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Adjuvant Chemotherapy for CRLM: Indications and Results

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Colorectal Cancer Liver Metastases

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Abstract

Colorectal cancer is the third most frequent malignant neoplasia in the world. Liver metastases are frequent and complicating events in colorectal cancer population. Surgical approach is the treatment of choice allowing for a real curative possibility. Unfortunately, 60% of patients will have a liver or systemic relapse after a complete resection. Combined chemotherapy regimens have been successful in improving survival rates of patients with widespread disease and reducing relapses after resection of the primary colorectal tumor. In order to reduce the relapse rate after a complete resection of colorectal liver metastasis, systemic chemotherapy has been tried pre-, peri-, or postoperatively. Despite many clinical trials, there are controversies about the overall survival benefits. Although adjuvant chemotherapy has been widely employed after complete resection of colorectal liver metastasis, hard evidence has been lacking. This chapter critically summarizes the available evidence of clinical trials, aiming at the attainment of a rational use of chemotherapy in this setting.

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References

  1. Abdalla EK, Vauthey JN, Ellis LM, Ellis V, Pollock R, Broglio KR, Hess K, Curley SA. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg. 2004;239:818–25; discussion 825–7.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Alderson P. Absence of evidence is not evidence of absence. BMJ. 2004;328:476–7.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Altman DG, Bland JM. Absence of evidence is not evidence of absence. BMJ. 1995;311:485.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Andre T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, De Gramont A. 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. 2009;27:3109–16.

    Article  PubMed  CAS  Google Scholar 

  5. Ayez N, Van Der Stok EP, De Wilt H, Radema SA, Van Hillegersberg R, Roumen RM, Vreugdenhil G, Tanis PJ, Punt CJ, Dejong CH, Jansen RL, Verheul HM, De Jong KP, Hospers GA, Klaase JM, Legdeur MC, Van Meerten E, Eskens FA, Van Der Meer N, Van Der Holt B, Verhoef C, Grunhagen DJ. Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: the CHARISMA randomized multicenter clinical trial. BMC Cancer. 2015a;15:180.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Ayez N, Van Der Stok EP, Grunhagen DJ, Rothbarth J, Van Meerten E, Eggermont AM, Verhoef C. The use of neo-adjuvant chemotherapy in patients with resectable colorectal liver metastases: clinical risk score as possible discriminator. Eur J Surg Oncol. 2015b;41:859–67.

    Article  PubMed  CAS  Google Scholar 

  7. Benson AB 3rd, Bekaii-Saab T, Chan E, Chen YJ, Choti MA, Cooper HS, Engstrom PF, Enzinger PC, Fakih MG, Fenton MJ, Fuchs CS, Grem JL, Hunt S, Kamel A, Leong LA, Lin E, May KS, Mulcahy MF, Murphy K, Rohren E, Ryan DP, Saltz L, Sharma S, Shibata D, Skibber JM, Small W Jr, Sofocleous CT, Venook AP, Willett CG, Gregory KM, Freedman-Cass DA. Metastatic colon cancer, version 3.2013: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw. 2013;11:141–52; quiz 152.

    Article  PubMed  CAS  Google Scholar 

  8. De Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, De Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18:2938–47.

    Article  PubMed  Google Scholar 

  9. De Jong MC, Pulitano C, Ribero D, Strub J, Mentha G, Schulick RD, Choti MA, Aldrighetti L, Capussotti L, Pawlik TM. Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: an international multi-institutional analysis of 1669 patients. Ann Surg. 2009;250:440–8.

    PubMed  Google Scholar 

  10. De Kort SJ, Willemse PH, Habraken JM, De Haes HC, Willems DL, Richel DJ. Quality of life versus prolongation of life in patients treated with chemotherapy in advanced colorectal cancer: a review of randomized controlled clinical trials. Eur J Cancer. 2006;42:835–45.

    Article  PubMed  CAS  Google Scholar 

  11. Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000;355:1041–7.

    Article  PubMed  CAS  Google Scholar 

  12. Engstrand J, Kartalis N, Stromberg C, Broberg M, Stillstrom A, Lekberg T, Jonas E, Freedman J, Nilsson H. The impact of a hepatobiliary multidisciplinary team assessment in patients with colorectal cancer liver metastases: a population-based study. Oncologist. 2017;22:1067–74.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.

    Article  CAS  PubMed  Google Scholar 

  14. Fernandez FG, Drebin JA, Linehan DC, Dehdashti F, Siegel BA, Strasberg SM. Five-year survival after resection of hepatic metastases from colorectal cancer in patients screened by positron emission tomography with F-18 fluorodeoxyglucose (FDG-PET). Ann Surg. 2004;240:438–47; discussion 447–50.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Figueras J, Torras J, Valls C, Llado L, Ramos E, Marti-Rague J, Serrano T, Fabregat J. 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 

  16. George B, Kopetz S. Predictive and prognostic markers in colorectal cancer. Curr Oncol Rep. 2011;13:206–15.

    Article  PubMed  CAS  Google Scholar 

  17. Grothey A, Sargent D, Goldberg RM, Schmoll HJ. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol. 2004;22:1209–14.

    Article  PubMed  CAS  Google Scholar 

  18. Hasegawa K, Saiura A, Takayama T, Miyagawa S, Yamamoto J, Bandai Y, Teruya M, Yoshimi F, Kawasaki S, Koyama H, Oba M, Takahashi M, Yamashita S, Mizunuma N, Matsuyama Y, Watanabe T, Makuuchi M, Kokudo N, Group TULS. Oral adjuvant chemotherapy using uracil-tegafur (UFT) with leucovorin (LV) after resection of colorectal cancer liver metastases: long-term survival results of the phase III UFT/LV study. J Clin Oncol. 2017;35:672.

    Article  Google Scholar 

  19. Jiang Q, Yan X, Wang K, Bao Q, Sun Y, Wang H, Jin K, Xing B. [Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer-a multifactorial model of 191 patients]. Zhonghua Wai Ke Za Zhi. 2014;52:171–4.

    Google Scholar 

  20. Kobayashi A, Hasegawa K, Saiura A, Takayama T, Miyagawa S, Yamamoto J, Bandai Y, Teruya M, Yoshimi F, Kawasaki S, Koyama H, Oba M, Takahashi M, Mizunuma N, Matsuyama Y, Watanabe T, Makuuchi M, Kokudo N. A randomized controlled trial evaluating efficacy of adjuvant oral uracil-tegafur (UFT) with leucovorin (LV) after resection of colorectal cancer liver metastases: the UFT/LV study. J Clin Oncol. 2014;32:3584.

    Article  Google Scholar 

  21. Kokudo N, Hasegawa K, Makuuchi M. Control arm for surgery alone is needed but difficult to obtain in randomized trials for adjuvant chemotherapy after liver resection for colorectal metastases. J Clin Oncol. 2007;25:1299–300; author reply 1300.

    Article  PubMed  Google Scholar 

  22. Leporrier J, Maurel J, Chiche L, Bara S, Segol P, Launoy G. A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer. Br J Surg. 2006;93:465–74.

    Article  PubMed  CAS  Google Scholar 

  23. Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg. 2006;244:254–9.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Mccahill LE, Hamel-Bissell BP. The patient lived experience for surgical treatment of colorectal liver metastases: a phenomenological study. Palliat Support Care. 2009;7:65–73.

    Article  PubMed  Google Scholar 

  25. Mitry E, Fields AL, Bleiberg H, Labianca R, Portier G, Tu D, Nitti D, Torri V, Elias D, O’Callaghan C, Langer B, Martignoni G, Bouche O, Lazorthes F, Van Cutsem E, Bedenne L, Moore MJ, Rougier P. Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol. 2008;26:4906–11.

    Article  CAS  PubMed  Google Scholar 

  26. Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Mauer M, Tanis E, Van Cutsem E, Scheithauer W, Gruenberger T, EORTC Gastro-Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und–tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO); Australasian Gastro-Intestinal Trials Group (AGITG); Fédération Francophone de Cancérol. 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. 2013;14:1208–15.

    Article  CAS  PubMed  Google Scholar 

  27. Parks R, Gonen M, Kemeny N, Jarnagin W, D’Angelica M, Dematteo R, Garden OJ, Blumgart LH, Fong Y. Adjuvant chemotherapy improves survival after resection of hepatic colorectal metastases: analysis of data from two continents. J Am Coll Surg. 2007;204:753–61; discussion 761–3.

    Article  PubMed  Google Scholar 

  28. Portier G, Elias D, Bouche O, Rougier P, Bosset JF, Saric J, Belghiti J, Piedbois P, Guimbaud R, Nordlinger B, Bugat R, Lazorthes F, Bedenne L. 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;24:4976–82.

    Article  CAS  PubMed  Google Scholar 

  29. Poston GJ, Tait D, O’Connell S, Bennett A, Berendse S, Guideline Development G. Diagnosis and management of colorectal cancer: summary of NICE guidance. BMJ. 2011;343:d6751.

    Article  PubMed  CAS  Google Scholar 

  30. Primrose J, Falk S, Finch-Jones M, Valle J, O’Reilly D, Siriwardena A, Hornbuckle J, Peterson M, Rees M, Iveson T, Hickish T, Butler R, Stanton L, Dixon E, Little L, Bowers M, Pugh S, Garden OJ, Cunningham D, Maughan T, Bridgewater J. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the new EPOC randomised controlled trial. Lancet Oncol. 2014;15:601–11.

    Article  CAS  PubMed  Google Scholar 

  31. Rees M, Tekkis PP, Welsh FK, O’Rourke T, John TG. Evaluation of long-term survival after hepatic resection for metastatic colorectal cancer: a multifactorial model of 929 patients. Ann Surg. 2008;247:125–35.

    Article  PubMed  Google Scholar 

  32. Saltz LB, Douillard JY, Pirotta N, Alakl M, Gruia G, Awad L, Elfring GL, Locker PK, Miller LL. Irinotecan plus fluorouracil/leucovorin for metastatic colorectal cancer: a new survival standard. Oncologist. 2001;6:81–91.

    Article  PubMed  CAS  Google Scholar 

  33. Sargent D, Sobrero A, Grothey A, O’Connell MJ, Buyse M, Andre T, Zheng Y, Green E, Labianca R, O’Callaghan C, Seitz JF, Francini G, Haller D, Yothers G, Goldberg R, De Gramont A. Evidence for cure by adjuvant therapy in colon cancer: observations based on individual patient data from 20,898 patients on 18 randomized trials. J Clin Oncol. 2009;27:872–7.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Scheele J, Stangl R, Altendorf-Hofmann A. Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural history. Br J Surg. 1990;77:1241–6.

    Article  PubMed  CAS  Google Scholar 

  35. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29.

    Article  PubMed  Google Scholar 

  36. Simmonds PC. Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. Colorectal Cancer Collaborative Group. BMJ. 2000;321:531–5.

    Article  PubMed  CAS  Google Scholar 

  37. Simmonds PC, Primrose JN, Colquitt JL, Garden OJ, Poston GJ, Rees M. Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies. Br J Cancer. 2006;94:982–99.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Snoeren N, Van Hillegersberg R, Schouten SB, Bergman AM, Van Werkhoven E, Dalesio O, Tollenaar RA, Verheul HM, Van Der Sijp J, Borel Rinkes IH, Voest EE, Hepatica Study Group. Randomized phase III study to assess efficacy and safety of adjuvant CAPOX with or without bevacizumab in patients after resection of colorectal liver metastases: HEPATICA study. Neoplasia. 2017;19:93–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Stintzing S, Stremitzer S, Sebio A, Lenz HJ. Predictive and prognostic markers in the treatment of metastatic colorectal cancer (mCRC): personalized medicine at work. Hematol Oncol Clin North Am. 2015;29:43–60.

    Article  PubMed  Google Scholar 

  40. Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, Esser R, Lenz HJ, Heinemann V. Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: retrospective analyses of the CRYSTAL and FIRE-3 trials. JAMA Oncol. 2017;3(2):194–201.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Tomlinson JS, Jarnagin WR, Dematteo RP, Fong Y, Kornprat P, Gonen M, Kemeny N, Brennan MF, Blumgart LH, D’Angelica M. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25:4575–80.

    Article  PubMed  Google Scholar 

  42. Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D’Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Kohne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Osterlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taieb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27:1386–422.

    Article  PubMed  Google Scholar 

  43. Van Der Pool AE, De Wilt JH, Lalmahomed ZS, Eggermont AM, Ijzermans JN, Verhoef C. Optimizing the outcome of surgery in patients with rectal cancer and synchronous liver metastases. Br J Surg. 2010;97:383–90.

    Article  PubMed  Google Scholar 

  44. Wang X, Hershman DL, Abrams JA, Feingold D, Grann VR, Jacobson JS, Neugut AI. Predictors of survival after hepatic resection among patients with colorectal liver metastasis. Br J Cancer. 2007;97:1606–12.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Ychou M, Hohenberger W, Thezenas S, Navarro M, Maurel J, Bokemeyer C, Shacham-Shmueli E, Rivera F, Kwok-Keung Choi C, Santoro A. 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;20:1964–70.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Instituto Nacional de Câncer, Americas Centro de Oncologia Integrado, Hospital Pró-Cardíaco, Rio de Janeiro, Brazil

    Carlos José Coelho de Andrade

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  1. Carlos José Coelho de Andrade
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Editors and Affiliations

  1. National Cancer Institute, Rio de Janeiro, Brazil

    Mauro Monteiro Correia

  2. Banner MD Anderson Cancer Center, Phoenix, AZ, USA

    Michael A. Choti

  3. Virginia Mason Medical Center, Seattle, WA, USA

    Flavio G. Rocha

  4. Center for Advanced Treatment of HBP Diseases, Ageo Central General Hospital, Ageo Shi, Saitama, Japan

    Go Wakabayashi

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de Andrade, C.J.C. (2020). Adjuvant Chemotherapy for CRLM: Indications and Results. In: Correia, M., Choti, M., Rocha, F., Wakabayashi, G. (eds) Colorectal Cancer Liver Metastases. Springer, Cham. https://doi.org/10.1007/978-3-030-25486-5_19

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