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Guidelines

Guidelines Summary

Guidelines on lung cancer screening have been issued by the following organizations:

American Cancer Society (ACS)
American College of Chest Physicians (CHEST)
American Association for Thoracic Surgery (AATS)
National Comprehensive Cancer Network (NCCN)
U.S. Preventive Services Task Force (USPSTF)

Most of the guidelines recommend offering annual screening with low-dose, computed tomography (LDCT) scanning to asymptomatic patients aged 55 to 74 years and who have at least a 30 pack-year smoking history and either continue to smoke or have quit within the past 15 years.^{[25, 72, 28, 73, 26]}

In 2021, the USPSTF extended its screening recommendation to include persons aged 50 to 80 with at least a 20 pack-year smoking history. The USPSTF recommends discontinuing screening once 15 years have gone by since the patient stopped smoking, or if the patient develops a health problem that "substantially limits life expectancy or the ability or willingness to have curative lung surgery."^[26]

Diagnosis

The American College of Chest Physicians (CHEST) updated its comprehensive set of lung cancer guidelines in 2013. The guideline set of more than 275 recommendations includes an executive summary of current recommendations for diagnosis and treatment, along with additional recommendations for screening, chemoprevention, and treatment of tobacco use in patients with lung cancer.^{[29, 74]}

In 2015, the American Society of Clinical Oncology (ASCO) endorsed the CHEST guidelines, with the addition of minor qualifying statements.^[75]

Diagnosis of Pleural Abnormalities

The CHEST recommendations for diagnosis of pleural abnormalities include the following^{[29, 74]}:

In patients suspected of having small cell lung cancer (SCLC) based on the radiographic and clinical findings, the diagnosis should be confirmed by the least invasive method (eg, sputum cytology, thoracentesis, fine needle aspiration (FNA), bronchoscopy including transbronchial needle aspiration), as dictated by the patient's presentation
For individuals who have a solitary extrathoracic site suspicious of a metastasis, tissue confirmation of the metastatic site should be obtained if FNA or biopsy of the site is feasible
In individuals in whom biopsy of a metastatic site would be technically difficult, diagnosis of the primary lung lesion should be obtained by the least invasive method
In patients suspected of having lung cancer who have an accessible pleural effusion, thoracentesis is recommended to identify the cause of the pleural effusion; ultrasound-guided thoracentesis is recommended for performing diagnostic thoracentesis
In patients suspected of having lung cancer who have an accessible pleural effusion, if pleural fluid cytology is negative, pleural biopsy (via image-guided pleural biopsy, medical or surgical thoracoscopy) is recommended as the next step

Diagnosis of Primary Tumor

The CHEST recommendations for diagnosis of primary tumor include the following^{[29, 74]}:

If lung cancer is suspected and sputum cytology is negative for carcinoma, further testing should be performed
In patients who have a central lesion, bronchoscopy should be used to confirm the diagnosis; however, further testing should be performed if bronchoscopy results are non-diagnostic and suspicion of lung cancer remains
As an adjunct imaging modality when a tissue sample is required due to diagnostic uncertainty or poor surgical candidacy, radial endobronchial ultrasound can confirm in real time the ideal location of bronchoscopic sampling and increase the diagnostic yield over conventional bronchoscopy for peripheral nodules.
With peripheral lung lesions difficult to reach with conventional bronchoscopy, electromagnetic navigation guidance can be used if the equipment and the expertise are available; otherwise, transthoracic needle aspiration (TTNA) is recommended
In patients who have a peripheral lesion and who require tissue diagnosis before further management can be planned, TTNA is diagnostic option; however, further testing should be performed if TTNA results are nondiagnostic and suspicion of lung cancer remains
The possibility of an erroneous diagnosis of SCLC on a cytology specimen must be kept in mind if the clinical presentation or clinical course is not consistent with that of SCLC; in such a case, further testing should be performed to establish a definitive cell type

National Comprehensive Cancer Network (NCCN) guidelines recommend the following initial evaluation in patients found to have SCLC (or combined SCLC and non–small cell lung cancer [NSCLC]) on biopsy or cytology of a primary or metastatic site^[28]:

History and physical examination
Pathology review
Complete blood count (CBC)
Electrolytes, liver and kidney function tests
Chest/abdomen/pelvis computed tomography (CT) with contrast
Brain magnetic resonance imaging (MRI)(preferred) or CT with contrast
Positron emission tomography (PET)/CT scan (skull base to mid-thigh), if needed to clarify extent of disease
Smoking cessation counseling and intervention
Molecular profiling, in patients who have never smoked tobacco, or smoked only lightly, and have extensive-stage SCLC ^[76]

Staging

The National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) practice guidelines recommend using the American Joint Commission for Cancer (AJCC) tumor, node, metastasis (TNM) system for staging SCLC.^{[28, 14, 32]}The American College of Chest Physicians (CHEST) guidelines recommend use of both the TNM system and the Veterans Administration Lung Study Group (VALSG) system (limited-stage vs extensive-stage) to classify the tumor stage.^[29]

SCLC consists of two stages: limited-stage and extensive-stage. Under the AJCC TNM staging system, limited-stage SCLC is defined as any T, any N, M0; the exception is T3-4, owing to multiple lung nodules that extend beyond a single radiation field.^[32]

Extensive-stage disease describes tumors that extend beyond the ipsilateral hemithorax, such as those that reach the contralateral lung and/or contralateral lymph nodes or that find their way to distant organs (eg, bone marrow). The AJCC TNM staging system classifies extensive-stage disease as any T, any N, M1a/b, and T3-4, due to involvement of multiple nodules.^[32]

CHEST does not recommend positron emission tomography (PET) scanning in the routine staging of SCLC.^[29]However, in a qualifying statement, the American Society of Clinical Oncology (ASCO) recognizes that PET scanning is a widely used initial staging tool in patients with lung cancer, and recommends that when a PET scan is obtained for patients with either limited-stage or extensive-stage disease, a bone scan may be omitted.^[75]The NCCN guidelines recommend combined PET–computed tomography scanning if limited-stage disease or metastasis is suspected.^[28]

Treatment for Limited-Stage SCLC

The American College of Chest Physician (CHEST) guidelines recommend that limited-stage small cell lung cancer (LS-SCLC) be treated with curative intent, based on an expected 20% to 25% 5-year survival.^[29]The ACCP recommendations for treatment of LS-SCLC also include the following:

Surgical resection is indicated for carefully selected stage I SCLC after a thorough evaluation of distant and invasive mediastinal stage
Patients who have undergone surgical resection should be treated with platinum-based adjuvant chemotherapy
Accelerated hyper-fractionated radiation therapy (twice-daily treatment) should be administered early in the course of treatment, concurrently with chemotherapy consisting of four cycles of a platinum agent and etoposide

In addition, National Comprehensive Cancer Network (NCCN) clinical practice guidelines recommend sequential therapy for patients unable to tolerate concurrent chemoradiation. Chemotherapy is given first, followed by radiation therapy, because of the high rate of responsiveness to chemotherapy for SCLC.^[28]

The 2021 European Society for Medical Oncology (ESMO) practice guidelines include the following treatment recommendations for patients with clinical stages I and II (cT1-2N0) SCLC^[14]:

Surgery may be considered in patients following a multidisciplinary board decision.
Pathological mediastinal staging is required.
Sublobular resection is not recommended.
Surgery should include systematic nodal dissection.

For patients with pT1-2/N0-1 disease who have an R0 resection, ESMO recommends four cycles of adjuvant cisplatin plus etoposide. Carboplatin may be substituted for cisplatin if that agent is contraindicated because of comorbidities.

Concurrent thoracic radiation therapy (RT) and adjuvant chemotherapy is recommended in patients with an R1-R2 resection or positive mediastinal lymph nodes (N2) and in patients with T1-4/N0-3/M0 tumors and a good performance status (PS 0-1).

Thoracic RT should be initiated as early as possible, preferably on the first or second chemotherapy cycle. The recommended dose fractionation schedule is 45 Gy BID in 30 fractions. Sequential chemoradiotherapy (CRT) is an option for patients who are not candidates for concurrent CRT due to poor PS, comorbidities and/or disease volume. Selective node irradiation (ie, RT for involved nodes defined as FDG avid on PET–CT, enlarged on CT, and/or biopsy-positive) is preferred.

Granulocyte colony-stimulating factor (G-CSF) is an option to prevent hematologic toxicity.

The CHEST and the NCCN guidelines recommend prophylactic cranial irradiation (PCI) in patients with limited-stage disease who have achieved a complete remission or in those with stage I disease who have undergone a complete resection, although the NCCN advises against its use in patients with poor performance status or impaired neurocognitive function.^{[28, 29]}

ESMO practice guidelines recommend offering PCI to patients with a PS of 0-1 and a response to CRT, and considering PCI in patients with a PS of 2. The recommended dose is 25 Gy in 10 daily fractions. ESMO recommends shared decision making regarding PCI in patients with stage I-II SCLC, who have a lower risk of developing brain metastases, and in those of age > 70 years or who are frail, as the role of PCI is not as well defined in those circumstances.^[14]

Treatment for Extensive-Stage SCLC

Guidelines from the American College of Chest Physicians (CHEST), the National Comprehensive Cancer Network (NCCN), and the European Society for Medical Oncology (ESMO) recommend that patients with extensive-stage disease be treated with combination chemotherapy alone.^{[14, 28, 29]}

CHEST recommends combining palliative care with standard oncology care early in the treatment course. Conversations about the goals of care and end-of-life options should be initiated with all patients with extensive-stage SCLC.^[29]

In patients who have mixed histologic features of SCLC and non-SCLC, the CHEST and NCCN guidelines recommend following treatment recommendations for SCLC.^{[28, 29]}

According to the NCCN guidelines, dose-dense or dose-escalation chemotherapy regimens are not recommended outside of a randomized clinical trial.^[28]

CHEST recommends offering further chemotherapy to patients with relapsed or refractory SLCL.^[29]However, except in the setting of a clinical trial, CHEST does not recommend either of the following:

Maintenance treatment for patients with limited- or extensive-stage disease that is in partial (PR) or complete remission (CR)
Dose-dense/intense initial/induction or maintenance treatment for limited- or extensive-stage disease

ESMO recommendations for extensive-stage SCLC are as follows^[14]:

A PD-L1 inhibitor (atezolizumab or durvalumab) can be added in patients with treatment-naive extensive-stage SCLC, a PS of 0-1, and no contraindications for immunotherapy.
For immunotherapy-ineligible patients, the preferred first-line treatment of extensive-stage SCLC (PS 0-1 and PS 2 due to SCLC) is four to six cycles of a platinum agent plus etoposide.
Alternative treatment options are cisplatin with irinotecan or oral topotecan and, in poor- prognosis patients, gemcitabine plus carboplatin.
In patients responsive to chemotherapy and with a PS of 0-2, RT to the residual primary tumor and lymph nodes (30 Gy/10 fractions) is a treatment option.
Prophylactic cranial irradiation (PCI), 20 Gy/5 fractions and 25 Gy/10 fractions, is justified without prior MRI staging or follow-up in patients of age < 75 years and a PS of 0-2 who have responded to chemotherapy.
PCI can be omitted in patients with extensive-stage SCLC who do not have brain metastases on MRI after chemotherapy and who can be followed up with regular brain MRI.

Treatment of SCLC in the Elderly

The American College of Chest Physicians (CHEST) recommends that elderly patients with SCLC who have a good performance status (PS) (ie, Eastern Cooperative Oncology Group [ECOG] PS 0 or 1) and intact organ function receive standard carboplatin-based chemotherapy. However, even patients who have poor prognostic factors (eg, poor PS, medically significant concomitant conditions) may still be considered for chemotherapy if appropriate precautions are taken to avoid excessive toxicity and further decline in PS.^[29]

Long-Term Monitoring

The National Comprehensive Cancer Network recommends that after recovery from primary therapy, patients should receive oncology follow-up visits on the following schedule^[28]:

Years 1-2: Every 3–4 mo
Years 3-5: Every 6 mo
Subsequent years: Annuallly

At every visit, the patient should receive the following:

History and physical examination
Chest imaging (with workup for potential new primary if a new pulmonary nodule is detected)
Blood work as clinically indicated
Smoking cessation intervention, if necessary

Positron emission tomography/computed tomography (PET/CT) is not recommended for routine follow-up.

The European Society for Medical Oncology recommends that patients with limited-stage SLCLC who have received potentially curative treatment undergo CT scans every 3-6 months for 2 years, with lengthening of intervals thereafter. Regular brain MRIs (every 3 months in the first year and then every 6 months) are advised in patients who did not undergo prophylactic cranial irradiation.^[14]

Medication

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].

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High-power photomicrograph of small cell carcinoma on the left side of the image with normal ciliated respiratory epithelium on the right side of the image.
This coronal positron emission tomogram shows a large, focal, hypermetabolic area on the right that is consistent with a large mass in the central portion of the right upper pulmonary lobe. Multiple other smaller hypermetabolic areas suggest lymph-node metastatic disease in the chest, abdomen, and right supraclavicular region.

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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]