Squamous, large cell, and adenocarcinoma, collectively termed non-small cell lung cancer (NSCLC), are diagnosed in approximately 75% of patients with lung cancer in the United States. The treatment of these three tumor cell types is approached in virtually identical fashion because, in contrast to small cell carcinoma of the lung, NSCLC more frequently presents with localized disease at the time of diagnosis and is thus more often amenable to surgical resection but less frequently responds to chemotherapy and irradiation. Cigarette smoking is etiologically related to the development of NSCLC in the great majority of cases. Genetic mutations in dominant oncogenes such as K-ras, loss of genetic material on chromosomes 3p, 11p, and 17p, and deletions or mutations in tumor suppressor genes such as rb and p53 have been documented in NSCLC tumors and tumor cell lines. NSCLC is diagnosed because of symptoms related to the primary tumor or regional or distant metastases, as an incidental finding on chest radiograph, or rarely because of a paraneoplastic syndrome such as hypercalcemia or hypertrophic pulmonary osteoarthropathy. Screening smokers with periodic chest radiographs and sputum cytologic examination has not been shown to reduce mortality. The diagnosis of NSCLC is usually established by fiberoptic bronchoscopy or percutaneous fine-needle aspiration, by biopsy of a regional or distant metastatic site, or at the time of thoracotomy. Pathologically, NSCLC arises in a setting of bronchial mucosal metaplasia and dysplasia that progressively increase over time. Squamous carcinoma more often presents as a central endobronchial lesion, while large cell and adenocarcinoma have a tendency to arise in the lung periphery and invade the pleura. Once the diagnosis is made, the extent of tumor dissemination is determined. Since most NSCLC patients who survive 5 years or longer have undergone surgical resection of their cancers, the focus of the staging process is to determine whether the patient is a candidate for thoracotomy with curative intent. The dominant prognostic factors in NSCLC are extent of tumor dissemination, ambulatory or performance status, and degree of weight loss. Stages I and II NSCLC, which are confined within the pleural reflection, are managed by surgical resection whenever possible, with approximate 5-year survival of 45% and 25%, respectively. Patients with stage IIIa cancers, in which the primary tumor has extended through the pleura or metastasized to ipsilateral or subcarinal lymph nodes, can occasionally be surgically resected but are often managed with definitive thoracic irradiation and have 5-year survival of approximately 15%. In completely surgically resected NSCLC, postoperative irradiation reduces the local recurrence rate but has not been shown to improve survival. Stage IIIb cancer, which is more advanced than stage IIIa but without distant metastases, is frequently treated with chest irradiation; 5-year survival is less than 5%. Thoracic radiotherapy can cure a small fraction of stage III NSCLC patients and perhaps up to 15% to 20% of stages I and II patients with medical contraindications to surgery. Although higher doses of irradiation up to 6,000 cGy with conventional fractionation are associated with improved response rates and better local control, survival is not improved, almost certainly because of the predominant effects of distant metatases in determining eventual outcome. Patients with stage IV NSCLC, in which distant metastases are present at diagnosis, have only anecdotal 5-year survival. In the past decase, however, some evidence of biologic effects of cisplatin-based combination chemotherapy has been documented. Although chemotherapy cannot be said to unequivocally improve survival in any stage of NSCLC, some prospective randomized trials have shown survival or disease-free survival advantages in patients with overt stage IV disease or as an adjuvant treatment before or after definitive irradiation or surgery. Other such trials have been negative, however, and continued clinical trials will be required before a role for chemotherapy in NSCLC can be considered to be established. At present, outside the setting of a clinical trial, patients should receive chemotherapy only if they are categorically incurable by surgery or irradiation, have no significant symptoms that could be readily palliated with irradiation, are fully ambulatory, have assessable tumor lesions so that treatment can be discontinued if ineffective, and desire therapy after being informed of its limitations.
ASJC Scopus subject areas
- Cancer Research