Interpretation of the 2026 version 1-3 update to the NCCN Clinical Practice Guidelines in Oncology: Non-small cell lung cancer and Chinese clinical practice_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

ZHAO Kejia , MEI Jiandong ,  LIU Lunxu

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, P. R. China;

Corresponding?author：

LIU Lunxu, Email: lunxu_liu@aliyun.com

Keywords：

Non-small cell lung carcinoma; National Comprehensive Cancer Network (NCCN); practice guidelines; biomarkers; targeted therapy; immunotherapy; conversion therapy; Chinese population

DOI：

10.7507/1007-4848.202601015

Video：

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Abstract Full text Figures/Tables Video References Cited by

The management of non-small cell lung cancer is rapidly advancing toward precision and individualized care. The National Comprehensive Cancer Network (NCCN) has recently released the 2026 version 1, 2, and 3 updates of the NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. These updated guidelines introduce significant revisions in several core areas, including the adoption of the AJCC 9th Edition TNM Staging System, optimization of recommendations for lung cancer screening and mediastinal staging, updates on perioperative immunotherapy and targeted therapy strategies, and the inclusion of emerging biomarkers such as neuregulin 1 (NRG1) fusions and mesenchymal-epithelial transition factor (MET) protein overexpression. This article provides a systematic interpretation of these key updates and focuses on integrating international guidelines with clinical practice in China. Specifically, considering the high prevalence of epidermal growth factor receptor (EGFR) mutations in the Chinese population, it analyzes the first-line positioning of osimertinib- and lazertinib-based combination regimens and evaluates the clinical value of domestic third-generation tyrosine kinase inhibitors. In response to the NCCN's cautious stance on "conversion therapy" for initially unresectable disease, the article elaborates on China's exploratory efforts and the evolving evidence base for conversion strategies utilizing programmed death receptor 1 (PD-1) inhibitors (e.g., tislelizumab, toripalimab). Furthermore, it clarifies the "dual-track" diagnostic approach distinguishing MET pathway mutations from protein overexpression. Aimed at aligning with China's clinical context, this review seeks to offer clinicians a practical reference that synthesizes cutting-edge international perspectives with local applicability.

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2.	Torre LA, Siegel RL, Jemal A. Lung cancer statistics. Adv Exp Med Biol, 2016, 893: 1-19.
3.	Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent, 2024, 4(1): 47-53.
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8.	Rami-Porta R, Nishimura KK, Giroux DJ, et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: proposals for revision of the TNM stage groups in the forthcoming (ninth) edition of the TNM classification for lung cancer. J Thorac Oncol, 2024, 19(7): 1007-1027.
9.	趙珂嘉, 劉成武, 劉倫旭. 《IASLC第九版肺癌TNM分期》解讀. 中國胸心血管外科臨床雜志, 2024, 31(4): 489-497.Zhao KJ, Liu CW, Liu LX. Interpretation of the IASLC 9th edition lung cancer TNM staging. Chin J Clin Thorac Cardiovasc Surg, 2024, 31(4): 489-497.
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12.	Ye T, Deng L, Wang S, et al. Lung adenocarcinomas manifesting as radiological part-solid nodules define a special clinical subtype. J Thorac Oncol, 2019, 14(4): 617-627.
13.	Zhang Y, Fu F, Chen H. Management of ground-glass opacities in the lung cancer spectrum. Ann Thorac Surg, 2020, 110(6): 1796-1804.
14.	Suzuki K, Koike T, Asakawa T, et al. A prospective radiological study of thin-section computed tomography to predict pathological noninvasiveness in peripheral clinical ⅠA lung cancer (Japan Clinical Oncology Group 0201). J Thorac Oncol, 2011, 6(4): 751-756.
15.	Gulani V, Calamante F, Shellock FG, et al. Gadolinium deposition in the brain: summary of evidence and recommendations. Lancet Neurol, 2017, 16(7): 564-570.
16.	Cho BC, Lu S, Felip E, et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med, 2024, 391(16): 1486-1498.
17.	Lu S, Dong X, Jian H, et al. AENEAS: A randomized phase Ⅲ trial of aumolertinib versus gefitinib as first-line therapy for locally advanced or metastatic non-small-cell lung cancer with EGFR exon 19 deletion or L858R mutations. J Clin Oncol, 2022, 40(27): 3162-3171.
18.	Shi Y, Chen G, Wang X, et al. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study. Lancet Respir Med, 2022, 10(11): 1019-1028.
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21.	Zhou C, Li X, Wang Q, et al. Pyrotinib in HER2-mutant advanced lung adenocarcinoma after platinum-based chemotherapy: a multicenter, open-label, single-arm, phase II study. J Clin Oncol, 2020, 38(24): 2753-2761.
22.	Lu S, Zhang W, Wu L, et al. Perioperative toripalimab plus chemotherapy for patients with resectable non-small cell lung cancer: the Neotorch randomized clinical trial. JAMA, 2024, 331(3): 201-211.
23.	Yue D, Wang W, Liu H, et al. Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer (RATIONALE-315): an interim analysis of a randomised clinical trial. Lancet Respir Med, 2025, 13(2): 119-129.
24.	Bott MJ, Cools-Lartigue J, Tan KS, et al. Safety and feasibility of lung resection after immunotherapy for metastatic or unresectable tumors. Ann Thorac Surg, 2018, 106(1): 178-183.
25.	Iyengar P, Hu C, Gomez DR, et al. NRG-LU002: randomized phase Ⅱ/Ⅲ trial of maintenance systemic therapy versus local consolidative therapy (LCT) plus maintenance systemic therapy for limited metastatic non-small cell lung cancer (NSCLC). J Clin Oncol, 2024, 42(16): 9001.
26.	Wang X, Bai Y, Verma V, et al. Randomized trial of first-line tyrosine kinase inhibitor with or without radiotherapy for synchronous oligometastatic EGFR-mutated non-small cell lung cancer (Publication with Expression of Concern). J Natl Cancer Inst, 2023, 115(6): 742-748.
27.	Peng P, Gong J, Zhang Y, et al. 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. Radiother Oncol, 2023, 184: 109681.
28.	Sun H, Li M, Huang W, et al. Thoracic radiotherapy improves the survival in patients with EGFR-mutated oligo-organ metastatic non-small cell lung cancer treated with epidermal growth factor receptor-tyrosine kinase inhibitors: a multicenter, randomized, controlled, phase Ⅲ trial. J Clin Oncol, 2025, 43(4): 319-329.
29.	Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: long-term results of the SABR-COMET phase Ⅱ randomized trial. J Clin Oncol, 2020, 38(25): 2830-2838.
30.	Cascone T, Awad MM, Spicer JD, et al. Perioperative nivolumab in resectable lung cancer. N Engl J Med, 2024, 390(19): 1756-1769.
31.	Forde PM, Spicer JD, Provencio M, et al. Overall survival with neoadjuvant nivolumab plus chemotherapy in lung cancer. N Engl J Med, 2025, 393(8): 741-752.
32.	Wakelee H, Liberman M, Kato T, et al. Perioperative pembrolizumab for early-stage non-small-cell lung cancer. N Engl J Med, 2023, 389(6): 491-503.
33.	Horita N, Fujiwara Y. Perioperative durvalumab for resectable non-small-cell lung cancer. N Engl J Med, 2024, 390(3): 287-288.
34.	Zhou Q, Chen M, Jiang O, et al. Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage Ⅲ non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol, 2022, 23(2): 209-219.
35.	He J, Tsuboi M, Weder W, et al. Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non-Small Cell Lung Cancer. J Clin Oncol, 2025, 43(26): 2875-2887.
36.	Tsuboi M, Herbst RS, John T, et al. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med, 2023, 389(2): 137-147.
37.	Rosas D, Raez LE, Russo A, et al. Neuregulin 1 gene (NRG1). A potentially new targetable alteration for the treatment of lung cancer. Cancers (Basel), 2021, 13(20): 5038.
38.	Severson E, Achyut BR, Nesline M, et al. RNA sequencing identifies novel NRG1 fusions in solid tumors that lack co-occurring oncogenic drivers. J Mol Diagn, 2023, 25(7): 454-466.
39.	Werr L, Plenker D, Dammert MA, et al. CD74-NRG1 fusions are oncogenic in vivo and induce therapeutically tractable ERBB2: ERBB3 heterodimerization. Mol Cancer Ther, 2022, 21(5): 821-830.
40.	Schram AM, Goto K, Kim DW, et al; eNRGy Investigators. Efficacy of zenocutuzumab in NRG1 fusion-positive cancer. N Engl J Med, 2025, 392(6): 566-576.
41.	Jonna S, Feldman RA, Swensen J, et al. Detection of NRG1 gene fusions in solid tumors. Clin Cancer Res, 2019, 25(16): 4966-4972.
42.	Benayed R, Offin M, Mullaney K, et al. High yield of RNA sequencing for targetable kinase fusions in lung adenocarcinomas with no mitogenic driver alteration detected by DNA sequencing and low tumor mutation burden. Clin Cancer Res, 2019, 25(15): 4712-4722.
43.	Drilon A, Cappuzzo F, Ou SI, et al. Targeting MET in lung cancer: will expectations finally be MET? J Thorac Oncol, 2017, 12(1): 15-26.
44.	Davies KD, Lomboy A, Lawrence CA, et al. DNA-based versus RNA-based detection of MET exon 14 skipping events in lung cancer. J Thorac Oncol, 2019, 14(4): 737-741.
45.	Wolf J, Seto T, Han JY, et al. Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer. N Engl J Med, 2020, 383(10): 944-957.
46.	Paik PK, Felip E, Veillon R, et al. Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med, 2020, 383(10): 931-943.
47.	Lu S, Fang J, Li X, et al. Once-daily savolitinib in Chinese patients with pulmonary sarcomatoid carcinomas and other non-small-cell lung cancers harbouring MET exon 14 skipping alterations: a multicentre, single-arm, open-label, phase 2 study. Lancet Respir Med, 2021, 9(10): 1154-1164.
48.	Yu Y, Zhou J, Li X, et al. Gumarontinib in patients with non-small-cell lung cancer harbouring MET exon 14 skipping mutations: a multicentre, single-arm, open-label, phase 1b/2 trial. EClinicalMedicine, 2023, 59: 101952.
49.	Camidge DR, Bar J, Horinouchi H, et al. Telisotuzumab vedotin monotherapy in patients with previously treated c-Met protein-overexpressing advanced nonsquamous EGFR-wildtype non-small cell lung cancer in the phase Ⅱ LUMINOSITY trial. J Clin Oncol, 2024, 42(25): 3036-3046.

1. Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin, 2024, 74(1):12-49.
2. Torre LA, Siegel RL, Jemal A. Lung cancer statistics. Adv Exp Med Biol, 2016, 893: 1-19.
3. Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent, 2024, 4(1): 47-53.
4. Smolarz B, ?ukasiewicz H, Samulak D, et al. Lung cancer-epidemiology, pathogenesis, treatment and molecular aspect (review of literature). Int J Mol Sci, 2025, 26(5): 2049.
5. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: non-small cell lung cancer version 1.2026. https://www.nccn.org/guidelines. Accessed on 2026-01-01.
6. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: non-small cell lung cancer version 2.2026. https://www.nccn.org/guidelines. Accessed on 2026-01-01.
7. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: non-small cell lung cancer version 3.2026. https://www.nccn.org/guidelines. Accessed on 2026-01-01.
8. Rami-Porta R, Nishimura KK, Giroux DJ, et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: proposals for revision of the TNM stage groups in the forthcoming (ninth) edition of the TNM classification for lung cancer. J Thorac Oncol, 2024, 19(7): 1007-1027.
9. 趙珂嘉, 劉成武, 劉倫旭. 《IASLC第九版肺癌TNM分期》解讀. 中國胸心血管外科臨床雜志, 2024, 31(4): 489-497.Zhao KJ, Liu CW, Liu LX. Interpretation of the IASLC 9th edition lung cancer TNM staging. Chin J Clin Thorac Cardiovasc Surg, 2024, 31(4): 489-497.
10. 中華醫學會. 中華醫學會肺癌臨床診療指南(2024版). 中華腫瘤雜志, 2024, 46(9): 805-843.Chinese Medical Association. Chinese Medical Association guideline for clinical diagnosis and treatment of lung cancer for patients (2024 edition). Chin J Onco 2024, 46(9): 805-843.
11. Adachi H, Ito H, Nagashima T, et al. Mediastinal lymph node dissection in segmentectomy for peripheral c-stage ⅠA (≤2 cm) non-small-cell lung cancer. J Thorac Cardiovasc Surg, 2025, 169(4): 1158-1166. e4.
12. Ye T, Deng L, Wang S, et al. Lung adenocarcinomas manifesting as radiological part-solid nodules define a special clinical subtype. J Thorac Oncol, 2019, 14(4): 617-627.
13. Zhang Y, Fu F, Chen H. Management of ground-glass opacities in the lung cancer spectrum. Ann Thorac Surg, 2020, 110(6): 1796-1804.
14. Suzuki K, Koike T, Asakawa T, et al. A prospective radiological study of thin-section computed tomography to predict pathological noninvasiveness in peripheral clinical ⅠA lung cancer (Japan Clinical Oncology Group 0201). J Thorac Oncol, 2011, 6(4): 751-756.
15. Gulani V, Calamante F, Shellock FG, et al. Gadolinium deposition in the brain: summary of evidence and recommendations. Lancet Neurol, 2017, 16(7): 564-570.
16. Cho BC, Lu S, Felip E, et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med, 2024, 391(16): 1486-1498.
17. Lu S, Dong X, Jian H, et al. AENEAS: A randomized phase Ⅲ trial of aumolertinib versus gefitinib as first-line therapy for locally advanced or metastatic non-small-cell lung cancer with EGFR exon 19 deletion or L858R mutations. J Clin Oncol, 2022, 40(27): 3162-3171.
18. Shi Y, Chen G, Wang X, et al. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study. Lancet Respir Med, 2022, 10(11): 1019-1028.
19. Chinese Society of Clinical Oncology. Chinese Society of Clinical Oncology (CSCO) guidelines for the diagnosis and treatment of non-small cell lung cancer 2025.
20. Moik F, Riedl JM, Ay C. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase ⅢMARIPOSA-2 study. Ann Oncol, 2024, 35(3): 277-289.
21. Zhou C, Li X, Wang Q, et al. Pyrotinib in HER2-mutant advanced lung adenocarcinoma after platinum-based chemotherapy: a multicenter, open-label, single-arm, phase II study. J Clin Oncol, 2020, 38(24): 2753-2761.
22. Lu S, Zhang W, Wu L, et al. Perioperative toripalimab plus chemotherapy for patients with resectable non-small cell lung cancer: the Neotorch randomized clinical trial. JAMA, 2024, 331(3): 201-211.
23. Yue D, Wang W, Liu H, et al. Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer (RATIONALE-315): an interim analysis of a randomised clinical trial. Lancet Respir Med, 2025, 13(2): 119-129.
24. Bott MJ, Cools-Lartigue J, Tan KS, et al. Safety and feasibility of lung resection after immunotherapy for metastatic or unresectable tumors. Ann Thorac Surg, 2018, 106(1): 178-183.
25. Iyengar P, Hu C, Gomez DR, et al. NRG-LU002: randomized phase Ⅱ/Ⅲ trial of maintenance systemic therapy versus local consolidative therapy (LCT) plus maintenance systemic therapy for limited metastatic non-small cell lung cancer (NSCLC). J Clin Oncol, 2024, 42(16): 9001.
26. Wang X, Bai Y, Verma V, et al. Randomized trial of first-line tyrosine kinase inhibitor with or without radiotherapy for synchronous oligometastatic EGFR-mutated non-small cell lung cancer (Publication with Expression of Concern). J Natl Cancer Inst, 2023, 115(6): 742-748.
27. Peng P, Gong J, Zhang Y, et al. 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. Radiother Oncol, 2023, 184: 109681.
28. Sun H, Li M, Huang W, et al. Thoracic radiotherapy improves the survival in patients with EGFR-mutated oligo-organ metastatic non-small cell lung cancer treated with epidermal growth factor receptor-tyrosine kinase inhibitors: a multicenter, randomized, controlled, phase Ⅲ trial. J Clin Oncol, 2025, 43(4): 319-329.
29. Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: long-term results of the SABR-COMET phase Ⅱ randomized trial. J Clin Oncol, 2020, 38(25): 2830-2838.
30. Cascone T, Awad MM, Spicer JD, et al. Perioperative nivolumab in resectable lung cancer. N Engl J Med, 2024, 390(19): 1756-1769.
31. Forde PM, Spicer JD, Provencio M, et al. Overall survival with neoadjuvant nivolumab plus chemotherapy in lung cancer. N Engl J Med, 2025, 393(8): 741-752.
32. Wakelee H, Liberman M, Kato T, et al. Perioperative pembrolizumab for early-stage non-small-cell lung cancer. N Engl J Med, 2023, 389(6): 491-503.
33. Horita N, Fujiwara Y. Perioperative durvalumab for resectable non-small-cell lung cancer. N Engl J Med, 2024, 390(3): 287-288.
34. Zhou Q, Chen M, Jiang O, et al. Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage Ⅲ non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol, 2022, 23(2): 209-219.
35. He J, Tsuboi M, Weder W, et al. Neoadjuvant Osimertinib for Resectable EGFR-Mutated Non-Small Cell Lung Cancer. J Clin Oncol, 2025, 43(26): 2875-2887.
36. Tsuboi M, Herbst RS, John T, et al. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med, 2023, 389(2): 137-147.
37. Rosas D, Raez LE, Russo A, et al. Neuregulin 1 gene (NRG1). A potentially new targetable alteration for the treatment of lung cancer. Cancers (Basel), 2021, 13(20): 5038.
38. Severson E, Achyut BR, Nesline M, et al. RNA sequencing identifies novel NRG1 fusions in solid tumors that lack co-occurring oncogenic drivers. J Mol Diagn, 2023, 25(7): 454-466.
39. Werr L, Plenker D, Dammert MA, et al. CD74-NRG1 fusions are oncogenic in vivo and induce therapeutically tractable ERBB2: ERBB3 heterodimerization. Mol Cancer Ther, 2022, 21(5): 821-830.
40. Schram AM, Goto K, Kim DW, et al; eNRGy Investigators. Efficacy of zenocutuzumab in NRG1 fusion-positive cancer. N Engl J Med, 2025, 392(6): 566-576.
41. Jonna S, Feldman RA, Swensen J, et al. Detection of NRG1 gene fusions in solid tumors. Clin Cancer Res, 2019, 25(16): 4966-4972.
42. Benayed R, Offin M, Mullaney K, et al. High yield of RNA sequencing for targetable kinase fusions in lung adenocarcinomas with no mitogenic driver alteration detected by DNA sequencing and low tumor mutation burden. Clin Cancer Res, 2019, 25(15): 4712-4722.
43. Drilon A, Cappuzzo F, Ou SI, et al. Targeting MET in lung cancer: will expectations finally be MET? J Thorac Oncol, 2017, 12(1): 15-26.
44. Davies KD, Lomboy A, Lawrence CA, et al. DNA-based versus RNA-based detection of MET exon 14 skipping events in lung cancer. J Thorac Oncol, 2019, 14(4): 737-741.
45. Wolf J, Seto T, Han JY, et al. Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer. N Engl J Med, 2020, 383(10): 944-957.
46. Paik PK, Felip E, Veillon R, et al. Tepotinib in non-small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med, 2020, 383(10): 931-943.
47. Lu S, Fang J, Li X, et al. Once-daily savolitinib in Chinese patients with pulmonary sarcomatoid carcinomas and other non-small-cell lung cancers harbouring MET exon 14 skipping alterations: a multicentre, single-arm, open-label, phase 2 study. Lancet Respir Med, 2021, 9(10): 1154-1164.
48. Yu Y, Zhou J, Li X, et al. Gumarontinib in patients with non-small-cell lung cancer harbouring MET exon 14 skipping mutations: a multicentre, single-arm, open-label, phase 1b/2 trial. EClinicalMedicine, 2023, 59: 101952.
49. Camidge DR, Bar J, Horinouchi H, et al. Telisotuzumab vedotin monotherapy in patients with previously treated c-Met protein-overexpressing advanced nonsquamous EGFR-wildtype non-small cell lung cancer in the phase Ⅱ LUMINOSITY trial. J Clin Oncol, 2024, 42(25): 3036-3046.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Latest ArticlesInterpretation of the 2026 version 1-3 update to the NCCN Clinical Practice Guidelines in Oncology: Non-small cell lung cancer and Chinese clinical practice

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