· 170,000 new cases were diagnosed in 1993
· About 150,000 patients will die of lung cancer this year
· 50 deaths per 100,000 persons per year in the U.S.
· 5-year survival in the 1950s was 6%; in the 1980s this increased to 13%
· Lung cancer is currently second to ischemic heart disease as the most frequent cause of death
· While heart disease mortality is decreasing, overall cancer mortality has increased, and much of this is due to lung cancer
A. Tobacco
· Surgeon General's landmark report (1964) implicated smoking as a causative agent in 85% of lung cancers
· In1964, 54% of Americans smoked; by 1989, this incidence had declined to 33% (80 million)
· The NCI target was 15% by 1990
· In spite of this decreased incidence of smoking, there remains a long latency period (15 years) between smoking cessation and normalization of risk
B. Asbestos
· Inhalation exposure is the most common occupational cause, accounting for 5% of all lung cancers
C. Tuberculosis
· Carcinoma can develop in scar regions from healed TB
· Risk is increased 5-10x over general population
· Most common cancer is adenocarcinoma in this setting
D. Radiation
· Radon and uranium have been implicated, although no direct evidence at this time
E. Air pollution
· Passive tobacco smoke is the most widely accepted substance for increasing risk of lung cancer
· Other compounds include exhaust, arsenic, and dioxin
A. Squamous cell carcinoma
· Most common (40-70%), centrally located, more common in men
· Local metastases, plentiful eosinophilic cytoplasm, keratin "pearls", bridging.
B. Adenocarcinoma
· Less common (5-15%), peripherally located, more common women
· Distant metastases, vacuolization, mucus synthesis, glandular differentiation
C. Undifferentiated carcinoma
· Two subtypes (20-30%)
· Large cell carcinoma: aggressive clinical behavior, moderate cytoplasm, no mucus or keratin
· Small cell carcinoma: nonsurgical lesion, high incidence of metastases, spindle or oat shaped cells, dense nuclei, sparse cytoplasm
D. Bronchoalveolar carcinoma
· Uncommon (3-7%) adenocarcinoma variant, favorable prognosis, alveolar "scaffolding", tends to recur as a second primary tumor
A. Natural History
· Multiple areas of carcinoma in situ have been found in the bronchi of cigarette smokers
· Lung carcinoma, especially small-cell, metastatizes early and widely, most commonly to brain, bone, lung, liver, adrenals, and skin
· Initial spread is usually first to the hilar nodes, secondly to the mediastinal nodes, and thirdly to the scalene nodes
B. Clinical Features
· Asymptomatic: any mass noted on CXR is cancer until proven otherwise
· Cough (most common - 75%)
· Anorexia and weight loss (70%)
· Dyspnea (60%)
· Chest pain (50%)
· Hemoptysis (33%)
· Other: wheezing, bone pain, pneumonia, pleural effusion, hoarseness, Cushing's syndrome, inappropriate ADH secretion, eosinophilia (tumor necrosis) and neuromyopathies
· CXR with review of previous films
· Chest CT (see #8 below)
· Sputum cytology
· Bronchoscopy - washings, brushings, and transbronchial biopsy: definitive diagnosis in about 85% of patients
· CT-transthoracic needle aspiration: near-100% specificity, false-negative rate 15%
· Open lung biopsy (VATS or thoracotomy)
| Stage I | All T1 tumors and T2 tumors without lymph node metastasis |
| Stage II | T1 and T2 tumors with involvement of ipsilateral hilar nodes |
| Stage IIIa | Ipsilateral mediastinal disease |
| Stage IIIb | More widespread disease |
| Stage IV | Unresectable disease |
Full TNM Staging Classification
A. Only 50% of patients with lung cancer are surgical candidates
B. 50% of surgical patients have mediastinal N2 disease
C. Mediastinal lymph node dissection provides the following strategy:
· Only definitive way of staging lung cancer
· Identifies patients with skip metastasis (33% incidence, most common in adenocarcinoma)
· Identifies intranodal vs. perinodal metastasis
· Identifies multilevel disease (poor prognosis)
· Required by many neoadjuvant and adjuvant protocols
· Part of complete resection strategy, which improves survival if the patient is staged correctly and receives proper adjuvant therapy when indicated
D. Mediastinoscopy
· Used in combination with CT
· Mediastinotomy performed instead if enlarged nodes are located in the aortopulmonary window
· Positive results are very accurate, but a negative biopsy does not rule out metastasis
· Surgeon is morally certain he or she has encompassed all tumor disease
· Proximal margins of resected specimen are microscopically free of tumor
· Within each major lymphatic drainage region, the most distal node is microscopically free of tumor
· Capsules of resected nodes are intact
· Current imaging techniques determine size but not histology of nodes
· Malignant mediastinal nodes are not always larger than benign lymph nodes (58% greater than 15 mm are benign)
· Small mediastinal nodes (less than 10 mm) are not infrequently malignant (15%)
· Benign adenopathy is more common in patients with acute pulmonary inflammation
· Pathologic confirmation rates are higher than radiologic estimation of malignancy
· CT identification of enlarged hilar/mediastinal nodes is not diagnostic of advanced stage disease
· CT therefore adds extra cost without contributing to the overall management plan
Squamous Cell
| Stage | 5-year survival |
| I | 50% |
| II | 30% |
| III | 15% |
Adenocarcinoma
| Stage | 5-year survival |
| I | 55% |
| II | 20% |
| III | 15% |
Bronchoalveolar
| Stage | 5-year survival |
| I | 60% |
| II | 20% |
| III | 15% |
Large Cell
| Stage | 5-year survival |
| I | 45% |
| II | 15% |
| III | 5% |
A. Predictors of poor outcome
· FEV1 less than 800 mL/s
· PaO2 less than 50 torr on room air
· PaCO2 greater than 45 torr on room air
B. Factors influencing survival in N2 disease:
· Multiple levels of involvement
· Nodal vs extranodal disease
· Superior vs inferior mediastinum
· Bulky clinical vs discrete CT nodes
· Recurrences - 80% within 2 years
· Second primary 3-4% per year, especially in high risk patients
C. Postoperative Management
· Repeat CXR every 6 months for 2 years, and then annually
· CEA levels which rise after postoperative normal levels may predict recurrence
· Completion pneumonectomy may improve survival for recurrent lung cancer
· Distant metastases (absolute)
· Trachea or contralateral main bronchus involvement
· Malignant pleural effusion (absolute)
· Superior vena cava obstruction
· Horner's syndrome
· Vocal cord paralysis
· Phrenic nerve paralysis
· Small cell carcinoma
A. Rationale for ongoing trials:
· Surgical resection disrupts blood supply and adjuvant therapy may not be deliverable
· Preoperative therapy may minimize seeding
· Preoperative therapy may accomplish downstaging
· Tumor growth is inversely related to size and micrometastases may grow more quickly
· Chemotherapy-related cell death follows first order of kinetics, and with each cell division, cells become resistant due to continued mutation
B. Non-Small-Cell Cancer
· The Lung Cancer Study Group (LCSG) found no evidence that postoperative radiation improved survival in stage II or III disease compared to surgery alone
· Combined chemotherapy and radiation, however, improved median survival in stage III disease when compared to radiation alone
· Neoadjuvant therapy in mestastatic disease has not demonstrated a survival advantage
· Factors predicting a response to chemotherapy include absence of bone/liver/skin metastastasis, female gender, histology other than large-cell carcinoma, and absence of weight loss
C. Small-Cell Cancer
· Chemotherapy is the cornerstone of treatment
· Complete response can be achieved in 50% of patients with limited disease and 20% of patients with extensive disease
· Median survival is about 14 months in limited disease and 8 months in extensive disease
· Most patients will relapse and die from small-cell cancer, even if a complete response was achieved
· The unusual patient with a peripheral stage I small-cell lesion should undergo surgical resection and postoperative chemotherapy, as 5-year survival can approach 50%
· Discovered by Dr. Henry K. Pancoast (1932)
· Rare (0.5%), from lung cancers arising from the apex
· Pancoast syndrome: pain, Horner's syndrome, wasting and weakness
· Paulson protocol: preoperative radiation therapy followed by resection
· Prognosis (like all lung cancers) depends on nodal involvement
· Extensive involvement of brachial plexus
· Extensive involvement of subclavian artery (rare)
· Mediastinal node involvement or perinodal involvement (relative contraindication)
· Extensive involvement of vertebra
· Superior vena caval involvement (rare)
· Recurrent laryngeal nerve involvement (rare)
· Distant metastasis or malignant pleural effusion
· Incidence of about 5%
· Does not imply a hopeless prognosis
· Mortality and morbidity for surgical resection are acceptable
· Extensive resections are possible