Impact of Extracapsular Extension of Lymph Node in Adenocarcinoma of the Stomach

Abstract

Background

Extracapsular extension (ECE) of lymph node may have important prognostic impact for patients with adenocarcinoma of the stomach, but it generally is ignored in staging systems and prognostic models. This study aimed to examine the impact that ECE of lymph node has on prognosis for patients with adenocarcinoma of the stomach.

Methods

The study analyzed 321 consecutive patients with gastric cancer who underwent radical gastrectomy between January 2008 and December 2015. None of these patients had distant metastases. Lymph node metastases were found in 187 patients. The ECE grade was evaluated according to the previously described system used in head and neck cancers. Deposits of cancer cells in sub-serosal fat without a recognizable lymph node were classified as ECE grade 4. Survival outcomes were compared using Kaplan–Meier and Cox regression analyses. A nomogram was constructed using identified significant prognostic factors. The predictive accuracy and model performance were measured by the concordance index (C-index).

Results

Patients with ECE(+) showed significantly worse 3-year overall survival (OS) and disease-free survival (DFS) than those without ECE. In the sensitivity analysis, ECE had independent prognostic value for both 3-year OS and 3-year DFS, whereas ECE grading showed little impact on mortality trend or disease progression trend. The ECE-based nomogram showed a significantly higher C-index than the pathological tumor and node staging (pTN) staging system.

Conclusions

The adverse prognostic impact of ECE was validated. Sub-serosal tumor deposits without recognizable lymph node tissue are recommended for inclusion in the ECE definition. A nomogram involving ECE could provide better individual prediction of survival for patients with lymph node-positive gastric cancer.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2

References

  1. 1.

    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. https://doi.org/10.3322/caac.21492.

    Article  PubMed  Google Scholar 

  2. 2.

    Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65:87–108. https://doi.org/10.3322/caac.21262.

    Article  PubMed  Google Scholar 

  3. 3.

    Amin MB, American Joint Committee on Cancer, American Cancer Society. AJCC Cancer Staging Manual. 8th ed. In: American Joint Committee on Cancer. Springer, Chicago IL, 2017.

  4. 4.

    Alakus H, Holscher AH, Grass G, et al. Extracapsular lymph node spread: a new prognostic factor in gastric cancer. Cancer. 2010;116:309–15. https://doi.org/10.1002/cncr.24764.

    Article  PubMed  Google Scholar 

  5. 5.

    Okamoto T, Tsuburaya A, Kameda Y, et al. Prognostic value of extracapsular invasion and fibrotic focus in single lymph node metastasis of gastric cancer. Gastric Cancer. 2008;11:160–7. https://doi.org/10.1007/s10120-008-0473-8.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Lewis JS Jr, Carpenter DH, Thorstad WL, Zhang Q, Haughey BH. Extracapsular extension is a poor predictor of disease recurrence in surgically treated oropharyngeal squamous cell carcinoma. Mod Pathol. 2011;24:1413–20. https://doi.org/10.1038/modpathol.2011.105.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma, 2nd English edition. Gastric Cancer. 1998;1:10–24. https://doi.org/10.1007/s101209800016.

    Article  Google Scholar 

  8. 8.

    Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma, 3rd English edition. Gastric Cancer. 2011;14:101–12. https://doi.org/10.1007/s10120-011-0041-5.

    Article  Google Scholar 

  9. 9.

    Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (version 3). Gastric Cancer. 2011;14:113–23. https://doi.org/10.1007/s10120-011-0042-4.

    Article  Google Scholar 

  10. 10.

    Mathoulin-Pelissier S, Gourgou-Bourgade S, Bonnetain F, Kramar A. Survival end point reporting in randomized cancer clinical trials: a review of major journals. J Clin Oncol. 2008;26:3721–6. https://doi.org/10.1200/jco.2007.14.1192.

    Article  PubMed  Google Scholar 

  11. 11.

    Altman DG, De Stavola BL, Love SB, Stepniewska KA. Review of survival analyses published in cancer journals. Br J Cancer. 1995;72:511–8. https://doi.org/10.1038/bjc.1995.364.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Harrell FE. Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis. Springer, New York, 2001.

    Google Scholar 

  13. 13.

    Hanley JA, McNeil BJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology. 1983;148:839–43. https://doi.org/10.1148/radiology.148.3.6878708.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20. https://doi.org/10.1056/nejmoa072252.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Sasako M, Sakuramoto S, Katai H, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29:4387–93. https://doi.org/10.1200/jco.2011.36.5908.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Bang YJ, Kim YW, Yang HK, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012;379:315–21. https://doi.org/10.1016/s0140-6736(11)61873-4.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Noh SH, Park SR, Yang HK, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15:1389–96. https://doi.org/10.1016/s1470-2045(14)70473-5.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Depypere LP, Moons J, Mariette C, et al. Impact of extracapsular lymph node involvement after neoadjuvant chemoradiation therapy followed by surgery in carcinoma of the esophagus: a multicenter study. Ann Surg. 2018;268:1000–7. https://doi.org/10.1097/sla.0000000000002425.

    Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Simon Law MBBChir(Cantab), MA, MS(HK), PhD(HK), FRCSEd, FCSHK, HKAM(Surgery), FACS.

Ethics declarations

Disclosures

The laboratory of Dr. Anthony Wing Ip Lo receives sponsorships from AstraZeneca (Hong Kong), Roche (Hong Kong), and MSD (Hong Kong) to provide companion diagnostic tests to public patients. The remaining authors have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 560 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, B., Wong, I.Y., Chan, F.S. et al. Impact of Extracapsular Extension of Lymph Node in Adenocarcinoma of the Stomach. Ann Surg Oncol 27, 4225–4232 (2020). https://doi.org/10.1245/s10434-020-08541-3

Download citation