Small cell lung cancer (SCLC) is a highly aggressive malignant epithelial tumor. Patients typically present with rapidly growing, symptomatic disease, and distant metastases at diagnosis are common. Most cases are highly sensitive to chemotherapy, but the disease frequently recurs, and most patients will die of their disease. SCLC remains a therapeutic challenge.
Approximately 219,440 patients in the United States are diagnosed with lung cancer every year, and approximately 159,390 will die of their disease (1). Small cell lung cancer currently accounts for approximately 13% of all lung cancers in the United States, compared to its incidence in the 1980s when it represented 18% of cases (2). Historically, a majority of patients with SCLC were male, but recent analyses show that equal numbers of men and women are affected, probably due to increasing use of tobacco among women starting in the 1960s (2).
Cigarette smoking is the single most important risk factor for development of SCLC. It has been estimated that well over 90% of small cell lung cancers are attributable to cigarette smoking (3), and in our experience, it is rare to see a nonsmoking patient diagnosed with small cell lung cancer. The risk is related to both the duration and intensity of tobacco use, and the risk for former smokers is lower than that for current smokers, though still far higher than that of nonsmokers (4). Some studies suggest that the risk of small cell lung cancer is greater for smoking women than for men (3). Other than the association of tobacco, exposure to asbestos, benzene, coal tar, and radon gas has been associated with risk, usually as co-carcinogens with tobacco. Smoking cessation counseling is a widely accepted method of primary prevention. Even after diagnosis of SCLC, smoking cessation should be encouraged, as there is evidence of worse outcomes in patients who continue to smoke through and after treatment (5).
The natural history of SCLC was documented in the placebo arm of an early randomized trial from the Veterans Administration Lung Cancer Study Group which tested the effect of three doses of intravenous cyclophosphamide (6). In this trial, the median survival time for patients in the placebo arm was 6 weeks for patients with obvious metastatic disease, known as extensive disease, and 12 weeks for patients who appeared to have disease limited to one hemithorax, known as limited disease. Given the era, staging in this trial was rudimentary and, thus, outcomes in both groups would probably be better today because of stage shift. Cyclophosphamide treatment increased the median survival time by 75 days in both groups of patients, tripling the survival of patients with metastases and doubling that of patients with chest-confined disease. This was the first observation foretelling the important role chemotherapy would come to play in management of small cell lung cancer.