Advertisement

Resection of colorectal liver metastases after second-line chemotherapy: is it worthwhile? A LiverMetSurvey analysis of 6415 patients

  • Author Footnotes
    1 These authors contributed equally to this work.
    René Adam
    Correspondence
    Corresponding author: Hepatobiliary Center, AP-HP Hôpital Paul Brousse, Université Paris-Sud, Inserm U935, 12 Avenue Paul Vaillant Couturier, 94804 Villejuif, France. Fax: +33 1 45 59 38 57.
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Hepatobiliary Center, AP-HP Hôpital Paul Brousse, Université Paris-Sud, Inserm U935, Villejuif, France
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
    Bin Yi
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Hepatobiliary Center, AP-HP Hôpital Paul Brousse, Université Paris-Sud, Inserm U935, Villejuif, France

    Eastern Hepatobiliary Surgery Hospital/National Liver Cancer Center, Second Military Medical University, Shanghai, China
    Search for articles by this author
  • Author Footnotes
    2 Current address: Cancer Chronotherapy Unit, Cancer Research Centre, Warwick Medical School, Warwick University, Coventry, Warwickshire, UK.
    ,
    Author Footnotes
    3 Current address: Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
    Pasquale F. Innominato
    Footnotes
    2 Current address: Cancer Chronotherapy Unit, Cancer Research Centre, Warwick Medical School, Warwick University, Coventry, Warwickshire, UK.
    3 Current address: Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
    Affiliations
    Department of Oncology, AP-HP Hôpital Paul Brousse, Université Paris-Sud, Inserm U935, Villejuif, France
    Search for articles by this author
  • Eduardo Barroso
    Affiliations
    Department of HPB Surgery and Transplantation, Curry Cabral Hospital, Lisbon, Portugal
    Search for articles by this author
  • Christophe Laurent
    Affiliations
    Department of Digestive Surgery, Hôpital Saint André, Bordeaux, France
    Search for articles by this author
  • Felice Giuliante
    Affiliations
    Hepatobiliary Surgery Unit, Agostino Gemelli Hospital, Catholic University of the Sacred Heart, Rome, Italy
    Search for articles by this author
  • Lorenzo Capussotti
    Affiliations
    Department of HPB and Digestive Surgery, Ospedale Mauriziano Umberto I, Turin, Italy
    Search for articles by this author
  • Réal Lapointe
    Affiliations
    HPB Surgery and Transplantation Unit, Hôpital Saint-Luc, Centre Hospitalier de l'Université de Montréal, Montréal, Canada
    Search for articles by this author
  • Jean-Marc Regimbeau
    Affiliations
    Department of Oncology and Digestive Surgery, CHU Amiens-Picardie, Amiens, France
    Search for articles by this author
  • Santiago Lopez-Ben
    Affiliations
    Hepatobiliary and Pancreatic Surgery Unit, Department of Surgery, Dr. Josep Trueta Hospital, IdlBGi, Girona, Spain
    Search for articles by this author
  • Helena Isoniemi
    Affiliations
    Department of Transplantation and Liver Surgery, Helsinki University Hospital, Helsinki, Finland
    Search for articles by this author
  • Catherine Hubert
    Affiliations
    Unit of HPB Surgery, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
    Search for articles by this author
  • Jen-Kou Lin
    Affiliations
    Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

    School of Medicine, National Yang-Ming University, Taipei, Taiwan
    Search for articles by this author
  • Thomas Gruenberger
    Affiliations
    Department of Surgery, Medical University of Vienna, General Hospital, Vienna, Austria
    Search for articles by this author
  • Dominique Elias
    Affiliations
    Department of Oncologic Surgery, Institut Gustave Roussy, Villejuif, France
    Search for articles by this author
  • Oleg G. Skipenko
    Affiliations
    Research Center of Surgery, Russian Academy of Medical Science, Moscow, Russia
    Search for articles by this author
  • Alfredo Guglielmi
    Affiliations
    Division of Surgery A, Department of Surgery, GB Rossi Hospital, University of Verona, Verona, Italy
    Search for articles by this author
  • theLiverMetSurvey International Contributing Centers
  • Author Footnotes
    1 These authors contributed equally to this work.
    2 Current address: Cancer Chronotherapy Unit, Cancer Research Centre, Warwick Medical School, Warwick University, Coventry, Warwickshire, UK.
    3 Current address: Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Published:April 10, 2017DOI:https://doi.org/10.1016/j.ejca.2017.03.009

      Highlights

      • A heavier tumour burden was found in patients with colorectal liver metastases (CLM) resection after 2nd-line preoperative chemotherapy (PCT).
      • The 49% 5-year overall survival (OS) from CLM diagnosis in this group was similar to that after 1st-line.
      • OS or disease-free survival was comparable for the subsets of initially unresectable of two PCT groups.
      • Surgery of CLM may be proposed to resect CLM ever after 2nd-line chemotherapy.

      Abstract

      Purpose

      Patient outcome after resection of colorectal liver metastases (CLM) following second-line preoperative chemotherapy (PCT) performed for insufficient response or toxicity of the first-line, is little known and has here been compared to the outcome following first-line.

      Patients and methods

      From January 2005 to June 2013, 5624 and 791 consecutive patients of a prospective international cohort received 1 and 2 PCT lines before CLM resection (group 1 and 2, respectively). Survival and prognostic factors were analysed.

      Results

      After a mean follow-up of 30.1 months, there was no difference in survival from CLM diagnosis (median, 3-, and 5-year overall survival [OS]: 58.6 months, 76% and 49% in group 2 versus 58.9 months, 71% and 49% in group 1, respectively, P = 0.32). After hepatectomy, disease-free survival (DFS) was however shorter in group 2: 17.2 months, 27% and 15% versus 19.4 months, 32% and 23%, respectively (P = 0.001). Among the initially unresectable patients of group 1 and 2, no statistical difference in OS or DFS was observed. Independent predictors of worse OS in group 2 were positive primary lymph nodes, extrahepatic disease, tumour progression on second line, R2 resection and number of hepatectomies/year <50. Positive primary nodes, synchronous and bilateral metastases were predictors of shorter DFS. Initial unresectability did not impact OS or DFS in group 2.

      Conclusion

      CLM resection following second-line PCT, after oncosurgically favourable selection, could bring similar OS compared to what observed after first-line. For initially unresectable patients, OS or DFS is comparable between first- and second-line PCT. Surgery should not be denied after the failure of first-line chemotherapy.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Adam R.
        • Delvart V.
        • Pascal G.
        • Valeanu A.
        • Castaing D.
        • Azoulay D.
        • et al.
        Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival.
        Ann Surg. 2004; 240: 644-657
        • Giacchetti S.
        • Itzhaki M.
        • Gruia G.
        • Adam R.
        • Zidani R.
        • Kunstlinger F.
        • et al.
        Long-term survival of patients with unresectable colorectal cancer liver metastases following infusional chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin and surgery.
        Ann Oncol. 1999; 10: 663-669
      1. LiverMetSurvey: International registry of patients operated for colorectal liver metastasis. Available at: http://www.livermetsurvey.org.

        • Adam R.
        • De Gramont A.
        • Figueras J.
        • Guthrie A.
        • Kokudo N.
        • Kunstlinger F.
        • et al.
        The oncosurgery approach to managing liver metastases from colorectal cancer: a multidisciplinary international consensus.
        Oncologist. 2012; 17: 1225-1239
        • Ahlgren J.D.
        • Trocki O.
        • Gullo J.J.
        • Goldberg R.
        • Muir W.A.
        • Sisk R.
        • et al.
        Protracted infusion of 5-FU with weekly low-dose cisplatin as second-line therapy in patients with metastatic colorectal cancer who have failed 5-FU monotherapy.
        Cancer Invest. 1991; 9: 27-33
        • Bertrand M.
        • Doroshow J.H.
        • Multhauf P.
        • Blayney D.W.
        • Carr B.I.
        • Cecchi G.
        • et al.
        High-dose continuous infusion folinic acid and bolus 5-fluorouracil in patients with advanced colorectal cancer: a phase II study.
        J Clin Oncol. 1986; 4: 1058-1061
        • Tournigand C.
        • André T.
        • Achille E.
        • Lledo G.
        • Flesh M.
        • Mery-Mignard D.
        • et al.
        FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study.
        J Clin Oncol. 2004; 22: 229-237
        • Van Cutsem E.
        • Cervantes A.
        • Adam R.
        • Sobrero A.
        • Van Krieken J.H.
        • Aderka D.
        • et al.
        ESMO consensus guidelines for the management of patients with metastatic colorectal cancer.
        Ann Oncol. 2016; 27: 1386-1422
        • Therasse P.
        • Arbuck S.G.
        • Eisenhauer E.A.
        • Wanders J.
        • Kaplan R.S.
        • Rubinstein L.
        • et al.
        New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada.
        J Natl Cancer Inst. 2000; 92: 205-216
        • Brouquet A.
        • Overman M.J.
        • Kopetz S.
        • Maru D.M.
        • Loyer E.M.
        • Andreou A.
        • et al.
        Is resection of colorectal liver metastases after a second-line chemotherapy regimen justified?.
        Cancer. 2011; 117: 4484-4492
        • Kanas G.P.
        • Taylor A.
        • Primrose J.N.
        • Langeberg W.J.
        • Kelsh M.A.
        • Mowat F.S.
        • et al.
        Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors.
        Clin Epidemiol. 2012; 4: 283-301
        • Van Cutsem E.
        • Tabernero J.
        • Lakomy R.
        • Prenen H.
        • Prausová J.
        • Macarulla T.
        • et al.
        Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen.
        J Clin Oncol. 2012; 30: 3499-3506
        • Bennouna J.
        • Sastre J.
        • Arnold D.
        • Österlund P.
        • Greil R.
        • Van Cutsem E.
        • et al.
        Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial.
        Lancet Oncol. 2013; 14: 29-37
        • Simmonds P.C.
        • Primrose J.N.
        • Colquitt J.L.
        • Garden O.J.
        • Poston G.J.
        • Rees M.
        Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies.
        Br J Cancer. 2006; 94: 982-999
        • Adam R.
        • Pascal G.
        • Castaing D.
        • Azoulay D.
        • Delvart V.
        • Paule B.
        • et al.
        Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases?.
        Ann Surg. 2004; 240: 1052-1061
        • Hamady Z.Z.
        • Cameron I.C.
        • Wyatt J.
        • Prasad R.K.
        • Toogood G.J.
        • Lodge J.P.
        Resection margin in patients undergoing hepatectomy for colorectal liver metastasis: a critical appraisal of the 1 cm rule.
        Eur J Surg Oncol. 2006; 32: 557-563
        • Muratore A.
        • Ribero D.
        • Zimmitti G.
        • Mellano A.
        • Langella S.
        • Capussotti L.
        Resection margin and recurrence-free survival after liver resection of colorectal metastases.
        Ann Surg Oncol. 2010; 17: 1324-1329
        • Inoue Y.
        • Hayashi M.
        • Komeda K.
        • Masubuchi S.
        • Yamamoto M.
        • Yamana H.
        • et al.
        Resection margin with anatomic or nonanatomic hepatectomy for liver metastasis from colorectal cancer.
        J Gastrointest Surg. 2012; 16: 1171-1180
        • Adam R.
        • Aloia T.
        • Lévi F.
        • Wicherts D.A.
        • de Haas R.J.
        • Paule B.
        • et al.
        Hepatic resection after rescue cetuximab treatment for colorectal liver metastases previously refractory to conventional systemic therapy.
        J Clin Oncol. 2007; 25: 4593-4602
        • Boige V.
        • Malka D.
        • Elias D.
        • Castaing M.
        • De Baere T.
        • Goere D.
        • et al.
        Hepatic arterial infusion of oxaliplatin and intravenous LV5FU2 in unresectable liver metastases from colorectal cancer after systemic chemotherapy failure.
        Ann Surg Oncol. 2008; 15: 219-226
        • D'Angelica M.I.
        • Correa-Gallego C.
        • Paty P.B.
        • Cercek A.
        • Gewirtz A.N.
        • Chou J.F.
        • et al.
        Phase II trial of hepatic artery infusional and systemic chemotherapy for patients with unresectable hepatic metastases from colorectal cancer: conversion to resection and long-term outcomes.
        Ann Surg. 2015; 261: 353-360
        • Venook A.P.
        • Niedzwiecki D.
        • Lenz H.-J.
        • Innocenti F.
        • Mahoney M.
        • O'Neil B.
        • et al.
        CALGB/SWOG 80405: phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab or cetuximab for patients with KRAS wild-type untreated metastatic adenocarcinoma of the colon or rectum (MCRC). ASCO Annual Meeting.
        J Clin Oncol. 2014; 32 (suppl; abstr LBA3): 5s
        • Venook A.P.
        • Niedzwiecki D.
        • Lenz H.-J.
        • Mahoney M.
        • Innocenti F.
        • O'Neil B.
        • et al.
        CALGB/SWOG 80405: analysis of patients undergoing surgery as part of treatment strategy. ESMO Annual Meeting.
        Ann Oncol. 2014; 25 (LBA10): 1-41