Pattern of lymph node dissection in non-small cell lung cancer: A systematic review and meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

JING Tao ¹ , FENG Haiming ¹ , MA Jianxing ¹ , WANG Cheng ¹ ,  LI Bin ¹ , ZHANG Jianhua ²

1. Department of Thoracic Surgery, the Second Hospital of Lanzhou University, Lanzhou, 730000, P.R.China;
2. Department of Thoracic Surgery, Shenzhen Hospital of Southern Medical University, Shenzhen, 518100, Guangdong, P.R.China;

Corresponding author：

LI Bin, Email: dr.leebin@outlook.com

Keywords：

Non-small cell lung cancer; systematic mediastinal lymph node dissection; lymph node sampling; lobe-specific lymph node dissection; meta-analysis

DOI：

10.7507/1007-4848.201706065

Video：

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Objective To compare lymph node sampling (LN-S) and lobe-specific lymph node dissection (L-SLD) in the clinical efficacy and safety for early-stage non-small cell lung cancer (NSCLC). Methods PubMed, Medline, EMbase, Web of Science and The Cochrane Library databases were searched up to March 2017 for English language studies. We collected randomized controlled trials (RCTs) and cohort studies (CS) which used the systematic mediastinal lymph node dissection (SMLD) and LN-S or L-SLD for the treatment of NSCLC. Direct meta-analysis was performed using RevMan 5.3 software and indirect meta-analysis with ITC software after two researchers screened the literature, extracted the data and evaluated the risk of bias independently. Results A total of 18 articles were included (4 RCTs and 14 CS, and 10 714 patients). Meta-analysis results showed that in the CS, compared with the the SMLD group, overall survival increased in the L-SLD group (HR=0.99, 95%CI 0.78 to 1.25, P=0.92), and overall survival decreased in the LN-S group with significant difference in CS (HR=1.43, 95%CI 1.17 to 1.75, P=0.000 4), but was not statistically significant in RCT (P=0.35). In terms of disease-free survival, there was no significant difference between the SMLD group and the LN-S group (HR=1.25, 95%CI 0.90, 1.62, P=0.10) as well as the L-SLD group (HR=1.15, 95%CI 0.92 to 1.43, P=0.23) in the CS. There was no significant difference in the local recurrence rate or distant metastasis rate between the non-systematic lymph node dissection (NSMLD) and SMLD in CS and RCTs (CS: P=0.43, P=0.39; RCT: P=0.43, P=0.10). There was no significant difference in the postoperative complications between NSMLD and SMLD in the CS (OR=0.79, 95%CI0.58 to 1.09, P=0.15) and RCTs (OR=0.36, 95%CI 0.09 to 1.45, P=0.15). Indirect meta-analysis showed that risk of death decreased by 31% and risk of recurrence by 35% in the L-SLD group compared with the LN-S group (HR=0.69, 95% CI 0.51 to 0.95, P=0.46; HR=0.65, 95% CI 0.65 to 1.30, P=0.72), but the difference was not statistically significant. Conclusion For early-stage NSCLC, L-SLD is not statistically different from SMLD in terms of survival; however, the overall survival of LN-S is lower than that of systematic lymphadenectomy. Indirect meta-analysis shows that L-SLD reduces the risk of death and recurrence risk compared with LN-S. There is no evidence to support both direct comparison of the prognosis of LN-S and L-SLD, therefore further prospective studies are still needed to verify.

Citation： JING Tao, FENG Haiming, MA Jianxing, WANG Cheng, LI Bin, ZHANG Jianhua. Pattern of lymph node dissection in non-small cell lung cancer: A systematic review and meta-analysis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2018, 25(8): 659-669. doi: 10.7507/1007-4848.201706065 Copy

1.	Chen W, Zhang S, Zou X. Estimation and projection of lung cancer incidence and mortality in China. Zhongguo Fei Ai Za Zhi, 2010, 13(5): 488-493.
2.	Darling GE, Maziak DE, Inculet RI, et al. Positron emission tomography-computed tomography compared with invasive mediastinal staging in non-small cell lung cancer: results of mediastinal staging in the early lung positron emission tomography trial. J Thorac Oncol, 2011, 6(8): 1367-1372.
3.	Verhagen AF, Bulten J, Shirango H, et al. The clinical value of lymphatic micrometastases in patients with non-small cell lung cancer. J Thorac Oncol, 2010, 5(8): 1201-1205.
4.	Yue D, Gong L, You J, et al. Survival analysis of patients with non-small cell lung cancer who underwent surgical resection following 4 lung cancer resection guidelines. BMC Cancer, 2014, 14: 422.
5.	李胜, 张超, 原瑞霞, 等. 间接比较软件简介. 中国循证医学杂志, 2015, (3): 362-366.
6.	曾宪涛, 曹世义, 孙凤, 等. Meta 分析系列之六: 间接比较及网状 Meta 分析. 中国循证心血管医学杂志,2012, 4(5):399-402.
7.	Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials, 2007, 8: 16.
8.	Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ, 2011, 343: d5928.
9.	Wells G, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale for assessing the quality of nonrandomised studies in meta-analyses. http://wwwohri ca/programs/clinical epidemiology/oxford htm.
10.	Ma W, Zhang ZJ, Li Y, et al. Comparison of lobe-specific mediastinal lymphadenectomy versus systematic mediastinal lymphadenectomy for clinical stage T1aN0M0 non-small cell lung cancer. J Cancer Res Ther, 2013, 9 Suppl 2:S101-105.
11.	Darling GE, Allen MS, Decker PA, 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): 662-670.
12.	Wu Y, Huang ZF, Wang SY, et al. A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer. Lung Cancer, 2002, 36(1): 1-6.
13.	Sugi K, Nawata K, Fujita N, et al. Systematic lymph node dissection for clinically diagnosed peripheral non-small-cell lung cancer less than 2 cm in diameter. World J Surg, 1998, 22(3): 290-294.
14.	Adachi H, Sakamaki K, Nishii T, et al. Lobe-Specific lymph node dissection as a standard procedure in surgery for non-small cell lung cancer: a propensity score matching study. J Thorac Oncol, 2017, 12(1): 85-93.
15.	Flores RM, Nicastri D, Bauer T, et al. Computed tomography screening for lung cancer: mediastinal lymph node resection in stage ⅠA nonsmall cell lung cancer manifesting as subsolid and solid nodules. Ann Surg, 2017, 265(5): 1025-1033.
16.	Wang Y, Wu N, Chen J, et al. Is radical mediastinal lymphadenectomy necessary for elderly patients with clinical N-negative non-small-cell lung cancer? A single center matched-pair study. J Surg Res, 2015, 193(1): 435-441.
17.	Wu N, Yan S, Lv C, et al. Does an extended mediastinal lymphadenectomy improve outcome after R0 resection in lung cancer? Chin J Cancer Res, 2014, 26(2):183-191.
18.	Jeon HW, Moon MH, Kim KS, et al. Extent of removal for mediastinal nodal stations for patients with clinical stage I non-small cell lung cancer: effect on outcome. Thorac Cardiovasc Surg, 2014, 62(7): 599-604.
19.	Shapiro M, Kadakia S, Lim J, et al. Lobe-specific mediastinal nodal dissection is sufficient during lobectomy by video-assisted thoracic surgery or thoracotomy for early-stage lung cancer. Chest, 2013, 144(5): 1615-1621.
20.	Maniwa T, Okumura T, Isaka M, et al. Recurrence of mediastinal node cancer after lobe-specific systematic nodal dissection for non-small-cell lung cancer. Eur J Cardiothorac Surg, 2013, 44(1): e59-e64.
21.	Jiang W, Chen X, Xi J, et al. Selective mediastinal lymphadenectomy without intraoperative frozen section examinations for clinical stage Ⅰ non-small-cell lung cancer: retrospective study of 403 cases. World J Surg, 2013, 37(2): 392-397.
22.	Takizawa H, Kondo K, Matsuoka H, et al. Effect of mediastinal lymph nodes sampling in patients with clinical stage Ⅰ non-small cell lung cancer. J Med Invest, 2008, 55(1-2): 37-43.
23.	Su X, Wang X, Long H, et al. Mediastinal lymph node dissection affects survival in patients with stage Ⅰ non-small cell lung cancer. Thorac Cardiovasc Surg, 2008, 56(4): 226-230.
24.	Ma K, Chang D, He B, et al. Radical systematic mediastinal lymphadenectomy versus mediastinal lymph node sampling in patients with clinical stage ⅠA and pathological stage T1 non-small cell lung cancer. J Cancer Res Clin Oncol, 2008, 134(12): 1289-1295.
25.	Okada M, Sakamoto T, Yuki T, et al. Selective mediastinal lymphadenectomy for clinico-surgical stage Ⅰ non-small cell lung cancer. Ann Thorac Surg, 2006, 81(3): 1028-1032.
26.	Lardinois D, Suter H, Hakki H, et al. Morbidity, survival, and site of recurrence after mediastinal lymph-node dissection versus systematic sampling after complete resection for non-small cell lung cancer. Ann Thorac Surg, 2005, 80(1): 268-274.
27.	Doddoli C, Aragon A, Barlesi F, et al. Does the extent of lymph node dissection influence outcome in patients with stage Ⅰ non-small-cell lung cancer? Eur J Cardiothorac Surg, 2005, 27(4): 680-685.
28.	Allen MS, Darling GE, Pechet TT, et al. Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial. Ann Thorac Surg, 2006, 81(3): 1013-1019.
29.	Wu J, Ohta Y, Minato H, et al. Nodal occult metastasis in patients with peripheral lung adenocarcinoma of 2.0 cm or less in diameter. Ann Thorac Surg, 2001, 71(6): 1772-1777.
30.	Gu CD, Osaki T, Oyama T, et al. Detection of micrometastatic tumor cells in pN0 lymph nodes of patients with completely resected nonsmall cell lung cancer: impact on recurrence and Survival. Ann Surg, 2002, 235(1): 133-139.
31.	Oda M, Watanabe Y, Shimizu J, et al. Extent of mediastinal node metastasis in clinical stage Ⅰ non-small-cell lung cancer: the role of systematic nodal dissection. Lung Cancer, 1998, 22(1): 23-30.
32.	Bollen EC, van Duin CJ, Theunissen PH, et al. Mediastinal lymph node dissection in resected lung cancer: morbidity and accuracy of staging. Ann Thorac Surg, 1993, 55(4): 961-966.
33.	Okada M, Tsubota N, Yoshimura M, et al. Prognosis of completely resected pN2 non-small cell lung carcinomas: What is the significant node that affects survival? J Thorac Cardiovasc Surg, 1999, 118(2): 270-275.
34.	Watanabe S, Asamura H, Suzuki K, et al. The new strategy of selective nodal dissection for lung cancer based on segment-specific patterns of nodal spread. Interact Cardiovasc Thorac Surg, 2005, 4(2): 106-109.
35.	Huang X, Wang J, Chen Q, et al. Mediastinal lymph node dissection versus mediastinal lymph node sampling for early stage non-small cell lung cancer: a systematic review and meta-analysis. PLoS One, 2014, 9(10): e109979.

1. Chen W, Zhang S, Zou X. Estimation and projection of lung cancer incidence and mortality in China. Zhongguo Fei Ai Za Zhi, 2010, 13(5): 488-493.
2. Darling GE, Maziak DE, Inculet RI, et al. Positron emission tomography-computed tomography compared with invasive mediastinal staging in non-small cell lung cancer: results of mediastinal staging in the early lung positron emission tomography trial. J Thorac Oncol, 2011, 6(8): 1367-1372.
3. Verhagen AF, Bulten J, Shirango H, et al. The clinical value of lymphatic micrometastases in patients with non-small cell lung cancer. J Thorac Oncol, 2010, 5(8): 1201-1205.
4. Yue D, Gong L, You J, et al. Survival analysis of patients with non-small cell lung cancer who underwent surgical resection following 4 lung cancer resection guidelines. BMC Cancer, 2014, 14: 422.
5. 李胜, 张超, 原瑞霞, 等. 间接比较软件简介. 中国循证医学杂志, 2015, (3): 362-366.
6. 曾宪涛, 曹世义, 孙凤, 等. Meta 分析系列之六: 间接比较及网状 Meta 分析. 中国循证心血管医学杂志,2012, 4(5):399-402.
7. Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials, 2007, 8: 16.
8. Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ, 2011, 343: d5928.
9. Wells G, Shea B, O’Connell D, et al. The Newcastle-Ottawa Scale for assessing the quality of nonrandomised studies in meta-analyses. http://wwwohri ca/programs/clinical epidemiology/oxford htm.
10. Ma W, Zhang ZJ, Li Y, et al. Comparison of lobe-specific mediastinal lymphadenectomy versus systematic mediastinal lymphadenectomy for clinical stage T1aN0M0 non-small cell lung cancer. J Cancer Res Ther, 2013, 9 Suppl 2:S101-105.
11. Darling GE, Allen MS, Decker PA, 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): 662-670.
12. Wu Y, Huang ZF, Wang SY, et al. A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer. Lung Cancer, 2002, 36(1): 1-6.
13. Sugi K, Nawata K, Fujita N, et al. Systematic lymph node dissection for clinically diagnosed peripheral non-small-cell lung cancer less than 2 cm in diameter. World J Surg, 1998, 22(3): 290-294.
14. Adachi H, Sakamaki K, Nishii T, et al. Lobe-Specific lymph node dissection as a standard procedure in surgery for non-small cell lung cancer: a propensity score matching study. J Thorac Oncol, 2017, 12(1): 85-93.
15. Flores RM, Nicastri D, Bauer T, et al. Computed tomography screening for lung cancer: mediastinal lymph node resection in stage ⅠA nonsmall cell lung cancer manifesting as subsolid and solid nodules. Ann Surg, 2017, 265(5): 1025-1033.
16. Wang Y, Wu N, Chen J, et al. Is radical mediastinal lymphadenectomy necessary for elderly patients with clinical N-negative non-small-cell lung cancer? A single center matched-pair study. J Surg Res, 2015, 193(1): 435-441.
17. Wu N, Yan S, Lv C, et al. Does an extended mediastinal lymphadenectomy improve outcome after R0 resection in lung cancer? Chin J Cancer Res, 2014, 26(2):183-191.
18. Jeon HW, Moon MH, Kim KS, et al. Extent of removal for mediastinal nodal stations for patients with clinical stage I non-small cell lung cancer: effect on outcome. Thorac Cardiovasc Surg, 2014, 62(7): 599-604.
19. Shapiro M, Kadakia S, Lim J, et al. Lobe-specific mediastinal nodal dissection is sufficient during lobectomy by video-assisted thoracic surgery or thoracotomy for early-stage lung cancer. Chest, 2013, 144(5): 1615-1621.
20. Maniwa T, Okumura T, Isaka M, et al. Recurrence of mediastinal node cancer after lobe-specific systematic nodal dissection for non-small-cell lung cancer. Eur J Cardiothorac Surg, 2013, 44(1): e59-e64.
21. Jiang W, Chen X, Xi J, et al. Selective mediastinal lymphadenectomy without intraoperative frozen section examinations for clinical stage Ⅰ non-small-cell lung cancer: retrospective study of 403 cases. World J Surg, 2013, 37(2): 392-397.
22. Takizawa H, Kondo K, Matsuoka H, et al. Effect of mediastinal lymph nodes sampling in patients with clinical stage Ⅰ non-small cell lung cancer. J Med Invest, 2008, 55(1-2): 37-43.
23. Su X, Wang X, Long H, et al. Mediastinal lymph node dissection affects survival in patients with stage Ⅰ non-small cell lung cancer. Thorac Cardiovasc Surg, 2008, 56(4): 226-230.
24. Ma K, Chang D, He B, et al. Radical systematic mediastinal lymphadenectomy versus mediastinal lymph node sampling in patients with clinical stage ⅠA and pathological stage T1 non-small cell lung cancer. J Cancer Res Clin Oncol, 2008, 134(12): 1289-1295.
25. Okada M, Sakamoto T, Yuki T, et al. Selective mediastinal lymphadenectomy for clinico-surgical stage Ⅰ non-small cell lung cancer. Ann Thorac Surg, 2006, 81(3): 1028-1032.
26. Lardinois D, Suter H, Hakki H, et al. Morbidity, survival, and site of recurrence after mediastinal lymph-node dissection versus systematic sampling after complete resection for non-small cell lung cancer. Ann Thorac Surg, 2005, 80(1): 268-274.
27. Doddoli C, Aragon A, Barlesi F, et al. Does the extent of lymph node dissection influence outcome in patients with stage Ⅰ non-small-cell lung cancer? Eur J Cardiothorac Surg, 2005, 27(4): 680-685.
28. Allen MS, Darling GE, Pechet TT, et al. Morbidity and mortality of major pulmonary resections in patients with early-stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial. Ann Thorac Surg, 2006, 81(3): 1013-1019.
29. Wu J, Ohta Y, Minato H, et al. Nodal occult metastasis in patients with peripheral lung adenocarcinoma of 2.0 cm or less in diameter. Ann Thorac Surg, 2001, 71(6): 1772-1777.
30. Gu CD, Osaki T, Oyama T, et al. Detection of micrometastatic tumor cells in pN0 lymph nodes of patients with completely resected nonsmall cell lung cancer: impact on recurrence and Survival. Ann Surg, 2002, 235(1): 133-139.
31. Oda M, Watanabe Y, Shimizu J, et al. Extent of mediastinal node metastasis in clinical stage Ⅰ non-small-cell lung cancer: the role of systematic nodal dissection. Lung Cancer, 1998, 22(1): 23-30.
32. Bollen EC, van Duin CJ, Theunissen PH, et al. Mediastinal lymph node dissection in resected lung cancer: morbidity and accuracy of staging. Ann Thorac Surg, 1993, 55(4): 961-966.
33. Okada M, Tsubota N, Yoshimura M, et al. Prognosis of completely resected pN2 non-small cell lung carcinomas: What is the significant node that affects survival? J Thorac Cardiovasc Surg, 1999, 118(2): 270-275.
34. Watanabe S, Asamura H, Suzuki K, et al. The new strategy of selective nodal dissection for lung cancer based on segment-specific patterns of nodal spread. Interact Cardiovasc Thorac Surg, 2005, 4(2): 106-109.
35. Huang X, Wang J, Chen Q, et al. Mediastinal lymph node dissection versus mediastinal lymph node sampling for early stage non-small cell lung cancer: a systematic review and meta-analysis. PLoS One, 2014, 9(10): e109979.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Pattern of lymph node dissection in non-small cell lung cancer: A systematic review and meta-analysis

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