67 LUNG CANCER
Harrison’s Manual of Medicine
Lung cancer is diagnosed in about 90,000 men and 75,000 women in the U.S. each year, and 86% of pts die within 5 years. Lung cancer, the leading cause of cancer death, accounts for 32% of all cancer deaths in men and 25% in women. Peak incidence occurs between ages 55 and 65 years.
Four major types account for 88% of primary lung cancers: epidermoid (squamous), 29%; adenocarcinoma (including bronchioloalveolar), 32%; large cell, 9%; and small cell (or oat cell), 18%. Histology (small cell versus non-small cell types) is a major determinant of treatment approach. Small cell is usually widely disseminated at presentation, while non-small cell may be localized. Epidermoid and small cell typically present as central masses, while adenocarcinomas and large cell usually present as peripheral nodules or masses. Epidermoid and large cell cavitate in 20–30% of pts.
The major cause of lung cancer is tobacco use, particularly cigarette smoking. Lung cancer cells may have ³10 acquired genetic lesions, most commonly point mutations in ras oncogenes; amplification, rearrangement, or transcriptional activation of myc family oncogenes; overexpression of bcl-2, Her-2/neu, and telomerase; and deletions involving chromosomes 1p, 1q, 3p12-13, 3p14 (FHIT gene region), 3p21, 3p24-25, 3q, 5q, 9p (p16 and p15 cyclin-dependent kinase inhibitors), 11p13, 11p15, 13q14 (rbgene), 16q, and 17p13 (p53 gene). Loss of 3p and 9p are the earliest events, detectable even in hyperplastic bronchial epithelium; p53 abnormalities and ras point mutations are usually found only in invasive cancers.
Only 5–15% are detected while asymptomatic. Central endobronchial tumors cause cough, hemoptysis, wheeze, stridor, dyspnea, pneumonitis. Peripheral lesions cause pain, cough, dyspnea, symptoms of lung abscess resulting from cavitation. Metastatic spread of primary lung cancer may cause tracheal obstruction, dysphagia, hoarseness, Horner’s syndrome. Other problems of regional spread include superior vena cava syndrome, pleural effusion, respiratory failure. Extrathoracic metastatic disease affects 50% of pts with epidermoid cancer, 80% with adenocarcinoma and large cell, and >95% with small cell. Clinical problems result from brain metastases, pathologic fractures, liver invasion, and spinal cord compression. Paraneoplastic syndromes may be a presenting finding of lung cancer or first sign of recurrence (Chap. 75). Systemic symptoms occur in 30% and include weight loss, anorexia, fever. Endocrine syndromes occur in 12% and include hypercalcemia (epidermoid), syndrome of inappropriate antidiuretic hormone secretion (small cell), gynecomastia (large cell). Skeletal connective tissue syndromes include clubbing in 30% (most often non-small cell) and hypertrophic pulmonary osteoarthropathy in 1–10% (most often adenocarcinomas), with clubbing, pain, and swelling.
Staging See Table 67-1
Table 67-1 International TNM Staging System for Lung Cancer
Two parts to staging are: (1) determination of location (anatomic staging) and (2) assessment of pt’s ability to withstand antitumor treatment (physiologic staging). Non-small cell tumors are staged by the TNM/International Staging System (ISS). The T (tumor), N (regional node involvement), and M (presence or absence of distant metastasis) factors are taken together to define different stage groups. Small cell tumors are staged by two-stage system: limited stage disease—confined to one hemithorax and regional lymph nodes; extensive disease—involvement beyond this. General staging procedures include careful ENT examination, CXR, and chest CT scanning. CT scans may suggest mediastinal lymph node involvement and pleural extension in non-small cell lung cancer, but definitive evaluation of mediastinal spread requires histologic examination. Routine radionuclide scans are not obtained in asymptomatic pts. If a mass lesion is on CXR and no obvious contraindications to curative surgical approach are noted, mediastinum should be investigated. Major contraindications to curative surgery include extrathoracic metastases, superior vena cava syndrome, vocal cord and phrenic nerve paralysis, malignant pleural effusions, metastases to contralateral lung, and histologic diagnosis of small cell cancer.
See Table 67-2.
Table 67-2 Summary of Treatment Approach to Lung Cancer Patients
1. Surgery in pts with localized disease and non-small cell cancer; however, majority initially thought to have curative resection ultimately succumb to metastatic disease.
2. Solitary pulmonary nodule: factors suggesting resection include cigarette smoking, age ³35, relatively large (>2 cm) lesion, lack of calcification, chest symptoms, and growth of lesion compared to old CXR.
3. For unresectable stage II non-small cell lung cancer, combined thoracic radiation therapy and cisplatin-based chemotherapy reduces mortality by about 25% at 1 year.
4. For unresectable non-small cell cancer, metastatic disease, or refusal of surgery: consider for radiation therapy; addition of cisplatin-based chemotherapy may reduce death risk by 13% at 2 years and improve quality of life.
5. Small cell cancer: combination chemotherapy is standard mode of therapy; response after 6–12 weeks predicts median- and long-term survival.
6. Addition of radiation therapy to chemotherapy in limited stage small cell lung cancer can increase 5-year survival from about 11% to 20%.
7. Prophylactic cranial irradiation improves survival of limited stage small cell lung cancer by another 5%.
8. Laser obliteration of tumor through bronchoscopy in presence of bronchial obstruction.
9. Radiation therapy for brain metastases, spinal cord compression, symptomatic masses, bone lesions.
10. Encourage cessation of smoking.
At time of diagnosis, only 20% of pts have localized disease. Overall 5-year survival is 30% for males and 50% for females with localized disease and 5% for pts with advanced disease.
For a more detailed discussion, see Minna JD: Neoplasms of the Lung, Chap. 88, p. 562, in HPIM-15.