Impact of number of positive regional lymph nodes in N1 stage on the prognosis of patients with non-small cell lung cancer: A propensity score matching study_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

LIU Dandan ^1,2 , WANG Jiachen ³ , CHANG Lidan ² , CHEN Jia ⁴ , KONG Ranran ¹ , LIU Shiyuan ¹ , ZHU Minxia ⁵ , JIANG Jiantao ¹ , LI Shaomin ¹ ,  XU Zhengshui ¹

1. Department of Thoracic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, P. R. China;
2. Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, P. R. China;
3. Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710001, P. R. China;
4. Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China;
5. Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, P. R. China;

Corresponding author：

XU Zhengshui, Email: xuzhengshui@xjtu.edu.cn

Keywords：

Non-small cell lung cancer; N1 stage subclassification; overall survival; lung cancer-specific survival; number of positive regional lymph nodes

DOI：

10.7507/1007-4848.202401010

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Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1∶1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.05). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.

1.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2.	Duma N, Santana-Davila R, Molina JR. Non-small cell lung cancer: Epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc, 2019, 94(8): 1623-1640.
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4.	Huang J, Osarogiagbon RU, Giroux DJ, et al. The IASLC Lung Cancer Staging Project: Proposals for the revision of the N descriptors in the forthcoming 9th edition of the TNM classification for lung cancer. J Thorac Oncol, 2024, 4: S1556-0864(24)00060-1.
5.	Osaki T, Nagashima A, Yoshimatsu T, et al. Survival and characteristics of lymph node involvement in patients with N1 non-small cell lung cancer. Lung Cancer, 2004, 43(2): 151-157.
6.	Martini N, Flehinger BJ, Nagasaki F, et al. Prognostic significance of N1 disease in carcinoma of the lung. J Thorac Cardiovasc Surg, 1983, 86(5): 646-653.
7.	Riquet M, Manac'h D, Le Pimpec-Barthes F, et al. Prognostic significance of surgical-pathologic N1 disease in non-small cell carcinoma of the lung. Ann Thorac Surg, 1999, 67(6): 1572-1576.
8.	Varlotto JM, Medford-Davis LN, Recht A, et al. Failure rates and patterns of recurrence in patients with resected N1 non-small-cell lung cancer. Int J Radiat Oncol Biol Phys, 2011, 81(2): 353-359.
9.	Tsitsias T, Okiror L, Veres L, et al. New N1/N2 classification and lobe specific lymphatic drainage: Impact on survival in patients with non-small cell lung cancer treated with surgery. Lung Cancer, 2021, 151: 84-90.
10.	Lee JG, Lee CY, Park IK, et al. Number of metastatic lymph nodes in resected non-small cell lung cancer predicts patient survival. Ann Thorac Surg, 2008, 85(1): 211-215.
11.	Fukui T, Mori S, Yokoi K, et al. Significance of the number of positive lymph nodes in resected non-small cell lung cancer. J Thorac Oncol, 2006, 1(2): 120-125.
12.	Giuliano AE, Connolly JL, Edge SB, et al. Breast cancer: Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin, 2017, 67(4): 290-303.
13.	Rice TW, Ishwaran H, Ferguson MK, et al. Cancer of the esophagus and esophagogastric junction: An eighth edition staging primer. J Thorac Oncol, 2017, 12(1): 36-42.
14.	Sano T, Coit DG, Kim HH, et al. Proposal of a new stage grouping of gastric cancer for TNM classification: International Gastric Cancer Association Staging Project. Gastric Cancer, 2017, 20(2): 217-225.
15.	Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest, 2009, 136(1): 260-271.
16.	Rusch VW, Crowley J, Giroux DJ, et al. The IASLC Lung Cancer Staging Project: Proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol, 2007, 2(7): 603-612.
17.	Asamura H, Chansky K, Crowley J, et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the revision of the N descriptors in the forthcoming 8th edition of the TNM classification for lung cancer. J Thorac Oncol, 2015, 10(12): 1675-1684.
18.	Xu L, Su H, She Y, et al. Which N descriptor is more predictive of prognosis in resected non-small cell lung cancer: The number of involved nodal stations or the location-based pathological N stage? Chest, 2021, 159(6): 2458-2469.
19.	Park BJ, Kim TH, Shin S, et al. Recommended change in the N descriptor proposed by the International Association for the Study of Lung Cancer: A validation study. J Thorac Oncol, 2019, 14(11): 1962-1969.
20.	Yun JK, Lee GD, Choi S, et al. Comparison between lymph node station- and zone-based classification for the future revision of node descriptors proposed by the International Association for the Study of Lung Cancer in surgically resected patients with non-small-cell lung cancer. Eur J Cardiothorac Surg, 2019, 56(5): 849-857.
21.	Dziedzic DA, Cackowski MM, Zbytniewski M, et al. The influence of the number of lymph nodes removed on the accuracy of a newly proposed N descriptor classification in patients with surgically-treated lung cancer. Surg Oncol, 2021, 37: 101514.
22.	Osarogiagbon RU, Van Schil P, Giroux DJ, et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Overview of challenges and opportunities in revising the nodal classification of lung cancer. J Thorac Oncol, 2023, 18(4): 410-418.
23.	Rami-Porta R. Future perspectives on the TNM staging for lung cancer. Cancers (Basel), 2021, 13(8): 1940.
24.	Saji H, Tsuboi M, Yoshida K, et al. Prognostic impact of number of resected and involved lymph nodes at complete resection on survival in non-small cell lung cancer. J Thorac Oncol, 2011, 6(11): 1865-1871.
25.	Wei S, Asamura H, Kawachi R, et al. Which is the better prognostic factor for resected non-small cell lung cancer: The number of metastatic lymph nodes or the currently used nodal stage classification? J Thorac Oncol, 2011, 6(2): 310-318.
26.	Saji H, Tsuboi M, Shimada Y, et al. A proposal for combination of total number and anatomical location of involved lymph nodes for nodal classification in non-small cell lung cancer. Chest, 2013, 143(6): 1618-1625.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Duma N, Santana-Davila R, Molina JR. Non-small cell lung cancer: Epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc, 2019, 94(8): 1623-1640.
3. Mountain CF. A new international staging system for lung cancer. Chest, 1986, 89(4 Suppl): 225S-233S.
4. Huang J, Osarogiagbon RU, Giroux DJ, et al. The IASLC Lung Cancer Staging Project: Proposals for the revision of the N descriptors in the forthcoming 9th edition of the TNM classification for lung cancer. J Thorac Oncol, 2024, 4: S1556-0864(24)00060-1.
5. Osaki T, Nagashima A, Yoshimatsu T, et al. Survival and characteristics of lymph node involvement in patients with N1 non-small cell lung cancer. Lung Cancer, 2004, 43(2): 151-157.
6. Martini N, Flehinger BJ, Nagasaki F, et al. Prognostic significance of N1 disease in carcinoma of the lung. J Thorac Cardiovasc Surg, 1983, 86(5): 646-653.
7. Riquet M, Manac'h D, Le Pimpec-Barthes F, et al. Prognostic significance of surgical-pathologic N1 disease in non-small cell carcinoma of the lung. Ann Thorac Surg, 1999, 67(6): 1572-1576.
8. Varlotto JM, Medford-Davis LN, Recht A, et al. Failure rates and patterns of recurrence in patients with resected N1 non-small-cell lung cancer. Int J Radiat Oncol Biol Phys, 2011, 81(2): 353-359.
9. Tsitsias T, Okiror L, Veres L, et al. New N1/N2 classification and lobe specific lymphatic drainage: Impact on survival in patients with non-small cell lung cancer treated with surgery. Lung Cancer, 2021, 151: 84-90.
10. Lee JG, Lee CY, Park IK, et al. Number of metastatic lymph nodes in resected non-small cell lung cancer predicts patient survival. Ann Thorac Surg, 2008, 85(1): 211-215.
11. Fukui T, Mori S, Yokoi K, et al. Significance of the number of positive lymph nodes in resected non-small cell lung cancer. J Thorac Oncol, 2006, 1(2): 120-125.
12. Giuliano AE, Connolly JL, Edge SB, et al. Breast cancer: Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin, 2017, 67(4): 290-303.
13. Rice TW, Ishwaran H, Ferguson MK, et al. Cancer of the esophagus and esophagogastric junction: An eighth edition staging primer. J Thorac Oncol, 2017, 12(1): 36-42.
14. Sano T, Coit DG, Kim HH, et al. Proposal of a new stage grouping of gastric cancer for TNM classification: International Gastric Cancer Association Staging Project. Gastric Cancer, 2017, 20(2): 217-225.
15. Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest, 2009, 136(1): 260-271.
16. Rusch VW, Crowley J, Giroux DJ, et al. The IASLC Lung Cancer Staging Project: Proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol, 2007, 2(7): 603-612.
17. Asamura H, Chansky K, Crowley J, et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the revision of the N descriptors in the forthcoming 8th edition of the TNM classification for lung cancer. J Thorac Oncol, 2015, 10(12): 1675-1684.
18. Xu L, Su H, She Y, et al. Which N descriptor is more predictive of prognosis in resected non-small cell lung cancer: The number of involved nodal stations or the location-based pathological N stage? Chest, 2021, 159(6): 2458-2469.
19. Park BJ, Kim TH, Shin S, et al. Recommended change in the N descriptor proposed by the International Association for the Study of Lung Cancer: A validation study. J Thorac Oncol, 2019, 14(11): 1962-1969.
20. Yun JK, Lee GD, Choi S, et al. Comparison between lymph node station- and zone-based classification for the future revision of node descriptors proposed by the International Association for the Study of Lung Cancer in surgically resected patients with non-small-cell lung cancer. Eur J Cardiothorac Surg, 2019, 56(5): 849-857.
21. Dziedzic DA, Cackowski MM, Zbytniewski M, et al. The influence of the number of lymph nodes removed on the accuracy of a newly proposed N descriptor classification in patients with surgically-treated lung cancer. Surg Oncol, 2021, 37: 101514.
22. Osarogiagbon RU, Van Schil P, Giroux DJ, et al. The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Overview of challenges and opportunities in revising the nodal classification of lung cancer. J Thorac Oncol, 2023, 18(4): 410-418.
23. Rami-Porta R. Future perspectives on the TNM staging for lung cancer. Cancers (Basel), 2021, 13(8): 1940.
24. Saji H, Tsuboi M, Yoshida K, et al. Prognostic impact of number of resected and involved lymph nodes at complete resection on survival in non-small cell lung cancer. J Thorac Oncol, 2011, 6(11): 1865-1871.
25. Wei S, Asamura H, Kawachi R, et al. Which is the better prognostic factor for resected non-small cell lung cancer: The number of metastatic lymph nodes or the currently used nodal stage classification? J Thorac Oncol, 2011, 6(2): 310-318.
26. Saji H, Tsuboi M, Shimada Y, et al. A proposal for combination of total number and anatomical location of involved lymph nodes for nodal classification in non-small cell lung cancer. Chest, 2013, 143(6): 1618-1625.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Latest ArticlesImpact of number of positive regional lymph nodes in N1 stage on the prognosis of patients with non-small cell lung cancer: A propensity score matching study

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