Small Cell Lung Cancer


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.

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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 ....

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]


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.


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.


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.


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:

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.

Dexamethasone (Decadron, Dexamethasone Intensol, Dexasone)

Clinical Context:  Dexamethasone is a synthetic adrenocortical steroid with multiple indications. This agent is widely used in combination with serotonin (5-HT) receptor antagonists to prevent nausea and vomiting caused by highly emetogenic agents (eg, cisplatin).

Metoclopramide (Metozolv ODT, Reglan)

Clinical Context:  Metoclopramide is a dopamine antagonist that enhances the response to acetylcholine of tissue in the upper GI tract, causing antiemetic activity. At higher doses, metoclopramide blocks serotonin receptors in the chemoreceptor trigger zone of the central nervous system (CNS).

Ondansetron (Zofran, Zofran ODT, Zuplenz)

Clinical Context:  Ondansetron is a selective serotonin (5-HT3)-receptor antagonist that is used to prevent chemotherapy-induced nausea and vomiting.

Granisetron (Kytril, Granisol, Sancuso)

Clinical Context:  Granisetron is a selective 5-HT3-receptor antagonist that is used to prevent chemotherapy-induced nausea and vomiting.

Dolasetron (Anzemet)

Clinical Context:  Dolasetron binds to 5-HT3 receptors located on vagal neurons in the GI tract, blocking signals to the vomiting center, thus preventing nausea and vomiting.

Palonosetron (Aloxi)

Clinical Context:  Palonosetron is a selective 5-HT3 receptor antagonist with long half-life (40 h) that blocks 5-HT3 receptors peripherally and centrally in the chemoreceptor trigger zone. This agent is indicated for the prevention of chemotherapy-induced nausea and vomiting.

Cyclophosphamide (Cytoxan, Neosar)

Clinical Context:  Cyclophosphamide is chemically related to the nitrogen mustards. As an alkylating agent, the mechanism of action of its active metabolites may involve cross-linking of DNA, which may interfere with the growth of normal and neoplastic cells. Fatal cardiotoxicity has been reported with coadministration of pentostatin.

Carboplatin (Paraplatin)

Clinical Context:  Carboplatin is a platinum alkylating agent that interferes with the function of DNA by producing interstrand DNA cross-links. It can be used for the treatment of small cell lung cancer (SCLC), which is an off-label indication. Carboplatin has black box warnings, including bone marrow suppression, anaphylactic reactions, and vomiting.


Clinical Context:  Cisplatin is a platinum-containing compound that exerts an antineoplastic effect by covalently binding to DNA, with preferential binding to the N-7 position of guanine and adenosine. It can react with 2 different sites on DNA to produce cross-links. The platinum complex can also bind to nuclear and cytoplasmic protein. Cisplatin has black box warnings, including anaphylacticlike reactions, ototoxicity, and renal toxicity.

Ifosfamide (Ifex)

Clinical Context:  Ifosfamide is a nitrogen mustard alkylating agent that inhibits DNA and protein synthesis. Although not FDA approved, ifosfamide is often used as a treatment for relapsed SCLC.

Irinotecan (Camptosar)

Clinical Context:  Irinotecan binds reversibly to the topoisomerase I-DNA complex and prevents the ligation of the cleaved DNA strand. It has been used off label for the treatment of extensive-stage small cell lung cancer. Black box warnings for irinotecan include bone marrow suppression and diarrhea.

Topotecan (Hycamtin)

Clinical Context:  Topotecan inhibits topoisomerase I and thereby inhibits DNA replication. This agent may interact with other antineoplastic drugs to cause prolonged neutropenia and thrombocytopenia in addition to increasing morbidity/mortality. Topotecan is indicated for the treatment of relapsed or refractory small cell lung cancer (SCLC).

Doxorubicin (Adriamycin, Caelyx, Rubex)

Clinical Context:  Doxorubicin is an anthracycline antineoplastic that causes DNA strand breakage through its effects on topoisomerase II and through direct intercalation into DNA, which causes DNA polymerase inhibition. It has a labeled indication for the treatment of small cell lung cancer (SCLC). Doxorubicin has several black box warnings, including bone marrow suppression, myocardial toxicity, and secondary malignancy.

Vincristine (Oncovin)

Clinical Context:  Vincristine inhibits tubulin polymerization during mitosis. This agent is G2-phase specific. Vincristine may interact with mitomycin-C and cause an acute pulmonary reaction.

Vinorelbine (Navelbine)

Clinical Context:  Vinorelbine is a vinca alkaloid that inhibits tubulin polymerization during G2 phase of cell division, thereby inhibiting mitosis.

Paclitaxel (Taxol, Abraxane)

Clinical Context:  Paclitaxel promotes microtubule assembly, interferes with the G2 mitotic phase, and inhibits cell replication. It has an off-label indication for the treatment of small cell lung cancer (SCLC). Black box warnings for paclitaxel include bone marrow suppression and hypersensitivity reactions.

Docetaxel (Taxotere, Docefrez)

Clinical Context:  Docetaxel inhibits the depolymerization of tubulin, which inhibits DNA, RNA, and protein synthesis. It can be used for the treatment of relapsed SCLC, which is an off-label indication. Docetaxel has several black box warnings, such as bone marrow suppression, fluid retention, and hypersensitivity reactions. This drug is not recommended for use in certain patients with hepatic impairment. Patients undergoing docetaxel treatment should be premedicated with corticosteroids the day before administration, to help reduce fluid retention and hypersensitivity reactions.

Gemcitabine (Gemzar)

Clinical Context:  Gemcitabine is a pyrimidine analog. After intracellular metabolism to its active nucleotide, it inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. Although use of this drug as a treatment for refractory or relapsed small cell lung cancer (SCLC) has not been approved by the US Food and Drug Administration (FDA), gemcitabine is often used for this purpose.

Etoposide (Toposar, VePesid)

Clinical Context:  Etoposide inhibits topoisomerase II and appears to cause DNA strand breakage. It has been shown to delay transit of cells through the S phase and arrest cells in the late S or early G2 portion of the cell cycle. Etoposide is used in combination chemotherapy for the treatment of small cell lung cancer (SCLC).

Teniposide (vm 26, Vumon)

Clinical Context:  Teniposide inhibits topoisomerase II and appears to cause DNA strand breakage, preventing mitosis. This agent is used in combination chemotherapy for the treatment of SCLC. Black box warnings for teniposide include myelosuppression and hypersensitivity reactions.


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

Disclosure: Nothing to disclose.


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

Disclosure: Nothing to disclose.

Chief Editor

Nagla Abdel Karim, MD, PhD, Associate Professor of Medicine, Associate Director of Experimental Therapeutics, Division of Hematology/Oncology, University of Cincinnati Cancer Institute, Department of Internal Medicine, University of Cincinnati College of Medicine

Disclosure: Nothing to disclose.


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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.

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.