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Published in: Annals of Surgical Oncology 8/2021

01-08-2021 | NSCLC | Thoracic Oncology

Validation of the 8th Edition Nodal Staging and Proposal of New Nodal Categories for Future Editions of the TNM Classification of Non-Small Cell Lung Cancer

Authors: Shaolei Li, MD, Shi Yan, MD, Fangliang Lu, MD, Chao Lv, MD, Yaqi Wang, MD, Xiang Li, MD, Yuzhao Wang, MD, Yue Yang, MD, Nan Wu, MD

Published in: Annals of Surgical Oncology | Issue 8/2021

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Abstract

Background

The International Association for the Study of Lung Cancer (IASLC) N classifications, which depend on the location and involvement of the lymph nodes, provide accurate prognoses. This study validated the efficiency of classifications using a single-institution dataset and proposed a modified system based on 5-level N1 node dissection.

Methods

From January 2005 to December 2014, 1851 patients with completely resected non-small cell lung cancer were reviewed. According to the IASLC recommendations, N1 is further subdivided into N1a (single) and N1b (multiple), N2 is divided into N2a1 (single station without N1), N2a2 (single station with N1), and N2b (multiple station). Additionally, we evaluated dividing N0 into N0a (with level 13/14 examination) and N0b (without level 13/14 examination), and N1 into N1a* (only level 13/14 positive) and N1b* (level 10–12 positive). Overall survival was also compared.

Results

Multivariate analysis showed that the N classifications recommended by the IASLC and those proposed and evaluated by this study could both significantly predict the prognoses of patients (p < 0.001, respectively). There was no significant difference in survival between N1b and N1a (hazard ratio [HR] 1.049, p = 0.83) and N2a1 and N1b (HR 1.314, p = 0.261); however, there were significant differences between N0a and N0b (HR 1.778, p < 0.001) and N1a* and N1b* (HR 2.014, p = 0.019). The survival curve of N1a* overlapped N0b (HR 0.997, p = 0.991), and N2a1 overlapped N1b* (HR 0.842, p = 0.444).

Conclusion

More detailed nodal information is required to facilitate future revisions of N staging.
Literature
1.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRef Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424.CrossRef
2.
go back to reference Detterbeck FC, Boffa DJ, Kim AW, Tanoue LT. The eighth edition lung cancer stage classification. Chest. 2017;151:193–203.CrossRef Detterbeck FC, Boffa DJ, Kim AW, Tanoue LT. The eighth edition lung cancer stage classification. Chest. 2017;151:193–203.CrossRef
3.
go back to reference Wei S, Asamura H, Kawachi R, Sakurai H, Watanabe S. 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;6:310–18.CrossRef Wei S, Asamura H, Kawachi R, Sakurai H, Watanabe S. 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;6:310–18.CrossRef
4.
go back to reference Saji H, Tsuboi M, Shimada Y, Kato Y, Yoshida K, Nomura M, 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;143:1618–25.CrossRef Saji H, Tsuboi M, Shimada Y, Kato Y, Yoshida K, Nomura M, 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;143:1618–25.CrossRef
5.
go back to reference Asamura H, Chansky K, Crowley J, Goldstraw P, Rusch VW, Vansteenkiste JF, 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;10:1675–84.CrossRef Asamura H, Chansky K, Crowley J, Goldstraw P, Rusch VW, Vansteenkiste JF, 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;10:1675–84.CrossRef
6.
go back to reference Darling GE, Allen MS, Decker PA, Ballman K, Malthaner RA, Inculet RI, et al. Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030 Trial. J Thorac Cardiovasc Surg. 2011;141:662-70.CrossRef Darling GE, Allen MS, Decker PA, Ballman K, Malthaner RA, Inculet RI, et al. Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030 Trial. J Thorac Cardiovasc Surg. 2011;141:662-70.CrossRef
7.
go back to reference Rami-Porta R, Asamura H, Travis WD, Rusch VW. Lung cancer - major changes in the American Joint Committee on Cancer Eighth Edition cancer staging manual. CA Cancer J Clin. 2017;67:138-55.CrossRef Rami-Porta R, Asamura H, Travis WD, Rusch VW. Lung cancer - major changes in the American Joint Committee on Cancer Eighth Edition cancer staging manual. CA Cancer J Clin. 2017;67:138-55.CrossRef
8.
go back to reference Rami-Porta R, Bolejack V, Giroux DJ, Chansky K, Crowley J, Asamura H, et al. International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Advisory Board Members and Participating Institutions. The IASLC lung cancer staging project: the new database to inform the eighth edition of the TNM classification of lung cancer. J Thorac Oncol. 2014;9:1618–24.CrossRef Rami-Porta R, Bolejack V, Giroux DJ, Chansky K, Crowley J, Asamura H, et al. International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Advisory Board Members and Participating Institutions. The IASLC lung cancer staging project: the new database to inform the eighth edition of the TNM classification of lung cancer. J Thorac Oncol. 2014;9:1618–24.CrossRef
9.
go back to reference Varlotto JM, Recht A, Nikolov M, Flickinger JC, Decamp MM. Extent of lymphadenectomy and outcome for patients with stage I nonsmall cell lung cancer. Cancer. 2009;115:851–58.CrossRef Varlotto JM, Recht A, Nikolov M, Flickinger JC, Decamp MM. Extent of lymphadenectomy and outcome for patients with stage I nonsmall cell lung cancer. Cancer. 2009;115:851–58.CrossRef
10.
go back to reference Ajmani GS, Wang CH, Kim KW, Howington JA, Krantz SB. Surgical quality of wedge resection affects overall survival in patients with early stage non-small cell lung cancer. J Thorac Cardiovasc Surg. 2018;156:380–91 e382. Ajmani GS, Wang CH, Kim KW, Howington JA, Krantz SB. Surgical quality of wedge resection affects overall survival in patients with early stage non-small cell lung cancer. J Thorac Cardiovasc Surg. 2018;156:380–91 e382.
11.
go back to reference Licht PB, Jorgensen OD, Ladegaard L, Jakobsen E. A national study of nodal upstaging after thoracoscopic versus open lobectomy for clinical stage I lung cancer. Ann Thorac Surg. 2013;96:943–9; discussion 949–50.CrossRef Licht PB, Jorgensen OD, Ladegaard L, Jakobsen E. A national study of nodal upstaging after thoracoscopic versus open lobectomy for clinical stage I lung cancer. Ann Thorac Surg. 2013;96:943–9; discussion 949–50.CrossRef
12.
go back to reference Kent M, Landreneau R, Mandrekar S, Hillman S, Nichols F, Jones D, et al. Segmentectomy versus wedge resection for non-small cell lung cancer in high-risk operable patients. Ann Thorac Surg. 2013;96:1747-54; discussion 1754-45.CrossRef Kent M, Landreneau R, Mandrekar S, Hillman S, Nichols F, Jones D, et al. Segmentectomy versus wedge resection for non-small cell lung cancer in high-risk operable patients. Ann Thorac Surg. 2013;96:1747-54; discussion 1754-45.CrossRef
13.
go back to reference Smeltzer MP, Faris NR, Ray MA, Osarogiagbon RU. Association of pathologic nodal staging quality with survival among patients with non-small cell lung cancer after resection with curative intent. JAMA Oncol. 2018;4:80–7.CrossRef Smeltzer MP, Faris NR, Ray MA, Osarogiagbon RU. Association of pathologic nodal staging quality with survival among patients with non-small cell lung cancer after resection with curative intent. JAMA Oncol. 2018;4:80–7.CrossRef
14.
go back to reference Ramirez RA, Wang CG, Miller LE, Adair CA, Berry A, Yu X, et al. Incomplete intrapulmonary lymph node retrieval after routine pathologic examination of resected lung cancer. J Clin Oncol. 2012;30:2823–28.CrossRef Ramirez RA, Wang CG, Miller LE, Adair CA, Berry A, Yu X, et al. Incomplete intrapulmonary lymph node retrieval after routine pathologic examination of resected lung cancer. J Clin Oncol. 2012;30:2823–28.CrossRef
15.
go back to reference Osarogiagbon RU, Allen JW, Farooq A, Berry A, O’Brien T. Pathologic lymph node staging practice and stage-predicted survival after resection of lung cancer. Ann Thorac Surg. 2011;91:1486–92.CrossRef Osarogiagbon RU, Allen JW, Farooq A, Berry A, O’Brien T. Pathologic lymph node staging practice and stage-predicted survival after resection of lung cancer. Ann Thorac Surg. 2011;91:1486–92.CrossRef
16.
go back to reference Eichhorn F, Klotz LV, Muley T, Kobinger S, Winter H, Eichhorn ME. Prognostic relevance of regional lymph-node distribution in patients with N1-positive non-small cell lung cancer: a retrospective single-center analysis. Lung Cancer. 2019;138:95–101.CrossRef Eichhorn F, Klotz LV, Muley T, Kobinger S, Winter H, Eichhorn ME. Prognostic relevance of regional lymph-node distribution in patients with N1-positive non-small cell lung cancer: a retrospective single-center analysis. Lung Cancer. 2019;138:95–101.CrossRef
17.
go back to reference Maeshima AM, Tsuta K, Asamura H, Tsuda H. Prognostic implication of metastasis limited to segmental (level 13) and/or subsegmental (level 14) lymph nodes in patients with surgically resected nonsmall cell lung carcinoma and pathologic N1 lymph node status. Cancer. 2012;118:4512–18.CrossRef Maeshima AM, Tsuta K, Asamura H, Tsuda H. Prognostic implication of metastasis limited to segmental (level 13) and/or subsegmental (level 14) lymph nodes in patients with surgically resected nonsmall cell lung carcinoma and pathologic N1 lymph node status. Cancer. 2012;118:4512–18.CrossRef
18.
go back to reference Yun JK, Lee GD, Choi S, Kim HR, Kim YH, Kim DK, 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;56:849–57.CrossRef Yun JK, Lee GD, Choi S, Kim HR, Kim YH, Kim DK, 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;56:849–57.CrossRef
19.
go back to reference Osarogiagbon RU, Allen JW, Farooq A, Berry A, Spencer D, O’Brien T. Outcome of surgical resection for pathologic N0 and Nx non-small cell lung cancer. J Thorac Oncol. 2010;5:191–6.CrossRef Osarogiagbon RU, Allen JW, Farooq A, Berry A, Spencer D, O’Brien T. Outcome of surgical resection for pathologic N0 and Nx non-small cell lung cancer. J Thorac Oncol. 2010;5:191–6.CrossRef
20.
go back to reference Wang X, Yan S, Wang Y, Li X, Lyu C, Wang Y, et al. Adjuvant chemotherapy may improve outcome of patients with non-small-cell lung cancer with metastasis of intrapulmonary lymph nodes after systematic dissection of N1 nodes. Chin J Cancer Res. 2018;30:588–95.CrossRef Wang X, Yan S, Wang Y, Li X, Lyu C, Wang Y, et al. Adjuvant chemotherapy may improve outcome of patients with non-small-cell lung cancer with metastasis of intrapulmonary lymph nodes after systematic dissection of N1 nodes. Chin J Cancer Res. 2018;30:588–95.CrossRef
21.
go back to reference Yeh YC, Kadota K, Nitadori J, Sima CS, Rizk NP, Jones DR, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification predicts occult lymph node metastasis in clinically mediastinal node-negative lung adenocarcinoma. Eur J Cardiothorac Surg. 2016;49:e9–15.CrossRef Yeh YC, Kadota K, Nitadori J, Sima CS, Rizk NP, Jones DR, et al. International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification predicts occult lymph node metastasis in clinically mediastinal node-negative lung adenocarcinoma. Eur J Cardiothorac Surg. 2016;49:e9–15.CrossRef
22.
go back to reference Bille A, Woo KM, Ahmad U, Rizk NP, Jones DR. Incidence of occult pN2 disease following resection and mediastinal lymph node dissection in clinical stage I lung cancer patients. Eur J Cardiothorac Surg. 2017;51:674–9.CrossRef Bille A, Woo KM, Ahmad U, Rizk NP, Jones DR. Incidence of occult pN2 disease following resection and mediastinal lymph node dissection in clinical stage I lung cancer patients. Eur J Cardiothorac Surg. 2017;51:674–9.CrossRef
23.
go back to reference Kanzaki R, Higashiyama M, Fujiwara A, Tokunaga T, Maeda J, Okami J, et al. Occult mediastinal lymph node metastasis in NSCLC patients diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT: risk factors, pattern, and histopathological study. Lung Cancer. 2011;71:333–7.CrossRef Kanzaki R, Higashiyama M, Fujiwara A, Tokunaga T, Maeda J, Okami J, et al. Occult mediastinal lymph node metastasis in NSCLC patients diagnosed as clinical N0-1 by preoperative integrated FDG-PET/CT and CT: risk factors, pattern, and histopathological study. Lung Cancer. 2011;71:333–7.CrossRef
24.
go back to reference Xu YP, Li B, Xu XL, Mao WM. Is there a survival benefit in patients with stage IIIA (N2) non-small cell lung cancer receiving neoadjuvant chemotherapy and/or radiotherapy prior to surgical resection: a systematic review and meta-analysis. Medicine (Baltimore). 2015;94:e879.CrossRef Xu YP, Li B, Xu XL, Mao WM. Is there a survival benefit in patients with stage IIIA (N2) non-small cell lung cancer receiving neoadjuvant chemotherapy and/or radiotherapy prior to surgical resection: a systematic review and meta-analysis. Medicine (Baltimore). 2015;94:e879.CrossRef
25.
go back to reference Ramnath N, Dilling TJ, Harris LJ, Kim AW, Michaud GC, Balekian AA, et al. Treatment of stage III non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e314S–e340S.CrossRef Ramnath N, Dilling TJ, Harris LJ, Kim AW, Michaud GC, Balekian AA, et al. Treatment of stage III non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143:e314S–e340S.CrossRef
26.
go back to reference Auperin A, Le Pechoux C, Rolland E, Curran WJ, Furuse K, Fournel P, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:2181–90.CrossRef Auperin A, Le Pechoux C, Rolland E, Curran WJ, Furuse K, Fournel P, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:2181–90.CrossRef
27.
go back to reference Chang JY, Kestin LL, Barriger RB, Chetty IJ, Ginsburg ME, Kumar S, et al. ACR Appropriateness Criteria(R) nonsurgical treatment for locally advanced non-small-cell lung cancer: good performance status/definitive intent. Oncology (Williston Park) 2014;28:706-10, 12, 14 passim. Chang JY, Kestin LL, Barriger RB, Chetty IJ, Ginsburg ME, Kumar S, et al. ACR Appropriateness Criteria(R) nonsurgical treatment for locally advanced non-small-cell lung cancer: good performance status/definitive intent. Oncology (Williston Park) 2014;28:706-10, 12, 14 passim.
Metadata
Title
Validation of the 8th Edition Nodal Staging and Proposal of New Nodal Categories for Future Editions of the TNM Classification of Non-Small Cell Lung Cancer
Authors
Shaolei Li, MD
Shi Yan, MD
Fangliang Lu, MD
Chao Lv, MD
Yaqi Wang, MD
Xiang Li, MD
Yuzhao Wang, MD
Yue Yang, MD
Nan Wu, MD
Publication date
01-08-2021
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 8/2021
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-09461-y

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