Skip to main content

Advertisement

SpringerLink
Log in

Circulating Tumor Cells and Prognosis of Patients with Resectable Colorectal Liver Metastases or Widespread Metastatic Colorectal Cancer: A Meta-Analysis

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

Abstract

Background

We performed a systematic review and meta-analysis to investigate the prognostic value of tumor cells in blood (circulating tumor cells [CTCs]) or bone marrow (BM) (disseminated tumor cells) of patients with resectable colorectal liver metastases or widespread metastatic colorectal cancer (CRC).

Materials and Methods

The following databases were searched in May 2011: MEDLINE, EMBASE, Science Citation Index, BIOSIS, Cochrane Library. Studies that investigated the association between tumor cells in blood or BM and long-term outcome in patients with metastatic CRC were included. We extracted hazard ratios (HRs) and confidence intervals (CIs) from the included studies and performed random-effects meta-analyses for survival outcomes.

Results

The literature search yielded 16 studies representing 1,491 patients. The results of 12 studies representing 1,329 patients were suitable for pooled analysis. The overall survival (HR, 2.47; 95 % CI 1.74–3.51) and progression-free survival (PFS) (HR, 2.07; 95 % CI 1.44–2.98) were worse in patients with CTCs. The subgroup of studies with more than 35 % CTC-positive patients was the only subgroup with a statistically significant worse PFS. All eight studies that performed multivariable analysis identified the detection of CTCs as an independent prognostic factor for survival.

Conclusion

The detection of CTCs in peripheral blood of patients with resectable colorectal liver metastases or widespread metastatic CRC is associated with disease progression and poor survival.

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

References

  1. Globocan Project. http://globocan.iarc.fr/factsheets/populations/factsheet.asp?uno=900#BOTH (2008). Accessed 5 May 2012.

  2. Chaffer CL, Weinberg RA. A perspective on cancer cell metastasis. Science. 2011;331:1559–64.

    Article  PubMed  CAS  Google Scholar 

  3. Arnold D, Seufferlein T. Targeted treatments in colorectal cancer: state of the art and future perspectives. Gut. 2010;59:838–58.

    Article  PubMed  CAS  Google Scholar 

  4. de Haas RJ, Wicherts DA, Andreani P, Pascal G, Saliba F, Ichai P, et al. Impact of expanding criteria for resectability of colorectal metastases on short- and long-term outcomes after hepatic resection. Ann Surg. 2011;253:1069–79.

    Article  PubMed  Google Scholar 

  5. Rahbari NN, Aigner M, Thorlund K, Mollberg N, Motschall E, Jensen K, et al. Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer. Gastroenterology. 2010;138:1714–26.

    Article  PubMed  Google Scholar 

  6. Cohen SJ, Punt CJ, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY, et al. Prognostic significance of circulating tumor cells in patients with metastatic colorectal cancer. Ann Oncol. 2009;20:1223–9.

    Article  PubMed  CAS  Google Scholar 

  7. Vlems FA, Diepstra JH, Punt CJ, Ligtenberg MJ, Cornelissen IM, van Krieken JH, et al. Detection of disseminated tumour cells in blood and bone marrow samples of patients undergoing hepatic resection for metastasis of colorectal cancer. Br J Surg. 2003;90:989–95.

    Article  PubMed  CAS  Google Scholar 

  8. Schoppmeyer K, Fruhauf N, Oldhafer K, Seeber S, Kasimir-Bauer S. Tumor cell dissemination in colon cancer does not predict extrahepatic recurrence in patients undergoing surgery for hepatic metastases. Oncol Rep. 2006;15:449–54.

    PubMed  CAS  Google Scholar 

  9. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6:e1000100.

    Article  PubMed  Google Scholar 

  10. Cohen SJ, Alpaugh RK, Gross S, O’Hara SM, Smirnov DA, Terstappen LW, et. al. Isolation and characterization of circulating tumor cells in patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2006;6:125–32.

    Article  PubMed  CAS  Google Scholar 

  11. Gazzaniga P, Gradilone A, Petracca A, Nicolazzo C, Raimondi C, Iacovelli R, et al. Molecular markers in circulating tumour cells from metastatic colorectal cancer patients. J Cell Mol Med. 2010;14:2073–7.

    Article  PubMed  CAS  Google Scholar 

  12. Rahbari NN, Reissfelder C, Muhlbayer M, Weidmann K, Kahlert C, Büchler MW, et al. Correlation of circulating angiogenic factors with circulating tumor cells and disease recurrence in patients undergoing curative resection for colorectal liver metastases. Ann Surg Oncol. 2011;18:2182–91.

    Article  PubMed  Google Scholar 

  13. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.

    Article  PubMed  Google Scholar 

  14. Hiraiwa K, Takeuchi H, Hasegawa H, Saikawa Y, Suda K, Ando T, et al. Clinical significance of circulating tumor cells in blood from patients with gastrointestinal cancers. Ann Surg Oncol. 2008;15:3092–100.

    Article  PubMed  Google Scholar 

  15. Koch M, Kienle P, Hinz U, Antolovic D, Schmidt J, Herfarth C, et al. Detection of hematogenous tumor cell dissemination predicts tumor relapse in patients undergoing surgical resection of colorectal liver metastases. Ann Surg. 2005;241:199–205.

    Article  PubMed  Google Scholar 

  16. Königsberg R, Gneist M, Jahn-Kuch D, Pfeiler G, Hager G, Hudec M, et al. Circulating tumor cells in metastatic colorectal cancer: efficacy and feasibility of different enrichment methods. Cancer Lett. 2010;293:117–23.

    Article  PubMed  Google Scholar 

  17. Matsusaka S, Suenaga M, Mishima Y, Kuniyoshi R, Takagi K, Terui Y, et al. Circulating tumor cells as a surrogate marker for determining response to chemotherapy in Japanese patients with metastatic colorectal cancer. Cancer Sci. 2011;102:1188–92.

    Article  PubMed  CAS  Google Scholar 

  18. Papavasiliou P, Fisher T, Kuhn J, Nemunaitis J, Lamont J. Circulating tumor cells in patients undergoing surgery for hepatic metastases from colorectal cancer. Baylor Univ Med Cent Proc. 2010;23:11–4.

    Google Scholar 

  19. Staritz P, Kienle P, Koch M, Benner A, von Knebel Doeberitz M, Rudi J, et al. Detection of disseminated tumour cells as a potential surrogate-marker for monitoring palliative chemotherapy in colorectal cancer patients. J Exp Clin Cancer Res. 2004;23:633–9.

    PubMed  CAS  Google Scholar 

  20. Tol J, Koopman M, Miller MC, Tibbe A, Cats A, Creemers GJ, et al. Circulating tumour cells early predict progression-free and overall survival in advanced colorectal cancer patients treated with chemotherapy and targeted agents. Ann Oncol. 2010;21:1006–12.

    Article  PubMed  CAS  Google Scholar 

  21. Vogelaar FJ, Mesker WE, Rijken AM, van Pelt GW, van Leeuwen AM, Tanke HJ, et al. Clinical impact of different detection methods for disseminated tumor cells in bone marrow of patients undergoing surgical resection of colorectal liver metastases: a prospective follow-up study. BMC Cancer. 2010;10:153.

    Article  PubMed  Google Scholar 

  22. Wyld DK, Selby P, Perren TJ, Jonas SK, Allen-Mersh TG, Wheeldon J, et al. Detection of colorectal cancer cells in peripheral blood by reverse-transcriptase polymerase chain reaction for cytokeratin 20. Int J Cancer. 1998;79:288–93.

    Article  PubMed  CAS  Google Scholar 

  23. Yen LC, Yeh YS, Chen CW, Wang HM, Tsai HL, Lu CY, et al. Detection of KRAS oncogene in peripheral blood as a predictor of the response to cetuximab plus chemotherapy in patients with metastatic colorectal cancer. Clin Cancer Res. 2009;15:4508–13.

    Article  PubMed  CAS  Google Scholar 

  24. Poston GJ, Figueras J, Giuliante F, Nuzzo G, Sobrero AF, Gigot JF, et. al. Urgent need for a new staging system in advanced colorectal cancer. J Clin Oncol. 2008;26:4828–33.

    Article  PubMed  Google Scholar 

  25. Denlinger CS, Cohen SJ. Progress in the development of prognostic and predictive markers for gastrointestinal malignancies. Curr Treat Options Oncol. 2007;8:339–51.

    Article  PubMed  Google Scholar 

  26. Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, et al. Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature. 2007;450:1235–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by a grant of the Dutch Cancer Society (KWF) (Grant No. UVA 2011 4973).

Disclosure

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Bas Groot Koerkamp MD, PhD

  2. Department of Surgery, University of Heidelberg, Heidelberg, Germany

    Nuh N. Rahbari MD, Markus W. Büchler MD, Moritz Koch MD & Jürgen Weitz MD

Authors
  1. Bas Groot Koerkamp MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nuh N. Rahbari MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Markus W. Büchler MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Moritz Koch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jürgen Weitz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bas Groot Koerkamp MD, PhD.

Additional information

Bas Groot Koerkamp and Nuh N. Rahbari contributed equally to this study.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 315 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Groot Koerkamp, B., Rahbari, N.N., Büchler, M.W. et al. Circulating Tumor Cells and Prognosis of Patients with Resectable Colorectal Liver Metastases or Widespread Metastatic Colorectal Cancer: A Meta-Analysis. Ann Surg Oncol 20, 2156–2165 (2013). https://doi.org/10.1245/s10434-013-2907-8

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-013-2907-8

Keywords

Search

Navigation