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Adjuvant Therapy After Liver Resection for Colorectal Cancer Metastasis: What is the Evidence?

  • Published:
Current Colorectal Cancer Reports

Abstract

Synchronous or metachronous liver metastases of colorectal origin (colorectal liver metastases, CLM), although being the expression of systemic disease, allow a curative approach for about 25% to 35% of patients. Patients presenting with CLM should receive a multimodal management in order to increase the number of patients undergoing R0 surgery and to decrease the rate of recurrence. Current data do not allow to recommend the use of locally applied chemotherapy using hepatic artery infusion after resection of CLM. Postoperative and/or preoperative systemic chemotherapy shows a trend toward a benefit regarding progression-free and overall survival, without increasing postoperative complication rates. However, all available trials failed to show a statistical significance, so that a “formal” treatment standard is not accepted and recommendations differ between no treatment and a 5-FU/oxaliplatin combination to be considered as standard of care. Future research will help in defining treatment regimens and patients selection criteria to obtain a better approach in this setting.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Boyle P, Ferlay J. Cancer incidence and mortality in Europe, 2004. Ann Oncol. 2005;16(3):481–8.

    Article  PubMed  CAS  Google Scholar 

  2. Weiss L, Grundmann E, Torhorst J, et al. Haematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies. J Pathol. 1986;150(3):195–203.

    Article  PubMed  CAS  Google Scholar 

  3. Weber SM, Jarnagin WR, DeMatteo RP, et al. Survival after resection of multiple hepatic colorectal metastases. Ann Surg Oncol. 2000;7(9):643–50.

    Article  PubMed  CAS  Google Scholar 

  4. Choti MA, Sitzmann JV, Tiburi MF, et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg. 2002;235(6):759–66.

    Article  PubMed  Google Scholar 

  5. Tomlinson JS, Jarnagin WR, DeMatteo RP, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25(29):4575–80.

    Article  PubMed  Google Scholar 

  6. Scheele J, Stang R, Altendorf-Hofmann A, Paul M. Resection of colorectal liver metastases. World J Surg. 1995;19(1):59–71.

    Article  PubMed  CAS  Google Scholar 

  7. Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230(3):309–18. discussion 318-21.

    Article  PubMed  CAS  Google Scholar 

  8. de Jong MC, Pulitano C, Ribero D, et al. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009;250(3):440–8.

    PubMed  Google Scholar 

  9. Hughes KS, Simon R, Songhorabodi S, et al. Resection of the liver for colorectal carcinoma metastases: a multi-institutional study of patterns of recurrence. Surgery. 1986;100(2):278–84.

    PubMed  CAS  Google Scholar 

  10. Merkel S, Bialecki D, Meyer T, et al. Comparison of clinical risk scores predicting prognosis after resection of colorectal liver metastases. J Surg Oncol. 2009;100(5):349–57.

    Article  PubMed  Google Scholar 

  11. Nagashima I, Takada T, Nagawa H, et al. Proposal of a new and simple staging system of colorectal liver metastasis. World J Gastroenterol. 2006;12(43):6961–5.

    PubMed  Google Scholar 

  12. • Poston GJ, Figueras J, Giuliante F, et al. Urgent need for a new staging system in advanced colorectal cancer. J Clin Oncol. 2008;26(29):4828–33. Relevant manuscript defining the need for a new staging system in CRC metastases.

    Article  PubMed  Google Scholar 

  13. Van Cutsem E, Nordlinger B, Adam R, et al. Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer. 2006;42(14):2212–21.

    Article  PubMed  Google Scholar 

  14. Yamaguchi T, Mori T, Takahashi K, et al. A new classification system for liver metastases from colorectal cancer in Japanese multicenter analysis. Hepatogastroenterology. 2008;55(81):173–8.

    PubMed  Google Scholar 

  15. • Nordlinger B, Van Cutsem E, Gruenberger T, et al. Combination of surgery and chemotherapy and the role of targeted agents in the treatment of patients with colorectal liver metastases: recommendations from an expert panel. Ann Oncol. 2009;20(6):985–92. Comprehensive review of perioperative CLM treatment, with a focus on "conversion" treatment.

    Article  PubMed  CAS  Google Scholar 

  16. •• Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008;371(9617):1007–16. To date, the only completed trial for a perioperative treatment in CLM. However, due to the distinct subgroup analysis, it is still a matter of discussion.

    Article  PubMed  CAS  Google Scholar 

  17. Portier G, Elias D, Bouche O, et al. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol. 2006;24(31):4976–82.

    Article  PubMed  CAS  Google Scholar 

  18. Langer B, Bleiberg H, Labianca R, et al. Fluorouracil (FU) plus l-leucovorin (l-LV) versus observation after potentially curative resection of liver or lung metastases from colorectal cancer (CRC): results of the ENG (EORTC/NCIC CTG/GIVIO) randomized trial. Proc Am Soc Clin Oncol. 2002;21:592 (abstr).

  19. • Mitry E, Fields AL, Bleiberg H, et al. Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol. 2008;26(30):4906–11. Combined analysis of the two prematurely closed trials in adjuvant treatment.

    Article  PubMed  CAS  Google Scholar 

  20. Ychou M, Hohenberger W, Thezenas S, et al. A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acid with FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. Ann Oncol. 2009;20(12):1964–70.

    Article  PubMed  CAS  Google Scholar 

  21. Van Cutsem E, Labianca R, Bodoky G, et al. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol. 2009;27(19):3117–25.

    Article  PubMed  Google Scholar 

  22. Parks R, Gonen M, Kemeny N, et al. Adjuvant chemotherapy improves survival after resection of hepatic colorectal metastases: analysis of data from two continents. J Am Coll Surg. 2007;204(5):753–61. discussion 761-3.

    Article  PubMed  Google Scholar 

  23. Lorenz M, Muller HH, Schramm H, et al. Interim analysis of a prospective, randomized multi-center study by the "Liver Metastases" Study Group: adjuvant intra-arterial chemotherapy after curative liver resection of colorectal metastases. Langenbecks Arch Chir Suppl Kongressbd. 1998;115(Suppl I):523–8.

    PubMed  CAS  Google Scholar 

  24. Kemeny MM, Adak S, Gray B, et al. Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy–an intergroup study. J Clin Oncol. 2002;20(6):1499–505.

    Article  PubMed  Google Scholar 

  25. Kemeny N, Huang Y, Cohen AM, et al. Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med. 1999;341(27):2039–48.

    Article  PubMed  CAS  Google Scholar 

  26. Kemeny NE, Niedzwiecki D, Hollis DR, et al. Final analysis of hepatic arterial infusion (HAI) versus systemic therapy for hepatic metastases from colorectal cancer; a CALGB randomized trial of efficacy, quality of life (QOL), cost effectiveness, and molecular markers. Proceedings from the Gastrointestinal Cancer Symposium. 2005; Abstract 183.

  27. Tono T, Hasuike Y, Ohzato H, et al. Limited but definite efficacy of prophylactic hepatic arterial infusion chemotherapy after curative resection of colorectal liver metastases: a randomized study. Cancer. 2000;88(7):1549–56.

    Article  PubMed  CAS  Google Scholar 

  28. Wagman LD, Kemeny MM, Leong L, et al. A prospective, randomized evaluation of the treatment of colorectal cancer metastatic to the liver. J Clin Oncol. 1990;8(11):1885–93.

    PubMed  CAS  Google Scholar 

  29. Rudroff C, Altendorf-Hoffmann A, Stangl R, Scheele J. Prospective randomised trial on adjuvant hepatic-artery infusion chemotherapy after R0 resection of colorectal liver metastases. Langenbecks Arch Surg. 1999;384(3):243–9.

    Article  PubMed  CAS  Google Scholar 

  30. Lygidakis NJ, Ziras N, Parissis J. Resection versus resection combined with adjuvant pre- and post-operative chemotherapy–immunotherapy for metastatic colorectal liver cancer. A new look at an old problem Hepatogastroenterology. 1995;42(2):155–61.

    CAS  Google Scholar 

  31. Nelson R, Freels S. Hepatic artery adjuvant chemotherapy for patients having resection or ablation of colorectal cancer metastatic to the liver. Cochrane Database Syst Rev. 2006;(4): CD003770.

  32. • Wieser M, Sauerland S, Arnold D, et al. Peri-operative chemotherapy for the treatment of resectable liver metastases from colorectal cancer: a systematic review and meta-analysis of randomized trials. BMC Cancer. 2010;10(1):309. New meta-analysis also including the most recent results of perioperative modalities.

  33. Kemeny NE, Jarnagin WR. A randomized phase II trial of adjuvant hepatic arterial infusion and systemic chemotherapy with or without bevacizumab in patients with resected hepatic metastases from colorectal cancer. J Clin Oncol. 2010;28 Suppl 7:3557 (abstr).

    Google Scholar 

  34. Power DG, Capanu M. Unexpected increased biliary toxicity when systemic bevacizumab is added to hepatic arterial infusion. J Clin Oncol. 2010;28 Suppl 7:3559 (abstr).

    Google Scholar 

  35. Tol J, Koopman M, Cats A, et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. N Engl J Med. 2009;360(6):563–72.

    Article  PubMed  CAS  Google Scholar 

  36. Gruenberger B, Tamandl D, Schueller J, et al. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol. 2008;26(11):1830–5.

    Article  PubMed  CAS  Google Scholar 

  37. Schmiegel W, Pox C, Arnold D, et al. Colorectal carcinoma: the management of polyps, (neo)adjuvant therapy, and the treatment of metastases. Dtsch Arztebl Int. 2009;106(51–52):843–8.

    PubMed  Google Scholar 

  38. De Gramont A, Van Cutsem E. AVANT: Results from a randomized, three-arm multinational phase III study to investigate bevacizumab with either XELOX or FOLFOX4 versus FOLFOX4 alone as adjuvant treatment for colon cancer. J Clin Oncol. 2011;29 Suppl 4:362 (abstr).

    Google Scholar 

  39. Allegra CJ, Yothers G, O'Connell MJ, et al. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol. 2011;29(1):11–6.

    Article  PubMed  CAS  Google Scholar 

  40. Alberts SR, Sargent D. Adjuvant mFOLFOX6 with or without cetuxiumab (Cmab) in KRAS wild-type (WT) patients (pts) with resected stage III colon cancer (CC): results from NCCTG Intergroup Phase III Trial N0147. J Clin Oncol. 2010;28 Suppl 18: CRA3507.

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Disclosure

D. Arnold: honoraria from Roche, Sanofi-Aventis, Merck Serono, and Amgen, and research support from Roche and Sanofi-Aventis; A. Stein: none.

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  1. Hubertus Wald Tumor Center, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    Dirk Arnold & Alexander Stein

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  1. Dirk Arnold
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  2. Alexander Stein
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Correspondence to Dirk Arnold.

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Arnold, D., Stein, A. Adjuvant Therapy After Liver Resection for Colorectal Cancer Metastasis: What is the Evidence?. Curr Colorectal Cancer Rep 7, 180–186 (2011). https://doi.org/10.1007/s11888-011-0096-z

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  • DOI: https://doi.org/10.1007/s11888-011-0096-z

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