Lung cancer, which was first given status as a global epidemic in the 1950s, continues to be the leading cause of cancer-related deaths among both men and women.1 Based on best available data, the worldwide incidence of lung cancer accounts for 1.2 million new cases and 1.1 million cancer deaths annually.2 In 2007 in the United States alone, there were approximately 213,380 new cases of lung cancer and 160,390 lung cancer deaths.1 It is the most common thoracic malignancy compared with esophageal cancer and mesothelioma, which account for approximately 12,000 and 3000 yearly cancer deaths, respectively. More deaths in the United States are due to lung cancer than to breast, prostate, and colorectal cancer combined.1
The bulk of patients with lung cancer are divisible into two major groups based on treatment and prognosis: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC is the more aggressive form and usually has spread systemically by the time of diagnosis. The malignancy is characterized by a proliferation of small anaplastic cells. Because of its tendency to early metastasis, the cancer usually is not amenable to surgical resection, and hence, surgery does not play a primary role in the management of SCLC. It is, however, more responsive to systemic treatment with chemotherapy. The combination of etoposide and cisplatin remains the standard of care for both limited and extensive disease.3 Radiotherapy rather than surgery has been used for local tumor control. Recent innovations, including the addition of thoracic radiation to systemic chemotherapy protocols, increasing the intensity of thoracic radiation, neoadjuvant thoracic radiation, and prophylactic cranial irradiation,4 have produced some benefit in terms of prolonging disease-free intervals and survival.5 Untreated, the mean survival is 2–4 months. Median survival with treatment is between 18 and 36 months. Currently, SCLC accounts for 15–20% of new lung cancer cases per year in the United States.
NSCLC comprises of three major histopathologic subtypes, including squamous cell carcinoma, adenocarcinoma (including bronchioloaveolar cancer), and large cell (or undifferentiated/mixed) carcinoma. These cancers constitute approximately 80% of lung malignancies. They tend to spread more slowly than SCLC, and hence there are more opportunities for early intervention. Nevertheless, many patients with NSCLC have advanced disease at presentation. Surgery is the basis of treatment for early-stage NSCLC (stages I and II) and offers the best chance for cure. Stage III or IV lung cancers generally are treated palliatively with a variety of multimodality protocols, although selected patients with stage III disease have the potential for cure with resection depending on the degree of invasion of local structures and the extent of mediastinal nodal disease.6 A small proportion of lung cancers (<1%) exhibit no radiologic evidence of tumor. These cancers, termed occult, are diagnosed by screening bronchoscopy and sputum cytology.
All lung cancers share a common etiology in environmental or direct exposure to smoking tobacco. Cigarette smokers experience a 15- to 50-fold increased risk of developing lung cancer in comparison with lifetime nonsmokers. ...