Original article
Vol. 151 No. 0506 (2021)
Lymphovascular invasion is an independent prognostic factor for survival in pathologically proven N2 non-small cell lung cancer
- Laura C. Guglielmetti
- Didier Schneiter
- Sven Hillinger
- Isabelle Opitz
- Claudio Caviezel
- Walter Weder
- Ilhan Inci
Summary
BACKGROUND
We aimed to analyse the nodal spread of our non-small cell lung cancer pN2 cohort according to tumour location, the possible implications of an unusual spreading pattern, and other factors influencing postoperative survival after anatomical lung resection.
METHODS
In this retrospective observational study, clinical data was collected for 124 consecutive non-small cell lung cancer (NSCLC) patients with a pathological N2 (stage IIIA or B) undergoing anatomical lung resection at our institution between 2001 and 2010. Cox regression was used to analyse independent predictors of 5-year overall survival and recurrence-free survival.
RESULTS
A total of 105 patients were included in the final analysis. Tumour location in the right upper lobe and middle lobe was significantly more often associated with involvement of lymph node stations 2 and 4 than NSCLC in the right lower lobe (station 2: right upper vs right lower lobe, p = 0.001 and middle vs right lower lobe, p = 0.038; station 4: right upper vs right lower lobe, p<0.001 and middle vs right lower lobe, p = 0.056), while tumours in the right upper lobe showed significantly less involvement of stations 7 and 8 compared with right lower lobe tumours (station 7 p <0.001, station 8 p = 0.004). Left sided tumours in the upper lobe had significantly more involvement of station 5 compared to lower lobe tumours (p = 0.009). However, atypical lymphatic nodal zone involvement did not emerge as a significant predictor of survival. Lymphovascular invasion was the only independent prognostic factor for 5-year overall survival (hazard ratio [HR] 2.10, p = 0.015) and recurrence-free survival (HR 1.68, p = 0.049) when controlled for adjuvant therapy.
CONCLUSION
Lymphovascular invasion was identified as the only independent prognostic factor for 5-year overall survival and recurrence-free survival in our pathologically proven N2 NSCLC cohort when controlled for adjuvant therapy. This study extends the current evidence of an adverse prognostic effect of lymphovascular invasion on a stage III population, confirms the adverse prognostic effect of lymphovascular invasion detected by immunohistochemistry, and thereby reveals another subgroup within the pN2 population with worse prognosis regarding 5-year overall survival and recurrence-free survival.
References
- 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(6):1618–25. doi:.https://doi.org/10.1378/chest.12-0750
- Lardinois D, De Leyn P, Van Schil P, Porta RR, Waller D, Passlick B, et al. ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer. Eur J Cardiothorac Surg. 2006;30(5):787–92. doi:.https://doi.org/10.1016/j.ejcts.2006.08.008
- Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WE, et al.; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee Advisory Boards and Participating Institutions. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2016;11(1):39–51. doi:.https://doi.org/10.1016/j.jtho.2015.09.009
- Yoo C, Yoon S, Lee DH, Park SI, Kim DK, Kim YH, et al. Prognostic Significance of the Number of Metastatic pN2 Lymph Nodes in Stage IIIA-N2 Non-Small-Cell Lung Cancer After Curative Resection. Clin Lung Cancer. 2015;16(6):e203–12. doi:.https://doi.org/10.1016/j.cllc.2015.04.004
- Riquet M, Rivera C, Pricopi C, Arame A, Mordant P, Foucault C, et al. Is the lymphatic drainage of lung cancer lobe-specific? A surgical appraisal. Eur J Cardiothorac Surg. 2015;47(3):543–9. doi:.https://doi.org/10.1093/ejcts/ezu226
- Ohtaki Y, Shimizu K, Kaira K, Nagashima T, Obayashi K, Nakazawa S, et al. Risk factors associated with recurrence of surgically resected node-positive non-small cell lung cancer. Surg Today. 2016;46(10):1196–208. doi:.https://doi.org/10.1007/s00595-015-1301-5
- Shimada Y, Saji H, Kakihana M, Honda H, Usuda J, Kajiwara N, et al. Retrospective analysis of nodal spread patterns according to tumor location in pathological N2 non-small cell lung cancer. World J Surg. 2012;36(12):2865–71. doi:.https://doi.org/10.1007/s00268-012-1743-5
- Sun Y, Gao W, Zheng H, Jiang G, Chen C, Zhang L. Mediastinal lymph-nodes metastasis beyond the lobe-specific: an independent risk factor toward worse prognoses. Ann Thorac Cardiovasc Surg. 2014;20(4):284–91. doi:.https://doi.org/10.5761/atcs.oa.13-00028
- Kawasaki K, Sato Y, Suzuki Y, Saito H, Nomura Y, Yoshida Y. Prognostic Factors for Surgically Resected N2 Non-small Cell Lung Cancer. Ann Thorac Cardiovasc Surg. 2015;21(3):217–22. doi:.https://doi.org/10.5761/atcs.oa.14-00218
- Rusch VW, Asamura H, Watanabe H, Giroux DJ, Rami-Porta R, Goldstraw P ; Members of IASLC Staging Committee. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009;4(5):568–77. doi:.https://doi.org/10.1097/JTO.0b013e3181a0d82e
- Higgins KA, Chino JP, Ready N, D’Amico TA, Berry MF, Sporn T, et al. Lymphovascular invasion in non-small-cell lung cancer: implications for staging and adjuvant therapy. J Thorac Oncol. 2012;7(7):1141–7. doi:.https://doi.org/10.1097/JTO.0b013e3182519a42
- Andre F, Grunenwald D, Pignon JP, Dujon A, Pujol JL, Brichon PY, et al. Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol. 2000;18(16):2981–9. doi:.https://doi.org/10.1200/JCO.2000.18.16.2981
- Douketis JD, Spyropoulos AC, Kaatz S, Becker RC, Caprini JA, Dunn AS, et al.; BRIDGE Investigators. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. N Engl J Med. 2015;373(9):823–33. doi:.https://doi.org/10.1056/NEJMoa1501035
- Wu Y, Huang ZF, Wang SY, Yang XN, Ou W. A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer. Lung Cancer. 2002;36(1):1–6. doi:.https://doi.org/10.1016/S0169-5002(01)00445-7
- 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(3):662–70. doi:.https://doi.org/10.1016/j.jtcvs.2010.11.008
- Cerfolio RJ, Bryant AS. Distribution and likelihood of lymph node metastasis based on the lobar location of nonsmall-cell lung cancer. Ann Thorac Surg. 2006;81(6):1969–73, discussion 1973. doi:.https://doi.org/10.1016/j.athoracsur.2005.12.067
- Asamura H, Chansky K, Crowley J, Goldstraw P, Rusch VW, Vansteenkiste JF, et al.; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Board Members, and Participating Institutions. 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):1675–84. doi:.https://doi.org/10.1097/JTO.0000000000000678
- Chen CY, Wu BR, Chen CH, Cheng WC, Chen WC, Liao WC, et al. Prognostic Value of Tumor Size in Resected Stage IIIA-N2 Non-Small-Cell Lung Cancer. J Clin Med. 2020;9(5):1307. doi:.https://doi.org/10.3390/jcm9051307
- Liao Y, Wang X, Zhong P, Yin G, Fan X, Huang C. A nomogram for the prediction of overall survival in patients with stage II and III non-small cell lung cancer using a population-based study. Oncol Lett. 2019;18(6):5905–16. doi:.https://doi.org/10.3892/ol.2019.10977
- Castello A, Toschi L, Rossi S, Finocchiaro G, Grizzi F, Mazziotti E, et al. Predictive and Prognostic Role of Metabolic Response in Patients With Stage III NSCLC Treated With Neoadjuvant Chemotherapy. Clin Lung Cancer. 2020;21(1):28–36. doi:.https://doi.org/10.1016/j.cllc.2019.07.004
- Wu R, Glen P, Ramsay T, Martel G. Reporting quality of statistical methods in surgical observational studies: protocol for systematic review. Syst Rev. 2014;3(1):70. doi:.https://doi.org/10.1186/2046-4053-3-70
- Hickey GL, Dunning J, Seifert B, Sodeck G, Carr MJ, Burger HU, et al.; EJCTS and ICVTS Editorial Committees. Statistical and data reporting guidelines for the European Journal of Cardio-Thoracic Surgery and the Interactive CardioVascular and Thoracic Surgery. Eur J Cardiothorac Surg. 2015;48(2):180–93. doi:.https://doi.org/10.1093/ejcts/ezv168
- Matsumura Y, Hishida T, Shimada Y, Ishii G, Aokage K, Yoshida J, et al. Impact of extratumoral lymphatic permeation on postoperative survival of non-small-cell lung cancer patients. J Thorac Oncol. 2014;9(3):337–44. doi:.https://doi.org/10.1097/JTO.0000000000000073
- Wang J, Wang B, Zhao W, Guo Y, Chen H, Chu H, et al. Clinical significance and role of lymphatic vessel invasion as a major prognostic implication in non-small cell lung cancer: a meta-analysis. PLoS One. 2012;7(12):e52704. doi:.https://doi.org/10.1371/journal.pone.0052704
- Salvati F. Lymphovascular invasion in non-small-cell lung cancer. J Thorac Oncol. 2013;8(1):e8–9. doi:.https://doi.org/10.1097/JTO.0b013e3182797de5
- Rami-Porta R. Adjuvant therapy for resected non-small-cell lung cancer with lymphovascular invasion. J Thorac Oncol. 2013;8(1):e9–10. doi:.https://doi.org/10.1097/JTO.0b013e3182797f3b