Prognostic spotlight on N1 disease in NSCLC patients and its relation with tumor characteristics

Abstract

Lung cancer is still one of the most common and potentially lethal cancers. N1 is considering a bad prognostic factor. We aimed to re-identify its prognostic aspects and its relation with the T descriptor. We have operated on 865 patients who were operated on for non-small cell lung cancer (NSCLC) between 2005-2019. Patients with any mediastinal lymph node and distal metastasis were excluded. A total of 667 T1-4N0-1M0 patients were investigated. Survival analysis was made via Cox regression. Five-year survival rate was 72% months in N1 patients. We have shown that increased tumor size and T score were related to higher incidence of N1 positivity T1 has the lowest rate while T3 and T4 have the highest (p<0.001). Lymphovascular invasion decreases overall survival (OR:0.540, p=0.008). The number of parenchymal and hilar lymph nodes was associated with survival regardless of the lymph node positivity (p=0.017). The mean survival of solitary hilar lymph node metastasis 129 months (95% Confidence Interval: 114-143 months) like N0 patients who had overall survival of 133 months (95% Confidence Interval: 125-142 months). Higher T stage is related with higher chance of N1 disease. Surgical and pathological LND from N1 stations are more important in these cases. N1 diseases with STAS and LVI positivity should be assessed with care, and one shall beware with potentially lower survival. Solitary hilar lymph node metastasis with no parenchymal lymph node metastasis had similar survival outcome to N0 patients which may indicate a need for reevaluation in staging.

Keywords

• NSCLC
• survival
• lymph node dissection
• parenchymal lymph nodes
• N1 disease

References

1. Tarver T. Cancer Facts & Figures 2012. American Cancer Society (ACS). J Consum Health Internet. 2012;16:366–367.American Cancer Society. Cancer Facts & Figures 2021 [Internet]. 2021. [Erişim Tarihi: 17 Ekim 2021]. Erişim adresi: 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.
2. Yaldız D, Yakut FC, Örs Kaya Ş, et al. The Role of Sublobar Resection in T1 N0 Non-Small-Cell Pulmonary Carcinoma. Turk Thorac J. 2020;21:308–313.
3. Asare EA, Grubbs EG, Gershenwald JE, et al. Setting the “stage” for Surgical Oncology fellows: Pierre Denoix and TNM staging. J Surg Oncol. 2019;119:823.
4. Mountain CF, Carr DT, Anderson WA. A system for the clinical staging of lung cancer. Am J Roentgenol Radium Ther Nucl Med. 1974;120:130–138.
5. Mountain CF. Revisions in the International System for Staging Lung Cancer. Chest. 1997;111:1710–1717.
6. Raptis CA, Bhalla S. The 7th Edition of the TNM staging system for lung cancer: what the radiologist needs to know. Radiol Clin North Am. 2012;50:915–933.
7. Chansky K, Detterbeck FC, Nicholson AG, et al. The IASLC Lung Cancer Staging Project: External Validation of the Revision of the TNM Stage Groupings in the Eighth Edition of the TNM Classification of Lung Cancer. J Thorac Oncol. 2017;12:1109–1121.
8. Huang J, Osarogiagbon RU, Giroux DJ, Nishimura KK, Bille A, Cardillo G, Detterbeck F, et al.The International Association for the Study of Lung Cancer Staging Project for Lung Cancer: Proposals for the Revision of the N Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2023 Oct 20:S1556-0864(23)02310-9

9. Rami-Porta R, Bolejack V, Crowley J, et al. The IASLC Lung Cancer Staging Project: Proposals for the Revisions of the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2015;10:990–1003.
10. Liu Q-X, Deng X-F, Zhou D, et al. Visceral pleural invasion impacts the prognosis of non-small cell lung cancer: A meta-analysis. Eur J Surg Oncol. 2016;42:1707–1713.
11. Travis WD, Brambilla E, Rami-Porta R, et al. Visceral pleural invasion: pathologic criteria and use of elastic stains: proposal for the 7th edition of the TNM classification for lung cancer. J Thorac Oncol. 2008;3:1384–1390.
12. Sakakura N, Mizuno T, Kuroda H, et al. The eighth TNM classification system for lung cancer: A consideration based on the degree of pleural invasion and involved neighboring structures. Lung Cancer. 2018;118:134–138.
13. Yilmaz A, Duyar SS, Cakir E, Aydin E, Demirag F, Karakaya J, Yazici U, Erdogan Y. Clinical impact of visceral pleural, lymphovascular and perineural invasion in completely resected non-small cell lung cancer. Eur J Cardiothorac Surg. 2011 Sep;40(3):664-70. doi: 10.1016/j.ejcts.2010.12.059. Epub 2011 Feb 21. PMID: 21334917.
14. Mollberg NM, Bennette C, Howell E, et al. Lymphovascular invasion as a prognostic indicator in stage I non-small cell lung cancer: a systematic review and meta-analysis. Ann Thorac Surg. 2014;97:965–971.
15. Wang S, Zhang B, Qian J, et al. Proposal on incorporating lymphovascular invasion as a T-descriptor for stage I lung cancer. Lung Cancer. 2018;125:245–252.
16. Travis WD, Brambilla E, Burke A, et al. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. International Agency for Research on Cancer Available from: https://play.google.com/store/books/details?id=nKO1rQEACAAJ. 2015.
17. Kadota K, Nitadori J-I, Sima CS, et al. Tumor Spread through Air Spaces is an Important Pattern of Invasion and Impacts the Frequency and Location of Recurrences after Limited Resection for Small Stage I Lung Adenocarcinomas. J Thorac Oncol. 2015;10:806–814.
18. Blaauwgeers H, Flieder D, Warth A, et al. A Prospective Study of Loose Tissue Fragments in Non-Small Cell Lung Cancer Resection Specimens: An Alternative View to “Spread Through Air Spaces.” Am J Surg Pathol. 2017;41:1226–1230.
19. Mino-Kenudson M. Significance of tumor spread through air spaces (STAS) in lung cancer from the pathologist perspective. Transl Lung Cancer Res. 2020 Jun;9(3):847-859. doi: 10.21037/tlcr.2020.01.06. PMID: 32676351; PMCID: PMC7354155.
20. Saji H, Okada M, Tsuboi M, Nakajima R, Suzuki K, Aokage K, Aoki T, Okami J, Yoshino I, Ito H, Okumura N, Yamaguchi M, Ikeda N, Wakabayashi M, Nakamura K, Fukuda H, Nakamura S, Mitsudomi T, Watanabe SI, Asamura H; West Japan Oncology Group and Japan Clinical Oncology Group. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, phase 3, randomised, controlled, non-inferiority trial. Lancet. 2022 Apr 23;399(10335):1607-1617. doi: 10.1016/S0140-6736(21)02333-3. PMID: 35461558.
21. Altorki NK, Wang X, Wigle D, Gu L, Darling G, Ashrafi AS, Landrenau R, Miller D, Liberman M, Jones DR, Keenan R, Conti M, Wright G, Veit LJ, Ramalingam SS, Kamel M, Pass HI, Mitchell JD, Stinchcombe T, Vokes E, Kohman LJ. Perioperative mortality and morbidity after sublobar versus lobar resection for early-stage non-small-cell lung cancer: post-hoc analysis of an international, randomised, phase 3 trial (CALGB/Alliance 140503). Lancet Respir Med. 2018 Dec;6(12):915-924. doi: 10.1016/S2213-2600(18)30411-9. Epub 2018 Nov 12. PMID: 30442588; PMCID: PMC6396275.
22. Gossot D, Mariolo AV, Lefevre M, et al. Strategies of Lymph Node Dissection During Sublobar Resection for Early-Stage Lung Cancer. Front Surg. 2021;8:725005.
23. Gossot D, Lutz JA, Grigoroiu M, et al. Unplanned Procedures During Thoracoscopic Segmentectomies. Ann Thorac Surg. 2017;104:1710–1717.
24. Cao C, Tian DH, Wang DR, et al. Sublobar resections-current evidence and future challenges. Journal of thoracic disease. 2017;9:4853–4855.
25. Detterbeck FC, Nishimura KK, Cilento VJ, et al.; International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee and Advisory Boards. The International Association for the Study of Lung Cancer Staging Project: Methods and Guiding Principles for the Development of the Ninth Edition TNM Classification. J Thorac Oncol. 2022 Jun;17(6):806-815.