– Epidermal growth factor inhibitor.– Second line therapy.– Asian, never smoking, women,

adenocarcinoma / bronchoalveolar cell CA.– PO.

– Rash, diarrhea.

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 < 1%.

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.

Question

• 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?

Question

• 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.

Answer

• 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.

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.)

Evaluation of the Solitary Pulmonary Nodule

• Malignant nodules 49% of all SPN’s:– 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%

Evaluation of the Solitary Pulmonary Nodule

• Malignant Characteristics:– Spiculations.– Irregular contour.

– Eccentric calcifications.

– > 3 cm.

• Benign Characteristics:– Smooth & round.– Well circumscribed.

– Central, densely calcified, laminated, or “popcorn.”

– < 3 cm.

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.

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

Solitary Nodule

• Follow up CT’s:– 3, 6, 12, 24 months.– If stable at 2 years, no further follow up.

Common Paraneoplastic Syndromes:

Syndrome Frequent Histology

• Hypercalcemia• SIADH• Cushing’s Syndrome• Eaton-Lambert

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

Question

• 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?

Question

• A) Annual chest x-ray.

• B) Sputum for cytology.

• C) Spiral CT scan.

• D) Flexible bronchoscopy +/- flourescence.

• E) None of the above.

Answer

• A) Annual chest x-ray.

• B) Sputum for cytology.

• C) Spiral CT scan.

• D) Flexible bronchoscopy +/- flourescence.

• E) None of the above.

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

Lung Cancer Screening:Spiral 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!

Lung Cancer and Smoking

• In North America– 50 million current tobacco smokers– 50 million former smokers

• Primary prevention is key especially among the youth