Small-cell carcinoma

Small-cell lung carcinoma (SCLC) has long been divided into two clinicopathological stages, termed limited stage (LS) and extensive stage (ES).{{cite journal | vauthors = Chan BA, Coward JI | title = Chemotherapy advances in small-cell lung cancer | journal = Journal of Thoracic Disease | volume = 5 | issue = Suppl 5 | pages = S565–S578 | date = October 2013 | pmid = 24163749 | pmc = 3804877 | doi = 10.3978/j.issn.2072-1439.2013.07.43 }} The stage is generally determined by the presence or absence of metastases, whether or not the tumor appears limited to the thorax, and whether or not the entire tumor burden within the chest can feasibly be encompassed within a single radiotherapy portal.{{cite journal | vauthors = Argiris A, Murren JR | title = Staging and clinical prognostic factors for small-cell lung cancer | journal = Cancer Journal | volume = 7 | issue = 5 | pages = 437–447 | year = 2001 | pmid = 11693903 }} In general, if the tumor is confined to one lung and the lymph nodes close to that lung, the cancer is said to be LS. If cancer has spread beyond that, it is said to be ES.

Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for the highest mortality rates among both men and women. When associated with the lung, SCLC is sometimes called "oat cell carcinoma" due to the flat cell shape and scanty cytoplasm. Small cell mesothelioma – an extremely rare subtype of lung cancer – can be mistaken for small cell lung cancer.{{cite web | vauthors = Selby K | work = The Mesothelioma Center | title = Small Cell Mesothelioma | url = https://www.asbestos.com/mesothelioma/small-cell/ }}

Small-cell carcinoma is most often more rapidly and widely metastatic than non-small-cell lung carcinoma{{cite book |author1=Cotran, Ramzi S. |author2=Kumar, Vinay |author3=Fausto, Nelson |author4=Nelso Fausto |author5=Robbins, Stanley L. |author6=Abbas, Abul K. |title=Robbins and Cotran pathologic basis of disease |publisher=Elsevier Saunders |location=St. Louis, Mo |year=2005 |isbn=978-0-7216-0187-8 |page=759}} (and hence staged differently). There is usually early involvement of the hilar and mediastinal lymph nodes.{{cite book |chapter=Ch. 13, box on morphology of small-cell lung carcinoma |author1=Mitchell, Richard Sheppard |author2=Kumar, Vinay |author3=Abbas, Abul K. |author4=Fausto, Nelson |title=Robbins Basic Pathology|publisher=Saunders |location=Philadelphia |year= 2007|isbn=978-1-4160-2973-1 |edition=8th}} The mechanisms of its metastatic progression are not well understood.

{{main|Combined small-cell lung carcinoma}}

When SCLC is found with one or more differentiated forms of lung cancer, such as squamous cell carcinoma or adenocarcinoma, the malignant tumor is then diagnosed and classified as a combined small cell lung carcinoma (c-SCLC). Small-cell lung carcinoma can occur in combination with a wide variety of other histological variants of lung cancer,{{cite book |title=Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart | veditors = Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC |publisher=IARC Press |location=Lyon |year=2004 |series=World Health Organization Classification of Tumours |isbn=978-92-832-2418-1 |url=http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/bb10-cover.pdf |access-date=27 March 2010 |url-status=live |archive-url=https://web.archive.org/web/20090823210304/http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/bb10-cover.pdf |archive-date=23 August 2009 }} including extremely complex malignant tissue admixtures.{{cite journal | vauthors = Pelosi G, Sonzogni A, Galetta D, Perrone F, Braidotti P, Manzotti M, Fabbri A, Spaggiari L, Veronesi G, Viale G | title = Combined small-cell carcinoma of the lung with quadripartite differentiation of epithelial, neuroendocrine, skeletal muscle, and myofibroblastic type | journal = Virchows Archiv | volume = 458 | issue = 4 | pages = 497–503 | date = April 2011 | pmid = 21210145 | doi = 10.1007/s00428-010-1011-8 | s2cid = 19159554 }}

{{cite journal | vauthors = Gotoh M, Yamamoto Y, Huang CL, Yokomise H | title = A combined small cell carcinoma of the lung containing three components: small cell, spindle cell and squamous cell carcinoma | journal = European Journal of Cardio-Thoracic Surgery | volume = 26 | issue = 5 | pages = 1047–1049 | date = November 2004 | pmid = 15519208 | doi = 10.1016/j.ejcts.2004.08.002 | doi-access = free }}

C-SCLC is the only currently recognized subtype of SCLC.

Very rarely, the primary site for small-cell carcinoma is outside of the lungs and pleural space; in these cases, it is referred to as extrapulmonary small-cell carcinoma (EPSCC). Outside of the respiratory tract, small-cell carcinoma can appear in the cervix, prostate, liver, pancreas, gastrointestinal tract, or bladder.{{cite journal | vauthors = Ismaili N | title = A rare bladder cancer--small cell carcinoma: review and update | journal = Orphanet Journal of Rare Diseases | volume = 6 | issue = 75 | pages = 75 | date = November 2011 | pmid = 22078012 | pmc = 3253713 | doi = 10.1186/1750-1172-6-75 | doi-access = free }} It is estimated to account for 1,000 new cases a year in the U.S. Histologically similar to small-cell lung cancer, therapies for small-cell lung cancer are usually used to treat EPSCC.{{EMedicine|article|284288|Extrapulmonary Small Cell Carcinoma}} First-line treatment is usually with cisplatin and etoposide. In Japan, first-line treatment is shifting to irinotecan and cisplatin. When the primary site is in the skin, it is referred to as a Merkel-cell carcinoma.{{Cite web|url=https://www.dynamed.com/condition/merkel-cell-carcinoma|title=Merkel-cell carcinima|website=Dynamed|access-date=2021-08-01}}

This is an extremely rare type of small cell, and there has been little information in the scientific community. It appears to occur in only one or more lymph nodes, and nowhere else in the body. Treatment is similar to small-cell lung cancer, but survival rates are much higher than other small-cell carcinomas.{{cite journal | vauthors = Cicin I, Usta U, Karagol H, Uzunoglu S, Kocak Z | title = Extrapulmonary small cell carcinoma localized in lymph nodes: is it a different clinical entity? | journal = Acta Oncologica | volume = 48 | issue = 3 | pages = 354–360 | year = 2009 | pmid = 18979286 | doi = 10.1080/02841860802495370 | doi-access = free }}

Small-cell carcinoma of the prostate (SCCP) is a rare form of prostate cancer (approximately 1% of prostate cancers).{{cite journal | vauthors = Nutting C, Horwich A, Fisher C, Parsons C, Dearnaley DP | title = Small-cell carcinoma of the prostate | journal = Journal of the Royal Society of Medicine | volume = 90 | issue = 6 | pages = 340–341 | date = June 1997 | pmid = 9227387 | pmc = 1296316 | doi = 10.1177/014107689709000615 }} Symptomatic metastasis of SCCP to the brain is rare, and carries a poor prognosis.{{cite journal | vauthors = Erasmus CE, Verhagen WI, Wauters CA, van Lindert EJ | title = Brain metastasis from prostate small cell carcinoma: not to be neglected | journal = The Canadian Journal of Neurological Sciences. Le Journal Canadien des Sciences Neurologiques | volume = 29 | issue = 4 | pages = 375–377 | date = November 2002 | pmid = 12463494 | doi = 10.1017/S0317167100002250 | doi-access = free }}

File:LK-small cell3683.jpg showing a probable S2–S3 small cell carcinoma in the right side lung.]]

Small-cell carcinoma of the lung usually presents in the central airways and infiltrates the submucosa leading to the narrowing of bronchial airways. Common symptoms include cough, dyspnea, weight loss, and debility. Over 70% of patients with small-cell carcinoma present with metastatic disease; common sites include the liver, adrenals, bone, and brain.{{cite journal | vauthors = Nakazawa K, Kurishima K, Tamura T, Kagohashi K, Ishikawa H, Satoh H, Hizawa N | title = Specific organ metastases and survival in small cell lung cancer | journal = Oncology Letters | volume = 4 | issue = 4 | pages = 617–620 | date = October 2012 | pmid = 23205072 | pmc = 3506697 | doi = 10.3892/ol.2012.792 }}{{cite journal | vauthors = Ko J, Winslow MM, Sage J | title = Mechanisms of small cell lung cancer metastasis | journal = EMBO Molecular Medicine | volume = 13 | issue = 1 | pages = e13122 | date = January 2021 | pmid = 33296145 | pmc = 7799359 | doi = 10.15252/emmm.202013122 }}

Due to its high grade neuroendocrine nature, small-cell carcinomas can produce ectopic hormones, including adrenocorticotropic hormone (ACTH) and anti-diuretic hormone (ADH). Ectopic production of large amounts of ADH leads to syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).{{cite journal | vauthors = Babar SM | title = SIADH associated with ciprofloxacin | journal = The Annals of Pharmacotherapy | volume = 47 | issue = 10 | pages = 1359–1363 | date = October 2013 | pmid = 24259701 | doi = 10.1177/1060028013502457 | s2cid = 36759747 }} Lambert–Eaton myasthenic syndrome is a well-known paraneoplastic condition linked to small-cell carcinoma.{{cite journal | vauthors = Titulaer MJ, Verschuuren JJ | title = Lambert-Eaton myasthenic syndrome: tumor versus nontumor forms | journal = Annals of the New York Academy of Sciences | volume = 1132 | issue = 1 | pages = 129–134 | year = 2008 | pmid = 18567862 | doi = 10.1196/annals.1405.030 | s2cid = 22482871 | bibcode = 2008NYASA1132..129T }} Approximately half of all individuals diagnosed with Lambert–Eaton myasthenic syndrome will eventually be found to have a small-cell carcinoma of the lung.

TP53 is mutated in 70 to 90% of SCLCs. RB1 and the retinoblastoma pathway are inactivated in most SCLCs. PTEN is mutated in 2 to 10%. MYC amplifications and amplification of MYC family members are found in 30% of SCLCs. Loss of heterozygocity on chromosome arm 3p is found in more than 80% of SCLCs, including the loss of FHIT.{{cite web|url=http://atlasgeneticsoncology.org/Tumors/TranslocLungSmallCellCarcID6651.html|title=Lung: Translocations in Small Cell Carcinoma|website=atlasgeneticsoncology.org|access-date=30 April 2018|url-status=live|archive-url=http://archive.wikiwix.com/cache/20150130183844/http://atlasgeneticsoncology.org/Tumors/TranslocLungSmallCellCarcID6651.html|archive-date=30 January 2015}} One hundred translocations have been reported in SCLCs.{{cite web|url=http://cgap.nci.nih.gov/Chromosomes/Mitelman|title=Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer|url-status=live|archive-url=http://archive.wikiwix.com/cache/20160529012710/http://cgap.nci.nih.gov/Chromosomes/Mitelman|archive-date=2016-05-29}}{{cite web|url=http://Atlasgeneticsoncology.org|title=Atlas of Genetics and Cytogenetics in Oncology and Haematology|work=atlasgeneticsoncology.org|url-status=live|archive-url=http://archive.wikiwix.com/cache/20110223164445/http://atlasgeneticsoncology.org/|archive-date=2011-02-23}}

File:Histopathology of small cell carcinoma, annotated.png

Image:Lung small cell carcinoma (1) by core needle biopsy.jpg.]]

Small-cell carcinoma is an undifferentiated neoplasm composed of primitive-appearing cells. As the name implies, the cells in small-cell carcinomas are smaller than normal cells and barely have room for any cytoplasm. Some researchers identify this as a failure in the mechanism that controls the size of the cells.{{cite journal | vauthors = Leslie M | title = Mysteries of the cell. How does a cell know its size? | journal = Science | volume = 334 | issue = 6059 | pages = 1047–1048 | date = November 2011 | pmid = 22116854 | doi = 10.1126/science.334.6059.1047 }}

At the time of diagnosis, 60–70% of people already have metastases.{{cite journal | vauthors = Tammela T, Sage J | title = Investigating Tumor Heterogeneity in Mouse Models | journal = Annual Review of Cancer Biology | volume = 4 | issue = 1 | pages = 99–119 | date = March 2020 | pmid = 34164589 | pmc = 8218894 | doi = 10.1146/annurev-cancerbio-030419-033413 | doi-access = free }}

Chest X-rays are typically the first step to evaluate someone for any type of lung cancer. If images show suspicious spots on the patient's lung, a healthcare provider may order chest CT, PET, needle biopsy or bronchoscopy for further check.{{cite web |title=Small Cell Lung Cancer: Symptoms, Causes & Treatment |url=https://my.clevelandclinic.org/health/diseases/6202-small-cell-lung-cancer |website=Cleveland Clinic |access-date=11 January 2025 |language=en}}

It is possible to use bronchoscopic biopsy to diagnose Lung small-cell carcinoma. However, small-cell carcinoma tissue obtained through bronchoscopy is prone to tissue compression and unclear morphology. However, pathologists can stain lesions with immunohistochemistry Ki-67, CD56, TTF-1, CgA, Syn, P63, CK5/6, LCA, and 34βE12 to help, in order to make a differential diagnosis.{{cite journal | vauthors = Wang Y, Qu L, Hao Y | title = [The pitfall of transbronchial lung biopsy in the small cell carcinoma--attach 64 cases immunohistochemistry research.] | journal = Zhongguo Fei Ai Za Zhi = Chinese Journal of Lung Cancer | volume = 12 | issue = 8 | pages = 901–904 | date = August 2009 | pmid = 20719180 | doi = 10.3779/j.issn.1009-3419.2009.08.14 | doi-access = free }}
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The common metastasis sites of SCLC include the lung, brain, bone, adrenal gland, liver, colorectum, and lymph nodes.

If the tumor metastasises to the brain, It is necessary to comprehensively evaluate the patient's condition in combination with PET/CT and MRI. In patients with brain metastases from small cell lung cancer, MRI has specificity and sensitivity of 75% to 90% and 70% to 85%, respectively.{{cite journal | vauthors = Cheng H, Perez-Soler R | title = Leptomeningeal metastases in non-small-cell lung cancer | journal = The Lancet. Oncology | volume = 19 | issue = 1 | pages = e43-e55 | date = January 2018 | pmid = 29304362 | doi = 10.1016/S1470-2045(17)30689-7 }} In MRI, T1- and T2-weighted images had medium-to-high signal intensity. Presently, brain metastasis diagnosis by FDG-PET/CT often uses TBR ≥1.6 of increased absorption as the appropriate diagnostic index for positive brain metastasis.{{cite journal | vauthors = Ganti AK, Loo BW, Bassetti M, Blakely C, Chiang A, D'Amico TA, D'Avella C, Dowlati A, Downey RJ, Edelman M, Florsheim C, Gold KA, Goldman JW, Grecula JC, Hann C, Iams W, Iyengar P, Kelly K, Khalil M, Koczywas M, Merritt RE, Mohindra N, Molina J, Moran C, Pokharel S, Puri S, Qin A, Rusthoven C, Sands J, Santana-Davila R, Shafique M, Waqar SN, Gregory KM, Hughes M | title = Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology | journal = Journal of the National Comprehensive Cancer Network | volume = 19 | issue = 12 | pages = 1441–1464 | date = December 2021 | pmid = 34902832 | pmc = 10203822 | doi = 10.6004/jnccn.2021.0058 }}{{cite journal | vauthors = Zhang-Yin JT, Girard A, Bertaux M | title = What Does PET Imaging Bring to Neuro-Oncology in 2022? A Review | journal = Cancers | volume = 14 | issue = 4 | date = February 2022 | pmid = 35205625 | pmc = 8870476 | doi = 10.3390/cancers14040879 | doi-access = free }}
{{Cc-notice|cc=by4}} Researchers also found cerebellum is the risk site with a high incidence of metastasis.{{cite journal | vauthors = Wang Y, Xia W, Liu B, Zhou L, Ni M, Zhang R, Shen J, Bai Y, Weng G, Yuan S, Gao X | title = Exploration of spatial distribution of brain metastasis from small cell lung cancer and identification of metastatic risk level of brain regions: a multicenter, retrospective study | journal = Cancer Imaging | volume = 21 | issue = 1 | pages = 41 | date = June 2021 | pmid = 34120659 | pmc = 8201893 | doi = 10.1186/s40644-021-00410-w | doi-access = free }}
{{Cc-notice|cc=by4}} In patients with SCLC brain metastasis, the general manifestation on plain CT is of low and medium density, and high-density signals of lesions are rare. However, the imaging with enhanced CT is more clear, showing obvious enhanced signals of cancer lesions. The extensive low-density edema zone of finger edema can be observed. What's more, it is difficult to detect small metastasis in the brain <0.5 cm, which contributes to the high false-positive rate of brain CT.{{cite journal |last1=Zhu |first1=Yingze |last2=Cui |first2=Yishuang |last3=Zheng |first3=Xuan |last4=Zhao |first4=Yue |last5=Sun |first5=Guogui |title=Small-cell lung cancer brain metastasis: From molecular mechanisms to diagnosis and treatment |journal=Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease |date=December 2022 |volume=1868 |issue=12 |pages=166557 |doi=10.1016/j.bbadis.2022.166557 |pmid=36162624|doi-access=free}}}
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In cases of LS-SCLC, combination chemotherapy is administered together with concurrent chest radiotherapy.{{Cite web |url=https://www.uptodate.com/contents/limited-stage-small-cell-lung-cancer-initial-management |title=Limited-stage small cell lung cancer: Initial management |website=www.uptodate.com |publisher=UpToDate |access-date=2019-06-02}}{{Cite web |url=https://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq |title=Small Cell Lung Cancer Treatment |date=1980-01-01 |website=National Cancer Institute |publisher=National Cancer Institute, United States Department of Health and Human Services |location=U.S. |access-date=2019-06-02}}{{cite journal | vauthors = Sherman CA, Rocha Lima CM, Turrisi AT | title = Limited small-cell lung cancer: a potentially curable disease | journal = Oncology | volume = 14 | issue = 10 | pages = 1395–403; discussion 1403–4, 1409 | date = October 2000 | pmid = 11098505 | url = https://www.cancernetwork.com/oncology-journal/limited-small-cell-lung-cancer-potentially-curable-disease | access-date = 2021-08-01 | archive-date = 2019-02-05 | archive-url = https://web.archive.org/web/20190205003101/http://www.cancernetwork.com/oncology-journal/limited-small-cell-lung-cancer-potentially-curable-disease | url-status = dead }} Chest radiotherapy has been shown to improve survival in LS-SCLC.{{cite journal | vauthors = Singer L, Yom SS | title = Consolidative radiation therapy for extensive-stage small cell lung cancer | journal = Translational Lung Cancer Research | volume = 4 | issue = 3 | pages = 211–214 | date = June 2015 | pmid = 26207205 | pmc = 4483471 | doi = 10.3978/j.issn.2218-6751.2015.04.02 }} Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to chemotherapy and/or radiotherapy, there has been little role for surgery in this disease since the 1970s.{{cite journal | vauthors = Mountain CF | title = Clinical biology of small cell carcinoma: relationship to surgical therapy | journal = Seminars in Oncology | volume = 5 | issue = 3 | pages = 272–279 | date = September 1978 | pmid = 211638 }} However, in cases of small, asymptomatic, node-negative SCLC's ("very limited stage"), surgical excision may improve survival when used prior to chemotherapy.{{cite journal | vauthors = Shepherd FA | title = Surgery for limited stage small cell lung cancer: time to fish or cut bait | journal = Journal of Thoracic Oncology | volume = 5 | issue = 2 | pages = 147–149 | date = February 2010 | pmid = 20101141 | doi = 10.1097/JTO.0b013e3181c8cbf5 | doi-access = free }}

In ES-SCLC, platinum-based combination chemotherapy is the standard of care.{{cite journal | vauthors = Pelayo Alvarez M, Westeel V, Cortés-Jofré M, Bonfill Cosp X | title = Chemotherapy versus best supportive care for extensive small cell lung cancer | journal = The Cochrane Database of Systematic Reviews | issue = 11 | pages = CD001990 | date = November 2013 | pmid = 24282143 | doi = 10.1002/14651858.CD001990.pub3 | pmc = 11364206 }}

Combination chemotherapy consists of a wide variety of agents, including cisplatin, cyclophosphamide, vincristine and carboplatin. Response rates are high even in extensive disease, with between 15% and 30% of subjects having a complete response to a combination chemotherapy, and the vast majority having at least some objective response. Responses in ES-SCLC are often of short duration, and the evidence surrounding the risk of treatment compared to the potential benefit of chemotherapy for people who have extensive SCLC is not clear.

Small-cell lung cancer is most commonly treated with chemotherapy in a combination of two drugs, which is more effective than one drug alone.

1. Cisplatin and etoposide,
2. Carboplatin and etoposide.

The drug paclitaxel may be useful in the treatment of cisplatin-resistant cancer. About 68.1% of cisplatin-resistant cells appear to be sensitive to paclitaxel and 66.7% of paclitaxel-resistant cells to cisplatin. The mechanism for this activity is unknown.{{cite journal | vauthors = Stordal B, Pavlakis N, Davey R | title = A systematic review of platinum and taxane resistance from bench to clinic: an inverse relationship | journal = Cancer Treatment Reviews | volume = 33 | issue = 8 | pages = 688–703 | date = December 2007 | pmid = 17881133 | doi = 10.1016/j.ctrv.2007.07.013 | hdl = 2123/4068 | url = https://eprints.mdx.ac.uk/14437/1/2007-StordalCTR-Paclitaxel.pdf }} Paclitaxel-based chemotherapy showed modest activity in SCLC patients refractory to both etoposide- and camptothecin-based chemotherapy.{{cite journal | vauthors = Kim SH, Kim MJ, Kim YJ, Chang H, Kim JW, Lee JO, Lee KW, Kim JH, Bang SM, Lee JS | title = Paclitaxel as third-line chemotherapy for small cell lung cancer failing both etoposide- and camptothecin-based chemotherapy | journal = Medicine | volume = 96 | issue = 42 | pages = e8176 | date = October 2017 | pmid = 29049199 | pmc = 5662365 | doi = 10.1097/MD.0000000000008176 }} The newer agent lurbinectedin is active in relapsed SCLC and was approved for medical use in the United States in June 2020.{{cite web | title=Zepzelca: FDA-Approved Drugs | website=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=213702 | access-date=15 June 2020}}{{cite web | title=Zepzelca- lurbinectedin injection, powder, lyophilized, for solution | website=DailyMed | date=15 June 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=632bb50c-3bcb-4c85-9056-fc33410550ae | access-date=24 September 2020}}{{cite press release | publisher=Jazz Pharmaceuticals | title=Jazz Pharmaceuticals Announces U.S. FDA Accelerated Approval of Zepzelca (lurbinectedin) for the Treatment of Metastatic Small Cell Lung Cancer | via=PR Newswire | date=15 June 2020 | url=https://www.prnewswire.com/news-releases/jazz-pharmaceuticals-announces-us-fda-accelerated-approval-of-zepzelca-lurbinectedin-for-the-treatment-of-metastatic-small-cell-lung-cancer-301077082.html | access-date=15 June 2020}}{{cite web | title=FDA grants accelerated approval to lurbinectedin for metastatic small | website=U.S. Food and Drug Administration (FDA) | date=15 June 2020 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-lurbinectedin-metastatic-small-cell-lung-cancer | access-date=16 June 2020}} {{PD-notice}}{{cite web | title=Drug Trials Snapshots: Zepzelca | website=U.S. Food and Drug Administration (FDA) | date=15 June 2020 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-zepzelca | access-date=28 June 2020}} {{PD-notice}}

The FDA has approved three immunotherapies for small cell lung cancer:

• Nivolumab (Opdivo), a PD-1 inhibitor (2018){{Cite web|url=https://www.curetoday.com/view/fda-approves-opdivo-for-small-cell-lung-cancer-treatment|title=FDA Approves Opdivo for Small Cell Lung Cancer Treatment|website=Cure Today|date=17 August 2018 }}{{cite web | title = FDA Approves Opdivo (Nivolumab) for Small Cell Lung Cancer | url = https://www.cancer.org/latest-news/fda-approves-opdivo-nivolumab-for-small-cell-lung-cancer.html | work = cancer.org }}
• Atezolizumab (Tecentriq), a PD-L1 inhibitor (2018){{cite web | title = FDA approves atezolizumab for extensive-stage small cell lung cancer | url = https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm633814.htm | work = U.S. Food and Drug Administration }}{{cite web | title = Concurrent Tecentriq Adds First Survival Benefit Seen in Small Cell Lung Cancer in 20 Years | url = https://www.curetoday.com/articles/concurrent-tecentriq-adds-first-survival-benefit-seen-in-small-cell-lung-cancer-in-20-years | work = curetoday.com | date = 25 September 2018 }}
• Tarlatamab, a bi-specific T-cell engager (2024){{cite web |date=16 May 2024 |title=FDA grants accelerated approval to tarlatamab-dlle for extensive stage small cell lung cancer |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tarlatamab-dlle-extensive-stage-small-cell-lung-cancer |access-date=17 May 2024 |website=U.S. Food and Drug Administration (FDA)}} {{PD-notice}}{{cite press release |title=FDA approves Imdelltra (tarlatamab-dlle), the first and only T-cell engager therapy for the treatment of extensive-stage small cell lung cancer |publisher=Amgen |via=PR Newswire |date=16 May 2024 |url=https://www.prnewswire.com/news-releases/fda-approves-imdelltra-tarlatamab-dlle-the-first-and-only-t-cell-engager-therapy-for-the-treatment-of-extensive-stage-small-cell-lung-cancer-302148431.html |access-date=18 May 2024}}

Canadian regulator rejected funding Tecentriq (Atezolizumab) for extensive-stage small-cell lung cancer in 2020 "as too costly" followed by the United Kingdom also citing "drug’s cost-effectiveness."{{cite web | work = Reuters | title = Canadian regulator considers changes to new drug pricing plan | date = 20 February 2020 | url = https://ca.reuters.com/article/domesticNews/idCAKBN20E2LI | archive-url = https://web.archive.org/web/20200222031204/https://ca.reuters.com/article/domesticNews/idCAKBN20E2LI | url-status = dead | archive-date = February 22, 2020 }}{{cite web | agency = Reuters | title = NICE Cites Cost in Deciding Against Atezolizumab for Frontline Advanced Small Cell Lung Cancer | date = 6 January 2020 | url = https://www.onclive.com/web-exclusives/nice-cites-cost-in-deciding-against-atezolizumab-for-frontline-advanced-small-cell-lung-cancer }}

Chest radiation helps SCLC patients live longer by killing cancer cells and helping prevention of cancer recurrence.{{cite web | title = Study: Chest Radiation Helps Small Cell Lung Cancer Patients Live Longer | url = https://www.cancer.org/latest-news/study-chest-radiation-helps-small-cell-lung-cancer-patients-live-longer.html | work = cancer.org }} Another type of radiation, prophylactic cranial radiation, prevents central nervous system recurrence and can improve survival in patients with good performance status who have had a complete response or very good partial response to chemoradiation in LD or chemotherapy in ED.

If small cell lung cancer comes back after treatment, the following combination of drugs may be used as salvage therapy:{{cite web | title = Treatment for Small Cell Lung Cancer | work = Canadian Cancer Society | date = May 2020 | url = http://www.cancer.ca/en/cancer-information/cancer-type/lung/treatment/treatment-for-small-cell-lung-cancer/?region=nu }}

1. Cyclophosphamide (Cytoxan, Procytox),
2. Doxorubicin (Adriamycin) and
3. Vincristine (Oncovin)
4. Paclitaxel (Taxol)
5. Irinotecan (Camptosar) {{cite journal | vauthors = Mouri A, Yamaguchi O, Miyauchi S, Shiono A, Utsugi H, Nishihara F, Murayama Y, Kagamu H, Kobayashi K | title = Combination therapy with carboplatin and paclitaxel for small cell lung cancer | journal = Respiratory Investigation | volume = 57 | issue = 1 | pages = 34–39 | date = January 2019 | pmid = 30528688 | doi = 10.1016/j.resinv.2018.09.004 | s2cid = 54471245 }}

Guidelines recommended as of 2018 that patients who relapse > 6 months from initial therapy should be retreated with the original chemotherapy regimen. For patients who relapse in < 6 months, single-agent chemotherapy either topotecan second-line therapy, or paclitaxel can be used.{{cite journal | vauthors = Qin A, Kalemkerian GP | title = Treatment Options for Relapsed Small-Cell Lung Cancer: What Progress Have We Made? | journal = Journal of Oncology Practice | volume = 14 | issue = 6 | pages = 369–370 | date = June 2018 | pmid = 29894661 | doi = 10.1200/JOP.18.00278 | doi-access = free }}

Several newer agents, including temozolomide and bendamustine, have activity in relapsed SCLC. Of note, temozolomide yielded a response rate of 38% for brain metastases due to SCLC.

In a clinical trial of 50 patients, a combination of olaparib and temozolomide in relapsed small-cell lung cancer yielded an overall response rate of 41.7%, median progression-free survival of 4.2 months, and overall survival was 8.5 months.{{cite journal | vauthors = Farago AF, Yeap BY, Stanzione M, Hung YP, Heist RS, Marcoux JP, Zhong J, Rangachari D, Barbie DA, Phat S, Myers DT, Morris R, Kem M, Dubash TD, Kennedy EA, Digumarthy SR, Sequist LV, Hata AN, Maheswaran S, Haber DA, Lawrence MS, Shaw AT, Mino-Kenudson M, Dyson NJ, Drapkin BJ | title = Combination Olaparib and Temozolomide in Relapsed Small-Cell Lung Cancer | journal = Cancer Discovery | volume = 9 | issue = 10 | pages = 1372–1387 | date = October 2019 | pmid = 31416802 | pmc = 7319046 | doi = 10.1158/2159-8290.CD-19-0582 }}

Lurbinectedin showed an increased overall survival rate in relapsed small cell lung cancer in a trial.{{cite journal | vauthors = Paz-Ares LG, Trigo Perez JM, Besse B, Moreno V, Lopez R, Sala MA, Ponce Aix S, Fernandez CM, Siguero M, Kahatt CM, Zeaiter AH | title = Efficacy and safety profile of lurbinectedin in second-line SCLC patients: Results from a phase II single-agent trial. | journal = Journal of Clinical Oncology | volume = 37 | date = 2019 | issue = supl; abstr 8506 | page = 8506 | doi = 10.1200/JCO.2019.37.15_suppl.8506 | s2cid = 190884224 }} Lurbinectedin is {{as of|2019}} available in the U.S. under an expanded access program (EAP).{{Cite press release|url=https://www.prnewswire.com/news-releases/pharmamar-and-bionical-emas-launch-expanded-access-program-for-lurbinectedin-in-relapsed-small-cell-lung-cancer-in-the-us-300993470.html|title=PharmaMar and Bionical Emas Launch Expanded Access Program for Lurbinectedin in Relapsed Small Cell Lung Cancer in the U.S.| work = Bionical Emas| via = www.prnewswire.com}}{{cite journal | vauthors = Calvo E, Moreno V, Flynn M, Holgado E, Olmedo ME, Lopez Criado MP, Kahatt C, Lopez-Vilariño JA, Siguero M, Fernandez-Teruel C, Cullell-Young M, Soto Matos-Pita A, Forster M | title = Antitumor activity of lurbinectedin (PM01183) and doxorubicin in relapsed small-cell lung cancer: results from a phase I study | journal = Annals of Oncology | volume = 28 | issue = 10 | pages = 2559–2566 | date = October 2017 | pmid = 28961837 | pmc = 5834091 | doi = 10.1093/annonc/mdx357 | doi-access = free }}{{cite journal | vauthors = Farago AF, Drapkin BJ, Lopez-Vilarino de Ramos JA, Galmarini CM, Núñez R, Kahatt C, Paz-Ares L | title = ATLANTIS: a Phase III study of lurbinectedin/doxorubicin versus topotecan or cyclophosphamide/doxorubicin/vincristine in patients with small-cell lung cancer who have failed one prior platinum-containing line | journal = Future Oncology | volume = 15 | issue = 3 | pages = 231–239 | date = January 2019 | pmid = 30362375 | pmc = 6331752 | doi = 10.2217/fon-2018-0597 }}

Trilaciclib, a CKD4/6 inhibitor, reduces chemotherapy-induced toxicity in patients being treated for small-cell lung cancer.{{cite journal | vauthors = Weiss JM, Csoszi T, Maglakelidze M, Hoyer RJ, Beck JT, Domine Gomez M, Lowczak A, Aljumaily R, Rocha Lima CM, Boccia RV, Hanna W, Nikolinakos P, Chiu VK, Owonikoko TK, Schuster SR, Hussein MA, Richards DA, Sawrycki P, Bulat I, Hamm JT, Hart LL, Adler S, Antal JM, Lai AY, Sorrentino JA, Yang Z, Malik RK, Morris SR, Roberts PJ, Dragnev KH | title = Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial | journal = Annals of Oncology | volume = 30 | issue = 10 | pages = 1613–1621 | date = October 2019 | pmid = 31504118 | pmc = 6857609 | doi = 10.1093/annonc/mdz278 | doi-access = free }}{{Cite web|title=FDA Grants Priority Review to Trilaciclib to Treat Patients with SCLC|url=https://www.cancernetwork.com/view/fda-grants-priority-review-to-trilaciclib-to-treat-patients-with-sclc|access-date=2020-12-04|website=Cancer Network|date=17 August 2020 }}{{Cite web|title=Trilaciclib {{!}} intravenous CDK4/6 inhibitor {{!}} G1 Therapeutics, Inc.|url=https://www.g1therapeutics.com/pipeline/trilaciclib/|access-date=2020-12-28|website=www.g1therapeutics.com}}

In 2021, the FDA approved trilaciclib (Cosela) as a treatment to reduce the frequency of chemotherapy-induced myelosuppression for patients receiving certain types of chemotherapy for extensive-stage small-cell lung cancer.{{Cite web | author = Office of the Commissioner |date=2021-02-12|title=FDA Approves Drug to Reduce Bone Marrow Suppression Caused by Chemotherapy|url=https://www.fda.gov/news-events/press-announcements/fda-approves-drug-reduce-bone-marrow-suppression-caused-chemotherapy|access-date=2021-02-16|website=FDA|language=en}}

As of 2015, 5-year survival rates for small cell lung cancer (extensive and limited) range between 3.6% and 32.2% for women, and between 2.2% and 24.5% for men.{{cite web | title = Table 15.13: Small Cell Cancer of the Lung and Bronchus (Invasive), 5-Year Relative and Period Survival by Race, Sex, Diagnosis Year, Age and Stage at Diagnosis | work = The SEER Cancer Statistics Review 1975-2015 | publisher = Surveillance, Epidemiology, and End Results (SEER), U.S. National Cancer Institute | url = https://seer.cancer.gov/csr/1975_2015/browse_csr.php?sectionSEL=15&pageSEL=sect_15_table.13 }} Relative 5-year survival rate for both sexes has increased from 3.6% in 1975 to 6.7% in 2014. In limited-stage disease, the relative 5-year survival rate (both sexes, all races, all ages) is 21.3%; however, women have higher 5-year survival rates, 26.9%, and men have lower survival rates, 21.3%.{{cite web | url = https://seer.cancer.gov/explorer/application.php?site=611&data_type=4&graph_type=6&compareBy=stage&chk_sex_2=2&chk_race_1=1&chk_age_range_1=1&chk_stage_104=104&advopt_precision=1&showDataFor=sex_2_and_race_1_and_age_range_1 | title = Small cell carcinoma of the Lung and Bronchus SEER Relative Survival Rates by Time Since Diagnosis, 2004-2017 By Stage at Diagnosis, Male, All Races (includes Hispanic), All Ages | work = Surveillance, Epidemiology, and End Results (SEER) Relative Survival Rates by Time Since Diagnosis | publisher = U.S. National Cancer Institute | date = 2016 }} The prognosis is far grimmer in extensive-stage small-cell lung carcinoma where 5-year relative survival rate (both sexes, all races, all ages) is 2.8%; however, women have higher 5-year survival rates, 3.4%, and men have lower 5-year survival rates, 2.2%.

Small-cell carcinoma is very responsive to chemotherapy and radiotherapy, and in particular, regimens based on platinum-containing agents. However, most people with the disease relapse, and median survival remains low. The overall incidence and mortality rates of SCLC in the United States have decreased during the past few decades.{{cite web | url = https://www.oncolink.org/healthcare-professionals/nci/pqid-CDR00000629452 | work = National Cancer Institute | title = Small Cell Lung Cancer Treatment }}

Long-term survival of more than 5 years can be achieved with proper treatment. According to the 17th World Conference on Lung Cancer (WCLC), "patients who received chest radiation and prophylactic cranial irradiation along with a mean of five chemotherapy cycles could achieve a median survival of more than 5 years."{{cite web | vauthors = Davenport L | work = Medscape | title = Exceptional SCLC Survivors: 5-Year Median Survival | date = 20 December 2016 | url = https://www.medscape.com/viewarticle/873492 }} In some cases, long-term survival of 10+ years is achieved with chemotherapy and radiation alone.{{cite web | vauthors = Ketteler J | date = October 16, 2009 | work = Self | title = Lung cancer report: "They said it was bronchitis" | url = https://www.self.com/story/lung-cancer }}{{cite web | title = Focus on immunotherapy and patient perspective highlight the IASLC 2019 Small Cell Lung Cancer Meeting | date = 2019 | url = https://www.iaslc.org/iaslc-news/press-release/focus-immunotherapy-and-patient-perspective-highlight-iaslc-2019-small | work = The International Association for the Study of Lung Cancer (IASLC) }}

A 2023 article stated that the median overall survival is about 1 year, the worst of any lung cancer subtype.{{cite web | work = Cancer Network | url = https://www.cancernetwork.com/view/sclc-prognosis-remains-unsatisfactory-despite-numerous-treatment-options | title = SCLC Prognosis Remains 'Unsatisfactory' Despite Numerous Treatment Options | date = 12 April 2023 }}

File:Pie chart of lung cancers.svg types, with fractions of smokers versus non-smokers shown for each type.Smokers defined as current or former smokers of more than 1 year of duration. See image page in Commons for percentages in numbers. Reference:

• {{cite journal | vauthors = Kenfield SA, Wei EK, Stampfer MJ, Rosner BA, Colditz GA | title = Comparison of aspects of smoking among the four histological types of lung cancer | journal = Tobacco Control | volume = 17 | issue = 3 | pages = 198–204 | date = June 2008 | pmid = 18390646 | pmc = 3044470 | doi = 10.1136/tc.2007.022582 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044470/table/T2/ }}]]

Small cell lung carcinoma accounts for 15% of lung cancers in the United States.{{cite book|title=World Cancer Report 2014|date=2014|publisher=World Health Organization|isbn=978-9283204299|pages=Chapter 5.1}} Small cell lung cancer occurs almost exclusively in smokers – most commonly in heavy smokers and rarely in non-smokers.{{cite journal | vauthors = Ettinger DS, Aisner J | title = Changing face of small-cell lung cancer: real and artifact | journal = Journal of Clinical Oncology | volume = 24 | issue = 28 | pages = 4526–4527 | date = October 2006 | pmid = 17008688 | doi = 10.1200/jco.2006.07.3841 | doi-access = free }}{{cite journal | vauthors = Muscat JE, Wynder EL | title = Lung cancer pathology in smokers, ex-smokers and never smokers | journal = Cancer Letters | volume = 88 | issue = 1 | pages = 1–5 | date = January 1995 | pmid = 7850764 | doi = 10.1016/0304-3835(94)03608-l }}

In 2013, the US Congress passed the Recalcitrant Cancer Research Act, which mandated increased attention to certain recalcitrant cancers (cancers having a 5-year relative survival rate of less than 50%), including small cell lung cancer. That led to the National Cancer Institute supporting small cell-specific research.{{cite web | vauthors = Richards S | date = 7 February 2019 | work = Fred Hutch | title = A new focus on small cell lung cancer | url = https://www.fredhutch.org/en/news/center-news/2019/02/q-a-with-david-macpherson-lung-cancer.html }}{{cite journal | vauthors = Augert A, Eastwood E, Ibrahim AH, Wu N, Grunblatt E, Basom R, Liggitt D, Eaton KD, Martins R, Poirier JT, Rudin CM, Milletti F, Cheng WY, Mack F, MacPherson D | title = Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition | journal = Science Signaling | volume = 12 | issue = 567 | pages = eaau2922 | date = February 2019 | pmid = 30723171 | pmc = 6530478 | doi = 10.1126/scisignal.aau2922 }}

• Dustin Diamond, perhaps best known as an actor on Saved by the Bell, died one month after the diagnosis.{{Cite web|title=Dustin Diamond, 'Saved by the Bell' Star, Dead at 44|url=https://www.etonline.com/dustin-diamond-saved-by-the-bell-star-dead-at-44-159865|access-date=2021-02-06|website=Entertainment Tonight|date=February 2021 |language=en-US}}
• Asbjørn Sennels, Danish football player, died three months after the diagnosis.{{cite journal | url = https://www.ekstrabladet.dk/sport/fodbold/dansk_fodbold/superligaen/asbjoern-sennels-er-doed/9855084 | title = Asbjørn Sennels | journal = Ekstra Bladet | date = 9 July 2023 | trans-work = Extra Magazine | language = Danish }}

Image:Carcinoma microcellulare oatcell carcinoma or anaplastic carcinoma (lung)H&E magn 200x.jpg|Anaplastic (microcellular, oat cell) carcinoma from the lung (histopathology)

Image:Lung small cell carcinoma (2) by core needle biopsy.jpg|Histopathologic image of small-cell carcinoma of the lung. CT-guided core needle biopsy.

{{Reflist}}

{{Medical resources

| ICD10 =

| ICD9 =

| ICDO = {{ICDO|8041|3}}

| OMIM =

| OMIM_mult =

| MedlinePlus = 000122

| eMedicineSubj = med

| eMedicineTopic = 1336

| DiseasesDB =

| MeshID = D018288

| SNOMED CT = 11010461000119101

}}

{{Tumor histology}}

{{Respiratory tract neoplasia}}

{{Male genital neoplasia}}

{{DEFAULTSORT:Small Cell Carcinoma}}

Category:Carcinoma

Category:Cytopathology

Category:Infectious causes of cancer

Category:Lung cancer

Category:Rare diseases