Advertisement

Including positive lymph node count in the AJCC N staging may be a better predictor of the prognosis of NSCLC patients, especially stage III patients: a large population-based study

  • Yanling Fan
  • Yanfang Du
  • Wenqu Sun
  • Haiyong WangEmail author
Original Article

Abstract

Background

The study was designed to explore the value of including positive lymph node count in the TNM staging system of non-small cell lung cancer.

Patients and methods

The X-tile model was applied to determine the cutoff values of positive lymph node count. Survival curves were generated using the Kaplan–Meier method and differences in survival among subgroups were examined using the log-rank test. The influence of different variables on overall survival and lung cancer-specific survival was further evaluated using univariate and multivariate Cox proportional hazard models. All statistical analyses were performed using SPSS version 22.0 (SPSS, Chicago, IL, USA). All p values were 2-sided and p < 0.05 was considered statistically significant.

Results

The overall survival and lung cancer-specific survival between stage IIIA and IIIB classified by the sixth edition TNM staging system show no statistically significant difference (p = 0.479 for overall survival; p = 0.081 for lung cancer specific survival). The X-tile model was used to screen three different cutoff values including nN = 0, nN1–3 and nN4-. The nN value is a significant independent prognostic factor that affects overall survival and lung cancer-specific survival of non-small cell lung cancer patients (all, p < 0.001). We obtained the hypothesized TNM sub-stages based on location and the number of PLN. There were significant differences between the hypothesized stage IIIA and IIIB regarding overall survival and lung cancer-specific survival (all, p < 0.001).

Conclusions

It needs to be considered that N stage in combination with positive lymph node count may be used to predict the prognosis of non-small cell lung cancer for stage III cases with increased accuracy than category location-based stage.

Keywords

Non-small cell lung cancer Tumor-node-metastasis Lymph node Stage Prognosis 

Abbreviations

NSCLC

Non-small cell lung cancer

TNM

Tumor-node-metastasis

PLN

Positive lymph nodes

nN

Number of positive lymph nodes

LNs

Lymph nodes

SEER

Surveillance Epidemiology and End Results

AJCC

American Joint Committee on Cancer

OS

Overall survival

LCSS

Lung cancer-specific survival

HR

Hazard ratio

CI

Confidence interval

pN

Pathological lymph nodes

pT

Pathological tumor

Notes

Funding

The funding was received by National Natural Science Foundation of China (Grant no. 81603348), Special funds for Taishan Scholars Project (Grant no. tsqn201812149), Shandong Province key R & D Plan (Grant no. 2018GSF119014).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Jemal A, Center MM, DeSantis C et al (2010) Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Prev Biomark 19:1893–1907CrossRefGoogle Scholar
  2. 2.
    Goldstraw P, Chansky K, Crowley J et al (2016) 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 11:39–51CrossRefGoogle Scholar
  3. 3.
    Detterbeck FC et al (2009) The new lung cancer staging system. Chest 136(1):260–271CrossRefGoogle Scholar
  4. 4.
    Wei S, Asamura H, Kawachi R et al (2011) 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 6(2):310–318CrossRefGoogle Scholar
  5. 5.
    Surveillance, Epidemiology, and End Results (SEER) Program (http://www.seer.cancer.gov/) SEER*Stat Database: Incidence - SEER 9 Regs Research Data, Nov 2018 Sub (1975–2016) - Linked To County Attributes - Total U.S., 1969–2017 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, released April 2019, based on the November 2018 submission
  6. 6.
    Mirsadraee S, Oswal D, Alizadeh Y et al (2012) The 7th lung cancer TNM classification and staging system: review of the changes and implications. World J Radiol 4:128–134CrossRefGoogle Scholar
  7. 7.
    Saji H, Tsuboi M, Yoshida K et al (2011) Prognostic impact of number of resected and involved lymph nodes at complete resection on survival in non-small cell lung cancer. J Thorac Oncol 6:1865–1871CrossRefGoogle Scholar
  8. 8.
    Fukui T, Mori S, Yokoi K et al (2006) Significance of the number of positive lymph nodes in resected non-small cell lung cancer. J Thorac Oncol 1(2):120–125CrossRefGoogle Scholar
  9. 9.
    Lee JG, Lee CY, Park IK et al (2008) Number of metastatic lymph nodes in resected non-small cell lung cancer predicts patient survival. Ann Thorac Surg 85(1):211–215CrossRefGoogle Scholar
  10. 10.
    Ludwig MS, Goodman M, Miller DL et al (2005) Postoperative survival and the number of lymph nodes sampled during resection of node-negative non-small cell lung cancer. Chest 128(3):1545–1550CrossRefGoogle Scholar
  11. 11.
    Saji H, Kojima K, Nakamura H (2017) Improved lymph node staging in early-stage lung cancer in the national cancer database: commentary. Ann Thorac Surg 104:1805–1814CrossRefGoogle Scholar
  12. 12.
    Goldstraw P (2009) Staging manual in thoracic. 1st edn. Editorial Rx Press, Orange ParkGoogle Scholar
  13. 13.
    Shimada Y, Tsuboi M, Saji H et al (2009) The prognostic impact of main bronchial lymph node involvement in non-small cell lung carcinoma: suggestions for a modification of the staging system. Ann Thorac Surg 88(5):1583–1588CrossRefGoogle Scholar
  14. 14.
    Andre F, Grunenwald D, Pignon JP et al (2000) Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol 18(16):2981–2989CrossRefGoogle Scholar
  15. 15.
    Asamura H, Suzuki K, Kondo H et al (2000) Where is the boundary between N1 and N2 stations in lung cancer? Ann Thorac Surg 70(6):1839–1845CrossRefGoogle Scholar
  16. 16.
    Robinson LA, Ruckdeschel JC, Wagner H Jr et al (2007) Treatment of non-small cell lung cancer stage IIIA: ACCP evidence based clinical practice guidelines (2nd edition). Chest 132(Suppl 3):243S–265SCrossRefGoogle Scholar
  17. 17.
    Misthos P, Sepsas E, Athanassiadi K et al (2004) Skip metastases: analysis of their clinical significance and prognosis in the IIIA stage of non-small cell lung cancer. Eur J Cardiothorac Surg 25(4):502–508CrossRefGoogle Scholar
  18. 18.
    Rusch VW, Crowley J, Dorothy J et al (2007) 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 2(7):603–612CrossRefGoogle Scholar
  19. 19.
    Bria E, Milella M, Sperduti I et al (2009) A novel clinical prognostic score incorporating the number of resected lymph-nodes to predict recurrence and survival in non-small-cell lung cancer. Lung Cancer 66(3):365–371CrossRefGoogle Scholar
  20. 20.
    Tepper JE, O'Connell MJ, Niedzwiecki D et al (2001) Impact of number of nodes retrieved on outcome in patients with rectal cancer. J Clin Oncol 19(1):157–163CrossRefGoogle Scholar
  21. 21.
    Weir L, Speers C, D'yachkova Y et al (2002) Prognostic significance of the number of axillary lymph nodes removed in patients with node-negative breast cancer. J Clin Oncol 20(7):1793–1799CrossRefGoogle Scholar
  22. 22.
    Herr HW, Bochner BH, Dalbagni G et al (2002) Impact of the number of lymph nodes retrieved on outcome in patients with muscle invasive bladder cancer. J Urol 167:1295–1298CrossRefGoogle Scholar
  23. 23.
    Darling GE, Allen MS, Decker PA et al (2011) Number of lymph nodes harvested from a mediastinal lymphadenectomy: results of the randomized, prospective American College of Surgeons Oncology Group Z0030 trial. Chest 139(5):1124–1129CrossRefGoogle Scholar
  24. 24.
    Varlotto JM, Recht A, Nikolov M et al (2009) Extent of lymphadenectomy and outcome for patients with stage I nonsmall cell lung cancer. Cancer 115(4):851–858CrossRefGoogle Scholar
  25. 25.
    Saji H, Tsuboi M, Shimada Y et al (2013) A proposal for combination of total number and anatomical location of involved lymph nodes for nodal classification in non-small cell lung cancer. Chest 143(6):1618–1625CrossRefGoogle Scholar
  26. 26.
    Liang W, He J, Shen Y et al (2016) Impact of examined lymph node count on precise staging and long-term survival of resected non–small-cell lung cancer: a population study of the US SEER database and a Chinese multi-institutional registry. J Clin Oncol 35(11):1162–1172CrossRefGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  • Yanling Fan
    • 1
  • Yanfang Du
    • 1
  • Wenqu Sun
    • 2
  • Haiyong Wang
    • 3
    Email author
  1. 1.Department of Haematology and OncologyJinxiang People’s Hospital, Jinxiang Hospital Affiliated to Jining Medical UniversityJiningChina
  2. 2.Department of Cardiothoracic SurgeryJinxiang HongDa Hospital Affiliated to Jining Medical UniversityJiningChina
  3. 3.Department of Internal-Medicine OncologyShandong Cancer Hospital and Institute, Shandong Cancer Hospital Affiliated To Shandong University, Shandong Academy of Medical SciencesJinanChina

Personalised recommendations