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Small Cell Lung Cancer

  • Author: Winston W Tan, MD, FACP; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
 
Updated: Oct 06, 2015
 

Background

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. Moreover, 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 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, 11, 12] 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.[8, 11, 12] SCLC once accounted for 20-25% of all newly diagnosed lung cancers; it now comprises only about 15% of all lung cancers.[13]

For 2015, the estimates for lung cancer overall are 221,200 new cases and 158,040 deaths in the United States.[14]

International occurrence

Globally, lung cancer is the most frequent malignancy in men (in Europe, lung cancer is second only to prostate cancer[15] ) 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.[16]

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 has only recently reached a plateau.[7, 11, 12, 17]

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.[18] 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.[19]

Indicators of poor prognosis include relapsed disease, weight loss of greater than 10% of baseline body weight, and poor performance status. For all patients with SCLC, activity should be encouraged and a dietary consultation should be obtained.

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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.

Concerted efforts are required from government, public health agencies, and healthcare providers to increase public awareness of the hazards of smoking, devise tougher laws to restrict teen smoking, and restrict smoking in public places.

For patient education information, see the Cancer Center, as well as Lung Cancer and Bronchoscopy. In addition, see the National Cancer Institute's General Information About Small Cell Lung Cancer.

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Contributor Information and Disclosures
Author

Winston W Tan, MD, FACP Associate Professor of Medicine, Mayo Medical School; Consultant and Person-in-Charge of Genitourinary Oncology-Medical Oncology, Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic Jacksonville; Vice Chairman of Education, Division of Hematology/Oncology, Mayo Clinic Florida

Winston W Tan, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Hematology, Texas Medical Association, American Society of Clinical Oncology, Philippine Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Irfan Maghfoor, MD Consulting Oncologist, Department of Oncology, King Faisal Specialist Hospital and Research Center, Saudi Arabia

Irfan Maghfoor, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, FACP, FRCPC Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD, FACP, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Society of Hematology, Central Society for Clinical and Translational Research, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Acknowledgements

Michael Perry, MD, MS, MACP† Former Nellie B Smith Chair of Oncology Emeritus, Former Director, Division of Hematology and Medical Oncology, Former Deputy Director, Ellis Fischel Cancer Center, University of Missouri-Columbia School of Medicine

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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.
This coronal positron emission tomogram shows a large, focal, hypermetabolic area on the right that is consistent with a large mass in the central portion of the right upper pulmonary lobe. Multiple other smaller hypermetabolic areas suggest lymph-node metastatic disease in the chest, abdomen, and right supraclavicular region.
Table 1. Paraneoplastic Syndromes Affecting Endocrine and Neurologic Function in SCLC
Organ System Syndrome Mechanism Frequency
Endocrine SIADH Antidiuretic hormone 15%[20]
Ectopic secretion of ACTH ACTH 2-5%[21]
     
Neurologic Eaton-Lambert reverse myasthenic syndrome   3%[22]
Subacute cerebellar degeneration    
Subacute sensory neuropathy    
Limbic encephalopathy Anti-Hu, anti-Yo antibodies  
ACTH = adrenocorticotropic hormone; SCLC = small cell lung cancer; SIADH = syndrome of inappropriate antidiuretic hormone.



Sources:  (1) Campling BG, Sarda IR, Baer KA, et al. Secretion of atrial natriuretic peptide and vasopressin by small cell lung cancer. Cancer. May 15, 1995;75(10):2442-51[20] ; (2) Shepherd FA, Laskey J, Evans WK, et al. Cushing's syndrome associated with ectopic corticotropin production and small-cell lung cancer. J Clin Oncol. Jan 1992;10(1):21-7[21] ; (3) Sher E, Gotti C, Canal N, et al. Specificity of calcium channel autoantibodies in Lambert-Eaton myasthenic syndrome. Lancet. Sep 16, 1989;2(8664):640-3.[22]



Table 2. AJCC TNM Categories for Lung Cancer
Primary Tumor (T) Tumor Size Location of Involvement
TX Primary tumor can’t be assessed, or sputum cytology reveals tumor cells but the tumor is not seen on radiologic or bronchoscopic evaluation
T0 No evidence of a primary tumor
Tis Carcinoma in situ
T1 ≤3 cm in diameter Surrounded by lung or visceral pleura; no invasion more proximal than lobar bronchus
T2
  • >3 cm but ≤7 cm diameter, or
  • (see right column)
  • Main bronchus, ≥2 cm distal to carina, or
  • Visceral pleura, or
  • Hilar region, but not entire lung, associated with atelectasis/obstructive pneumonitis
T2a >3 cm but ≤5 cm diameter  
T2b >5 cm but ≤7 cm diameter  
T3
  • >7 cm diameter, or
  • (see right column)
Direct invasion of:
  • Parietal pleural chest wall, diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium, or
  • Main bronchus < 2 cm distal to carina (but not carina itself), or
  • Entire lung with associated atelectasis/obstructive pneumonitis, or
  • Same lobe, separate tumor nodule(s)
T4 Any size Invasion of:
  • Mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina
  • Different ipsilateral lobe, separate tumor nodule(s)
Node (N) Location of Regional Metastatic Involvement
NX Regional lymph nodes can’t be assessed
N0 No regional lymph node metastasis
N1
  • Ipsilateral peribronchial and/or ipsilateral hilar lymph nodes, and
  • Intrapulmonary nodes, including direct extension
N2 Ipsilateral mediastinal and/or subcarinal lymph node(s)
N3 Contralateral mediastinal, contralateral hilar, ipsilateral/contralateral scalene, or supraclavicular lymph node(s)
Metastasis (M) Location of Distant Metastatic Involvement
M0 No distant metastasis
M1 Distant metastasis
  M1a
  • Contralateral lobe tumor with separate tumor nodule(s), or
  • Malignant pleural effusion, or
  • Malignant pericardial effusion
  M1b Distant metastasis
AJCC = American Joint Committee on Cancer.



Adapted from:  (1) Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010:299-330[26] ; (2) National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology:Small Cell Lung Cancer [serial online]. 2013;v.2. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed December 5, 2011.[25]



Table 3. AJCC Stage Groupings for Lung Cancer
  Primary Tumor (T) Regional Node (N) Metastasis (M)
Occult Cancer TX N0 M0
Stage 0 Tis N0 M0
Stage I A T1 N0 M0
B T2a N0 M0
Stage IIA T2b N0 M0
T1 N1 M0
T2a N1 M0
Stage IIB T2b N1 M0
T3 N0 M0
Stage IIIA T1-2 N2 M0
T3 N1-2 M0
T4 N0-1 M0
Stage IIIB T1-2 N3 M0
T3 N3 M0
T4 N2-3 M0
Stage IV Any T Any N M1a
Any T Any N M1b
AJCC = American Joint Committee on Cancer.



Adapted from:  (1) Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010:299-330[26] ; (2) National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology:Small Cell Lung Cancer [serial online]. 2013;v.2. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Accessed December 5, 2011.[25]



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