Skip to main content

Advertisement

Log in

Timing of Multimodality Therapy for Resectable Synchronous Colorectal Liver Metastases: A Retrospective Multi-Institutional Analysis

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

Abstract

The optimal timing of chemotherapy relative to resection of synchronous colorectal liver metastases (SCRLM) is not known. The objective of this retrospective multi-institutional study was to assess the influence of chemotherapy administered before and after hepatic resection on long-term outcomes among patients with initially resectable SCRLM treated from 1995 to 2005. Clinicopathologic data, treatments, and long-term outcomes from patients with initially resectable SCRLM who underwent partial hepatectomy at three hepatobiliary centers were reviewed. Four hundred ninety-nine consecutive patients underwent resection; 297 (59.5%) and 264 (52.9%) were treated with chemotherapy before and after resection. Chemotherapy strategies included pre-hepatectomy alone (n = 148, 24.7%), post-hepatectomy alone (n = 115, 23.0%), perioperative (n = 149, 29.0%), and no chemotherapy (n = 87, 17.4%). Male gender (p = 0.0029, HR = 1.41 [1.12–1.77]), node-positive primary tumor (p = 0.0046, HR = 1.40 [1.11–1.77]), four or more SCRLM (p = 0.0005, HR = 1.65 [1.24–2.18]), and post-hepatectomy chemotherapy treatment for 6 months or longer (p = 0.039, HR = 0.75 [0.57–0.99]) were associated with recurrence-free survival after discovery of SCRLM. Carcinoembryonic antigen >200 ng/ml (p = 0.0003, HR = 2.33 [1.48–3.69]), extrahepatic metastatic disease (p = 0.0025, HR = 2.34 [1.35–4.05]), four or more SCRLM (p = 0.033, HR = 1.43 [1.03–2.00]), and post-hepatectomy chemotherapy treatment for 2 months or longer (p < 0.0001, HR = 0.59 [0.45–0.76]) were associated with overall survival. Pre-hepatectomy chemotherapy was not associated with recurrence-free or overall survival. Patients treated with perioperative chemotherapy had similar outcomes as patients treated with post-hepatectomy chemotherapy only. We conclude that chemotherapy administered after but not before resection of SCRLM was associated with improved recurrence-free and overall survival. However, prospective randomized trials are needed to determine the optimal timing of chemotherapy.

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

Access this article

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. Abdalla EK, Adam R, Bilchik AJ, et al. Improving respectability of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol. 2006;13:1271–80.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  3. Aloia TA, Vauthey JN, Loyer EM, et al. Solitary colorectal liver metastasis: resection determines outcome. Arch Surg. 2006;141:460–6.

    Article  PubMed  Google Scholar 

  4. Zakaria S, Donohue JH, Que FG, et al. Hepatic resection for colorectal metastases: value of risk scoring systems? Ann Surg. 2007;246:183–91.

    Article  PubMed  Google Scholar 

  5. Pawlik TM, Scoggins CR, Zorzi D, et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection of colorectal metastases. Ann Surg. 2005;241:715–22.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  7. Goldberg RM, Sargent DJ, Morton RF, et al. Randomized controlled trial of reduced-dose bolus fluorouracil plus leucovorin and irinotecan or infused fluorouracil plus leucovorin and oxaliplatin in patients with previously untreated metastatic colorectal cancer: a North American intergroup trial. J Clin Oncol. 2006;24:3347–53.

    Article  PubMed  CAS  Google Scholar 

  8. Tournigand C, Andre T, Achille E, et al. FOLFIRI followed by FOLFOX or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22:229–37.

    Article  PubMed  CAS  Google Scholar 

  9. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.

    Article  PubMed  CAS  Google Scholar 

  10. Portier G, Elias D, Rougier P, et al. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFDCD ACHBTHJ AURC 9002 trial. J Clin Oncol. 2006;24:4976–82.

    Article  PubMed  CAS  Google Scholar 

  11. Nordlinger B, Sorbye H, Glimelius B, et al. Peri-operative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomized controlled trial. Lancet. 2008;371:1007–16.

    Article  PubMed  CAS  Google Scholar 

  12. Minagawa M, Yamamoto Y, Miwa S, et al. Selection criteria for simultaneous resection in patients with synchronous liver metastasis. Arch Surg. 2006;141:1006–12.

    Article  PubMed  Google Scholar 

  13. Strasberg SM. Terminology of liver anatomy and liver resections: coming to grips with hepatic Babel. J Am Coll Surg. 1997;184:413–34.

    PubMed  CAS  Google Scholar 

  14. Reddy SK, Pawlik TM, Zorzi D, et al. Simultaneous resections of colorectal cancer and synchronous liver metastases: a multi-institutional review. Ann Surg Oncol. 2007;14:3481–91.

    Article  PubMed  Google Scholar 

  15. Benzoni E, Lorenzin D, Baccarani U, et al. Resective surgery for liver tumor: a multivariate analysis of causes and risk factors linked to postoperative complications. Hepatobiliary Pancreat Dis Int. 2006;5:526–33.

    PubMed  Google Scholar 

  16. Belghiti J, Hiramatsu K, Benoist S, et al. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg. 2000;191:38–46.

    Article  PubMed  CAS  Google Scholar 

  17. Jarnagin WR, Gonen M, Fong Y, et al. Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade. Ann Surg. 2002;236:397–407.

    Article  PubMed  Google Scholar 

  18. Imamura H, Seyama Y, Kokudo N, et al. One thousand fifty-six hepatectomies without mortality in 8 years. Arch Surg. 2003;138:1198–206.

    Article  PubMed  Google Scholar 

  19. Poon RT, Fan ST, Lo CM, et al. Improving perioperative outcome expands the role of hepatectomy in management of benign and malignant hepatobiliary diseases. Analysis of 1222 consecutive patients from a prospective database. Ann Surg. 2004;240:698–710.

    PubMed  Google Scholar 

  20. Dimick JB, Cowan JA, Knol JA, Upchurch GR. Hepatic resection in the United States: indications, outcomes, and hospital procedural volumes from a nationally representative database. Arch Surg. 2003;138:185–91.

    Article  PubMed  Google Scholar 

  21. Capussotti L, Ferrero A, Vigano L, et al. Bile leakage and liver resection: where is the risk? Arch Surg. 2006;141:690–4.

    Article  PubMed  Google Scholar 

  22. Lyass S, Zamir G, Matot I, et al. Combined colon and hepatic resection for synchronous colorectal liver metastases. J Surg Oncol. 2001;78:17–21.

    Article  PubMed  CAS  Google Scholar 

  23. Vogt P, Raab R, Ringe B, Pichlmayr R. Resection of synchronous liver metastases from colorectal cancer. World J Surg. 1991;15:62–7.

    Article  PubMed  CAS  Google Scholar 

  24. Weber JC, Bachellier P, Oussoultzoglou E, Jaeck D. Simultaneous resection of colorectal primary tumour and synchronous liver metastases. Br J Surg. 2003;90:956–62.

    Article  PubMed  CAS  Google Scholar 

  25. Doko M, Zovak M, Ledinsky M, et al. Safety of simultaneous resections of colorectal cancer and liver metastases. Coll Antropol. 2000;24:381–90.

    PubMed  CAS  Google Scholar 

  26. Tanaka K, Shimada H, Matsuo K, et al. Outcome after simultaneous colorectal and hepatic resection for colorectal cancer with synchronous metastases. Surgery. 2004;136:650–9.

    Article  PubMed  Google Scholar 

  27. Martin R, Paty P, Fong Y, et al. Simultaneous liver and colorectal resections are safe for synchronous colorectal liver metastases. J Am Coll Surg. 2003;197:233–42.

    Article  PubMed  Google Scholar 

  28. Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med. 2005;352:476–87.

    Article  PubMed  CAS  Google Scholar 

  29. Vauthey JN, Pawlik TM, Ribero D, et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol. 2006;24:2065–72.

    Article  PubMed  CAS  Google Scholar 

  30. Fernandez FG, Ritter J, Goodwin JW, et al. Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on respectability of hepatic colorectal metastases. J Am Coll Surg. 2005;200:845–53.

    Article  PubMed  Google Scholar 

  31. Aloia T, Sebagh M, Plasse M, et al. Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases. J Clin Oncol. 2006;24:4983–90.

    Article  PubMed  CAS  Google Scholar 

  32. Rubbia-Brandt L, Audard V, Sartoretti P, Roth AD, Brezault C, Le Charpentier M, et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004;15:460–6.

    Article  PubMed  CAS  Google Scholar 

  33. Pawlik TM, Olino K, Gleisner AL, et al. Preoperative chemotherapy for colorectal liver metastases: impact on hepatic histology and postoperative outcome. J Gastrointest Surg. 2007;11:860–8.

    Article  PubMed  Google Scholar 

  34. Karoui M, Penna C, Amin-Hashem M, et al. Influence of chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg. 2006;243:1–7.

    Article  PubMed  Google Scholar 

  35. Choti MA, Kaloma F, de Oliveira ML, et al. Patient variability in intraoperative ultrasonographic characteristics of colorectal liver metastases. Arch Surg. 2008;143:29–34.

    Article  PubMed  Google Scholar 

  36. Parks R, Gonen M, and 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;204:753–61.

    Article  PubMed  Google Scholar 

  37. Figueras J, Torras J, Valls C, et al. Surgical resection of colorectal liver metastases in patients with expanded indications: a single-center experience with 501 patients. Dis Colon Rectum. 2007;50:478–88.

    Article  PubMed  Google Scholar 

  38. Capussotti L, Vigano L, Ferrero A, et al. Timing of resection of liver metastases synchronous to colorectal tumor: proposal for prognosis-based decisional model. Ann Surg Oncol. 2007;14:1143–50.

    Google Scholar 

  39. Hewes JC, Dighe S, Morris RW, et al. Preoperative chemotherapy and the outcome of liver resection for colorectal metastases. World J Surg. 2007;31:353–64.

    Article  PubMed  CAS  Google Scholar 

  40. Kemeny NE, Capanu M, Huitzil-Melendez F, et al. Is neoadjuvant treatment necessary prior to liver resection in patients with resectable liver metastases from colorectal carcinoma treated with post-resection hepatic arterial infusion plus systemic chemotherapy? J Clin Oncol. 2007;25:abstr 14503.

    Google Scholar 

  41. Adam R, Pascal G, Castaing D, et al. Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? Ann Surg. 2004;240:1052–64.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Srinevas K. Reddy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reddy, S.K., Zorzi, D., Lum, Y.W. et al. Timing of Multimodality Therapy for Resectable Synchronous Colorectal Liver Metastases: A Retrospective Multi-Institutional Analysis. Ann Surg Oncol 16, 1809–1819 (2009). https://doi.org/10.1245/s10434-008-0181-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-008-0181-y

Keywords

Navigation