Small Cell Lung Cancer

Updated: Oct 17, 2016
  • Author: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD  more...
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Overview

Practice Essentials

Small cell lung cancer (SCLC), previously known as oat cell carcinoma, is considered distinct from other lung cancers, which are called non–small cell lung cancers (NSCLCs) because of their clinical and biologic characteristics. See the image below.

High-power photomicrograph of small cell carcinoma High-power photomicrograph of small cell carcinoma on the left side of the image with normal ciliated respiratory epithelium on the right side of the image.

See Small Cell Lung Cancer: Beating the Spread, a Critical Images slideshow, to help identify the key clinical and biologic characteristics of small cell lung cancer, the staging criteria, and the common sites of spread.

Also, see the Clinical Presentations of Lung Cancer: Slideshow and Lung Cancer Staging -- Radiologic Options slideshows for additional information on SCLC staging and treatment.

SCLC is an aggressive subtype of lung cancer. Without treatment, in a few weeks it could be fatal. It is important to determine if the cancer is limited or at an extensive stage. Limited-stage cancer is treated with chemotherapy and radiation. Extensive-stage cancer is treated with chemotherapy alone.

SCLC is a neuroendocrine carcinoma that exhibits aggressive behavior, rapid growth, early spread to distant sites, exquisite sensitivity to chemotherapy and radiation, and frequent association with distinct paraneoplastic syndromes, including hypercalcemia, Eaton-lambert syndrome, syndrome of inappropriate diuretic hormone, and many others. (See Pathophysiology, Etiology, and Presentation.) [1, 2, 3]

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Pathophysiology

Small cell lung carcinoma (SCLC) arises in peribronchial locations and infiltrates the bronchial submucosa. Widespread metastases occur early in the course of the disease, with common spread to the mediastinal lymph nodes, liver, bones, adrenal glands, and brain.

In addition, production of various peptide hormones leads to a wide range of paraneoplastic syndromes; the most common of these are the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and the syndrome of ectopic adrenocorticotropic hormone (ACTH) production. In addition, autoimmune phenomena may lead to various neurologic syndromes, such as Lambert-Eaton syndrome.

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Etiology

The predominant cause of small cell lung cancer (SCLC) (and non-SCLC) is tobacco smoking. Of all histologic types of lung cancer, SCLC and squamous cell carcinoma have the strongest correlation to tobacco. [4, 5] Approximately 98% of patients with SCLC have a smoking history. Patients with SCLC should be encouraged to stop smoking, as smoking cessation is associated with improved survival. [6]

All types of lung cancer occur with increased frequency in uranium miners, but SCLC is the most common. The incidence of lung cancer is increased further in these individuals if they also smoke tobacco.

Exposure to radon, an inert gas that is a product of uranium decay, has also been reported to cause SCLC.

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Epidemiology

Occurrence in the United States

Lung cancer overall is the second most common malignancy in both sexes in the United States, exceeded in frequency only by prostate cancer in men and breast cancer in women. [7, 8, 9, 10] Although less than half as many new cases of lung cancer than breast cancer are diagnosed in US women each year, almost twice as many US women die of lung cancer each year than from breast cancer.

The incidence of small cell lung cancer (SCLC) has declined over the last few years. SCLC once accounted for 20-25% of all newly diagnosed lung cancers; it now comprises only about 15% of all lung cancers. [11]

For 2016, the estimates for lung cancer overall are 224,390 new cases and 158,080 deaths in the United States. [10]

International occurrence

Globally, lung cancer is the most frequent malignancy in men (in Europe, lung cancer is second only to prostate cancer [12] ) and the fifth most common cancer in women. Although the incidence of lung cancer has been falling in the US, it is increasing at a staggering pace in developing countries due to the rising prevalence of tobacco use. According to World Health Organization (WHO) statistics, about 1.59 million deaths from lung cancer occur annually throughout the world. [13]

Separate worldwide data for small cell carcinoma are not available. The incidence of lung cancer started to decline among males in the early 1980s and has continued to do so over the past 20 years. In contrast, the incidence in women started to increase in the late 1970s and did not begin to decline until the mid-2000s. [7, 10]

Age-related demographics

As with other histopathologic types of lung cancer, most cases of SCLC occur in individuals aged 60-80 years.

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Prognosis

Approximately 60-70% of patients with small cell lung cancer (SCLC) have clinically disseminated or extensive disease at presentation. Extensive-stage SCLC is incurable. When given combination chemotherapy, patients with extensive-stage disease have a complete response rate of more than 20% and a median survival longer than 7 months; however, only 2% are alive at 5 years. [14] For individuals with limited-stage disease that is treated with combination chemotherapy plus chest radiation, a complete response rate of 80% and survival of 17 months have been reported; 12-15% of patients are alive at 5 years. [15]

Genome-wide association studies have identified single-nucleotide polymorphisms (eg, within the promoter region of YAP1 on chromosome 11q22) that may affect survival in patients with SCLC. [16, 17]  

Indicators of poor prognosis include the following:

  • Relapsed disease
  • Weight loss of greater than 10% of baseline body weight
  • Poor performance status
  • Hyponatremia [18]
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Patient Education

Because tobacco smoking is the predominant cause of lung cancer, the only means of decreasing the incidence of this disease overall, as well as that of small cell lung cancer (SCLC) specifically, is to decrease the prevalence of smoking. The evidence is clear that the declining incidence of lung cancer in men in the United States has coincided with a decrease in smoking among males.

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