79 LUNG CANCER
Jamie M. Brown M.D.

1. How common is lung cancer?

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The incidence of lung cancer is approximately 180,000 new cases annually or 54.2 per 100,000 patients. More than 162,000 patients die annually, so the overall survival rate is 10%. This number has not improved over the past 35 years despite some treatment advances because of:

1. Teenage smoking and smoking in general
2. Increased incidence in nonsmokers
3. Presentation of lung cancer in advanced stage in most patients

2. What risk factors are thought to be important in the development of lung cancer?

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* 90% of patients have a smoking history
* Chemicals (aromatic hydrocarbons, vinyl chloride)
* Radiation (radon gas and uranium)
* Asbestos
* Metals (chromium, nickel, lead, and arsenic)
* Environmental factors (air pollution, coal tar, petroleum products)

3. Do genes and heredity play a role in lung cancer?

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Yes. A family history of lung cancer probably increases the risk of getting lung cancer. Furthermore, a large array of important biomarkers that influence prognosis have been identified in lung cancer cells and lung cancer tissue.

* Past:Light microscopic evidence of vascular invasion
* Lymphatic invasion
* Cellular pleomorphism and mitotic figures

* Present:Proto-oncogenes, growth factors, growth factor receptors
o Insulin-like growth factor (IGF)
o Epidermal growth factor receptor (EGFR)
o K-ras mutation (cell growth regulation)
o C-myc overexpression (cell growth)
o bcl-2 underexpression (loss of apoptosis regulation)
* Loss of tumor suppressor genes
o p53
o Retinoblastoma (RB gene)
o Chromosomal allele loss
o Fragile histidine triad gene (FHit)
o Retinoic acid receptor α (RARα)
* Overactivation of angiogenesis
o Platelet-derived growth factor (PDGF)
o Vascular endothelial-derived growth factor (VEGF)

* Future:Gene therapy directed at above
* Antiangiogensis therapy
* Immunopotentiation
o Adoptive immunotherapy: isolation, expansion, and reinfusion of tumor-infiltrating
o lymphocytes
o Nonspecific immunostimulation
o Tumor vaccines

No single marker yet has a clear meaning with respect to prognosis in a given patient.

4. What are the major histologic types of lung cancer?

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The most important distinction is between small cell and non-small cell carcinoma because of fundamental differences in tumor biology and clinical behavior (Table 79-1). Patients with small cell lung cancer are classified as having either limited or extensive disease. Limited means that all known disease is confined to one hemithorax and regional lymph nodes, including mediastinal, contralateral hilar, and ipsilateral supraclavicular nodes. Extensive describes disease beyond these limits, including brain, bone marrow, and intra-abdominal metastases.
With small cell or neuroendocrine carcinoma, the small cell type is usually extensive at presentation, and 5-year survival is 5%. Neuroendocrine carcinoma, which is well differentiated, is known as atypical carcinoid and has a good prognosis but is not “benign.”
Table 79-1. MAJOR HISTOLOGIC TYPES OF LUNG CANCER

5. Is lung cancer screening effective?

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Old dogma: No.
Current thinking: Yes. The thinking is as follows: lung cancer accounts for more cancer deaths than other cancers. Eighty-five percent of patients present with advanced uncurable lung cancer. We have not changed survival for lung cancer. Early-stage cancers that are asymptomatic can be found by chest radiograph and helical computed tomography (CT). Unfortunately, public health policy does not endorse screening for lung cancer.

6. How do patients with lung cancer present?

7. What is a paraneoplastic syndrome?

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Paraneoplastic syndromes of lung cancer may be metabolic (e.g., hypercalcemia, Cushing’s syndrome), neurologic (e.g., peripheral neuropathy; polymyositis; or Lambert-Eaton syndrome, which is similar to myasthenia gravis), skeletal (e.g., clubbing, hypertrophic osteoarthropathy), hematologic (e.g., anemia, thrombocytosis, disseminated intravascular coagulation), or cutaneous (e.g., hyperkeratosis, acanthosis nigricans, dermatomyositis). Of interest, the presence of a paraneoplastic syndrome does not influence the ultimate curability of the lung cancer.

8. Does the staging system for lung cancer have prognostic and therapeutic importance?

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Yes. The patient’s survival is related to the stage at presentation (Table 79-2).
Table 79-2. STAGING OF LUNG CANCER

9. Describe the work-up of a patient with a mass on chest radiograph.

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The work-up should be directed toward diagnosis, staging, and risk assessment.

1. Diagnosis
* Sputum cytology-low diagnostic yield
* Brochoscopy-low diagnostic yield if tumor not visible
* CT-guided fine-needle aspiration
* Thoracoscopy and biopsy; wedge excision
2. Staging
* CT scan (chest)-tumor, mediastinal lymph node assessment
* Positron emission tomography (PET)-90% sensitive and 80% specific for nodes, mets
* Bronchoscopy-endobronchial invasion
* Thoracoscopy-lymph node sampling
* Mediastinoscopy-sample N2 and N3 nodes
3. Risk assessment
* Pulmonary
o Spirometry-V/Q screening; if borderline, must leave patient with ≥ of 800 mL FEV1 after resection
o Arterial blood gas analysis
* Cardiac
o Electrocardiogram
o History of myocardial infarction, prior intervention
* Cardiopulmonary
o Able to walk a flight of stairs; if yes, will tolerate lobectomy
o Maximal oxygen (O2) consumption < 15 mL/kg/min

10. How are patients with lung cancer treated?

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The most effective treatment for lung cancer is surgical resection. Unfortunately, 75% of patients present with advanced disease and are not candidates for resection. Fortunately, preoperative chemotherapy with a cisplatinum-containing regimen has increased the number of stage III patients who are candidates for resection. This recent innovative therapy may translate into improved survival rates. For stage III lung cancer, several clinical trials have shown an advantage to preoperative chemotherapy and radiation treatment called neoadjuvant therapy. Even lower-stage disease or tumors at high risk of recurrence may benefit from newer chemotherapeutic regimens.
KEY POINTS: LUNG CANCER

1. The overall survival rate for patients with lung cancer is 10%.
2. Ninety percent of patients have a smoking history.
3. The most effective treatment for lung cancer is surgical resection.

11. Does radiation therapy have a place in the therapy of lung cancer?

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Radiation therapy is effective palliative but not curative therapy for lung cancer. Specifically, patients who present with a superior vena cava syndrome or a blocked bronchus with distal pneumonia frequently can be “opened up” with radiation therapy. Radiation is also excellent for the palliation of pathologic bone pain. Some-but not all-clinical trials have shown some benefit from preoperative chemoradiation treatment in advanced-stage lung cancer.

12. What is the survival rate of patients treated for non-small cell lung cancer at 5 years?

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Note that for chest wall invasion with no lymph nodes, survival is 50% at 5 years, although this is still called stage IIb. Also, if stage Ia (small tumor, no positive nodes) cancer is not resected, survival decreases from 70% to 7%.

13. What is mediastinoscopy?

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Mediastinoscopy is a staging procedure in which the paratracheal, subcarinal, and proximal peribronchial lymph nodes are sampled from a small incision made in the suprasternal notch.

14. What are the indications for mediastinoscopy?

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Mediastinal staging is indicated in patients with either apparent or documented lung cancer who have:

* Known lung cancer with mediastinal lymph nodes > 1 cm accessible by cervical mediastinal exploration, as assessed by CT scan
* Adenocarcinoma of the lung and multiple mediastinal lymph nodes < 1 cm
* Central or large (> 5 cm) lung cancers with mediastinal lymph nodes < 1 cm
* Lung cancer and are at high risk of thoracotomy and lung resection

If the mediastinoscopy has negative results, the surgeon should proceed with thoracotomy, biopsy, and curative lung resection.

15. Is malignant pleural effusion or recurrent nerve involvement with tumor an absolute contraindication to surgical resection for lung cancer?

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A malignant pleural effusion is an absolute contraindication to surgical resective therapy. Conversely, both King George V and Arthur Godfrey had successful surgical resections in the face of recurrent nerve involvement with tumor.

References
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BIBLIOGRAPHY
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