Skip to main content

Advertisement

Log in

Colorectal liver metastases: state-of-the-art management and surgical approaches

  • Review Article
  • Published:
Langenbeck's Archives of Surgery Aims and scope Submit manuscript

Abstract

Background

The liver is the most common site of metastasis for patients with colorectal cancer, and resection is associated with significantly improved survival for selected patients. Advancements in perioperative care, operative technique, and multidisciplinary management have led to improved outcomes for patients with colorectal liver metastases (CLM).

Purpose

This review discusses recent advances in perioperative management, patient selection and prognostication, and surgical technique that make up the state-of-the-art management for patients with CLM.

Conclusion

Novel approaches to prognostication and measurement of treatment response, such as tumor somatic mutational profiling and circulating tumor DNA (ctDNA), are revolutionary instruments for patient selection and treatment sequence. Further, refinements to surgical approaches for patients with bilateral CLM, including two-stage hepatectomy (TSH), are available for these patients and may lead to improved surgical outcomes. The advances discussed in this review will result in more patients being considered for resection and refined selection for perioperative care strategies that will lead to improved survival for patients with CLM.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Fuchs HE (2021) Jemal A (2021) Cancer statistics. CA Cancer J Clin 71(1):7–33

    Article  PubMed  Google Scholar 

  2. Choti MA, Sitzmann JV, Tiburi MF, Sumetchotimetha W, Rangsin R, Schulick RD, Lillemoe KD, Yeo CJ, Cameron JL (2002) Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg 235(6):759–766

    Article  PubMed  PubMed Central  Google Scholar 

  3. Abdalla EK, Vauthey JN, Ellis LM, Ellis V, Pollock R, Broglio KR, Hess K, Curley SA (2004) Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg 239(6):818–825

    Article  PubMed  PubMed Central  Google Scholar 

  4. D’Angelica M, Kornprat P, Gonen M, DeMatteo RP, Fong Y, Blumgart LH, Jarnagin WR (2011) Effect on outcome of recurrence patterns after hepatectomy for colorectal metastases. Ann Surg Oncol 18(4):1096–1103

    Article  PubMed  Google Scholar 

  5. Benson AB, Venook AP, Al-Hawary MM, Arain MA, Chen YJ, Ciombor KK, Cohen S, Cooper HS, Deming D, Farkas L et al (2021) Colon cancer, version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 19(3):329–359

    Article  PubMed  Google Scholar 

  6. Benson AB, Venook AP, Al-Hawary MM, Cederquist L, Chen YJ, Ciombor KK, Cohen S, Cooper HS, Deming D, Engstrom PF et al (2018) Rectal cancer, version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 16(7):874–901

    Article  PubMed  Google Scholar 

  7. Kawaguchi Y, Vauthey JN (2020) The landmark series: randomized control trials examining perioperative chemotherapy and postoperative adjuvant chemotherapy for resectable colorectal liver metastasis. Ann Surg Oncol 27(11):4263–4270

    Article  PubMed  Google Scholar 

  8. Portier G, Elias D, Bouche O, Rougier P, Bosset JF, Saric J, Belghiti J, Piedbois P, Guimbaud R, Nordlinger B et al (2006) 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 24(31):4976–4982

    Article  CAS  PubMed  Google Scholar 

  9. Hasegawa K, Saiura A, Takayama T, Miyagawa S, Yamamoto J, Ijichi M, Teruya M, Yoshimi F, Kawasaki S, Koyama H et al (2016) Adjuvant oral uracil-tegafur with leucovorin for colorectal cancer liver metastases: a randomized controlled trial. PLoS ONE 11(9):e0162400

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Ychou M, Hohenberger W, Thezenas S, Navarro M, Maurel J, Bokemeyer C, Shacham-Shmueli E, Rivera F, Kwok-Keung Choi C, Santoro A (2009) 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 20(12):1964–1970

    Article  CAS  PubMed  Google Scholar 

  11. Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M et al (2008) 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 371(9617):1007–1016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M et al (2013) Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol 14(12):1208–1215

    Article  CAS  PubMed  Google Scholar 

  13. Primrose J, Falk S, Finch-Jones M, Valle J, O’Reilly D, Siriwardena A, Hornbuckle J, Peterson M, Rees M, Iveson T et al (2014) Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial. Lancet Oncol 15(6):601–611

    Article  CAS  PubMed  Google Scholar 

  14. Chun YS, Vauthey JN, Ribero D, Donadon M, Mullen JT, Eng C, Madoff DC, Chang DZ, Ho L, Kopetz S et al (2007) Systemic chemotherapy and two-stage hepatectomy for extensive bilateral colorectal liver metastases: perioperative safety and survival. J Gastrointest Surg 11(11):1498–1504

    Article  PubMed  Google Scholar 

  15. Schnitzbauer AA, Lang SA, Goessmann H, Nadalin S, Baumgart J, Farkas SA, Fichtner-Feigl S, Lorf T, Goralcyk A, Horbelt R et al (2012) Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg 255(3):405–414

    Article  PubMed  Google Scholar 

  16. Sandstrom P, Rosok BI, Sparrelid E, Larsen PN, Larsson AL, Lindell G, Schultz NA, Bjornbeth BA, Isaksson B, Rizell M et al (2018) ALPPS improves resectability compared with conventional two-stage hepatectomy in patients with advanced colorectal liver metastasis: results from a Scandinavian multicenter randomized controlled trial (LIGRO trial). Ann Surg 267(5):833–840

    Article  PubMed  Google Scholar 

  17. Wolmark N, Rockette H, Fisher B, Wickerham DL, Redmond C, Fisher ER, Jones J, Mamounas EP, Ore L, Petrelli NJ et al (1993) The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J Clin Oncol 11(10):1879–1887

    Article  CAS  PubMed  Google Scholar 

  18. Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350(23):2343–2351

    Article  CAS  PubMed  Google Scholar 

  19. Andre T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F et al (2009) Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 27(19):3109–3116

    Article  CAS  PubMed  Google Scholar 

  20. Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Gilberg F, Rittweger K, Schmoll HJ (2011) Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol 29(11):1465–1471

    Article  CAS  PubMed  Google Scholar 

  21. Kokudo T, Saiura A, Takayama T, Miyagawa S, Yamamoto J, Ijichi M, Teruya M, Yoshimi F, Kawasaki S, Koyama H et al (2021) Adjuvant chemotherapy can prolong recurrence-free survival but did not influence the type of recurrence or subsequent treatment in patients with colorectal liver metastases. Surgery 170(4):1151–1154

    Article  PubMed  Google Scholar 

  22. Bridgewater JA, Pugh SA, Maishman T, Eminton Z, Mellor J, Whitehead A, Stanton L, Radford M, Corkhill A, Griffiths GO et al (2020) Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis (New EPOC): long-term results of a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol 21(3):398–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J et al (2014) Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol 25(7):1346–1355

    Article  CAS  PubMed  Google Scholar 

  24. Van Cutsem E, Kohne CH, Lang I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S et al (2011) Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol 29(15):2011–2019

    Article  PubMed  CAS  Google Scholar 

  25. Ribero D, Wang H, Donadon M, Zorzi D, Thomas MB, Eng C, Chang DZ, Curley SA, Abdalla EK, Ellis LM et al (2007) Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer 110(12):2761–2767

    Article  PubMed  Google Scholar 

  26. Chun YS, Vauthey JN, Boonsirikamchai P, Maru DM, Kopetz S, Palavecino M, Curley SA, Abdalla EK, Kaur H, Charnsangavej C et al (2009) Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal liver metastases. JAMA 302(21):2338–2344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Overman MJ, Ferrarotto R, Raghav K, George B, Qiao W, Machado KK, Saltz LB, Mazard T, Vauthey JN, Hoff PM et al (2018) The addition of bevacizumab to oxaliplatin-based chemotherapy: impact upon hepatic sinusoidal injury and thrombocytopenia. J Natl Cancer Inst 110(8):888–894

    Article  PubMed  CAS  Google Scholar 

  28. Mazard T, Boonsirikamchai P, Overman MJ, Asran MA, Choi H, Herron D, Eng C, Maru DM, Ychou M, Vauthey JN et al (2018) Comparison of early radiological predictors of outcome in patients with colorectal cancer with unresectable hepatic metastases treated with bevacizumab. Gut 67(6):1095–1102

    Article  CAS  PubMed  Google Scholar 

  29. Jegatheeswaran S, Mason JM, Hancock HC, Siriwardena AK (2013) The liver-first approach to the management of colorectal cancer with synchronous hepatic metastases: a systematic review. JAMA Surg 148(4):385–391

    Article  CAS  PubMed  Google Scholar 

  30. Adam R, de Gramont A, Figueras J, Kokudo N, Kunstlinger F, Loyer E, Poston G, Rougier P, Rubbia-Brandt L, Sobrero A et al (2015) Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus. Cancer Treat Rev 41(9):729–741

    Article  PubMed  Google Scholar 

  31. Reddy SK, Barbas AS, Clary BM (2009) Synchronous colorectal liver metastases: is it time to reconsider traditional paradigms of management? Ann Surg Oncol 16(9):2395–2410

    Article  PubMed  Google Scholar 

  32. Lillemoe HA, Vauthey JN (2020) Surgical approach to synchronous colorectal liver metastases: staged, combined, or reverse strategy. Hepatobiliary Surg Nutr 9(1):25–34

    Article  PubMed  PubMed Central  Google Scholar 

  33. Tebbutt NC, Norman AR, Cunningham D, Hill ME, Tait D, Oates J, Livingston S, Andreyev J (2003) Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases. Gut 52(4):568–573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ruo L, Gougoutas C, Paty PB, Guillem JG, Cohen AM, Wong WD (2003) Elective bowel resection for incurable stage IV colorectal cancer: prognostic variables for asymptomatic patients. J Am Coll Surg 196(5):722–728

    Article  PubMed  Google Scholar 

  35. Benoist S, Pautrat K, Mitry E, Rougier P, Penna C, Nordlinger B (2005) Treatment strategy for patients with colorectal cancer and synchronous irresectable liver metastases. Br J Surg 92(9):1155–1160

    Article  CAS  PubMed  Google Scholar 

  36. Poultsides GA, Servais EL, Saltz LB, Patil S, Kemeny NE, Guillem JG, Weiser M, Temple LK, Wong WD, Paty PB (2009) Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial treatment. J Clin Oncol 27(20):3379–3384

    Article  PubMed  PubMed Central  Google Scholar 

  37. Giuliante F, Vigano L, De Rose AM, Mirza DF, Lapointe R, Kaiser G, Barroso E, Ferrero A, Isoniemi H, Lopez-Ben S et al. (2021) Liver-first approach for synchronous colorectal metastases: analysis of 7360 patients from the LiverMetSurvey registry. Ann Surg Oncol epub ahead of print.

  38. Abdalla EK, Denys A, Chevalier P, Nemr RA, Vauthey JN (2004) Total and segmental liver volume variations: implications for liver surgery. Surgery 135(4):404–410

    Article  PubMed  Google Scholar 

  39. Shindoh J, Tzeng CW, Aloia TA, Curley SA, Zimmitti G, Wei SH, Huang SY, Mahvash A, Gupta S, Wallace MJ et al (2013) Optimal future liver remnant in patients treated with extensive preoperative chemotherapy for colorectal liver metastases. Ann Surg Oncol 20(8):2493–2500

    Article  PubMed  Google Scholar 

  40. Vauthey JN, Abdalla EK, Doherty DA, Gertsch P, Fenstermacher MJ, Loyer EM, Lerut J, Materne R, Wang X, Encarnacion A et al (2002) Body surface area and body weight predict total liver volume in Western adults. Liver Transpl 8(3):233–240

    Article  PubMed  Google Scholar 

  41. Shindoh J, Truty MJ, Aloia TA, Curley SA, Zimmitti G, Huang SY, Mahvash A, Gupta S, Wallace MJ, Vauthey JN (2013) Kinetic growth rate after portal vein embolization predicts posthepatectomy outcomes: toward zero liver-related mortality in patients with colorectal liver metastases and small future liver remnant. J Am Coll Surg 216(2):201–209

    Article  PubMed  Google Scholar 

  42. Margonis GA, Sasaki K, Andreatos N, Kim Y, Merath K, Wagner D, Wilson A, Buettner S, Amini N, Antoniou E et al (2017) KRAS mutation status dictates optimal surgical margin width in patients undergoing resection of colorectal liver metastases. Ann Surg Oncol 24(1):264–271

    Article  PubMed  Google Scholar 

  43. Brudvik KW, Mise Y, Chung MH, Chun YS, Kopetz SE, Passot G, Conrad C, Maru DM, Aloia TA, Vauthey JN (2016) RAS mutation predicts positive resection margins and narrower resection margins in patients undergoing resection of colorectal liver metastases. Ann Surg Oncol 23(8):2635–2643

    Article  PubMed  PubMed Central  Google Scholar 

  44. Margonis GA, Buettner S, Andreatos N, Sasaki K, Ijzermans JNM, van Vugt JLA, Pawlik TM, Choti MA, Cameron JL, He J et al (2017) Anatomical resections improve disease-free survival in patients with KRAS-mutated colorectal liver metastases. Ann Surg 266(4):641–649

    Article  PubMed  Google Scholar 

  45. Joechle K, Vreeland TJ, Vega EA, Okuno M, Newhook TE, Panettieri E, Chun YS, Tzeng CD, Aloia TA, Lee JE et al (2020) Anatomic resection is not required for colorectal liver metastases with RAS mutation. J Gastrointest Surg 24(5):1033–1039

    Article  PubMed  Google Scholar 

  46. Passot G, Odisio BC, Zorzi D, Mahvash A, Gupta S, Wallace MJ, Kim BJ, Yamashita S, Conrad C, Aloia TA et al (2016) Eradication of missing liver metastases after fiducial placement. J Gastrointest Surg 20(6):1173–1178

    Article  PubMed  Google Scholar 

  47. Vauthey JN, Kawaguchi Y (2020) Innovation and future perspectives in the treatment of colorectal liver metastases. J Gastrointest Surg 24(2):492–496

    Article  PubMed  Google Scholar 

  48. Adam R, Laurent A, Azoulay D, Castaing D, Bismuth H (2000) Two-stage hepatectomy: a planned strategy to treat irresectable liver tumors. Ann Surg 232(6):777–785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Jaeck D, Bachellier P, Nakano H, Oussoultzoglou E, Weber JC, Wolf P, Greget M (2003) One or two-stage hepatectomy combined with portal vein embolization for initially nonresectable colorectal liver metastases. Am J Surg 185(3):221–229

    Article  PubMed  Google Scholar 

  50. Lygidakis NJ, Vlachos L, Raptis S, Rassidakis G, Balaskas C, Sgourakis G, Mourikis D, Kehagias D, Kittas C (1999) New frontiers in liver surgery. Two-stage liver surgery for the management of advanced metastatic liver disease. Hepatogastroenterology 46(28):2216–2228

    CAS  PubMed  Google Scholar 

  51. Brouquet A, Abdalla EK, Kopetz S, Garrett CR, Overman MJ, Eng C, Andreou A, Loyer EM, Madoff DC, Curley SA et al (2011) High survival rate after two-stage resection of advanced colorectal liver metastases: response-based selection and complete resection define outcome. J Clin Oncol 29(8):1083–1090

    Article  PubMed  PubMed Central  Google Scholar 

  52. Imai K, Benitez CC, Allard MA, Vibert E, Cunha AS, Cherqui D, Castaing D, Bismuth H, Baba H, Adam R (2015) Failure to achieve a 2-stage hepatectomy for colorectal liver metastases: how to prevent it? Ann Surg 262(5):772–778 (discussion 778-779)

  53. Faitot F, Soubrane O, Wendum D, Sandrini J, Afchain P, Balladur P, de Gramont A, Scatton O (2015) Feasibility and survival of 2-stage hepatectomy for colorectal metastases: definition of a simple and early clinicopathologic predicting score. Surgery 157(3):444–453

    Article  PubMed  Google Scholar 

  54. Dupre A, Lefranc A, Buc E, Delpero JR, Quenet F, Passot G, Evrard S, Rivoire M (2013) Use of bioresorbable membranes to reduce abdominal and perihepatic adhesions in 2-stage hepatectomy of liver metastases from colorectal cancer: results of a prospective, randomized controlled phase II trial. Ann Surg 258(1):30–36

    Article  PubMed  Google Scholar 

  55. Passot G, Chun YS, Kopetz SE, Zorzi D, Brudvik KW, Kim BJ, Conrad C, Aloia TA, Vauthey JN (2016) Predictors of safety and efficacy of 2-stage hepatectomy for bilateral colorectal liver metastases. J Am Coll Surg 223(1):99–108

    Article  PubMed  PubMed Central  Google Scholar 

  56. Nishioka Y, Odisio BC, Velasco JD, Ninan E, Huang SY, Mahvash A, Tzeng CD, Tran Cao HS, Gupta S, Vauthey JN (2021) Fast-track two-stage hepatectomy by concurrent portal vein embolization at first-stage hepatectomy in hybrid interventional radiology/operating suite. Surg Oncol 39:101648

    Article  PubMed  Google Scholar 

  57. Elias D, Baton O, Sideris L, Boige V, Malka D, Liberale G, Pocard M, Lasser P (2005) Hepatectomy plus intraoperative radiofrequency ablation and chemotherapy to treat technically unresectable multiple colorectal liver metastases. J Surg Oncol 90(1):36–42

    Article  PubMed  Google Scholar 

  58. Tanaka K, Shimada H, Nagano Y, Endo I, Sekido H, Togo S (2006) Outcome after hepatic resection versus combined resection and microwave ablation for multiple bilobar colorectal metastases to the liver. Surgery 139(2):263–273

    Article  PubMed  Google Scholar 

  59. Evrard S, Poston G, Kissmeyer-Nielsen P, Diallo A, Desolneux G, Brouste V, Lalet C, Mortensen F, Stattner S, Fenwick S et al (2014) Combined ablation and resection (CARe) as an effective parenchymal sparing treatment for extensive colorectal liver metastases. PLoS ONE 9(12):e114404

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Philips P, Groeschl RT, Hanna EM, Swan RZ, Turaga KK, Martinie JB, Iannitti DA, Schmidt C, Gamblin TC, Martin RC (2016) Single-stage resection and microwave ablation for bilobar colorectal liver metastases. Br J Surg 103(8):1048–1054

    Article  CAS  PubMed  Google Scholar 

  61. Imai K, Allard MA, Castro Benitez C, Vibert E, Sa Cunha A, Cherqui D, Castaing D, Baba H, Adam R (2017) Long-term outcomes of radiofrequency ablation combined with hepatectomy compared with hepatectomy alone for colorectal liver metastases. Br J Surg 104(5):570–579

    Article  CAS  PubMed  Google Scholar 

  62. Mizuno T, Cloyd JM, Omichi K, Chun YS, Conrad C, Tzeng CD, Wei SH, Aloia TA, Vauthey JN (2018) Two-stage hepatectomy vs one-stage major hepatectomy with contralateral resection or ablation for advanced bilobar colorectal liver metastases. J Am Coll Surg 226(5):825–834

    Article  PubMed  Google Scholar 

  63. Odisio BC, Yamashita S, Frota L, Huang SY, Kopetz SE, Ahrar K, Chun YS, Aloia TA, Hicks ME, Gupta S et al (2017) Planned treatment of advanced metastatic disease with completion ablation after hepatic resection. J Gastrointest Surg 21(4):628–635

    Article  PubMed  Google Scholar 

  64. Okuno M, Kawaguchi Y, De Bellis M, Vega EA, Huang SY, Ahrar K, Gupta S, Vauthey JN, Odisio BC (2021) A new sequential treatment strategy for multiple colorectal liver metastases: planned incomplete resection and postoperative completion ablation for intentionally-untreated tumors under guidance of cross-sectional imaging. Eur J Surg Oncol 47(2):311–316

    Article  PubMed  Google Scholar 

  65. Kawaguchi Y, Lillemoe HA, Vauthey JN (2019) Dealing with an insufficient future liver remnant: portal vein embolization and two-stage hepatectomy. J Surg Oncol 119(5):594–603

    Article  PubMed  PubMed Central  Google Scholar 

  66. Vega EA, Simoneau E, Tzeng CD, Odisio BC, Aloia TA, Chun YS, Vauthey JN (2019) Comment on Letter to the Editor regarding “ALPPS improves resectability compared with conventional two-stage hepatectomy in patients with advanced colorectal liver metastasis: when innovation is not enough.” Ann Surg 270(2):e35–e36

    Article  PubMed  Google Scholar 

  67. Hasselgren K, Rosok BI, Larsen PN, Sparrelid E, Lindell G, Schultz NA, Bjornbeth BA, Isaksson B, Larsson AL, Rizell M et al (2021) ALPPS improves survival compared with TSH in patients affected of CRLM: survival analysis from the randomized controlled trial LIGRO. Ann Surg 273(3):442–448

    Article  PubMed  Google Scholar 

  68. Chavez MI, Gholami S, Kim BJ, Margonis GA, Ethun CG, Tsai S, Christians KK, Clarke C, Mogal H, Maithel SK et al (2021) Two-stage hepatectomy for bilateral colorectal liver metastases: a multi-institutional analysis. Ann Surg Oncol 28(3):1457–1465

    Article  PubMed  PubMed Central  Google Scholar 

  69. Niekamp AS, Huang SY, Mahvash A, Odisio BC, Ahrar K, Tzeng CD, Vauthey JN (2020) Hepatic vein embolization after portal vein embolization to induce additional liver hypertrophy in patients with metastatic colorectal carcinoma. Eur Radiol 30(7):3862–3868

    Article  PubMed  Google Scholar 

  70. Laurent C, Fernandez B, Marichez A, Adam JP, Papadopoulos P, Lapuyade B, Chiche L (2020) Radiological simultaneous portohepatic vein embolization (RASPE) before major hepatectomy: a better way to optimize liver hypertrophy compared to portal vein embolization. Ann Surg 272(2):199–205

    Article  PubMed  Google Scholar 

  71. Kawaguchi Y, Kopetz S, Lillemoe HA, Hwang H, Wang X, Tzeng CD, Chun YS, Aloia TA, Vauthey JN (2020) A new surveillance algorithm after resection of colorectal liver metastases based on changes in recurrence risk and RAS mutation status. J Natl Compr Canc Netw 18(11):1500–1508

    Article  PubMed  Google Scholar 

  72. Kawaguchi Y, Lillemoe HA, Panettieri E, Chun YS, Tzeng CD, Aloia TA, Kopetz S, Vauthey JN (2019) Conditional recurrence-free survival after resection of colorectal liver metastases: persistent deleterious association with RAS and TP53 co-mutation. J Am Coll Surg 229(3):286-294 e281

    Article  PubMed  PubMed Central  Google Scholar 

  73. Vauthey JN, Zimmitti G, Kopetz SE, Shindoh J, Chen SS, Andreou A, Curley SA, Aloia TA, Maru DM (2013) RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg 258(4):619–626 (discussion 626-617)

    Article  PubMed  Google Scholar 

  74. Zimmitti G, Shindoh J, Mise Y, Kopetz S, Loyer EM, Andreou A, Cooper AB, Kaur H, Aloia TA, Maru DM et al (2015) RAS mutations predict radiologic and pathologic response in patients treated with chemotherapy before resection of colorectal liver metastases. Ann Surg Oncol 22(3):834–842

    Article  PubMed  Google Scholar 

  75. Newhook TE, Chun YS, Vauthey JN (2020) An odyssey into the land of deleterious rare mutations in colorectal liver metastases. Ann Surg Oncol 27(9):3115–3117

    Article  PubMed  Google Scholar 

  76. Kawaguchi Y, Kopetz S, Newhook TE, De Bellis M, Chun YS, Tzeng CD, Aloia TA, Vauthey JN (2019) Mutation status of RAS, TP53, and SMAD4 is superior to mutation status of RAS alone for predicting prognosis after resection of colorectal liver metastases. Clin Cancer Res 25(19):5843–5851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lillemoe HA, Passot G, Kawaguchi Y, DeBellis M, Glehen O, Chun YS, Tzeng CD, Aloia TA, Lopez J, Vauthey JN (2020) RAS/TP53 co-mutation is associated with worse survival after concurrent resection of colorectal liver metastases and extrahepatic disease. Ann Surg epub ahead of print.

  78. Mizuno T, Cloyd JM, Vicente D, Omichi K, Chun YS, Kopetz SE, Maru D, Conrad C, Tzeng CD, Wei SH et al (2018) SMAD4 gene mutation predicts poor prognosis in patients undergoing resection for colorectal liver metastases. Eur J Surg Oncol 44(5):684–692

    Article  PubMed  Google Scholar 

  79. Kawaguchi Y, Newhook TE, Tran Cao HS, Tzeng CD, Chun YS, Aloia TA, Dasari A, Kopetz S, Vauthey JN (2021) Alteration of FBXW7 is associated with worse survival in patients undergoing resection of colorectal liver metastases. J Gastrointest Surg 25(1):186–194

    Article  PubMed  Google Scholar 

  80. Margonis GA, Andreatos N, Weiss MJ (2018) BRAF V600E mutation as a negative prognostic determinant in resected colorectal liver metastases—reply. JAMA Surg 153(12):1163–1164

    Article  PubMed  Google Scholar 

  81. Margonis GA, Buettner S, Andreatos N, Kim Y, Wagner D, Sasaki K, Beer A, Schwarz C, Loes IM, Smolle M et al (2018) Association of BRAF mutations with survival and recurrence in surgically treated patients with metastatic colorectal liver cancer. JAMA Surg 153(7):e180996

    Article  PubMed  PubMed Central  Google Scholar 

  82. Gagniere J, Dupre A, Gholami SS, Pezet D, Boerner T, Gonen M, Kingham TP, Allen PJ, Balachandran VP, De Matteo RP et al (2020) Is hepatectomy justified for BRAF mutant colorectal liver metastases?: a multi-institutional analysis of 1497 patients. Ann Surg 271(1):147–154

    Article  PubMed  Google Scholar 

  83. Yaeger R, Cercek A, Chou JF, Sylvester BE, Kemeny NE, Hechtman JF, Ladanyi M, Rosen N, Weiser MR, Capanu M et al (2014) BRAF mutation predicts for poor outcomes after metastasectomy in patients with metastatic colorectal cancer. Cancer 120(15):2316–2324

    Article  CAS  PubMed  Google Scholar 

  84. Kawaguchi Y, Kopetz S, Kwong L, Xiao L, Morris JS, Tran Cao HS, Tzeng CD, Chun YS, Lee JE, Vauthey JN (2021) Genomic sequencing and insight into clinical heterogeneity and prognostic pathway genes in patients with metastatic colorectal cancer. J Am Coll Surg 233(2):272-284 e213

    Article  PubMed  PubMed Central  Google Scholar 

  85. Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM et al. (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6(224):224ra224.

  86. Diehl F, Schmidt K, Choti MA, Romans K, Goodman S, Li M, Thornton K, Agrawal N, Sokoll L, Szabo SA et al (2008) Circulating mutant DNA to assess tumor dynamics. Nat Med 14(9):985–990

    Article  CAS  PubMed  Google Scholar 

  87. Tie J, Cohen JD, Wang Y, Christie M, Simons K, Lee M, Wong R, Kosmider S, Ananda S, McKendrick J et al (2019) Circulating tumor DNA analyses as markers of recurrence risk and benefit of adjuvant therapy for stage III colon cancer. JAMA Oncol 5(12):1710–1717

    Article  PubMed  PubMed Central  Google Scholar 

  88. Wang Y, Li L, Cohen JD, Kinde I, Ptak J, Popoli M, Schaefer J, Silliman N, Dobbyn L, Tie J et al (2019) Prognostic potential of circulating tumor DNA measurement in postoperative surveillance of nonmetastatic colorectal cancer. JAMA Oncol 5(8):1118–1123

    Article  PubMed  PubMed Central  Google Scholar 

  89. Tie J, Wang Y, Tomasetti C, Li L, Springer S, Kinde I, Silliman N, Tacey M, Wong HL, Christie M et al. (2016) Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med 8(346):346ra392.

  90. Tie J, Kinde I, Wang Y, Wong HL, Roebert J, Christie M, Tacey M, Wong R, Singh M, Karapetis CS et al (2015) Circulating tumor DNA as an early marker of therapeutic response in patients with metastatic colorectal cancer. Ann Oncol 26(8):1715–1722

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Parikh AR, Van Seventer EE, Siravegna G, Hartwig AV, Jaimovich A, He Y, Kanter K, Fish MG, Fosbenner KD, Miao B et al. (2021) Minimal residual disease detection using a plasma-only circulating tumor DNA assay in patients with colorectal cancer. Clin Cancer Res, epub ahead of print.

  92. Overman MJ, Jaimovich A, Kennedy D, Tan M, Gavino D, Mortimer S, Chudova D, Talasaz A, Odegaard J, Kopetz S (2018) A priori filtering of post-operative (post-op) circulating tumor DNA (ctDNA) to predict recurrence in post-metastasectomy colorectal cancer patients (CRC pts) without knowledge of tumor genotype. J Clin Oncol 36(15(_suppl)):12044–12044

    Article  Google Scholar 

  93. Tie J, Wang Y, Cohen J, Li L, Hong W, Christie M, Wong HL, Kosmider S, Wong R, Thomson B et al (2021) Circulating tumor DNA dynamics and recurrence risk in patients undergoing curative intent resection of colorectal cancer liver metastases: a prospective cohort study. PLoS Med 18(5):e1003620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Kobayashi S, Nakamura Y, Taniguchi H, Odegaard JI, Nomura S, Kojima M, Sugimoto M, Konishi M, Gotohda N, Takahashi S et al (2021) Impact of preoperative circulating tumor DNA status on survival outcomes after hepatectomy for resectable colorectal liver metastases. Ann Surg Oncol 28(8):4744–4755

    Article  PubMed  Google Scholar 

  95. Narayan RR, Goldman DA, Gonen M, Reichel J, Huberman KH, Raj S, Viale A, Kemeny NE, Allen PJ, Balachandran VP et al (2019) Peripheral circulating tumor DNA detection predicts poor outcomes after liver resection for metastatic colorectal cancer. Ann Surg Oncol 26(6):1824–1832

    Article  PubMed  PubMed Central  Google Scholar 

  96. Scholer LV, Reinert T, Orntoft MW, Kassentoft CG, Arnadottir SS, Vang S, Nordentoft I, Knudsen M, Lamy P, Andreasen D et al (2017) Clinical implications of monitoring circulating tumor DNA in patients with colorectal cancer. Clin Cancer Res 23(18):5437–5445

    Article  CAS  PubMed  Google Scholar 

  97. Mason MC, Tzeng CD, Tran Cao HS, Aloia TA, Newhook TE, Overman MJ, Kopetz SE, Vauthey JN, Chun YS (2021) Preliminary analysis of liquid biopsy after hepatectomy for colorectal liver metastases. J Am Coll Surg 233(1):82-89 e81

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jean-Nicolas Vauthey.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Newhook, T.E., Vauthey, JN. Colorectal liver metastases: state-of-the-art management and surgical approaches. Langenbecks Arch Surg 407, 1765–1778 (2022). https://doi.org/10.1007/s00423-022-02496-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00423-022-02496-7

Keywords

Navigation