Skip to main content

Adjuvant Therapy for Colorectal Cancer

  • Chapter
  • First Online:
Textbook of Gastrointestinal Oncology

Abstract

Adjuvant therapy has afforded improved outcomes following resection of locoregional colorectal cancer. In stage III colon cancer, the addition of oxaliplatin to fluoropyrimidines represents the standard in the adjuvant setting. The role of adjuvant therapy in stage II colon cancer remains controversial, though adjuvant therapy (oxaliplatin-based combination therapy or fluoropyrimidine monotherapy) could be considered and justified in stage II disease with high-risk features for recurrence. The development of various gene expression signatures may provide additional information in determining candidates for adjuvant therapy in stage II colon cancer, particularly those at low risk of recurrence. In locally advanced rectal cancer, neoadjuvant chemoradiation followed by total mesorectal excision and adjuvant fluoropyrimidine and oxaliplatin-based therapy represents a currently favored treatment approach. There are growing data to support the use of perioperative or adjuvant therapy in resectable colorectal liver and pulmonary metastases. In this chapter, we highlight the historical development and recent advances in the adjuvant therapy of locally advanced colorectal cancer and resectable colorectal metastases.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Siegel R, Desantis C, Jemal A. Colorectal cancer statistics, 2014. CA Cancer J Clin. 2014;64(2):104–17.

    Article  PubMed  Google Scholar 

  2. Fakih MG. Metastatic colorectal cancer: current state and future directions. J Clin Oncol. 2015;33(16):1809–24.

    Article  CAS  PubMed  Google Scholar 

  3. Dienstmann R, Salazar R, Tabernero J. Personalizing colon cancer adjuvant therapy: selecting optimal treatments for individual patients. J Clin Oncol. 2015;33:1787–96.

    Article  CAS  PubMed  Google Scholar 

  4. Chen VW, Hsieh MC, Charlton ME, Ruiz BA, Karlitz J, Altekruse SF, et al. Analysis of stage and clinical/prognostic factors for colon and rectal cancer from SEER registries: AJCC and collaborative stage data collection system. Cancer. 2014;120:3793–806.

    Article  PubMed  Google Scholar 

  5. Hari DM, Leung AM, Lee JH, Sim MS, Vuong B, Chiu CG, et al. AJCC cancer staging manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment? J Am Coll Surg. 2013;217:181–90.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Anonymous. NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA. 1990;264:1444–50.

    Article  Google Scholar 

  7. Buyse M, Zeleniuch-Jacquotte A, Chalmers TC. Adjuvant therapy of colorectal cancer. Why we still don’t know. JAMA. 1988;259:3571–8.

    Article  CAS  PubMed  Google Scholar 

  8. Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Tangen CM, et al. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med. 1995;122:321–6.

    Article  CAS  PubMed  Google Scholar 

  9. Wolmark N, Rockette H, Fisher B, Wickerham DL, Redmond C, Fisher ER, et al. 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. 1993;11:1879–87.

    Article  CAS  PubMed  Google Scholar 

  10. Wolmark N, Rockette H, Mamounas E, Jones J, Wieand S, Wickerham DL, et al. Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with dukes’ b and c carcinoma of the colon: results from national surgical adjuvant breast and bowel project c-04. J Clin Oncol. 1999;17:3553–9.

    Article  CAS  PubMed  Google Scholar 

  11. Arkenau HT, Bermann A, Rettig K, Strohmeyer G, Porschen R, Onkologie AG. 5-fluorouracil plus leucovorin is an effective adjuvant chemotherapy in curatively resected stage III colon cancer: long-term follow-up results of the adjcca-01 trial. Ann Oncol. 2003;14:395–9.

    Article  CAS  PubMed  Google Scholar 

  12. Haller DG, Catalano PJ, Macdonald JS, O’Rourke MA, Frontiera MS, Jackson DV, et al. Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of intergroup 0089. J Clin Oncol. 2005;23:8671–8.

    Article  PubMed  Google Scholar 

  13. Lembersky BC, Wieand HS, Petrelli NJ, O’Connell MJ, Colangelo LH, Smith RE, et al. Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from national surgical adjuvant breast and bowel project protocol c-06. J Clin Oncol. 2006;24:2059–64.

    Article  CAS  PubMed  Google Scholar 

  14. Twelves C, Wong A, Nowacki MP, Abt M, Burris H, Carrato A, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005;352:2696–704.

    Article  CAS  PubMed  Google Scholar 

  15. Wolmark N, Colangelo L, Wieand S. National surgical adjuvant breast and bowel project trials in colon cancer. Semin Oncol. 2001;28:9–13.

    Article  CAS  PubMed  Google Scholar 

  16. Smith RE, Colangelo L, Wieand HS, Begovic M, Wolmark N. Randomized trial of adjuvant therapy in colon carcinoma: 10-year results of nsabp protocol c-01. J Natl Cancer Inst. 2004;96:1128–32.

    Article  CAS  PubMed  Google Scholar 

  17. Wolmark N, Rockette H, Wickerham DL, Fisher B, Redmond C, Fisher ER, et al. Adjuvant therapy of dukes’ a, b, and c adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of national surgical adjuvant breast and bowel project protocol c-02. J Clin Oncol. 1979;8:1466–75.

    Article  Google Scholar 

  18. Köhne CH, Bedenne L, Carrato A, Bouché O, Popov I, Gaspà L, et al. A randomised phase III intergroup trial comparing high-dose infusional 5-fluorouracil with or without folinic acid with standard bolus 5-fluorouracil/folinic acid in the adjuvant treatment of stage III colon cancer: the Pan-European trial in adjuvant colon cancer 2 study. Eur J Cancer. 2013;49:1868–75.

    Article  CAS  PubMed  Google Scholar 

  19. Andre T, Colin P, Louvet C, Gamelin E, Bouche O, Achille E, et al. Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer: results of a randomized trial. J Clin Oncol. 2003;21(15):2896–903.

    Article  CAS  PubMed  Google Scholar 

  20. André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350:2343–51.

    Article  PubMed  Google Scholar 

  21. André T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, et al. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015;33(35):4176–87. https://doi.org/10.1200/JCO.2015.63.4238.

    Article  CAS  PubMed  Google Scholar 

  22. Kuebler JP, Wieand HS, O’Connell MJ, Smith RE, Colangelo LH, Yothers G, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from nsabp c-07. J Clin Oncol. 2007;25:2198–204.

    Article  CAS  PubMed  Google Scholar 

  23. Yothers G, O’Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, et al. Oxaliplatin as adjuvant therapy for colon cancer: updated results of nsabp c-07 trial, including survival and subset analyses. J Clin Oncol. 2011;29:3768–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, et al. Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results of the no16968 randomized controlled phase III trial. J Clin Oncol. 2015;33:3733–40.

    Article  CAS  PubMed  Google Scholar 

  25. Saltz LB, Niedzwiecki D, Hollis D, Goldberg RM, Hantel A, Thomas JP, et al. Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803. J Clin Oncol. 2007;25:3456–61.

    Article  CAS  PubMed  Google Scholar 

  26. Van Cutsem E, Labianca R, Bodoky G, Barone C, Aranda E, Nordlinger B, et al. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: Petacc-3. J Clin Oncol. 2009;27:3117–25.

    Article  CAS  PubMed  Google Scholar 

  27. Ychou M, Raoul JL, Douillard JY, Gourgou-Bourgade S, Bugat R, Mineur L, et al. A phase III randomised trial of lv5fu2 + irinotecan versus lv5fu2 alone in adjuvant high-risk colon cancer (FNCLCC ACCORD02/FFCD9802). Ann Oncol. 2009;20:674–80.

    Article  CAS  PubMed  Google Scholar 

  28. Allegra CJ, Yothers G, O’Connell MJ, Sharif S, Petrelli NJ, Colangelo LH, et al. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of nsabp protocol c-08. J Clin Oncol. 2011;29:11–6.

    Article  CAS  PubMed  Google Scholar 

  29. Allegra CJ, Yothers G, O’Connell MJ, Sharif S, Petrelli NJ, Lopa SH, et al. Bevacizumab in stage II–III colon cancer: 5-year update of the national surgical adjuvant breast and bowel project c-08 trial. J Clin Oncol. 2013;31(3):359–64.

    Article  CAS  PubMed  Google Scholar 

  30. Pogue-Geile KL, Yothers G, Taniyama Y, Tanaka N, Gavin P, Colangelo L, et al. Defective mismatch repair and benefit from bevacizumab for colon cancer: findings from nsabp c-08. J Natl Cancer Inst. 2013;105:989–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. de Gramont A, Van Cutsem E, Schmoll HJ, Tabernero J, Clarke S, Moore MJ, et al. Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol. 2012;13:1225–33.

    Article  CAS  PubMed  Google Scholar 

  32. Midgley RS, Love S, Tomlinson I, Johnstone E, Scudder C, Pearson SR, et al. Final results from quasar2, a multicentre, international randomised phase III trial of capecitabine (CAP) +/− bevacizumab (BEV) in the adjuvant setting of stage II/III colorectal cancer (CRC). Ann Oncol. 2014;25 https://doi.org/10.1093/annonc/mdu1438.1010.

  33. Alberts SR, Sargent DJ, Nair S, Mahoney MR, Mooney M, Thibodeau SN, et al. Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA. 2012;307:1383–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Huang J, Nair SG, Mahoney MR, Nelson GD, Shields AF, Chan E, et al. Comparison of FOLFIRI with or without cetuximab in patients with resected stage III colon cancer; NCCTG (alliance) intergroup trial n0147. Clin Colorectal Cancer. 2014;13:100–9.

    Article  PubMed  Google Scholar 

  35. Taieb J, Tabernero J, Mini E, Subtil F, Folprecht G, Van Laethem JL, et al. Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (petacc-8): an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15:862–73.

    Article  CAS  PubMed  Google Scholar 

  36. Schrag D, Cramer LD, Bach PB, Begg CB. Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst. 2001;93:850–7.

    Article  CAS  PubMed  Google Scholar 

  37. Sargent DJ, Goldberg RM, Jacobson SD, Macdonald JS, Labianca R, Haller DG, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001;345:1091–7.

    Article  CAS  PubMed  Google Scholar 

  38. Haller DG, O’Connell MJ, Cartwright TH, Twelves CJ, McKenna EF, Sun W, et al. Impact of age and medical comorbidity on adjuvant treatment outcomes for stage III colon cancer: a pooled analysis of individual patient data from four randomized, controlled trials. Ann Oncol. 2015;26:715–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gross CP, McAvay GJ, Guo Z, Tinetti ME. The impact of chronic illnesses on the use and effectiveness of adjuvant chemotherapy for colon cancer. Cancer. 2007;109:2410–9.

    Article  PubMed  Google Scholar 

  40. Muss HB, Biganzoli L, Sargent DJ, Aapro M. Adjuvant therapy in the elderly: making the right decision. J Clin Oncol. 2007;25:1870–5.

    Article  PubMed  Google Scholar 

  41. Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Tangen CM, et al. Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/dukes’ b2 colon cancer. J Clin Oncol. 1995;13:2936–43.

    Article  CAS  PubMed  Google Scholar 

  42. Mamounas E, Wieand S, Wolmark N, Bear HD, Atkins JN, Song K, et al. Comparative efficacy of adjuvant chemotherapy in patients with dukes’ b versus dukes’ c colon cancer: results from four national surgical adjuvant breast and bowel project adjuvant studies (c-01, c-02, c-03, and c-04). J Clin Oncol. 1999;17:1349–55.

    Article  CAS  PubMed  Google Scholar 

  43. International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. Efficacy of adjuvant fluorouracil and folinic acid in b2 colon cancer. J Clin Oncol. 1999;17:1356–63.

    Article  Google Scholar 

  44. Quasar Collaborative Group, Gray R, Barnwell J, McConkey C, Hills RK, Williams NS, et al. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007;370:2020–9.

    Article  CAS  Google Scholar 

  45. Benson AB, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American society of clinical oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:3408–19.

    Article  PubMed  Google Scholar 

  46. National Comprehensive Cancer Network. NCCN guidelines: colon cancer, version 2.2016. http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf.

  47. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. A national cancer institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998;58:5248–57.

    CAS  PubMed  Google Scholar 

  48. Zaanan A, Fléjou JF, Emile JF, Des GG, Cuilliere-Dartigues P, Malka D, et al. Defective mismatch repair status as a prognostic biomarker of disease-free survival in stage III colon cancer patients treated with adjuvant FOLFOX chemotherapy. Clin Cancer Res. 2011;17:7470–8.

    Article  CAS  PubMed  Google Scholar 

  49. Des Guetz G, Lecaille C, Mariani P, Bennamoun M, Uzzan B, Nicolas P, et al. Prognostic impact of microsatellite instability in colorectal cancer patients treated with adjuvant FOLFOX. Anticancer Res. 2010;30:4297–301.

    CAS  PubMed  Google Scholar 

  50. Gavin PG, Paik S, Yothers G, Pogue-Geile KL. Colon cancer mutation: prognosis/prediction-response. Clin Cancer Res. 2013;19:1301.

    Article  PubMed  Google Scholar 

  51. Tougeron D, Sickersen G, Lecomte T, Mouillet G, Trouilloud I, Coriat R, et al. Impact of adjuvant chemotherapy with 5-FU or FOLFOX in colon cancers with microsatellite instability: an AGEO multicenter study. J Clin Oncol. 2014;32:Abstract 3508.

    Article  Google Scholar 

  52. Sargent DJ, Marsoni S, Monges G, Thibodeau SN, Labianca R, Hamilton SR, et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol. 2010;28:3219–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. You YN, Rustin RB, Sullivan JD. Oncotype dx(®) colon cancer assay for prediction of recurrence risk in patients with stage II and III colon cancer: a review of the evidence. Surg Oncol. 2015;24:61–6.

    Article  PubMed  Google Scholar 

  54. Gray RG, Quirke P, Handley K, Lopatin M, Magill L, Baehner FL, et al. Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. J Clin Oncol. 2011;29:4611–9.

    Article  PubMed  Google Scholar 

  55. Venook AP, Niedzwiecki D, Lopatin M, Ye X, Lee M, Friedman PN, et al. Biologic determinants of tumor recurrence in stage II colon cancer: validation study of the 12-gene recurrence score in cancer and leukemia group b (CALGB) 9581. J Clin Oncol. 2013;31:1775–81.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Yothers G, O’Connell MJ, Lee M, Lopatin M, Clark-Langone KM, Millward C, et al. Validation of the 12-gene colon cancer recurrence score in nsabp c-07 as a predictor of recurrence in patients with stage II and III colon cancer treated with fluorouracil and leucovorin (FU/LV) and FU/LV plus oxaliplatin. J Clin Oncol. 2013;31:4512–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Srivastava G, Renfro LA, Behrens RJ, Lopatin M, Chao C, Soori GS, et al. Prospective multicenter study of the impact of oncotype dx colon cancer assay results on treatment recommendations in stage II colon cancer patients. Oncologist. 2014;19:492–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sharif S, O’Connell MJ. Gene signatures in stage II colon cancer: a clinical review. Curr Colorectal Cancer Rep. 2012;8(3):225–31.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5–29.

    Article  PubMed  Google Scholar 

  60. Nelson H, Petrelli N, Carlin A, Couture J, Fleshman J, Guillem J, et al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst. [Guideline Practice Guideline Research Support, U.S. Gov’t, P.H.S.]. 2001;93(8):583–96.

    CAS  Google Scholar 

  61. Pilipshen SJ, Heilweil M, Quan SH, Sternberg SS, Enker WE. Patterns of pelvic recurrence following definitive resections of rectal cancer. Cancer. [Comparative Study]. 1984;53(6):1354–62.

    CAS  Google Scholar 

  62. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. [Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2001;345(9):638–46.

    CAS  Google Scholar 

  63. Schoellhammer HF, Gregorian AC, Sarkisyan GG, Petrie BA. How important is rigid proctosigmoidoscopy in localizing rectal cancer? Am J Surg. [Comparative Study]. 2008;196(6):904–8; discussion 908.

    Article  Google Scholar 

  64. Muthusamy VR, Chang KJ. Optimal methods for staging rectal cancer. Clin Cancer Res. [Review]. 2007;13(22 Pt 2):6877s–84s.

    Article  Google Scholar 

  65. Taylor FG, Quirke P, Heald RJ, Moran BJ, Blomqvist L, Swift IR, et al. Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the mercury study. J Clin Oncol. [Clinical Trial Research Support, Non-U.S. Gov’t]. 2014;32(1):34–43.

    Google Scholar 

  66. Nagtegaal ID, Quirke P. What is the role for the circumferential margin in the modern treatment of rectal cancer? J Clin Oncol. [Research Support, Non-U.S. Gov’t Review]. 2008;26(2):303–12.

    Google Scholar 

  67. Havenga K, Enker WE, Norstein J, Moriya Y, Heald RJ, van Houwelingen HC, et al. Improved survival and local control after total mesorectal excision or d3 lymphadenectomy in the treatment of primary rectal cancer: an international analysis of 1411 patients. Eur J Surg Oncol. [Multicenter Study]. 1999;25(4):368–74.

    Article  CAS  Google Scholar 

  68. Peeters KC, Marijnen CA, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, et al. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. [Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2007;246(5):693–701.

    Google Scholar 

  69. den Dulk M, Putter H, Collette L, Marijnen CA, Folkesson J, Bosset JF, et al. The abdominoperineal resection itself is associated with an adverse outcome: the European experience based on a pooled analysis of five European randomised clinical trials on rectal cancer. Eur J Cancer. [Research Support, Non-U.S. Gov’t]. 2009;45(7):1175–83.

    Google Scholar 

  70. Merkel S, Mansmann U, Siassi M, Papadopoulos T, Hohenberger W, Hermanek P. The prognostic inhomogeneity in pt3 rectal carcinomas. Int J Colorectal Dis. 2001;16(5):298–304.

    Article  CAS  PubMed  Google Scholar 

  71. Merkel S, Weber K, Schellerer V, Gohl J, Fietkau R, Agaimy A, et al. Prognostic subdivision of ypt3 rectal tumours according to extension beyond the muscularis propria. Br J Surg. 2014;101(5):566–72.

    Article  CAS  PubMed  Google Scholar 

  72. Dresen RC, Peters EE, Rutten HJ, Nieuwenhuijzen GA, Demeyere TB, van den Brule AJ, et al. Local recurrence in rectal cancer can be predicted by histopathological factors. Eur J Surg Oncol. 2009;35(10):1071–7.

    Article  CAS  PubMed  Google Scholar 

  73. Smith NJ, Barbachano Y, Norman AR, Swift RI, Abulafi AM, Brown G. Prognostic significance of magnetic resonance imaging-detected extramural vascular invasion in rectal cancer. Br J Surg. [Comparative Study Research Support, Non-U.S. Gov’t]. 2008;95(2):229–36.

    CAS  Google Scholar 

  74. Anonymous, Gastrointestinal tumor study group. Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med. [Clinical Trial Randomized Controlled Trial Research Support, U.S. Gov’t, P.H.S.]. 1985;312(23):1465–72.

    Google Scholar 

  75. Douglass HO Jr, Moertel CG, Mayer RJ, Thomas PR, Lindblad AS, Mittleman A, et al. Survival after postoperative combination treatment of rectal cancer. N Engl J Med. [Letter]. 1986;315(20):1294–5.

    Article  Google Scholar 

  76. Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from nsabp protocol r-01. J Natl Cancer Inst. [Clinical Trial Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S.]. 1988;80(1):21–9.

    CAS  Google Scholar 

  77. Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med. [Clinical Trial Comparative Study Randomized Controlled Trial Research Support, U.S. Gov’t, P.H.S.]. 1991;324(11):709–15.

    CAS  Google Scholar 

  78. Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. [Clinical Trial Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2004;351(17):1731–40.

    CAS  Google Scholar 

  79. Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. [Clinical Trial, Phase III Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2012;30(16):1926–33.

    CAS  Google Scholar 

  80. Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. [Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2009;373(9666):811–20.

    Google Scholar 

  81. Quirke P, Steele R, Monson J, Grieve R, Khanna S, Couture J, et al. Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial. Lancet. [Research Support, Non-U.S. Gov’t]. 2009;373(9666):821–8.

    Google Scholar 

  82. Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in t3–4 rectal cancers: results of FFCD 9203. J Clin Oncol. [Multicenter Study Randomized Controlled Trial]. 2006;24(28):4620–5.

    Google Scholar 

  83. Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. [Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. 2006;355(11):1114–23.

    CAS  Google Scholar 

  84. Bosset JF, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, et al. Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results–EORTC 22921. J Clin Oncol. [Clinical Trial Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S.]. 2005;23(24):5620–7.

    CAS  Google Scholar 

  85. Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. [Comparative Study Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. 2014;15(2):184–90.

    CAS  Google Scholar 

  86. O’Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, et al. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med. [Clinical Trial Randomized Controlled Trial Research Support, U.S. Gov’t, P.H.S.]. 1994;331(8):502–7.

    Google Scholar 

  87. Smalley SR, Benedetti JK, Williamson SK, Robertson JM, Estes NC, Maher T, et al. Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol. [Clinical Trial, Phase III Randomized Controlled Trial Research Support, N.I.H., Extramural]. 2006;24(22):3542–7.

    CAS  Google Scholar 

  88. Allegra CJ, Yothers G, O’Connell MJ, Beart RW, Wozniak TF, Pitot HC, et al. Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: a phase III randomized clinical trial. J Natl Cancer Inst. [Clinical Trial, Phase III Randomized Controlled Trial Research Support, N.I.H., Extramural]. 2015;107(11):pii: djv248.

    Google Scholar 

  89. Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. [Clinical Trial, Phase III Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2012;13(6):579–88.

    CAS  Google Scholar 

  90. Rodel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, et al. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. [Clinical Trial, Phase III Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2012;13(7):679–87.

    Google Scholar 

  91. Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, et al. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the star-01 randomized phase III trial. J Clin Oncol. [Clinical Trial, Phase III Multicenter Study Randomized Controlled Trial]. 2011;29(20):2773–80.

    CAS  Google Scholar 

  92. Gerard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, et al. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol. [Clinical Trial, Phase III Comparative Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2010;28(10):1638–44.

    CAS  Google Scholar 

  93. Schmoll HJ, Haustermans K, Price TJ, et al. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: disease-free survival results at interim analysis. J Clin Oncol. 2014;32(15_suppl):abstr 3501.

    Article  Google Scholar 

  94. Rodel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, et al. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. [Clinical Trial, Phase III Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2015;16(8):979–89.

    Google Scholar 

  95. Gerard JP, Azria D, Gourgou-Bourgade S, Martel-Lafay I, Hennequin C, Etienne PL, et al. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol. [Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2012;30(36):4558–65.

    CAS  Google Scholar 

  96. Crane CH, Eng C, Feig BW, Das P, Skibber JM, Chang GJ, et al. Phase II trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. [Clinical Trial, Phase II Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. 2010;76(3):824–30.

    CAS  Google Scholar 

  97. Spigel DR, Bendell JC, McCleod M, Shipley DL, Arrowsmith E, Barnes EK, et al. Phase II study of bevacizumab and chemoradiation in the preoperative or adjuvant treatment of patients with stage II/III rectal cancer. Clin Colorectal Cancer. [Clinical Trial, Phase II Multicenter Study Research Support, Non-U.S. Gov’t]. 2012;11(1):45–52.

    CAS  Google Scholar 

  98. Salazar R, Capdevila J, Laquente B, Manzano JL, Pericay C, Villacampa MM, et al. A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer: clinical and biological features. BMC Cancer. 2015;15:60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Landry JC, Feng Y, Prabhu RS, Cohen SJ, Staley CA, Whittington R, et al. Phase II trial of preoperative radiation with concurrent capecitabine, oxaliplatin, and bevacizumab followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: 5-year clinical outcomes ECOG-ACRIN cancer research group e3204. Oncologist. 2015;20(6):615–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Sclafani F, Gonzalez D, Cunningham D, Hulkki Wilson S, Peckitt C, Giralt J, et al. RAS mutations and cetuximab in locally advanced rectal cancer: results of the EXPERT-C trial. Eur J Cancer. [Clinical Trial, Phase II Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2014;50(8):1430–6.

    CAS  Google Scholar 

  101. Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish rectal cancer trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. [Clinical Trial Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2005;23(24):5644–50.

    Google Scholar 

  102. van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. [Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2011;12(6):575–82.

    Google Scholar 

  103. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg. [Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2006;93(10):1215–23.

    CAS  Google Scholar 

  104. Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, et al. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with t3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. [Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2012;30(31):3827–33.

    Google Scholar 

  105. Sloothaak DA, Geijsen DE, van Leersum NJ, Punt CJ, Buskens CJ, Bemelman WA, et al. Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer. Br J Surg. 2013;100(7):933–9.

    Article  CAS  PubMed  Google Scholar 

  106. Khrizman P, Niland JC, ter Veer A, Milne D, Bullard Dunn K, Carson WE 3rd, et al. Postoperative adjuvant chemotherapy use in patients with stage II/III rectal cancer treated with neoadjuvant therapy: a national comprehensive cancer network analysis. J Clin Oncol. 2013;31(1):30–8.

    Article  PubMed  Google Scholar 

  107. Benson AB 3rd, Venook AP, Bekaii-Saab T, Chan E, Chen YJ, Cooper HS, et al. Rectal cancer, version 2.2015. J National Compr Cancer Network: JNCCN. [Research Support, Non-U.S. Gov’t]. 2015;13(6):719–28; quiz 728.

    Article  Google Scholar 

  108. Andre T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, et al. 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. [Clinical Trial, Phase III Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2009;27(19):3109–16.

    CAS  Google Scholar 

  109. Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, et al. Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results of the no16968 randomized controlled phase III trial. J Clin Oncol. 2015;33(32):3733–40.

    Article  CAS  PubMed  Google Scholar 

  110. Petersen SH, Harling H, Kirkeby LT, Wille-Jorgensen P, Mocellin S. Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database Syst Rev. [Meta-Analysis Review]. 2012;3:CD004078.

    Google Scholar 

  111. Sainato A, Cernusco Luna Nunzia V, Valentini V, De Paoli A, Maurizi ER, Lupattelli M, et al. No benefit of adjuvant fluorouracil leucovorin chemotherapy after neoadjuvant chemoradiotherapy in locally advanced cancer of the rectum (LARC): long term results of a randomized trial (I-CNR-RT). Radiother Oncol. [Clinical Trial, Phase III Randomized Controlled Trial]. 2014;113(2):223–9.

    Google Scholar 

  112. Breugom AJ, van Gijn W, Muller EW, Berglund A, van den Broek CB, Fokstuen T, et al. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch colorectal cancer group (DCCG) randomized phase III trial. Ann Oncol. [Research Support, Non-U.S. Gov’t]. 2015;26(4):696–701.

    CAS  Google Scholar 

  113. Glynne-Jones R, Counsell N, Quirke P, Mortensen N, Maraveyas A, Meadows HM, et al. Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control. Ann Oncol. [Clinical Trial, Phase III Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2014;25(7):1356–62.

    CAS  Google Scholar 

  114. Schmoll HJSA, Hofheinz RD, Price TJ, Nordlinger B, Daisne J-F, et al. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin vs. Capecitabine alone in locally advanced rectal cancer: final analyses. Ann Oncol. 2016;27(suppl 6):467PD.

    Google Scholar 

  115. Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, et al. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (adore): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol. [Clinical Trial, Phase II Comparative Study Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2014;15(11):1245–53.

    CAS  Google Scholar 

  116. Al-Sukhni E, Milot L, Fruitman M, Beyene J, Victor JC, Schmocker S, et al. Diagnostic accuracy of MRI for assessment of t category, lymph node metastases, and circumferential resection margin involvement in patients with rectal cancer: a systematic review and meta-analysis. Ann Surg Oncol. [Meta-Analysis Research Support, Non-U.S. Gov’t]. 2012;19(7):2212–23.

    Google Scholar 

  117. Zorcolo L, Rosman AS, Restivo A, Pisano M, Nigri GR, Fancellu A, et al. Complete pathologic response after combined modality treatment for rectal cancer and long-term survival: a meta-analysis. Ann Surg Oncol. [Meta-Analysis]. 2012;19(9):2822–32.

    Article  Google Scholar 

  118. Haynes AB, You YN, Hu CY, Eng C, Kopetz ES, Rodriguez-Bigas MA, et al. Postoperative chemotherapy use after neoadjuvant chemoradiotherapy for rectal cancer: analysis of surveillance, epidemiology, and end results-Medicare data, 1998–2007. Cancer. [Research Support, N.I.H., Extramural]. 2014;120(8):1162–70.

    CAS  Google Scholar 

  119. Schrag D, Weiser MR, Goodman KA, Gonen M, Hollywood E, Cercek A, et al. Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol. [Clinical Trial, Phase II Research Support, Non-U.S. Gov’t]. 2014;32(6):513–8.

    CAS  Google Scholar 

  120. Perez K, Safran H, Sikov W, Vrees M, Klipfel A, Shah N, et al. Complete neoadjuvant treatment for rectal cancer: the brown university oncology group CONTRE study. Am J Clin Oncol. 2017;40(3):283–7.

    Article  CAS  PubMed  Google Scholar 

  121. Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, et al. Effect of adding mfolfox6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. [Clinical Trial, Phase II Multicenter Study Research Support, N.I.H., Extramural]. 2015;16(8):957–66.

    CAS  Google Scholar 

  122. Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, Gonen M, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25(29):4575–80.

    Article  PubMed  Google Scholar 

  123. Choti MA, Sitzmann JV, Tiburi MF, Sumetchotimetha W, Rangsin R, Schulick RD, et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg. 2002;235(6):759–66.

    Article  PubMed  PubMed Central  Google Scholar 

  124. Wei AC, Greig PD, Grant D, Taylor B, Langer B, Gallinger S. Survival after hepatic resection for colorectal metastases: a 10-year experience. Ann Surg Oncol. 2006;13(5):668–76.

    Article  PubMed  Google Scholar 

  125. Pawlik TM, Vauthey JN, Abdalla EK, Pollock RE, Ellis LM, Curley SA. Results of a single-center experience with resection and ablation for sarcoma metastatic to the liver. Arch Surg. 2006;141(6):537–43; discussion 543–4.

    Article  PubMed  Google Scholar 

  126. 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(3):438–47; discussion 447–50.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Abdalla EK, Vauthey JN, Ellis LM, Ellis V, Pollock R, Broglio KR, et al. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg. 2004;239(6):818–25; discussion 825–7.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Sanoff HK, Sargent DJ, Campbell ME, Morton RF, Fuchs CS, Ramanathan RK, et al. Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741. J Clin Oncol. 2008;26(35):5721–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Salah S, Watanabe K, Welter S, Park JS, Park JW, Zabaleta J, et al. Colorectal cancer pulmonary oligometastases: pooled analysis and construction of a clinical lung metastasectomy prognostic model. Ann Oncol. 2012;23(10):2649–55.

    Article  CAS  PubMed  Google Scholar 

  130. Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, et al. 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. 2008;371(9617):1007–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Portier G, Elias D, Bouche O, Rougier P, Bosset JF, Saric J, et al. 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(31):4976–82.

    Article  CAS  PubMed  Google Scholar 

  132. Mitry E, Fields AL, Bleiberg H, Labianca R, Portier G, Tu D, et al. Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol. 2008;26(30):4906–11.

    Article  CAS  PubMed  Google Scholar 

  133. Kobayashi A, Hasegawa K, Saiura A, Takayama T, Miyagawa S, Yamamoto J, et al. 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(5s_ Suppl):abstr 3584.

    Article  Google Scholar 

  134. Ychou M, Hohenberger W, Thezenas S, Navarro M, Maurel J, Bokemeyer C, et al. 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(12):1964–70.

    Article  CAS  PubMed  Google Scholar 

  135. Primrose J, Falk S, Finch-Jones M, Valle J, O’Reilly D, Siriwardena A, et al. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the new EPOC randomised controlled trial. Lancet Oncol. 2014;15(6):601–11.

    Article  CAS  PubMed  Google Scholar 

  136. Kemeny N, Huang Y, Cohen AM, Shi W, Conti JA, Brennan MF, et al. Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med. 1999;341(27):2039–48.

    Article  CAS  PubMed  Google Scholar 

  137. Kemeny NE, Gonen M. Hepatic arterial infusion after liver resection. N Engl J Med. 2005;352(7):734–5.

    Article  CAS  PubMed  Google Scholar 

  138. Kemeny NE, Niedzwiecki D, Hollis DR, Lenz HJ, Warren RS, Naughton MJ, et al. Hepatic arterial infusion versus systemic therapy for hepatic metastases from colorectal cancer: a randomized trial of efficacy, quality of life, and molecular markers (CALGB 9481). J Clin Oncol. 2006;24(9):1395–403.

    Article  CAS  PubMed  Google Scholar 

  139. Kemeny N, Gonen M, Sullivan D, Schwartz L, Benedetti F, Saltz L, et al. Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer. J Clin Oncol. 2001;19(10):2687–95.

    Article  CAS  PubMed  Google Scholar 

  140. Kemeny N, Jarnagin W, Gonen M, Stockman J, Blumgart L, Sperber D, et al. Phase I/II study of hepatic arterial therapy with floxuridine and dexamethasone in combination with intravenous irinotecan as adjuvant treatment after resection of hepatic metastases from colorectal cancer. J Clin Oncol. 2003;21(17):3303–9.

    Article  CAS  PubMed  Google Scholar 

  141. Onaitis MW, Petersen RP, Haney JC, Saltz L, Park B, Flores R, et al. Prognostic factors for recurrence after pulmonary resection of colorectal cancer metastases. Ann Thorac Surg. 2009;87(6):1684–8.

    Article  PubMed  Google Scholar 

  142. Saito Y, Omiya H, Kohno K, Kobayashi T, Itoi K, Teramachi M, et al. Pulmonary metastasectomy for 165 patients with colorectal carcinoma: a prognostic assessment. J Thorac Cardiovasc Surg. 2002;124(5):1007–13.

    Article  PubMed  Google Scholar 

  143. Hawkes EA, Ladas G, Cunningham D, Nicholson AG, Wassilew K, Barbachano Y, et al. Peri-operative chemotherapy in the management of resectable colorectal cancer pulmonary metastases. BMC Cancer. 2012;12:326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Park HS, Jung M, Shin SJ, Heo SJ, Kim CG, Lee MG, et al. Benefit of adjuvant chemotherapy after curative resection of lung metastasis in colorectal cancer. Ann Surg Oncol. 2016;23(3):928–35.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marwan Fakih .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Boland, P., Gong, J., Fakih, M. (2019). Adjuvant Therapy for Colorectal Cancer. In: Yalcin, S., Philip, P. (eds) Textbook of Gastrointestinal Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-18890-0_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-18890-0_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-18888-7

  • Online ISBN: 978-3-030-18890-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics