Impact of Resection Margin Status in Patients with Pancreatic Cancer: a National Cohort Study

Journal of Gastrointestinal Surgery (2020)Cite this article

Abstract

Aim

To assess the predictors and influence of resection margins and the role of neoadjuvant and adjuvant therapy on survival for a national cohort of patients with resected pancreatic cancer.

Methods

Using the National Cancer Data Base between 2004 and 2016, 56,532 patients were identified who underwent surgical resection for pancreatic adenocarcinoma. Univariate and multivariate models were employed to identify factors predicting R0/R1 resection and assess the impact on survival.

Results

In total, 48,367 (85.6%) patients were found to have negative margins (R0) compared to 8165 (14.4%) who had microscopic residual tumor (R1). Factors predicting positive margin on univariate analysis included male gender, Medicare, advanced stage, moderately or poorly differentiated tumor, lymphovascular invasion, and tumors > 2 cm. Factors predicting R0 resection included receipt of neoadjuvant therapy and treatment at an Academic/Research Center. Following adjustment for other factors, margin status remained an independent predictor for overall survival (HR: 1.24; 95% CI 1.22–1.27, p < 0.001) (1-, 3-, and 5-year overall survival rates (R0: 77%, 37%, and 25% vs R1: 62%, 19%, and 10%).

Conclusions

A positive margin predicts a poorer survival than R0 resections regardless of stage and receipt of adjuvant therapy. Several modifiable factors significantly predict the likelihood of R0 resection including neoadjuvant treatment and treatment at Academic/Research Programs. Knowledge about these factors can help guide patient management by offering neoadjuvant treatment modalities at Academic as well as Community hospitals.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

US$ 39.95

Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. 1.

    Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2020. CA Cancer J Clin 70, 7–30 (2020).

    Article  Google Scholar 

  2. 2.

    Morrison, A. H., Byrne, K. T. & Vonderheide, R. H. Immunotherapy and prevention of pancreatic cancer. Trends Cancer 4, 418–428 (2018).

    CAS  Article  Google Scholar 

  3. 3.

    Tummers, W. S. et al. Impact of resection margin status on recurrence and survival in pancreatic cancer surgery. Br. J. Surg. 106, 1055–1065 (2019).

    CAS  Article  Google Scholar 

  4. 4.

    Survival Rates for Pancreatic Cancer. at <https://www.cancer.org/cancer/pancreatic-cancer/detection-diagnosis-staging/survival-rates.html>

  5. 5.

    Baldwin, S. et al. Pancreatic cancer metastatic to a limited number of lymph nodes has no impact on outcome. HPB (Oxford) 18, 523–528 (2016).

    Article  Google Scholar 

  6. 6.

    Elshaer, M., Gravante, G., Kosmin, M., Riaz, A. & Al-Bahrani, A. A systematic review of the prognostic value of lymph node ratio, number of positive nodes and total nodes examined in pancreatic ductal adenocarcinoma. Ann R Coll Surg Engl 99, 101–106 (2017).

    CAS  Article  Google Scholar 

  7. 7.

    Ansari, D. et al. Relationship between tumour size and outcome in pancreatic ductal adenocarcinoma. Br. J. Surg. 104, 600–607 (2017).

    CAS  Article  Google Scholar 

  8. 8.

    Bilici, A. Prognostic factors related with survival in patients with pancreatic adenocarcinoma. World J. Gastroenterol. 20, 10802–10812 (2014).

    Article  Google Scholar 

  9. 9.

    Motoi, F. & Unno, M. Adjuvant and neoadjuvant treatment for pancreatic adenocarcinoma. Jpn. J. Clin. Oncol. (2020). doi:https://doi.org/10.1093/jjco/hyaa018

  10. 10.

    Ghaneh, P. et al. The impact of positive resection margins on survival and recurrence following resection and adjuvant chemotherapy for pancreatic ductal adenocarcinoma. Ann. Surg. 269, 520–529 (2019).

    Article  Google Scholar 

  11. 11.

    Acher, A. W., Bleicher, J., Cannon, A. & Scaife, C. Advances in surgery for pancreatic cancer. J. Gastrointest. Oncol. 9, 1037–1043 (2018).

    Article  Google Scholar 

  12. 12.

    Ocaña, J. et al. Relevance of positive resection margins in ductal pancreatic adenocarcinoma and prognostic factors. Cir Esp 98, 85–91 (2020).

    Article  Google Scholar 

  13. 13.

    Gnerlich, J. L. et al. Microscopic margins and patterns of treatment failure in resected pancreatic adenocarcinoma. Arch. Surg. 147, 753–760 (2012).

    Article  Google Scholar 

  14. 14.

    Verbeke, C. S. & Menon, K. V. Redefining resection margin status in pancreatic cancer. HPB (Oxford) 11, 282–289 (2009).

    Article  Google Scholar 

  15. 15.

    Seufferlein, T. & Ettrich, T. J. Treatment of pancreatic cancer-neoadjuvant treatment in resectable pancreatic cancer (PDAC). Transl. Gastroenterol. Hepatol. 4, 21 (2019).

    Article  Google Scholar 

  16. 16.

    Fenocchio, E. et al. Is there a standard adjuvant therapy for resected pancreatic cancer?. Cancers (Basel) 11, (2019).

  17. 17.

    Lambert, A. et al. An update on treatment options for pancreatic adenocarcinoma. Ther Adv Med Oncol 11, 1758835919875568 (2019).

    Article  Google Scholar 

  18. 18.

    Russo, S., Ammori, J., Eads, J. & Dorth, J. The role of neoadjuvant therapy in pancreatic cancer: a review. Future Oncol 12, 669–685 (2016).

    CAS  Article  Google Scholar 

  19. 19.

    Motoi, F. et al. Randomized phase II/III trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05). Jpn. J. Clin. Oncol. 49, 190–194 (2019).

    Article  Google Scholar 

  20. 20.

    Datta, S. K. et al. Survival outcomes between surgery with adjuvant therapy compared to neoadjuvant therapy with surgery in stage I pancreatic adenocarcinoma: Results from a large national cancer database. J. Clin. Oncol. 37, 335–335 (2019).

    Article  Google Scholar 

  21. 21.

    White, M. G. et al. A tale of two cancers: traveling to treat pancreatic and thyroid cancer. J. Am. Coll. Surg. 225, 125–136.e6 (2017).

    Article  Google Scholar 

  22. 22.

    Søreide, J. A., Sandvik, O. M. & Søreide, K. Improving pancreas surgery over time: Performance factors related to transition of care and patient volume. Int J Surg 32, 116–122 (2016).

    Article  Google Scholar 

  23. 23.

    Raoof, M. et al. Centralization of pancreatic cancer surgery: travel distances and disparities. J. Am. Coll. Surg. 223, e166 (2016).

    Article  Google Scholar 

  24. 24.

    Fong, Y., Gonen, M., Rubin, D., Radzyner, M. & Brennan, M. F. Long-term survival is superior after resection for cancer in high-volume centers. Ann. Surg. 242, 540–4; discussion 544 (2005).

    PubMed  PubMed Central  Google Scholar 

  25. 25.

    Strobel, O. et al. Pancreatic Cancer Surgery: The New R-status Counts. Ann. Surg. 265, 565–573 (2017).

    Article  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Surgery, University of Pittsburgh, 3459 Fifth Avenue, UPMC Montefiore, 7 South, Pittsburgh, PA, 15213-2582, USA

    Christof Kaltenmeier, Ibrahim Nassour, Richard S. Hoehn, Sidrah Khan, Alison Althans, David A. Geller, Alessandro Paniccia, Amer Zureikat & Samer Tohme

Authors
  1. Christof Kaltenmeier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ibrahim Nassour
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Richard S. Hoehn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sidrah Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alison Althans
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David A. Geller
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alessandro Paniccia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Amer Zureikat
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Samer Tohme
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Christof Kaltenmeier: data gathering, analysis, manuscript writing

Ibrahim Nassour: data gathering, manuscript editing

Richard S Hoehn: manuscript editing

Sidrah Khan: data gathering

Alison Althans: data gathering, manuscript editing

David A Geller: manuscript editing

Alessandro Paniccia: writing manuscript, editing

Amer Zureikat: editing manuscript

Samer Tohme: data gathering, analysis, writing manuscript

Corresponding author

Correspondence to Samer Tohme.

Ethics declarations

Conflict of interest statement

All authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. The University of Pittsburgh holds a Physician-Scientist Institutional Award from the Burroughs Wellcome Fund: C.K. S.K.

Additional information

Publisher’s Note

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kaltenmeier, C., Nassour, I., Hoehn, R.S. et al. Impact of Resection Margin Status in Patients with Pancreatic Cancer: a National Cohort Study. J Gastrointest Surg (2020). https://doi.org/10.1007/s11605-020-04870-6

Download citation

Keywords

  • Margin status
  • survival
  • predictors of R1 resection
  • pancreatic cancer