Skip to main content

Advertisement

SpringerLink
Log in

Clinical Impact of Positive Surgical Margins in Gastric Adenocarcinoma in the Era of Preoperative Therapy

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Microscopically positive (R1) surgical margins after gastrectomy increase gastric cancer recurrence risk, but optimal management after R1 gastrectomy is controversial. We sought to identify the impact of R1 margins on recurrence patterns and survival in the era of preoperative therapy for gastric cancer.

Methods

Patients who underwent gastrectomy for adenocarcinoma during 1998–2017 at a major cancer center were enrolled. Clinicopathologic factors associated with positive margins were examined, and incidence, sites, and timing of recurrence and survival outcomes were compared between patients with positive and negative margins.

Results

Of 688 patients, 432 (63%) received preoperative therapy. Thirty-four patients (5%) had R1 margins. Compared with patients with negative margins, patients with R1 margins more frequently had aggressive clinicopathologic features, such as linitis plastica (odds ratio [OR] 7.79, p < 0.001) and failure to achieve cT downstaging with preoperative treatment (OR 5.20, p = 0.005). The 5 year overall survival (OS) rate was lower in patients with R1 margins (6% vs 60%; p < 0.001), and R1 margins independently predicted worse OS (hazard ratio 2.37, 95% CI 1.51–3.75, p < 0.001). Most patients with R1 margins (58%) experienced peritoneal recurrence, and locoregional recurrence was relatively rare in this group (14%). Median time to recurrence was 8.5 months for peritoneal dissemination and 15.7 months for locoregional recurrence.

Conclusion

R1 margins after gastrectomy were associated with aggressive tumor biology, high incidence of peritoneal recurrence after a short interval, and poor OS. In patients with R1 margins, re-resection to achieve microscopically negative margins has to be considered with caution.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Kang YK, Yook JH, Park YK, et al. PRODIGY: a phase III study of neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery and adjuvant S-1 versus surgery and adjuvant S-1 for resectable advanced gastric cancer. J Clin Oncol. 2021;39(26):2903–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zhang X, Liang H, Li Z, et al. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial. The Lancet Oncol. 2021;22(8):1081–92.

    Article  CAS  PubMed  Google Scholar 

  3. Ajani JA, D’Amico TA, Bentrem DJ, et al. Gastric cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw. 2022;20(2):167–92.

    Article  CAS  Google Scholar 

  4. Japanese Gastric Cancer A. Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer. 2021;24(1):1–21.

    Article  Google Scholar 

  5. Wang S-Y, Yeh C-N, Lee H-L, et al. Clinical impact of positive surgical margin status on gastric cancer patients undergoing gastrectomy. Ann Surg Oncol. 2009;16(10):2738–43.

    Article  PubMed  Google Scholar 

  6. Nagata T, Ichikawa D, Komatsu S, et al. Prognostic impact of microscopic positive margin in gastric cancer patients. J Surg Oncol. 2011;104(6):592–7.

    Article  PubMed  Google Scholar 

  7. Bickenbach KA, Gonen M, Strong V, Brennan MF, Coit DG. Association of positive transection margins with gastric cancer survival and local recurrence. Ann Surg Oncol. 2013;20(8):2663–8.

    Article  CAS  PubMed  Google Scholar 

  8. Kumazu Y, Hayashi T, Yoshikawa T, et al. Risk factors analysis and stratification for microscopically positive resection margin in gastric cancer patients. BMC Surg. 2020;20(1):95.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zhao B, Lu H, Bao S, et al. Impact of proximal resection margin involvement on survival outcome in patients with proximal gastric cancer. J Clin Pathol. 2020;73(8):470–5.

    Article  PubMed  Google Scholar 

  10. Fujita S, Oshima Y, Yajima S, et al. What are the important prognostic factors in gastric cancer with positive duodenal margins? A multi-institutional analysis. Surg Today. 2021;51(4):561–7.

    Article  CAS  PubMed  Google Scholar 

  11. Nakanishi K, Kanda M, Ito S, et al. Prognostic impact of a microscopic positive margin in patients undergoing gastrectomy for gastric cancer: a propensity score-matched analysis of a multi-institutional dataset. Surg Today. 2022;52(4):559–66.

    Article  PubMed  Google Scholar 

  12. Tu RH, Lin JX, Wang W, et al. Pathological features and survival analysis of gastric cancer patients with positive surgical margins: a large multicenter cohort study. Eur J Surg Oncol. 2019;45(12):2457–64.

    Article  PubMed  Google Scholar 

  13. Bissolati M, Desio M, Rosa F, et al. Risk factor analysis for involvement of resection margins in gastric and esophagogastric junction cancer: an Italian multicenter study. Gastric Cancer. 2017;20(1):70–82.

    Article  PubMed  Google Scholar 

  14. Shen JG, Cheong JH, Hyung WJ, Kim J, Choi SH, Noh SH. Influence of a microscopic positive proximal margin in the treatment of gastric adenocarcinoma of the cardia. World J Gastroenterol. 2006;12(24):3883–6.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Postlewait LM, Maithel SK. The importance of surgical margins in gastric cancer. J Surg Oncol. 2016;113(3):277–82.

    Article  PubMed  Google Scholar 

  16. Mine S, Kurokawa Y, Takeuchi H, et al. Postoperative complications after a transthoracic esophagectomy or a transhiatal gastrectomy in patients with esophagogastric junctional cancers: a prospective nationwide multicenter study. Gastric Cancer. 2022;25(2):430–7.

    Article  PubMed  Google Scholar 

  17. Makuuchi R, Irino T, Tanizawa Y, Bando E, Kawamura T, Terashima M. Pancreaticoduodenectomy for gastric cancer. J Cancer Metastasis Treat. 2018;4(6):26.

    Article  Google Scholar 

  18. Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725–30.

    Article  CAS  PubMed  Google Scholar 

  19. Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20.

    Article  CAS  PubMed  Google Scholar 

  20. Ikoma N, Das P, Hofstetter W, et al. Preoperative chemoradiation therapy induces primary-tumor complete response more frequently than chemotherapy alone in gastric cancer: analyses of the National Cancer Database 2006–2014 using propensity score matching. Gastric Cancer. 2018;21(6):1004–13.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Ikoma N, Agnes A, Chen HC, et al. Linitis plastica: a distinct type of gastric cancer. J Gastrointest Surg. 2020;24(5):1018–25.

    Article  PubMed  Google Scholar 

  22. Amin MB, Greene FL, Edge SB, et al. The Eighth Edition AJCC Cancer Staging Manual Continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–9.

    Article  PubMed  Google Scholar 

  23. Burgart LJ, Chopp WV, Jain D. Protocol for the examination of specimens from patients with carcinoma of the stomach Version: 4.2.1.0. College of American Pathologists; 2021.

  24. Badgwell B, Blum M, Estrella J, et al. Predictors of survival in patients with resectable gastric cancer treated with preoperative chemoradiation therapy and gastrectomy. J Am Coll Surg. 2015;221(1):83–90.

    Article  PubMed  Google Scholar 

  25. Ajani JA, Mansfield PF, Janjan N, et al. Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma. J Clin Oncol. 2004;22(14):2774–80.

    Article  CAS  PubMed  Google Scholar 

  26. Ajani JA, Winter K, Okawara GS, et al. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006;24(24):3953–8.

    Article  CAS  PubMed  Google Scholar 

  27. Aurello P, Magistri P, Nigri G, et al. Surgical management of microscopic positive resection margin after gastrectomy for gastric cancer: a systematic review of gastric R1 management. Anticancer Res. 2014;34(11):6283–8.

    PubMed  Google Scholar 

  28. Squires MH 3rd, Kooby DA, Pawlik TM, et al. Utility of the proximal margin frozen section for resection of gastric adenocarcinoma: a 7-Institution Study of the US Gastric Cancer Collaborative. Ann Surg Oncol. 2014;21(13):4202–10.

    Article  PubMed  Google Scholar 

  29. Ajani JA, Lee J, Sano T, Janjigian YY, Fan D, Song S. Gastric adenocarcinoma. Nat Rev Dis Primers. 2017;3:17036.

    Article  PubMed  Google Scholar 

  30. Muneoka Y, Ohashi M, Ishizuka N, et al. Risk factors and oncological impact of positive resection margins in gastrectomy for cancer: are they salvaged by an additional resection? Gastric Cancer. 2022;25(1):287–96.

    Article  PubMed  Google Scholar 

  31. Li C, Oh SJ, Kim S, et al. Macroscopic Borrmann type as a simple prognostic indicator in patients with advanced gastric cancer. Oncology. 2009;77(3–4):197–204.

    Article  PubMed  Google Scholar 

  32. Jung K, Park MI, Kim SE, Park SJ. Borrmann type 4 advanced gastric cancer: focus on the development of scirrhous gastric cancer. Clin Endosc. 2016;49(4):336–45.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Song XH, Zhang WH, Kai L, et al. Prognostic impact of Borrmann classification on advanced gastric cancer: a retrospective cohort from a single institution in western China. World J Surg Oncol. 2020;18(1):204.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Cho BC, Jeung HC, Choi HJ, et al. Prognostic impact of resection margin involvement after extended (D2/D3) gastrectomy for advanced gastric cancer: a 15-year experience at a single institute. J Surg Oncol. 2007;95(6):461–8.

    Article  PubMed  Google Scholar 

  35. Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33:1005.

    Article  CAS  PubMed  Google Scholar 

  36. Aurello P, Sirimarco D, Magistri P, et al. Management of duodenal stump fistula after gastrectomy for gastric cancer: systematic review. World J Gastroenterol. 2015;21(24):7571–6.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

We thank Stephanie Deming, scientific editor, Research Medical Library, for editing this article.

Funding

Supported by the NIH/NCI under award number P30CA016672.

Author information

Authors and Affiliations

  1. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Yuki Hirata MD, PhD, Annamaria Agnes MD, Brian D. Badgwell MD, MS, Paul Mansfield MD & Naruhiko Ikoma MD, MS

  2. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jeannelyn S. Estrella MD

  3. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Mariela Blum Murphy MD & Jaffer A. Ajani MD

  4. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Prajnan Das MD, MS, MPH & Bruce D. Minsky MD

Authors
  1. Yuki Hirata MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annamaria Agnes MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeannelyn S. Estrella MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mariela Blum Murphy MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Prajnan Das MD, MS, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bruce D. Minsky MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jaffer A. Ajani MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Brian D. Badgwell MD, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Paul Mansfield MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Naruhiko Ikoma MD, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Naruhiko Ikoma MD, MS.

Ethics declarations

Disclosure

NI received a research grant from Intuitive Surgical. PD received honoraria from Bayer, ASTRO, ASCO, Conveners LLC, Physicians Education Resource, and Imedex.

Ethical Approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and regional) and with the Helsinki Declaration of 1975, as revised in 1983. Because this was a retrospective study of de-identified patients, no informed consent was required. Ethics approval for this work was obtained.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 111 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hirata, Y., Agnes, A., Estrella, J.S. et al. Clinical Impact of Positive Surgical Margins in Gastric Adenocarcinoma in the Era of Preoperative Therapy. Ann Surg Oncol 30, 4936–4945 (2023). https://doi.org/10.1245/s10434-023-13495-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-023-13495-3

Search

Navigation