Optimizing the selection of technically unresectable colorectal liver metastases

Published:November 13, 2022DOI:



      The prediction of conversion surgery in patients with technically unresectable colorectal liver metastases has not been generalized or well-established. We developed a predictive model for conversion surgery and assessed the long-term outcomes of patients with technically unresectable colorectal liver metastases.


      In this single-center, retrospective study, we analyzed the perioperative parameters and outcomes of 892 consecutive patients (2014–2021). Conversion surgery was indicated when the chemotherapy response allowed the complete resection of colorectal liver metastases with negative margins and adequate remnant liver volume.


      Of the 892 patients, 122 had technically unresectable colorectal liver metastases; 61 underwent conversion surgery (conversion surgery group) and 61 did not (nonconversion surgery group). The median overall survival was significantly higher in the conversion surgery group than in the nonconversion surgery group (5.6 vs 1.8 years, P < .001). After univariate and multivariate analyses, the predictive model for conversion surgery was constructed using 4 predictive factors: Rat sarcoma viral oncogene homolog status (mutant, +2 points), tumor number (≥15, +1), hepatic vein contact (≥2 hepatic veins, +1), and the presence of preservable sections (absence of preservable sections, +2). The area under the curve for conversion surgery was 0.889. Patients were graded according to the scores (A [0–2], B [3–4], and C [5–6]), and the conversion rates were 91.5% (A), 32.6% (B), and 10.3% (C) (P < .001). Grade A patients (median survival time, 5.7 years) had significantly better overall survival than grade B and C patients (median survival time, 2.2 and 1.6 years, respectively; P < .001).


      Patients who underwent conversion surgery for technically unresectable colorectal liver metastases had better prognoses, and our novel predictive model was useful in predicting conversion surgery and prognosis.
      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 to Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Adam R.
        • Delvart V.
        • Pascal G.
        • et al.
        Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival.
        Ann Surg. 2004; 240 (discussion 57–58): 644-657
        • Adam R.
        • de Gramont A.
        • Figueras J.
        • et al.
        Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus.
        Cancer Treat Rev. 2015; 41: 729-741
        • Adam R.
        • Wicherts D.A.
        • de Haas R.J.
        • et al.
        Patients with initially unresectable colorectal liver metastases: is there a possibility of cure?.
        J Clin Oncol. 2009; 27: 1829-1835
        • Barone C.
        • Nuzzo G.
        • Cassano A.
        • et al.
        Final analysis of colorectal cancer patients treated with irinotecan and 5-fluorouracil plus folinic acid neoadjuvant chemotherapy for unresectable liver metastases.
        Br J Cancer. 2007; 97: 1035-1039
        • Alberts S.R.
        • Horvath W.L.
        • Sternfeld W.C.
        • et al.
        Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: a North Central Cancer Treatment Group phase II study.
        J Clin Oncol. 2005; 23: 9243-9249
        • Falcone A.
        • Ricci S.
        • Brunetti I.
        • et al.
        Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest.
        J Clin Oncol. 2007; 25: 1670-1676
        • Folprecht G.
        • Gruenberger T.
        • Bechstein W.O.
        • et al.
        Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial.
        Lancet Oncol. 2010; 11: 38-47
        • Mise Y.
        • Hasegawa K.
        • Saiura A.
        • et al.
        A multicenter phase 2 trial to evaluate the efficacy of mFOLFOX6 + cetuximab as induction chemotherapy to achieve r0 surgical resection for advanced colorectal liver metastases (NEXTO Trial).
        Ann Surg Oncol. 2020; 27: 4188-4195
        • Hu H.
        • Wang K.
        • Huang M.
        • et al.
        Modified FOLFOXIRI with or without cetuximab as conversion therapy in patients with RAS/BRAF wild-type unresectable liver metastases colorectal cancer: the FOCULM multicenter phase II trial.
        Oncologist. 2021; 26: e90-e98
        • Morris E.J.
        • Forman D.
        • Thomas J.D.
        • et al.
        Surgical management and outcomes of colorectal cancer liver metastases.
        Br J Surg. 2010; 97: 1110-1118
        • Modest D.P.
        • Denecke T.
        • Pratschke J.
        • et al.
        Surgical treatment options following chemotherapy plus cetuximab or bevacizumab in metastatic colorectal cancer-central evaluation of FIRE-3.
        Eur J Cancer. 2018; 88: 77-86
        • Rees M.
        • Tekkis P.P.
        • Welsh F.K.
        • O'Rourke T.
        • John T.G.
        Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients.
        Ann Surg. 2008; 247: 125-135
        • Sasaki K.
        • Morioka D.
        • Conci S.
        • et al.
        The tumor burden score: a new “metro-ticket” prognostic tool for colorectal liver metastases based on tumor size and number of tumors.
        Ann Surg. 2018; 267: 132-141
        • Tsilimigras D.I.
        • Hyer J.M.
        • Bagante F.
        • et al.
        Resection of colorectal liver metastasis: prognostic impact of tumor burden vs KRAS mutational status.
        J Am Coll Surg. 2021; 232: 590-598
        • Yonekawa Y.
        • Uehara K.
        • Mizuno T.
        • et al.
        The survival benefit of neoadjuvant chemotherapy for resectable colorectal liver metastases with high tumor burden score.
        Int J Clin Oncol. 2021; 26: 126-134
        • Takeda Y.
        • Mise Y.
        • Takahashi Y.
        • et al.
        Limited prognostic value of KRAS in patients undergoing hepatectomy for colorectal liver metastases.
        Ann Surg Oncol. 2022; 29: 2383-2391
        • Kawakatsu S.
        • Mise Y.
        • Hiratsuka M.
        • et al.
        Clinical significance of subcentimeter pulmonary nodules in patients undergoing hepatectomy for colorectal liver metastases.
        J Surg Oncol. 2020; 122: 523-528
        • Matsuki R.
        • Mise Y.
        • Saiura A.
        • Inoue Y.
        • Ishizawa T.
        • Takahashi Y.
        Parenchymal-sparing hepatectomy for deep-placed colorectal liver metastases.
        Surgery. 2016; 160: 1256-1263
        • Matsumura M.
        • Mise Y.
        • Saiura A.
        • et al.
        Parenchymal-sparing hepatectomy does not increase intrahepatic recurrence in patients with advanced colorectal liver metastases.
        Ann Surg Oncol. 2016; 23: 3718-3726
        • Omichi K.
        • Inoue Y.
        • Mise Y.
        • et al.
        Hepatectomy with perioperative chemotherapy for multiple colorectal liver metastases is the available option for prolonged survival.
        Ann Surg Oncol. 2022; 29: 3567-3576
        • Dindo D.
        • Demartines N.
        • Clavien P.A.
        Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey.
        Ann Surg. 2004; 240: 205-213
        • Strasberg S.M.
        • Phillips C.
        Use and dissemination of the Brisbane 2000 nomenclature of liver anatomy and resections.
        Ann Surg. 2013; 257: 377-382
        • Ichida H.
        • Mise Y.
        • Ito H.
        • et al.
        Optimal indication criteria for neoadjuvant chemotherapy in patients with resectable colorectal liver metastases.
        World J Surg Oncol. 2019; 17: 100
        • Makuuchi M.
        • Thai B.L.
        • Takayasu K.
        • et al.
        Preoperative portal embolization to increase safety of major hepatectomy for hilar bile duct carcinoma: a preliminary report.
        Surgery. 1990; 107: 521-527
        • Wicherts D.A.
        • de Haas R.J.
        • Andreani P.
        • et al.
        Impact of portal vein embolization on long-term survival of patients with primarily unresectable colorectal liver metastases.
        Br J Surg. 2010; 97: 240-250
        • Kobayashi K.
        • Yamaguchi T.
        • Denys A.
        • et al.
        Liver venous deprivation compared to portal vein embolization to induce hypertrophy of the future liver remnant before major hepatectomy: a single center experience.
        Surgery. 2020; 167: 917-923
        • Chebaro A.
        • Buc E.
        • Durin T.
        • et al.
        Liver venous deprivation or associating liver partition and portal vein ligation for staged hepatectomy?: a retrospective multicentric study.
        Ann Surg. 2021; 274: 874-880
        • Saiura A.
        • Yamamoto J.
        • Sakamoto Y.
        • Koga R.
        • Seki M.
        • Kishi Y.
        Safety and efficacy of hepatic vein reconstruction for colorectal liver metastases.
        Am J Surg. 2011; 202: 449-454
        • Kawano F.
        • Mise Y.
        • Yamamoto J.
        • et al.
        Hepatic vein resection and reconstruction for liver malignancies: expanding indication and enhancing parenchyma-sparing hepatectomy.
        BJS Open. 2021; : 5
        • Imai K.
        • Allard M.A.
        • Castro Benitez C.
        • et al.
        Long-term outcomes of radiofrequency ablation combined with hepatectomy compared with hepatectomy alone for colorectal liver metastases.
        Br J Surg. 2017; 104: 570-579
        • Adam R.
        • Laurent A.
        • Azoulay D.
        • Castaing D.
        • Bismuth H.
        Two-stage hepatectomy: a planned strategy to treat irresectable liver tumors.
        Ann Surg. 2000; 232: 777-785
        • Imai K.
        • Benitez C.C.
        • Allard M.A.
        • et al.
        Failure to achieve a 2-stage hepatectomy for colorectal liver metastases: how to prevent it?.
        Ann Surg. 2015; 262 (discussion 8–9): 772-778
        • Schadde E.
        • Ardiles V.
        • Robles-Campos R.
        • et al.
        Early survival and safety of ALPPS: first report of the International ALPPS Registry.
        Ann Surg. 2014; 260 (discussion 36–38): 829-836
        • Linecker M.
        • Stavrou G.A.
        • Oldhafer K.J.
        • et al.
        The ALPPS risk score: avoiding futile use of ALPPS.
        Ann Surg. 2016; 264: 763-771
        • Fernandez F.G.
        • Ritter J.
        • Goodwin J.W.
        • Linehan D.C.
        • Hawkins W.G.
        • Strasberg S.M.
        Effect of steatohepatitis associated with irinotecan or oxaliplatin pretreatment on resectability of hepatic colorectal metastases.
        J Am Coll Surg. 2005; 200: 845-853
        • Soubrane O.
        • Brouquet A.
        • Zalinski S.
        • et al.
        Predicting high grade lesions of sinusoidal obstruction syndrome related to oxaliplatin-based chemotherapy for colorectal liver metastases: correlation with post-hepatectomy outcome.
        Ann Surg. 2010; 251: 454-460
        • Nordlinger B.
        • Vauthey J.N.
        • Poston G.
        • Benoist S.
        • Rougier P.
        • Van Cutsem E.
        The timing of chemotherapy and surgery for the treatment of colorectal liver metastases.
        Clin Colorectal Cancer. 2010; 9: 212-218