History

Fewer than 5% of patients with small cell lung cancer (SCLC) are asymptomatic at presentation. Common presenting signs and symptoms of the disease, which very often occur in advanced-stage disease, include the following:

Shortness of breath
Cough
Bone pain
Weight loss
Fatigue
Neurologic dysfunction

Most patients with this disease present with a short duration of symptoms, usually only 8-12 weeks before presentation. The clinical manifestations of SCLC can result from local tumor growth, intrathoracic spread, distant spread, and/or paraneoplastic syndromes.

Local tumor growth

SCLCs are usually centrally located and may cause irritation and/or obstruction of the major airways. Common symptoms resulting from local tumor growth include cough, dyspnea, and hemoptysis. Squamous cell cancer also presents as a central lesion, but unlike SCLC, it frequently exhibits central cavitation.

Rapid tumor growth may lead to obstruction of major airways, with distal collapse leading to postobstructive pneumonitis, infection, and fever.

Intrathoracic spread

SCLCs usually grow rapidly and metastasize to mediastinal lymph nodes relatively early in the course of the disease. At presentation, patients may have very large intrathoracic tumors, and distinguishing the primary tumor from lymph node metastases may be impossible.

Pressure on mediastinal structures can cause various symptoms, including the following:

Superior vena cava (SVC) obstruction
Hoarseness - Due to compression of the recurrent laryngeal nerve
Hemi-diaphragm paralysis - Due to phrenic nerve compression
Dysphagia - Due to esophageal compression
Stridor - Due to compression of the major airways

SCLC causes SVC obstruction more often than non-SCLC (NSCLC). Patients present with swelling of the face and upper extremities, and can develop stridor due to laryngeal edema or headache, dizziness, and other neurologic symptoms due to cerebral edema. Hoarseness of recent onset can be caused by compression of the left recurrent laryngeal nerve by a mediastinal mass involving the aortopulmonary window (ie, primary tumor or lymph node metastasis).

Compression of the phrenic nerve causes paralysis of the ipsilateral hemidiaphragm, contributing to shortness of breath. In addition, esophageal compression can lead to dysphagia and odynophagia, and compression of the mainstem bronchi and trachea can cause severe shortness of breath and stridor or wheezing.

Symptoms from distant spread

Common sites of hematogenous metastases include the brain, bones, liver, adrenal glands, and bone marrow. The symptoms depend upon the site of spread.

Neurologic dysfunction can occur due to brain metastases or spinal cord compression. Patients with symptomatic brain metastases may have raised intracranial pressure secondary to mass lesions and vasogenic edema. Common symptoms include the following:

Headache - Usually worse in the morning
Blurred vision
Photophobia
Nausea
Vomiting
Slurred speech
Confusion
Localizing symptoms - Such as extremity weakness

Suspected spinal cord compression is an oncologic emergency. Early recognition of vertebral and paraspinal metastases is important, because a delay in diagnosis and treatment frequently results in permanent loss of neurologic function. The initial symptom is usually back pain, with or without neurologic dysfunction. Once present, neurologic dysfunction can progress very rapidly (ie, within hours) to cause quadriplegia or paraplegia, depending upon the location of the lesion.

Other symptoms from distant metastasis may include pain from bone metastasis, as well as jaundice or abdominal/right upper quadrant pain due to liver metastasis.

Paraneoplastic syndromes

Paraneoplastic syndromes are rare disorders that are triggered by an altered immune system response to a neoplasm or ectopic production of a hormone or cytokine. Table 1, below, shows some examples of the paraneoplastic syndromes affecting the endocrine and neurologic systems in patients with SCLC.

See Paraneoplastic Diseases for more information.

Table 1. Paraneoplastic Syndromes Affecting Endocrine and Neurologic Function in SCLC (Open Table in a new window)

Organ System	Syndrome	Mechanism	Frequency
Endocrine	SIADH	Antidiuretic hormone	15%^[22]
	Ectopic secretion of ACTH	ACTH	2-5%^[23]

Neurologic	Eaton-Lambert reverse myasthenic syndrome		3%^[24]
	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^[22]; (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^[23]; (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.^[24]

Physical Examination

Physical findings in small cell lung cancer (SCLC) depend upon the extent of local and distant spread and the organ system involved.

Respiratory system

Patients usually experience shortness of breath; physical examination may reveal use of the accessory muscles of respiration (scalene muscles, intercostal muscles) and flaring of the nasal alae. In addition, by virtue of a central tumor location, patients may develop distal atelectasis and postobstructive pneumonia. With pleural effusion, the examination reveals dullness to percussion and decreased or absent breath sounds on the side of the effusion.

Cardiovascular system

Pericardial effusions may be asymptomatic when small, or they may result in tamponade if they are large or accumulate over a short period. Patients are usually short of breath and their heart sounds may be distant on auscultation. Jugular venous pulsation is elevated, and, paradoxically, it rises with inspiration.

Tamponade is an emergency and requires immediate decompression of the pericardium. Pulsus paradoxus is a classic sign of pericardial tamponade. If tamponade is suspected, an echocardiogram should be performed. The definitive diagnosis is established with cardiac catheterization, which reveals equalization of pressures in cardiac chambers. Definitive management may include chemotherapy and/or surgical creation of a pleuropericardial window.

Examination of the extremities may reveal clubbing, cyanosis, or edema. In the presence of superior vena cava (SVC) obstruction, the right upper extremity is usually edematous.

Central nervous system

Asymptomatic brain metastases occur in 5-10% of patients with SCLC (see Workup). Patients with symptomatic brain metastases may have raised intracranial pressure secondary to mass lesions and surrounding brain edema. The physical findings depend on the site of the brain lesions.

Perform funduscopy to look for signs of raised intracranial pressure, as well as a thorough neurologic examination and an evaluation of cerebellar function, coordination, and gait.

Gastrointestinal system

The liver is a common site of metastatic spread. Physical examination may reveal icterus (secondary to widespread liver metastasis or obstruction of biliary outflow) and/or hepatomegaly. However, most patients do not have any specific finding related to the gastrointestinal (GI) tract on examination. Very often patients are asymptomatic but may have mild elevation of liver enzyme levels.

Lymphatic system

Carefully perform a lymph node examination. Currently, enlarged ipsilateral supraclavicular lymph nodes are included in limited-stage disease, but enlarged axillary lymph nodes upstage the diagnosis to extensive-stage disease.

Complications

Multiple complications may be noted, depending on the site of metastasis or the metabolic factor that the tumor affects. Hypercalcemia could initially be asymptomatic but in late stages could lead to weakness, fatigue, and sleepiness, and in extreme cases to severe constipation and lethargy.

Brain metastasis is often asymptomatic but could manifest as a unilateral eye abnormality, focal neurologic deficit, or at times with a new-onset headache that wakes the patient up. Seizures are a possible manifestation.

Differential Diagnoses

Basumallik N, Agarwal M. Small Cell Lung Cancer. J Thorac Oncol. 2023 Jan. 14 (2):237-244. [QxMD MEDLINE Link]. [Full Text].
Malhotra 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. New York, NY: Oxford University Press; 2018. 327-54.
Pietanza MC, Krug LM, Wu AJ, Kris MG, Rudin CM, Travis WD. Small Cell and Neuroendocrine Tumors of the lung. DeVita VT Jr, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology. 10th ed. Philadelphia, Pa: Wolters Kluwer Health; 2015. 536-59.
Cascone T, Gold KA, Glisson BS. Small Cell Carcinoma of the Lung. Kantarjian H, Wolff R, eds. The MD Anderson Manual of Medical Oncology. 3rd ed. New York, NY: McGraw-Hill Education; 2016. 323-42.
Kalemkerian GP, Schneider BJ. Advances in Small Cell Lung Cancer. Hematol Oncol Clin North Am. 2017 Feb. 31 (1):143-156. [QxMD MEDLINE Link].
Gay CM, Stewart CA, Park EM, et al. Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Cancer Cell. 2021 Mar 8. 39 (3):346-360.e7. [QxMD MEDLINE Link]. [Full Text].
Wynder EL, Graham EA. Tobacco smoking as a possible etiologic factor in bronchiogenic carcinoma; a study of 684 proved cases. J Am Med Assoc. 1950 May 27. 143(4):329-36. [QxMD MEDLINE Link].
Pesch B, Kendzia B, Gustavsson P, Jockel KH, Johnen G,et al. Cigarette smoking and lung cancer--relative risk estimates for the major histological types from a pooled analysis of case-control studies. Int J Cancer. 2012 Sep 1. 131(5):1210-9. [QxMD MEDLINE Link]. [Full Text].
Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis: systematic review of observational studies with meta-analysis. BMJ. 2010 Jan 21. 340:b5569. [QxMD MEDLINE Link]. [Full Text].
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan. 73 (1):17-48. [QxMD MEDLINE Link]. [Full Text].
Govindan R, Page N, Morgensztern D, Read W, Tierney R, Vlahiotis A, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol. 2006 Oct 1. 24(28):4539-44. [QxMD MEDLINE Link].
American Cancer Society. Cancer Facts & Figures 2023. Available at https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf. Accessed: April 10, 2023.
Small Cell Lung Cancer Treatment (PDQ®): Health Professional Version. National Cancer Institute. Available at http://www.ncbi.nlm.nih.gov/books/NBK65909/#CDR0000062945__1. March 2, 2023; Accessed: April 10, 2023.
[Guideline] Dingemans AC, Früh M, Ardizzoni A, Besse B, Faivre-Finn C, Hendriks LE, et al. Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up^†. Ann Oncol. 2021 Apr 9. 24 Suppl 6:vi99-105. [QxMD MEDLINE Link]. [Full Text].
Cancer fact sheet. World Health Organization. Available at http://www.who.int/mediacentre/factsheets/fs297/en/. 3 February 2022; Accessed: April 10, 2023.
Jemal A, Miller KD, Ma J, Siegel RL, Fedewa SA, Islami F, et al. Higher Lung Cancer Incidence in Young Women Than Young Men in the United States. N Engl J Med. 2018 May 24. 378 (21):1999-2009. [QxMD MEDLINE Link].
Jackman DM, Johnson BE. Small-cell lung cancer. Lancet. 2005 Oct 15-21. 366(9494):1385-96. [QxMD MEDLINE Link].
Janne PA, Freidlin B, Saxman S, Johnson DH, Livingston RB, Shepherd FA, et al. Twenty-five years of clinical research for patients with limited-stage small cell lung carcinoma in North America. Cancer. 2002 Oct 1. 95(7):1528-38. [QxMD MEDLINE Link].
Wu C, Xu B, Yuan P, Miao X, Liu Y, Guan Y, et al. Genome-wide interrogation identifies YAP1 variants associated with survival of small-cell lung cancer patients. Cancer Res. 2010 Dec 1. 70(23):9721-9. [QxMD MEDLINE Link].
Xun WW, Brennan P, Tjonneland A, Vogel U, Overvad K, el at. Single-nucleotide polymorphisms (5p15.33, 15q25.1, 6p22.1, 6q27 and 7p15.3) and lung cancer survival in the European Prospective Investigation into Cancer and Nutrition (EPIC). Mutagenesis. 2011 Sep. 26(5):657-66. [QxMD MEDLINE Link].
Hermes A, Waschki B, Reck M. Hyponatremia as prognostic factor in small cell lung cancer--a retrospective single institution analysis. Respir Med. 2012 Jun. 106(6):900-4. [QxMD MEDLINE Link].
Campling BG, Sarda IR, Baer KA, Pang SC, Baker HM, Lofters WS, et al. Secretion of atrial natriuretic peptide and vasopressin by small cell lung cancer. Cancer. 1995 May 15. 75(10):2442-51. [QxMD MEDLINE Link].
Shepherd FA, Laskey J, Evans WK, Goss PE, Johansen E, Khamsi F. Cushing's syndrome associated with ectopic corticotropin production and small-cell lung cancer. J Clin Oncol. 1992 Jan. 10(1):21-7. [QxMD MEDLINE Link].
Sher E, Gotti C, Canal N, Scoppetta C, Piccolo G, Evoli A, et al. Specificity of calcium channel autoantibodies in Lambert-Eaton myasthenic syndrome. Lancet. 1989 Sep 16. 2(8664):640-3. [QxMD MEDLINE Link].
[Guideline] Wender R, Fontham ET, Barrera E Jr, Colditz GA, Church TR, Ettinger DS, et al. American Cancer Society lung cancer screening guidelines. CA Cancer J Clin. 2013 Mar-Apr. 63 (2):107-17. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Lung Cancer: Screening. U.S. Preventive Services Task Force. Available at http://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/lung-cancer-screening. March 9, 2021; Accessed: April 10, 2023.
Katki HA, Kovalchik SA, Petito LC, Cheung LC, Jacobs E, Jemal A, et al. Implications of Nine Risk Prediction Models for Selecting Ever-Smokers for Computed Tomography Lung Cancer Screening. Ann Intern Med. 15 May 2018. [Full Text].
[Guideline] NCCN Clinical Practice Guidelines in Oncology: Small Cell Lung Cancer. National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. Version 3.2023 — December 21, 2022; Accessed: April 10, 2023.
[Guideline] Detterbeck FC, Lewis SZ, Diekemper R, Addrizzo-Harris D, Alberts WM. Executive Summary: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May. 143 (5 Suppl):7S-37S. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Ung YC, Maziak DE, Vanderveen JA, Smith CA, Gulenchyn K, Evans WK, for the Lung Cancer Disease Site Group. 18-fluorodeoxyglucose positron emission tomography in the diagnosis and staging of lung cancer: a clinical practice guideline. Toronto, Ontario: Cancer Care Ontario; 2007. [Full Text].
Thomson D, Hulse P, Lorigan P, Faivre-Finn C. The role of positron emission tomography in management of small cell lung cancer. Lung Cancer. 2011 Aug. 73(2):121-6. [QxMD MEDLINE Link].
American Joint Committee on Cancer. Lung. AJCC Cancer Staging Manual Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, et al, eds. AJCC Cancer Staging Manual. 8th edition. New York, NY: Springer; 2016.
Dresler CM, Olak J, Herndon JE 2nd, Richards WG, el at. Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion. Chest. 2005 Mar. 127(3):909-15. [QxMD MEDLINE Link].
Zakowski MF. Pathology of small cell carcinoma of the lung. Semin Oncol. 2003 Feb. 30(1):3-8. [QxMD MEDLINE Link].
Small Cell Lung Cancer Stages. American Cancer Society. Available at http://www.cancer.org/cancer/lungcancer-smallcell/detailedguide/small-cell-lung-cancer-staging. October 1, 2019; Accessed: April 3, 2020.
Micke P, Faldum A, Metz T, Beeh KM, Bittinger F, Hengstler JG, et al. Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer--what limits limited disease?. Lung Cancer. 2002 Sep. 37(3):271-6. [QxMD MEDLINE Link].
[Guideline] National Collaborating Centre for Cancer. Lung cancer. The diagnosis and treatment of lung cancer. Publication no. 121. London, UK: National Institute for Health and Clinical Excellence; 2011. [Full Text].
Halvorsen TO, Sundstrøm S, Fløtten Ø, Brustugun OT, Brunsvig P, Aasebø U, et al. Comorbidity and outcomes of concurrent chemo- and radiotherapy in limited disease small cell lung cancer. Acta Oncol. 2016 Aug 23. 1-9. [QxMD MEDLINE Link].
Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, et al. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1. 29(16):2215-22. [QxMD MEDLINE Link].
Lally BE, Urbanic JJ, Blackstock AW, Miller AA, Perry MC. Small cell lung cancer: have we made any progress over the last 25 years?. Oncologist. 2007 Sep. 12(9):1096-104. [QxMD MEDLINE Link].
Hanna NH, Einhorn LH. Small-cell lung cancer: state of the art. Clin Lung Cancer. 2002 Sep. 4(2):87-94. [QxMD MEDLINE Link].
Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med. 2018 Dec 6. 379 (23):2220-2229. [QxMD MEDLINE Link]. [Full Text].
Harrison P. After Decades, New Standard of Care in Small Cell Lung Cancer. Medscape Medical News. Available at https://www.medscape.com/viewarticle/902700. September 28, 2018; Accessed: October 10, 2018.
Petty WJ, Paz-Ares L. Emerging Strategies for the Treatment of Small Cell Lung Cancer: A Review. JAMA Oncol. 2023 Mar 1. 9 (3):419-429. [QxMD MEDLINE Link].
Amarasena IU, Walters JA, Wood-Baker R, Fong K. Platinum versus non-platinum chemotherapy regimens for small cell lung cancer. Cochrane Database Syst Rev. 2008 Oct 8. CD006849. [QxMD MEDLINE Link].
Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002 Jan 10. 346(2):85-91. [QxMD MEDLINE Link].
Jiang L, Yang KH, Guan QL, Mi DH, Wang J. Cisplatin plus etoposide versus other platin-based regimens for patients with extensive small-cell lung cancer: a systematic review and meta-analysis of randomised, controlled trials. Intern Med J. 2012 Dec. 42(12):1297-309. [QxMD MEDLINE Link].
Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1. 24(13):2038-43. [QxMD MEDLINE Link].
Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, et al. Chemotherapy With or Without Maintenance Sunitinib for Untreated Extensive-Stage Small-Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Phase II Study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20. 33 (15):1660-5. [QxMD MEDLINE Link].
Schmittel A, Sebastian M, Fischer von Weikersthal L, et al. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug. 22(8):1798-804. [QxMD MEDLINE Link].
Rossi A, Di Maio M, Chiodini P, Rudd RM, Okamoto H, Skarlos DV, et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol. 2012 May 10. 30(14):1692-8. [QxMD MEDLINE Link].
Klasa RJ, Murray N, Coldman AJ. Dose-intensity meta-analysis of chemotherapy regimens in small-cell carcinoma of the lung. J Clin Oncol. 1991 Mar. 9(3):499-508. [QxMD MEDLINE Link].
Arriagada R, Le Chevalier T, Pignon JP, Riviere A, Monnet I, Chomy P, et al. Initial chemotherapeutic doses and survival in patients with limited small-cell lung cancer. N Engl J Med. 1993 Dec 16. 329(25):1848-52. [QxMD MEDLINE Link].
Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002 Jul 15. 20(14):3054-60. [QxMD MEDLINE Link].
Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999 Jan 28. 340(4):265-71. [QxMD MEDLINE Link].
Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007 Aug 16. 357(7):664-72. [QxMD MEDLINE Link].
Schild SE, Foster NR, Meyers JP, Ross HJ, Stella PJ, et al. Prophylactic cranial irradiation in small-cell lung cancer: findings from a North Central Cancer Treatment Group Pooled Analysis. Ann Oncol. 2012 Nov. 23(11):2919-24. [QxMD MEDLINE Link].
Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23. 394 (10212):1929-1939. [QxMD MEDLINE Link].
Natale R, Lara P, Chansky K, et al. A randomized phase III trial comparing irinotecan/cisplatin (IP) with etoposide/cisplatin (EP) in patients (pts) with previously untreated extensive stage small cell lung cancer (E-SCLC). J Clin Oncol. 2008;26 (suppl):400s.
Heigener D, Freitag L, Eschbach C et al. Topotecan/cisplatin (TP) compared to cisplatin/etoposide (PE) for patients with extensive disease-small cell lung cancer (ED-SCLC): final results of a randomised phase III trial. J Clin Oncol. 2008;26 (suppl):400s.
Slotman BJ, van Tinteren H, Praag JO, Knegjens JL, El Sharouni SY, Hatton M, et al. Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet. 2015 Jan 3. 385 (9962):36-42. [QxMD MEDLINE Link]. [Full Text].
Takahashi T, Yamanaka T, Seto T, Harada H, Nokihara H, Saka H, et al. Prophylactic cranial irradiation versus observation in patients with extensive-disease small-cell lung cancer: a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2017 May. 18 (5):663-671. [QxMD MEDLINE Link].
Harris S, Chan MD, Lovato JF, Ellis TL, Tatter SB, Bourland JD, et al. Gamma knife stereotactic radiosurgery as salvage therapy after failure of whole-brain radiotherapy in patients with small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2012 May 1. 83(1):e53-9. [QxMD MEDLINE Link].
Jotte R, Conkling P, Reynolds C, Galsky MD, Klein L, Fitzgibbons JF, et al. Randomized phase II trial of single-agent amrubicin or topotecan as second-line treatment in patients with small-cell lung cancer sensitive to first-line platinum-based chemotherapy. J Clin Oncol. 2011 Jan 20. 29(3):287-93. [QxMD MEDLINE Link].
Goto K, Ohe Y, Shibata T, Seto T, Takahashi T, Nakagawa K, et al. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2016 Aug. 17 (8):1147-1157. [QxMD MEDLINE Link].
Zepzelca (lurbinectedin) [package insert]. Palo Alto, CA: Jazz Pharmaceuticals, Inc. June 2020. Available at [Full Text].
Nivolumab Indication in Small Cell Lung Cancer Withdrawn in U.S. Market. The ASCO Post. Available at https://ascopost.com/issues/january-25-2021/nivolumab-indication-in-small-cell-lung-cancer-withdrawn-in-us-market/. January 25, 2021; Accessed: March 23, 2021.
Merck Provides Update on KEYTRUDA® (pembrolizumab) Indication in Metastatic Small Cell Lung Cancer in the US. Merck. Available at https://www.merck.com/news/merck-provides-update-on-keytruda-pembrolizumab-indication-in-metastatic-small-cell-lung-cancer-in-the-us/. March 1, 2021; Accessed: March 23, 2021.
Schreiber D, Rineer J, Vongtama D, et al. Surgery for limited-stage small cell lung cancer, should the paradigm shift? A SEER-based analysis. J Clin Oncol (Suppl). 2008. 26:403s.
Fu Z, Li D, Deng C, Zhang J, Bai J, Li Y, et al. Excellent survival of pathological N0 small cell lung cancer patients following surgery. Eur J Med Res. 2023 Feb 21. 28 (1):91. [QxMD MEDLINE Link]. [Full Text].
Anraku M, Waddell TK. Surgery for small-cell lung cancer. Semin Thorac Cardiovasc Surg. 2006 Fall. 18(3):211-6. [QxMD MEDLINE Link].
Mazzone 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. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Jaklitsch MT, Jacobson FL, Austin JH, Field JK, Jett JR, Keshavjee S, et al. The American Association for Thoracic Surgery guidelines for lung cancer screening using low-dose computed tomography scans for lung cancer survivors and other high-risk groups. J Thorac Cardiovasc Surg. 2012 Jul. 144 (1):33-8. [QxMD MEDLINE Link].
[Guideline] Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May. 143 (5 Suppl):e142S-65S. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Rudin CM, Ismaila N, Hann CL, Malhotra N, Movsas B, Norris K, et al. Treatment of Small-Cell Lung Cancer: American Society of Clinical Oncology Endorsement of the American College of Chest Physicians Guideline. J Clin Oncol. 2015 Dec 1. 33 (34):4106-11. [QxMD MEDLINE Link]. [Full Text].
Moffat GT, Wang T, Robinson AG. Small Cell Lung Cancer in Light/Never Smokers - A Role for Molecular Testing?. J Natl Compr Canc Netw. 2023 Feb 15. 21 (4):336-339. [QxMD MEDLINE Link].

Media Gallery

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.

of 2

Table 1. Paraneoplastic Syndromes Affecting Endocrine and Neurologic Function in SCLC

Organ System	Syndrome	Mechanism	Frequency
Endocrine	SIADH	Antidiuretic hormone	15%^[22]
	Ectopic secretion of ACTH	ACTH	2-5%^[23]

Neurologic	Eaton-Lambert reverse myasthenic syndrome		3%^[24]
	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^[22]; (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^[23]; (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.^[24]

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 greatest dimension	Surrounded by lung or visceral pleura; no invasion more proximal than lobar bronchus
	T1a	≤1 cm in greatest dimension
	T1b	>1 cm but ≤2 cm in greatest dimension
	T1c	>2 cm but ≤3 cm in greatest dimension
T2		>3 cm but ≤5 cm in greatest dimension, 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 ≤4 cm in greatest dimension
	T2b	>5 cm but ≤7 cm in greatest dimension
T3		>5 cm but ≤7 cm in greatest dimension, 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		>7 cm or (see right column)	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 cannot 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 Tumor with pleural nodules or malignant pleural or pericardial effusion
	M1b	Single extrathoracic metastasis in a single organ and involvement of a single distant (nonregional) node
	M1c	Multiple extrathoracic metastases in one or more organs
AJCC = American Joint Committee on Cancer. Adapted from: (1) Edge SB, Byrd DR, Compton CC, et al, eds. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2010:299-330^[32]; (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.^[32]

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 IA	IA1	T1a	N0	M0
	IA2	T1b	N0	M0
	IA3	T1c	N0	M0
Stage IIA		T2b	N0	M0
Stage IIB		T1a,b,c	N1	M0
		T2a,b	N1	M0
		T3	N0	M0
Stage IIIA		T1a,b,c	N2	M0
		T2a,b	N2	M0
		T3	N1-2	M0
		T4	N0-1	M0
Stage IIIB		T1a,b,c	N3	M0
		T2a,b	N3	M0
		T3	N2	M0
		T4	N2	M0
Stage IIIC		T3-4	N3	M0
Stage IVA		Any T	Any N	M1a,b
Stage IVB		Any T	Any N	M1c
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; 2016^[37]; (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.^[32]