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ERROR: type should be string, got "https://profreg.medscape.com/px/getpracticeprofile.do?method=getProfessionalProfile&urlCache=aHR0cHM6Ly9lbWVkaWNpbmUubWVkc2NhcGUuY29tL2FydGljbGUvMjgwMTA0LW92ZXJ2aWV3\nDrugs & Diseases > Oncology\nAuthor: Winston W Tan, MD, FACP; Chief Editor: Nagla Abdel Karim, MD, PhD more...\nSections Small Cell Lung Cancer\nWorkup\nApproach Considerations\nRoutine Laboratory Studies\nThoracic Imaging Studies\nBrain and Spinal Cord Imaging Studies\nSkeletal Radionuclide Imaging\nPET Scanning\nBronchoscopy and Fine Needle Aspiration\nSputum Cytology\nHistologic Findings\nStaging Overview\nVALSG and TNM Staging\nCombination Chemotherapy\nChemotherapy Dose Intensity and Density\nLimited-Stage SCLC - Standard Management\nExtensive-Stage SCLC - Standard Management\nManagement of Relapsed SCLC\nManagement of Brain Metastases and Spinal Cord Compression\nManagement of Complications\nLong-Term Monitoring\nGuidelines Summary\nACCP Diagnosis and Management Guidelines\nTreatment for Limited-Stage SCLC\nTreatment for Extensive-Stage SCLC\nTreatment of SCLC in the Elderly\nMedication Summary\nAntineoplastics, Alkylating\nAntineoplastics, Anthracycline\nAntineoplastics, Vinca Alkaloid\nAntineoplastics, Antimicrotubular\nAntineoplastics, Antimetabolite\nAntineoplastics, Podophyllotoxin Derivatives\nPD-1/PD-L1 Inhibitors\nAntiemetic Agents\nSmall 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.\nHigh-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.\nSCLC 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 antidiuretic hormone (SIADH) secretion, and many others. (See Pathophysiology, Etiology, and Presentation.) [1, 2, 3]\nIn patients who present with SCLC, it is important to determine whether the cancer is limited or at an extensive stage. Limited-stage cancer, which is potentially curable, is treated with chemotherapy and radiation, with surgical resection reserved for selected patients with stage I disease. Extensive-stage cancer is incurable; systemic chemotherapy is used to improve quality of life and prolong survival. [4]\nSee 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.\nAlso see the Clinical Presentations of Lung Cancer: Slideshow and Lung Cancer Staging -- Radiologic Options slideshows for additional information on SCLC staging and treatment.\nSmall 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.\nIn 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.\nThe 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. [5, 6] 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. [7]\nAll 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.\nExposure to radon, an inert gas that is a product of uranium decay, has also been reported to cause SCLC.\nOccurrence in the United States\nLung 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. [8, 9, 10] In both sexes, lung cancer is the most common cause of cancer death. 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.\nThe incidence of small cell lung cancer (SCLC) has declined over the last few years, as smoking rates have fallen. [10] SCLC once accounted for 20-25% of all newly diagnosed lung cancers; it now comprises only about 13% of all lung cancers. [11]\nFor 2019, the estimates for lung cancer overall in the United States are 228,150 new cases and 142,670 deaths. [10]\nInternational occurrence\nGlobally, 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 1.69 million deaths from lung cancer occur annually throughout the world. [13]\nSeparate worldwide data for small cell carcinoma are not available. The incidence of lung cancer started to decline among men 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. [8, 10]\nAge- and sex-related demographics\nAs with other histopathologic types of lung cancer, most cases of SCLC occur in individuals aged 60-80 years.\nOver the past two decades, the incidence of lung cancer has generally decreased in both men and women 30 to 54 years of age in all races and ethnic groups. However, the incidence has declined more steeply in men. As a result, lung cancer rates in younger women have become higher than those in younger men. In non-Hispanic whites and Hispanics ages 44 to 49 years, for example, the female-to-male rate ratio for lung cancer incidence rose from 0.88 during 1995-1999 to 1.17 during 2010-2014. [14]\nThis reversal can be explained in part by increased rates of cigarette smoking in women born since 1965. However, while the difference in smoking rates in that age group has narrowed, rates in women have generally not exceeded the rates in men, so other factors may be playing a role. For example, women may be more susceptible to the oncogenic effects of smoking. [14]\nApproximately 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. [15] 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. [16]\nGenome-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. [17, 18]\nIndicators of poor prognosis include the following:\nRelapsed disease\nWeight loss of greater than 10% of baseline body weight\nPoor performance status\nHyponatremia [19]\nBecause 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.\nMalhotra J, Boffetta P, Mucci L. Cancer of the lung, larynx, and pleura. Adami H, Hunter D, Laglou P, Mucci L, eds. Textbook of Cancer Epidemiology. 3rd ed. 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Philadelphia, Pa: WB Saunders Co; 1989. 6-15.\nMazzone PJ, Silvestri GA, Patel S, Kanne JP, Kinsinger LS, Wiener RS, et al. Screening for Lung Cancer: CHEST Guideline and Expert Panel Report. Chest. 2018 Apr. 153 (4):954-985. [Medline]. [Full Text].\nThis 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.\nTable 1. Paraneoplastic Syndromes Affecting Endocrine and Neurologic Function in SCLC\nTable 2. AJCC TNM Categories for Lung Cancer\nTable 3. AJCC Stage Groupings for Lung Cancer\nAntidiuretic hormone\n15% [20]\nEctopic secretion of ACTH\n2-5% [21]\nNeurologic\nEaton-Lambert reverse myasthenic syndrome\n3% [22]\nSubacute cerebellar degeneration\nSubacute sensory neuropathy\nLimbic encephalopathy\nAnti-Hu, anti-Yo antibodies\nACTH = adrenocorticotropic hormone; SCLC = small cell lung cancer; SIADH = syndrome of inappropriate antidiuretic hormone.\nSources: (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]\nPrimary Tumor (T)\nLocation of Involvement\nPrimary tumor can’t be assessed, or sputum cytology reveals tumor cells but the tumor is not seen on radiologic or bronchoscopic evaluation\nNo evidence of a primary tumor\n≤3 cm in greatest dimension\nSurrounded by lung or visceral pleura; no invasion more proximal than lobar bronchus\n>1 cm but ≤2 cm in greatest dimension\n>3 cm but ≤5 cm in greatest dimension, or\n(see right column)\nMain bronchus, ≥2 cm distal to carina, or\nVisceral pleura, or\nHilar region, but not entire lung, associated with atelectasis/obstructive pneumonitis\nDirect invasion of:\nParietal pleural chest wall, diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium, or\nMain bronchus < 2 cm distal to carina (but not carina itself), or\nEntire lung with associated atelectasis/obstructive pneumonitis, or\nSame lobe, separate tumor nodule(s)\n>7 cm or\nInvasion of:\nMediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, or carina\nDifferent ipsilateral lobe, separate tumor nodule(s)\nNode (N)\nLocation of Regional Metastatic Involvement\nRegional lymph nodes cannot be assessed\nNo regional lymph node metastasis\nIpsilateral peribronchial and/or ipsilateral hilar lymph nodes, and\nIntrapulmonary nodes, including direct extension\nIpsilateral mediastinal and/or subcarinal lymph node(s)\nContralateral mediastinal, contralateral hilar, ipsilateral/contralateral scalene, or supraclavicular lymph node(s)\nMetastasis (M)\nLocation of Distant Metastatic Involvement\nNo distant metastasis\nDistant metastasis\nContralateral lobe tumor with separate tumor nodule(s), or\nTumor with pleural nodules or malignant pleural or pericardial effusion\nSingle extrathoracic metastasis in a single organ and involvement of a single distant (nonregional) node\nMultiple extrathoracic metastases in one or more organs\nAJCC = American Joint Committee on Cancer.\nAdapted from: (1) Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2010:299-330 [31] ; (2) National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology:Small Cell Lung Cancer [serial online]. 2018;v.2. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. [31]\nRegional Node (N)\nOccult Cancer\nStage IA\nIA1\nStage IIA\nStage IIB\nT1a,b,c\nT2a,b\nStage IIIA\nStage IIIB\nStage IIIC\nStage IVA\nAny T\nAny N\nM1a,b\nStage IVB\nAdapted from: (1) Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2016 [36] ; (2) National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology:Small Cell Lung Cancer [serial online]. 2018;v.2. Available at: http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. [31]\nWinston 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, Division of Hematology/Oncology Education, Chair, Cancer Survivorship Program, Associate Chair, Department of Medicine Faculty Development, Mayo Clinic Florida; Vice President, Florida Society of Clinical Oncology\nWinston W Tan, MD, FACP is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, Philippine Medical Association, Texas Medical Association\nIrfan Maghfoor, MD Consulting Oncologist, Department of Oncology, King Faisal Specialist Hospital and Research Center, Saudi Arabia\nIrfan Maghfoor, MD is a member of the following medical societies: American Society of Hematology\nNagla 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\nNagla Abdel Karim, MD, PhD is a member of the following medical societies: American Medical Association, American Society of Clinical Oncology, Egyptian American Medical Association, Egyptian Cancer Society, International Association for the Study of Lung Cancer\nencoded search term (Small Cell Lung Cancer) and Small Cell Lung Cancer\nImaging in Lung Cancer Staging\nSmall Cell Lung Cancer Staging\nNon-Small Cell Lung Cancer (NSCLC) Staging\nImaging in Non-Small Cell Lung Cancer\nImaging in Small Cell Lung Cancer\nNon-Small Cell Lung Cancer (NSCLC)\nNew Targets in Lung Cancer Shape Treatment Options\nWhen Hurricanes Halt Treatment, Lung Cancer Patients Die Sooner\nThe Expression Level of HJURP has an Independent Prognostic Impact and Predicts the Sensitivity to Radiotherapy in Breast Cancer\nTop News From ESMO 2017: Slideshow\nAccording to Oncologist/Hematologists\n'Surgery Is Never Elegant When Women Are in the OR'\nModerate Intake of Red Meat Tied to Higher Colorectal Cancer Risk\nPoor Diet Linked to 80,000 Cancer Cases in the United States\nVenous Thromboembolism Clinical Practice Guidelines (2019)\nAfter a Patient Death, Top Cancer Center Issues Corrective Plan\nNews When Hurricanes Halt Treatment, Lung Cancer Patients Die Sooner\n2001 /viewarticle/915510\nDiseases & Conditions Small Cell Lung Cancer Staging\nNews Lung-Cancer Screening May Be Warranted in Bladder-Cancer Patients"