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Stage IV Non-Small Cell Lung Cancer

MedGen UID:
83018
•Concept ID:
C0278987
•
Neoplastic Process
Synonym: Metastatic Non-Small Cell Lung Cancer
SNOMED CT: Metastatic non-small cell lung cancer (457721000124104); Metastatic NSCLC - non-small cell lung cancer (457721000124104)

Definition

Stage IV includes: (Any T, Any N, M1a); (Any T, Any N, M1b). M1a: Lung cancer with separate tumor nodule(s) in a contralateral lobe; tumor with pleural nodules or malignant pleural (or pericardial) effusion. M1b: Distant metastasis. (AJCC 7th ed.) [from NCI]

Professional guidelines

PubMed

Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2023.1.
Singh N, Jaiyesimi IA, Ismaila N, Leighl NB, Mamdani H, Phillips T, Owen DH
J Clin Oncol 2023 May 20;41(15):e51-e62. Epub 2023 Apr 6 doi: 10.1200/JCO.23.00282. PMID: 37023387
Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline.
Singh N, Temin S, Baker S Jr, Blanchard E, Brahmer JR, Celano P, Duma N, Ellis PM, Elkins IB, Haddad RY, Hesketh PJ, Jain D, Johnson DH, Leighl NB, Mamdani H, Masters G, Moffitt PR, Phillips T, Riely GJ, Robinson AG, Rosell R, Schiller JH, Schneider BJ, Spigel DR, Jaiyesimi IA
J Clin Oncol 2022 Oct 1;40(28):3323-3343. Epub 2022 Jul 11 doi: 10.1200/JCO.22.00825. PMID: 35816668
Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline.
Singh N, Temin S, Baker S Jr, Blanchard E, Brahmer JR, Celano P, Duma N, Ellis PM, Elkins IB, Haddad RY, Hesketh PJ, Jain D, Johnson DH, Leighl NB, Mamdani H, Masters G, Moffitt PR, Phillips T, Riely GJ, Robinson AG, Rosell R, Schiller JH, Schneider BJ, Spigel DR, Jaiyesimi IA
J Clin Oncol 2022 Oct 1;40(28):3310-3322. Epub 2022 Jul 11 doi: 10.1200/JCO.22.00824. PMID: 35816666

Recent clinical studies

Etiology

EGFR-TKIs plus stereotactic body radiation therapy (SBRT) for stage IV Non-small cell lung cancer (NSCLC): A prospective, multicenter, randomized, controlled phase II study.
Peng P, Gong J, Zhang Y, Zhou S, Li Y, Han G, Meng R, Chen Y, Yang M, Shen Q, Chu Q, Xia S, Zhang P, Zhang L, Chen Y, Zhang L
Radiother Oncol 2023 Jul;184:109681. Epub 2023 Apr 25 doi: 10.1016/j.radonc.2023.109681. PMID: 37105304
Pain and Interventions in Stage IV Non-Small Cell Lung Cancer: A Province-Wide Analysis.
Tan VS, Tjong MC, Chan WC, Yan M, Delibasic V, Darling G, Davis LE, Doherty M, Hallet J, Kidane B, Mahar A, Mittmann N, Parmar A, Tan H, Wright FC, Coburn NG, Louie AV
Curr Oncol 2023 Mar 18;30(3):3461-3472. doi: 10.3390/curroncol30030262. PMID: 36975475Free PMC Article
EGFR-mutated stage IV non-small cell lung cancer: What is the role of radiotherapy combined with TKI?
Liu B, Liu H, Ma Y, Ding Q, Zhang M, Liu X, Liu M
Cancer Med 2021 Sep;10(18):6167-6188. Epub 2021 Aug 10 doi: 10.1002/cam4.4192. PMID: 34374490Free PMC Article
Real-world treatment patterns and survival in stage IV non-small-cell lung cancer in Canada.
Seung SJ, Hurry M, Walton RN, Evans WK
Curr Oncol 2020 Aug;27(4):e361-e367. Epub 2020 Aug 1 doi: 10.3747/co.27.6049. PMID: 32905294Free PMC Article
Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial.
Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M
Lancet 2014 Aug 23;384(9944):665-73. Epub 2014 Jun 2 doi: 10.1016/S0140-6736(14)60845-X. PMID: 24933332

Diagnosis

Clinical outcomes of stage-IV non-small-cell lung cancer in young patients and the impact of tumor markers.
Dos Santos PAR, Li Y, Ernani V, D'Cunha J, Aubry MC, Yang P
Cancer Treat Res Commun 2023;36:100723. Epub 2023 Jun 12 doi: 10.1016/j.ctarc.2023.100723. PMID: 37327571
EGFR-TKIs plus stereotactic body radiation therapy (SBRT) for stage IV Non-small cell lung cancer (NSCLC): A prospective, multicenter, randomized, controlled phase II study.
Peng P, Gong J, Zhang Y, Zhou S, Li Y, Han G, Meng R, Chen Y, Yang M, Shen Q, Chu Q, Xia S, Zhang P, Zhang L, Chen Y, Zhang L
Radiother Oncol 2023 Jul;184:109681. Epub 2023 Apr 25 doi: 10.1016/j.radonc.2023.109681. PMID: 37105304
Pain and Interventions in Stage IV Non-Small Cell Lung Cancer: A Province-Wide Analysis.
Tan VS, Tjong MC, Chan WC, Yan M, Delibasic V, Darling G, Davis LE, Doherty M, Hallet J, Kidane B, Mahar A, Mittmann N, Parmar A, Tan H, Wright FC, Coburn NG, Louie AV
Curr Oncol 2023 Mar 18;30(3):3461-3472. doi: 10.3390/curroncol30030262. PMID: 36975475Free PMC Article
EGFR-mutated stage IV non-small cell lung cancer: What is the role of radiotherapy combined with TKI?
Liu B, Liu H, Ma Y, Ding Q, Zhang M, Liu X, Liu M
Cancer Med 2021 Sep;10(18):6167-6188. Epub 2021 Aug 10 doi: 10.1002/cam4.4192. PMID: 34374490Free PMC Article
Real-world treatment patterns and survival in stage IV non-small-cell lung cancer in Canada.
Seung SJ, Hurry M, Walton RN, Evans WK
Curr Oncol 2020 Aug;27(4):e361-e367. Epub 2020 Aug 1 doi: 10.3747/co.27.6049. PMID: 32905294Free PMC Article

Therapy

EGFR-TKIs plus stereotactic body radiation therapy (SBRT) for stage IV Non-small cell lung cancer (NSCLC): A prospective, multicenter, randomized, controlled phase II study.
Peng P, Gong J, Zhang Y, Zhou S, Li Y, Han G, Meng R, Chen Y, Yang M, Shen Q, Chu Q, Xia S, Zhang P, Zhang L, Chen Y, Zhang L
Radiother Oncol 2023 Jul;184:109681. Epub 2023 Apr 25 doi: 10.1016/j.radonc.2023.109681. PMID: 37105304
Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline.
Singh N, Temin S, Baker S Jr, Blanchard E, Brahmer JR, Celano P, Duma N, Ellis PM, Elkins IB, Haddad RY, Hesketh PJ, Jain D, Johnson DH, Leighl NB, Mamdani H, Masters G, Moffitt PR, Phillips T, Riely GJ, Robinson AG, Rosell R, Schiller JH, Schneider BJ, Spigel DR, Jaiyesimi IA
J Clin Oncol 2022 Oct 1;40(28):3323-3343. Epub 2022 Jul 11 doi: 10.1200/JCO.22.00825. PMID: 35816668
Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline.
Singh N, Temin S, Baker S Jr, Blanchard E, Brahmer JR, Celano P, Duma N, Ellis PM, Elkins IB, Haddad RY, Hesketh PJ, Jain D, Johnson DH, Leighl NB, Mamdani H, Masters G, Moffitt PR, Phillips T, Riely GJ, Robinson AG, Rosell R, Schiller JH, Schneider BJ, Spigel DR, Jaiyesimi IA
J Clin Oncol 2022 Oct 1;40(28):3310-3322. Epub 2022 Jul 11 doi: 10.1200/JCO.22.00824. PMID: 35816666
Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO and OH (CCO) Joint Guideline Update.
Hanna NH, Robinson AG, Temin S, Baker S Jr, Brahmer JR, Ellis PM, Gaspar LE, Haddad RY, Hesketh PJ, Jain D, Jaiyesimi I, Johnson DH, Leighl NB, Moffitt PR, Phillips T, Riely GJ, Rosell R, Schiller JH, Schneider BJ, Singh N, Spigel DR, Tashbar J, Masters G
J Clin Oncol 2021 Mar 20;39(9):1040-1091. Epub 2021 Feb 16 doi: 10.1200/JCO.20.03570. PMID: 33591844
Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial.
Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M
Lancet 2014 Aug 23;384(9944):665-73. Epub 2014 Jun 2 doi: 10.1016/S0140-6736(14)60845-X. PMID: 24933332

Prognosis

Clinical outcomes of stage-IV non-small-cell lung cancer in young patients and the impact of tumor markers.
Dos Santos PAR, Li Y, Ernani V, D'Cunha J, Aubry MC, Yang P
Cancer Treat Res Commun 2023;36:100723. Epub 2023 Jun 12 doi: 10.1016/j.ctarc.2023.100723. PMID: 37327571
Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO and OH (CCO) Joint Guideline Update.
Hanna NH, Robinson AG, Temin S, Baker S Jr, Brahmer JR, Ellis PM, Gaspar LE, Haddad RY, Hesketh PJ, Jain D, Jaiyesimi I, Johnson DH, Leighl NB, Moffitt PR, Phillips T, Riely GJ, Rosell R, Schiller JH, Schneider BJ, Singh N, Spigel DR, Tashbar J, Masters G
J Clin Oncol 2021 Mar 20;39(9):1040-1091. Epub 2021 Feb 16 doi: 10.1200/JCO.20.03570. PMID: 33591844
Approach to stage IV non-small-cell lung cancer: how to select among first-line therapy options?
Pacheco JM
Curr Opin Pulm Med 2020 Jul;26(4):311-320. doi: 10.1097/MCP.0000000000000659. PMID: 31895119
Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial.
Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M
Lancet 2014 Aug 23;384(9944):665-73. Epub 2014 Jun 2 doi: 10.1016/S0140-6736(14)60845-X. PMID: 24933332
Extending survival of stage IV non-small cell lung cancer.
Carnio S, Novello S, Mele T, Levra MG, Scagliotti GV
Semin Oncol 2014 Feb;41(1):69-92. Epub 2013 Dec 21 doi: 10.1053/j.seminoncol.2013.12.013. PMID: 24565582

Clinical prediction guides

EGFR-TKIs plus stereotactic body radiation therapy (SBRT) for stage IV Non-small cell lung cancer (NSCLC): A prospective, multicenter, randomized, controlled phase II study.
Peng P, Gong J, Zhang Y, Zhou S, Li Y, Han G, Meng R, Chen Y, Yang M, Shen Q, Chu Q, Xia S, Zhang P, Zhang L, Chen Y, Zhang L
Radiother Oncol 2023 Jul;184:109681. Epub 2023 Apr 25 doi: 10.1016/j.radonc.2023.109681. PMID: 37105304
Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline.
Singh N, Temin S, Baker S Jr, Blanchard E, Brahmer JR, Celano P, Duma N, Ellis PM, Elkins IB, Haddad RY, Hesketh PJ, Jain D, Johnson DH, Leighl NB, Mamdani H, Masters G, Moffitt PR, Phillips T, Riely GJ, Robinson AG, Rosell R, Schiller JH, Schneider BJ, Spigel DR, Jaiyesimi IA
J Clin Oncol 2022 Oct 1;40(28):3323-3343. Epub 2022 Jul 11 doi: 10.1200/JCO.22.00825. PMID: 35816668
Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO and OH (CCO) Joint Guideline Update.
Hanna NH, Robinson AG, Temin S, Baker S Jr, Brahmer JR, Ellis PM, Gaspar LE, Haddad RY, Hesketh PJ, Jain D, Jaiyesimi I, Johnson DH, Leighl NB, Moffitt PR, Phillips T, Riely GJ, Rosell R, Schiller JH, Schneider BJ, Singh N, Spigel DR, Tashbar J, Masters G
J Clin Oncol 2021 Mar 20;39(9):1040-1091. Epub 2021 Feb 16 doi: 10.1200/JCO.20.03570. PMID: 33591844
Effect of Low-Dose Radiation Therapy on Abscopal Responses to Hypofractionated Radiation Therapy and Anti-PD1 in Mice and Patients With Non-Small Cell Lung Cancer.
Yin L, Xue J, Li R, Zhou L, Deng L, Chen L, Zhang Y, Li Y, Zhang X, Xiu W, Tong R, Gong Y, Huang M, Xu Y, Zhu J, Yu M, Li M, Lan J, Wang J, Mo X, Wei Y, Niedermann G, Lu Y
Int J Radiat Oncol Biol Phys 2020 Sep 1;108(1):212-224. Epub 2020 May 15 doi: 10.1016/j.ijrobp.2020.05.002. PMID: 32417411
Approach to stage IV non-small-cell lung cancer: how to select among first-line therapy options?
Pacheco JM
Curr Opin Pulm Med 2020 Jul;26(4):311-320. doi: 10.1097/MCP.0000000000000659. PMID: 31895119

Recent systematic reviews

Therapy for Stage IV Non-Small Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2023.3.
Jaiyesimi IA, Leighl NB, Ismaila N, Alluri K, Florez N, Gadgeel S, Masters G, Schenk EL, Schneider BJ, Sequist L, Singh N, Bazhenova L, Blanchard E, Freeman-Daily J, Furuya N, Halmos B, Azar IH, Kuruvilla S, Mullane M, Naidoo J, Reuss JE, Spigel DR, Owen DH, Patel JD
J Clin Oncol 2024 Apr 10;42(11):e23-e43. Epub 2024 Feb 28 doi: 10.1200/JCO.23.02746. PMID: 38417098
Therapy for Stage IV Non-Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.3.
Jaiyesimi IA, Leighl NB, Ismaila N, Alluri K, Florez N, Gadgeel S, Masters G, Schenk EL, Schneider BJ, Sequist L, Singh N, Bazhenova L, Blanchard E, Freeman-Daily J, Furuya N, Halmos B, Azar IH, Kuruvilla S, Mullane M, Naidoo J, Reuss JE, Spigel DR, Owen DH, Patel JD
J Clin Oncol 2024 Apr 10;42(11):e1-e22. Epub 2024 Feb 28 doi: 10.1200/JCO.23.02744. PMID: 38417091
Impact of programmed death-ligand 1 expression on the patients of stage IV non-small cell lung cancer harboring epidermal growth factor receptor mutation: a systematic review and meta-analysis.
Lee CC, Soon YY, Leong CN, Koh WY, Tey J
Acta Oncol 2020 Dec;59(12):1430-1437. Epub 2020 Aug 24 doi: 10.1080/0284186X.2020.1807600. PMID: 32835563
Metastatectomy for extra-cranial extra-adrenal non-small cell lung cancer solitary metastases: systematic review and analysis of reported cases.
Salah S, Tanvetyanon T, Abbasi S
Lung Cancer 2012 Jan;75(1):9-14. Epub 2011 Aug 23 doi: 10.1016/j.lungcan.2011.07.014. PMID: 21864934

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