Lung Cancer:

Diagnosis, Staging, and Treatment

Dene W. Daugherty, DO
Department 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 CANCER
(2007 American Cancer Society Data)

Relationship to Smoking
Etiology

Tobacco
active
passive

Percent
85-87
3-5

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

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

Suspected

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:
Smoker:
Smoker & asbestos worker:

5.17
10.85
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)
B)
C)
D)
E)

CT scan of the thorax with IV contrast.

Sputum cytology.
Flexible bronchoscopy.
CT-guided transthoracic needle biopsy.
Surgical resection.

Answer

A)
B)
C)
D)
E)

CT scan of the thorax with IV contrast.

Sputum cytology.
Flexible bronchoscopy.
CT-guided transthoracic needle biopsy.
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. PFTs.
E. CT scan of head.

Answer
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.

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)
40
35
30
Adenocarcinoma
Squamous
Large Cell
Bronchoalveolar
Small Cell

25
20
15
10
5
0

Percent of New Cases of Lung Cancer

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 Cancer

T 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 Cancer

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

NonSmall Cell Cancer

N 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 IIIB
T2 IB IIB IIIA IIIB
T3 IIB IIIA IIIA IIIB
T4 IIIB IIIB IIIB IIIB
M1 IV

Non Small Cell CA

Survival Months after Treatment
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

IV

19

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

Non Small Cell CA

Survival 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.

Malignant

Atypical carcinoid.

Intermediate

Typical carcinoid.

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 Cancer
Why 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 Cancer
Why 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)
B)
C)
D)
E)

Wedge resection.
Lobectomy.
Lobectomy with adjuvant chemotherapy.
Lobectomy with adjuvant radiation.
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 Cancer

Treatment
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 Cancer

Treatment
Stage 1B:
Lobectomy.
Adjuvant chemotherapy adds a 4-12% survival
benefit. Best in tumors > 4 cm.

NEJM 2004.
ASCO 2004.

Non Small Cell Lung Cancer

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

Non Small Cell Lung Cancer

Treatment
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 Cancer

Treatment
Stage IV:
Chemotherapy.

Non Small Cell Lung Cancer

Contraindications 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 Cancer

Contraindications 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)
B)
C)
D)
E)

CT chest with IV contrast.

CT-guided transthoracic needle biopsy.
Review prior chest X-rays.
Full body PET scan.
Surgical resection.

Answer

A)
B)
C)
D)
E)

CT chest with IV contrast.

CT-guided transthoracic needle biopsy.
Review prior chest X-rays.
Full body PET scan.
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 SPNs:
Primary lung cancer 38%, metastatic cancer 9%

Incidence of malignancy increases with age:

Ages 35-39
Ages 40-49
Ages 50-59
Ages 60+

:
:
:
:

3% are malignant.
15%
42%
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 CTs:
3, 6, 12, 24 months.
If stable at 2 years, no further follow up.

Common Paraneoplastic
Syndromes:

Syndrome

Frequent Histology

Hypercalcemia
SIADH
Cushings 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)
B)
C)
D)
E)

Annual chest x-ray.

Sputum for cytology.
Spiral CT scan.
Flexible bronchoscopy +/- flourescence.
None of the above.

Answer

A)
B)
C)
D)
E)

Annual chest x-ray.

Sputum for cytology.
Spiral CT scan.
Flexible bronchoscopy +/- flourescence.
None of the above.

NCI Cooperative Study

Results: 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