Skip to main content

Advertisement

SpringerLink
Log in

Impact of Preoperative CEA Uptrend on Survival Outcomes in Patients with Colorectal Liver Metastasis After Hepatectomy

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

Abstract

Background

Preoperative carcinoembryonic antigen (CEA) has been reported as a prognostic factor in patients with colorectal liver metastasis (CRLM) after hepatectomy. However, the impact of a preoperative “CEA uptrend” on prognosis after hepatectomy in these patients remains unknown. This study assessed the impact of CEA uptrend on prognosis in patients undergoing hepatectomy for CRLM.

Methods

Consecutive patients with CRLM who underwent hepatectomy between 2009 and 2018 were retrospectively analyzed. Patients with CRLM for whom CEA was measured both around 1 month before (CEA-1m) and within 3 days (CEA-3d) before hepatectomy were enrolled. A CEA-3d higher than both the upper limit of normal (5 ng/ml) and CEA-1m was defined as a CEA uptrend.

Results

Study participants comprised 212 patients with CRLM. Of these, 88 patients (41.5%) showed a CEA uptrend. CEA uptrend indicated better discriminatory ability (corrected Akaike information criteria, 733.72) and homogeneity (likelihood ratio chi-square value, 18.80) than CEA-3d or CEA-1m. Patients with CEA uptrend showed poorer overall survival than those without CEA uptrend (p < 0.001). After adjusting for known prognostic factors, the prognostic significance of CEA uptrend retained (hazard ratio 2.63, 95% confidence interval 1.63–4.26, p < 0.001). In subgroup analyses, the prognostic significance of CEA uptrend was retained irrespective of the status of RAS mutation or response to preoperative chemotherapy.

Conclusions

CEA uptrend offers better prediction of survival outcomes than conventional CEA measurements in patients undergoing hepatectomy for CRLM.

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
Fig. 3

Similar content being viewed by others

References

  1. Brennaer H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383(9927):1490–502.

    Article  Google Scholar 

  2. Engstrand J, Nilsson H, Strömberg C, et al. Colorectal cancer liver metastases: A population-based study on incidence, management and survival. BMC Cancer. 2018;18(1):78. https://doi.org/10.1186/s12885-017-3925-x.

    Article  PubMed  PubMed Central  Google Scholar 

  3. House MG, Ito H, Gonen M, et al. Survival after hepatic resection for metastatic colorectal cancer: trends in outcomes for 1,600 patients during two decades at a single institution. J Am Coll Surg. 2010;210(5):744–52.

    Article  Google Scholar 

  4. Sakamoto K, Honda G, Beppu T, et al. Comprehensive data of 3,820 patients newly diagnosed with colorectal liver metastasis between 2005 and 2007: report of a nationwide survey in Japan. J Hepatobiliary Pancreat Sci. 2018;25(2):115–23.

    Article  Google Scholar 

  5. Locker GY, Hamilton S, Harris J, et al. ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. J Clin Oncol. 2006;24(33):5313–27.

    Article  CAS  Google Scholar 

  6. Labianca R, Nordlinger B, Beretta GD, et al. Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(6):64–72.

    Article  Google Scholar 

  7. Duffy MJ, Lamerz R, Haglund C, et al. Tumor makers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update. Int J Cancer. 2014;134(11):2513–22.

    Article  CAS  Google Scholar 

  8. Araujo RL, Gönen M, Allen P, et al. Positive postoperative CEA is a strong predictor of recurrence for patients after resection for colorectal liver metastases. Ann Surg Oncol. 2015;22(9):3087–93. https://doi.org/10.1245/s10434-014-4358-2.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Neofytou K, Giakoustidis A, Neves MC, et al. Increased carcinoembryonic antigen (CEA) following neoadjuvant chemotherapy predicts poor prognosis in patients that undergo hepatectomy for liver-only colorectal metastases. Langenbecks Arch Surg. 2017;402(4):599–605.

    Article  Google Scholar 

  10. John SK, Robinson SM, Rehman S, et al. Prognostic factors and survival after resection of colorectal liver metastasis in the era of preoperative chemotherapy: an 11-year single-centre study. Dig Surg. 2013;30(4–6):293–301.

    Article  CAS  Google Scholar 

  11. Sakamoto Y, Miyamoto Y, Beppu T, et al. Post-chemotherapeutic CEA and CA19-9 are prognostic factors in patients with colorectal liver metastases treated with hepatic resection after oxaliplatin-based chemotherapy. Anticancer Res. 2015;35(4):2359–68.

    CAS  PubMed  Google Scholar 

  12. Okazaki S, Baba H, Iwata N, et al. Carcinoembryonic antigen testing after curative liver resection for synchronous liver metastasis of colorectal cancer: a Japanese multicenter analysis. Surg Today. 2017;47(10):1223–9.

    Article  CAS  Google Scholar 

  13. Bredt LC, Rachid AF. Predictors of recurrence after a first hepatectomy for colorectal cancer liver metastases: a retrospective analysis. World J Surg Oncol. 2014. https://doi.org/10.1186/1477-7819-12-391.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Nagai Y, Beppu T, Sakamoto Y, et al. Carcinoembryonic antigen half-life is an early predictor of therapeutic effects in induction chemotherapy for liver metastases from colorectal cancer. Anticancer Res. 2014;34(10):5529–35.

    CAS  PubMed  Google Scholar 

  15. Vauthey JN, Zimmitti G, Kopetz SE, et al. RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg. 2013;258(4):619–26.

    Article  Google Scholar 

  16. Misale S, Yaeger R, Hobor S, et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2015;486(7404):532–6.

    Article  Google Scholar 

  17. Gagnière J, Dupré A, Gholami SS, et al. Is hepatectomy justified for BRAF mutant colorectal lover metastases?: A multi-institutional analysis of 1497 patients. Ann Surg. 2020;271(1):147–54.

    Article  Google Scholar 

  18. Liu W, Zhang W, Xu Y, et al. A prognostic scoring system to predict survival outcome of resectable colorectal liver metastases in this modern era. Ann Surg Oncol. 2021;28(12):7709–18. https://doi.org/10.1245/s10434-021-10143-6.

    Article  PubMed  Google Scholar 

  19. Okuno M, Goumard C, Kopetz S, et al. RAS mutation is associated with unsalvageable recurrence following hepatectomy for colorectal cancer liver metastases. Ann Surg Oncol. 2018;25(8):2457–66. https://doi.org/10.1245/s10434-018-6517-3.

    Article  PubMed  Google Scholar 

  20. Tsilimigras DI, Ntanasis-Stathopoulos I, Bagante F, et al. Clinical significance and prognostic relevance of KRAS, BRAF, PI3K and TP53 genetic mutation analysis for resectable and unresectable colorectal liver metastases: a systematic review of the current evidence. Surg Oncol. 2018;27(2):280–8.

    Article  Google Scholar 

  21. Gau L, Ribeiro M, Pereira B, et al. Impact of BRAF mutations on clinical outcomes following liver surgery for colorectal liver metastases: an updated meta-analysis. Eur J Surg Oncol. 2021. https://doi.org/10.1016/j.ejso.2021.05.039.

    Article  PubMed  Google Scholar 

  22. Dijkstra M, Nieuwenhuizen S, Puijk RS, et al. Primary tumor sidedness, RAS and BRAF mutations and MSI status as prognostic factors in patients with colorectal liver metastases treated with surgery and thermal ablation: results from the Amsterdam Colorectal Liver Met Registry (AmCORE). Biomedicines. 2021;9(8): https://doi.org/10.3390/biomedicines9080962

  23. Wanebo HJ, Rao B, Pinsky CM, et al. Preoperative carcinoembryonic antigen level as a prognostic indicator in colorectal cancer. N Engl J Med. 1978;299(9):448–51.

    Article  CAS  Google Scholar 

  24. Clinical practice guidelines for the use of tumor makers in breast and colorectal cancer. Adopted on May, 17, 1996 by the American Society of Clinical Oncology. J Clin Oncol. 1996;14(10):2843-77.

  25. Weiser MR. AJCC 8th edition: colorectal cancer. Ann Surg Oncol. 2018;25(6):1454–5. https://doi.org/10.1245/s10434-018-6462-1.

    Article  PubMed  Google Scholar 

  26. Clavien PA, Barkun J, Oliveira ML, et al. The Clavien-Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250(2):187–96.

    Article  Google Scholar 

  27. Hashiguchi Y, Muro K, Saito Y, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2020;25(1):1–42.

    Article  Google Scholar 

  28. Couinald C. The anatomy of the liver. Ann Ital Chir. 1992;63(6):693–7.

    Google Scholar 

  29. Gehan EA. A generalized Wilcoxon test for comparing arbitrarily singly-censored samples. Biometrika. 1965;52:203–23.

    Article  CAS  Google Scholar 

  30. Yoh T, Seo S, Hatano E, et al. A novel biomarker-based preoperative prognostic grading system for predicting survival after surgery for intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2017;24(5):1351–7. https://doi.org/10.1245/s10434-016-5708-z.

    Article  PubMed  Google Scholar 

  31. Yoh T, Seo S, Ogiso S, et al. Proposal of a New Preoperative Prognostic Model for Solitary Hepatocellular Carcinoma Incorporating 18F-FDG-PET Imaging with the ALBI Grade. Ann Surg Oncol. 2018;25(2):542–9. https://doi.org/10.1245/s10434-017-6262-z.

    Article  PubMed  Google Scholar 

  32. Yamamoto H, Murata K, Fukunaga M, et al. Micrometastasis volume in lymph nodes determines disease recurrence rate of stage II colorectal cancer: a prospective multicenter trial. Clin Cancer Res. 2016;22(13):3201–8.

    Article  CAS  Google Scholar 

  33. Huang SC, Lin JK, Lin TC, et al. Concordance of carcinoembryonic antigen ratio and response evaluation criteria in solid tumors as prognostic surrogate indicators of metastatic colorectal cancer patients treated with chemotherapy. Ann Surg Oncol. 2015;22(7):2262–8. https://doi.org/10.1245/s10434-014-4228-y.

    Article  PubMed  Google Scholar 

  34. Saito G, Sadahiro S, Okada K, et al. Relation between carcinoembryonic antigen levels in colon cancer tissue and serum carcinoembryonic antigen levels at initial surgery and recurrence. Oncology. 2016;91(2):85–9.

    Article  CAS  Google Scholar 

  35. Pilati P, Mocellin S, Bertazza L, et al. Prognostic value of putative circulating cancer stem cells in patients undergoing hepatic resection for colorectal liver metastasis. Ann Surg Oncol. 2012;19(2):402–8. https://doi.org/10.1245/s10434-011-2132-2.

    Article  PubMed  Google Scholar 

  36. Hatano E, Okuno M, Nakamura K, et al. Conversion to complete resection with mFOLFOX6 with bevacizumab or cetuximab based on K-ras status for unresectable colorectal liver metastasis (BECK study). J Hepatobiliary Pancreat Sci. 2015;22(8):634–45.

    Article  Google Scholar 

  37. Okuno M, Hatano E, Toda R, et al. Conversion to complete resection with mFOLFOX6 with bevacizumab or cetuximab based on K-RAS status for unresectable colorectal liver metastasis (BECK study): long-term results of survival. J Hepatobiliary Pancreat Sci. 2020;27(8):496–509.

    Article  Google Scholar 

  38. Schnitzbauer AA, Lang SA, Goessmann H, et al. Right portal vein ligation combined with in situ splitting induces rapid left lateral liber lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size setting. Ann Surg. 2012;255(3):405–14.

    Article  Google Scholar 

  39. Tsilimigras DI, Ntanasis-Stathopoulos I, Bagante F, et al. Clinical significance and prognostic relevance of KRAS, BRAF, PI3K and TP53 genetic mutation analysis for resectable and unresectable colorectal liver metastasis: A systematic review of the current evidence. Surg Oncol. 2018;27(2):280–8.

    Article  Google Scholar 

  40. Kawaguchi Y, Kopetz S, Newhook TE, et al. Mutation status of RAS, TP53, and SMAD4 is superior to mutation status of RAS alone for predicting prognosis after resection of colorectal liver metastases. Clin Cancer Res. 2019;25(19):5843–51.

    Article  CAS  Google Scholar 

  41. Mizuno T, Cloyd JM, Vicente D, et al. SMAD4 gene mutation predicts poor prognosis in patients undergoing resection for colorectal liver metastases. Eur J Surg Oncol. 2018;44(5):684–92.

    Article  Google Scholar 

Download references

Funding

No financial support was received with respect to this manuscript.

Author information

Authors and Affiliations

  1. Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Yutaro Hori MD, Satoru Seo MD, PhD, Tomoaki Yoh MD, PhD, Koshiro Morino MD, PhD, Rei Toda MD, Takahiro Nishio MD, PhD, Yukinori Koyama MD, PhD, Ken Fukumitsu MD, PhD, Takamichi Ishii MD, PhD, Koichiro Hata MD, PhD, Toshihiko Masui MD, PhD, Kojiro Taura MD, PhD & Etsuro Hatano MD, PhD

  2. Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Kentaro Ueno MS

Authors
  1. Yutaro Hori MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Satoru Seo MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tomoaki Yoh MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kentaro Ueno MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Koshiro Morino MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rei Toda MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takahiro Nishio MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yukinori Koyama MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ken Fukumitsu MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Takamichi Ishii MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Koichiro Hata MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Toshihiko Masui MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kojiro Taura MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Etsuro Hatano MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Satoru Seo MD, PhD.

Ethics declarations

Disclosure

The authors who have taken part in this study declare that they do not have anything to disclose regarding funding or conflicts of interest with respect to this manuscript.

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 55 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hori, Y., Seo, S., Yoh, T. et al. Impact of Preoperative CEA Uptrend on Survival Outcomes in Patients with Colorectal Liver Metastasis After Hepatectomy. Ann Surg Oncol 29, 6745–6754 (2022). https://doi.org/10.1245/s10434-022-11973-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-022-11973-8

Search

Navigation