Skip to main content
SpringerLink
Log in

Treatment of Rectal Cancer

  • Chapter
  • First Online:
Textbook of Gastrointestinal Oncology

  • 844 Accesses

Abstract

Rectal cancer (RC) represents approximately 30% of all CRC. In the last two decades, new multimodality strategies have reduced the local recurrence (LR) rate and extended the duration of overall survival (OS). The mainstay of treatment remains surgery; however, downsizing the tumor by neoadjuvant treatment and adjuvant therapy for systemic disease has shown significant additional benefit. The standardization of total mesorectal excision (TME), radiation treatment (RT) dose delivery, optimal timing, and sequencing of treatment modalities with the use of prolonged administration of a fluoropyrimidine concurrent with RT have significantly decreased the rates of LR in the patients with locally advanced rectal cancer (LARC).

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

Access this chapter

Log in via an institution
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. Bailey CE, Hu C-Y, You YN, Bednarski BK, Rodriguez-Bigas MA, Skibber JM, et al. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975–2010. JAMA Surg. 2015;150:17.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Musio D, De Felice F, Bulzonetti N, Guarnaccia R, Caiazzo R, Bangrazi C, et al. Neoadjuvant-intensified treatment for rectal cancer: time to change? World J Gastroenterol. 2013;19:3052–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bosset J-F. Adjuvant treatment of rectal cancer: improving patient selection. Gastrointest Cancer Res. 2008;2:37–8.

    PubMed  PubMed Central  Google Scholar 

  4. Kornmann M, Staib L, Wiegel T, Kreuser E-D, Kron M, Baumann W, et al. Adjuvant chemoradiotherapy of advanced resectable rectal cancer: results of a randomised trial comparing modulation of 5-fluorouracil with folinic acid or with interferon-α. Br J Cancer. 2010;103:1163–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Samee A, Selvasekar CR. Current trends in staging rectal cancer. World J Gastroenterol. 2011;17:828–34.

    Article  PubMed  PubMed Central  Google Scholar 

  6. De Divitiis C, Nasti G, Montano M, Fisichella R, Iaffaioli RV, Berretta M. Prognostic and predictive response factors in colorectal cancer patients: between hope and reality. World J Gastroenterol. 2014;20:15049–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hansen MH, Balteskard L, Dørum LM, Eriksen MT, Vonen B. Locally recurrent rectal cancer in Norway. Br J Surg. 2009;96:1176–82.

    Article  CAS  PubMed  Google Scholar 

  8. Lemmens V, van SL, Janssen-Heijnen M, Martijn H, Rutten H, Coebergh JW. Trends in colorectal cancer in the south of the Netherlands 1975–2007: rectal cancer survival levels with colon cancer survival. Acta Oncol (Madr). 2010;49:784–96.

    Article  Google Scholar 

  9. Bosset J-F, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355:1114–23.

    Article  CAS  PubMed  Google Scholar 

  10. Gerard J-P. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24:4620–5.

    Article  PubMed  Google Scholar 

  11. 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. 2011;29:2773–80.

    Article  CAS  PubMed  Google Scholar 

  12. Dewdney A, Cunningham D, Tabernero J, Capdevila J, Glimelius B, Cervantes A, et al. Multicenter randomized phase II clinical trial comparing neoadjuvant Oxaliplatin, Capecitabine, and preoperative radiotherapy with or without Cetuximab followed by total Mesorectal excision in patients with high-risk rectal cancer (EXPERT-C). J Clin Oncol. 2012;30(14):1620–7.

    Article  CAS  PubMed  Google Scholar 

  13. Gérard J-P, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne P-L, 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. 2010;28:1638–44.

    Article  CAS  PubMed  Google Scholar 

  14. Leighl N, Gattellari M, Butow P, Brown R, Tattersall MH. Discussing adjuvant cancer therapy. J Clin Oncol. 2001;19:1768–78.

    Article  CAS  PubMed  Google Scholar 

  15. 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 

  16. Sterzing F, Hoehle F, Ulrich A, Jensen A, Debus J, Muenter M. Clinical results and toxicity for short-course preoperative radiotherapy and total mesorectal excision in rectal cancer patients. J Radiat Res. 2014;56:169–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bipat S, Glas AS, Slors FJM, Zwinderman AH, Bossuyt PMM, Stoker J. Rectal cancer: local staging and assessment of lymph node involvement with endoluminal US, CT, and MR imaging–a meta-analysis. Radiology. 2004;232:773–83.

    Article  PubMed  Google Scholar 

  18. Suzuki C, Torkzad MR, Tanaka S, Palmer G, Lindholm J, Holm T, et al. The importance of rectal cancer MRI protocols on iInterpretation accuracy. World J Surg Oncol. 2008;6:89.

    Article  PubMed  PubMed Central  Google Scholar 

  19. MERCURY Study Group. Extramural depth of tumor invasion at thin-section MR in patients with rectal cancer: results of the MERCURY study. Radiology. 2007;243:132–9.

    Article  Google Scholar 

  20. Persiani R, Biondi A, Pennestrì F, Fico V, De Simone V, Tirelli F, et al. Transanal total mesorectal excision vs laparoscopic total mesorectal excision in the treatment of low and middle rectal cancer: a propensity score matching analysis. Dis Colon Rectum. 2018;61(7):809–16.

    PubMed  Google Scholar 

  21. Heald RJ. A new approach to rectal cancer. Br J Hosp Med. 1979;22:277–81.

    CAS  PubMed  Google Scholar 

  22. Cass AW, Million RR, Pfaff WW. Patterns of recurrence following surgery alone for adenocarcinoma of the colon and rectum. Cancer. 1976;37:2861–5.

    Article  CAS  PubMed  Google Scholar 

  23. Gunderson LL, Sosin H. Areas of failure found at reoperation (second or symptomatic look) following “curative surgery” for adenocarcinoma of the rectum. Clinicopathologic correlation and implications for adjuvant therapy. Cancer. 1974;34:1278–92.

    Article  CAS  PubMed  Google Scholar 

  24. Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, et al., editors. AJCC cancer staging manual. 8th ed. New York: Springer; 2017.

    Google Scholar 

  25. Lin H-H, Lin J-K, Lin C-C, Lan Y-T, Wang H-S, Yang S-H, et al. Circumferential margin plays an independent impact on the outcome of rectal cancer patients receiving curative total mesorectal excision. Am J Surg. 2013;206:771–7.

    Article  PubMed  Google Scholar 

  26. Tocchi A, Mazzoni G, Lepre L, Liotta G, Costa G, Agostini N, et al. Total mesorectal excision and low rectal anastomosis for the treatment of rectal cancer and prevention of pelvic recurrences. Arch Surg. 2001;136:216–20.

    Article  CAS  PubMed  Google Scholar 

  27. Wibe A, Eriksen MT, Syse A, Myrvold HE, Søreide O. Total mesorectal excision for rectal cancer–what can be achieved by a national audit? Color Dis. 2003;5:471–7.

    Article  CAS  Google Scholar 

  28. Guillou PJ, Quirke P, Thorpe H, Walker J, Jayne DG, Smith AM, et al. MRC CLASICC trial group. Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial. Lancet. 2005;365(9472):1718–26.

    Article  PubMed  Google Scholar 

  29. van der Pas MH, Haglind E, Cuesta MA, Fürst A, Lacy AM, Hop WC, et al. COlorectal cancer Laparoscopic or Open Resection II (COLOR II) Study Group. Laparoscopic versus open surgery for rectal cancer (COLOR II): short-term outcomes of a randomised, phase 3 trial. Lancet Oncol. 2013;14(3):210–8.

    Article  PubMed  Google Scholar 

  30. Jeong SY, Park JW, Nam BH, Kim S, Kang SB, Lim SB, et al. Open versus laparoscopic surgery for mid-rectal or low-rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): survival outcomes of an open-label, non-inferiority, randomised controlled trial. Lancet Oncol. 2014;15(7):767–74.

    Article  PubMed  Google Scholar 

  31. Bonjer HJ, Deijen CL, Abis GA, Cuesta MA, van der Pas MH, de Lange-de Klerk ES, et al. COLOR II Study Group. A randomized trial of laparoscopic versus open surgery for rectal cancer. N Engl J Med. 2015;372(14):1324–32.

    Article  CAS  PubMed  Google Scholar 

  32. Stevenson AR, Solomon MJ, Lumley JW, Hewett P, Clouston AD, Gebski VJ, et al. ALaCaRT investigators. Effect of laparoscopic-assisted resection vs open resection on pathological outcomes in rectal cancer: the ALaCaRT randomized clinical trial. JAMA. 2015;314(13):1356–63.

    Article  CAS  PubMed  Google Scholar 

  33. Fleshman J, Branda M, Sargent DJ, Boller AM, George V, Abbas M, et al. Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes: the ACOSOG Z6051 randomized clinical trial. JAMA. 2015;314(13):1346–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Jayne D, Pigazzi A, Marshall H, Croft J, Corrigan N, Copeland J, et al. Effect of robotic-assisted vs conventional laparoscopic surgery on risk of conversion to open laparotomy among patients undergoing resection for rectal cancer: the ROLARR randomized clinical trial. JAMA. 2017;318(16):1569–80.

    Article  PubMed  PubMed Central  Google Scholar 

  35. de Lacy AM, Rattner DW, Adelsdorfer C, Tasende MM, Fernández M, Delgado S, et al. Transanal natural orifice transluminal endoscopic surgery (NOTES) rectal resection: “down-to-up” total mesorectal excision (TME)–short-term outcomes in the first 20 cases. Surg Endosc. 2013;27(9):3165–72.

    Article  PubMed  Google Scholar 

  36. Deijen CL, Velthuis S, Tsai A, Mavroveli S, de Lange-de Klerk ES, Sietses C, et al. COLOR III: a multicentre randomised clinical trial comparing transanal TME versus laparoscopic TME for mid and low rectal cancer. Surg Endosc. 2016;30(8):3210–5.

    Article  PubMed  Google Scholar 

  37. no authors listed. Preoperative short-term radiation therapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Rectal Cancer Study Group. Cancer. 1990;66(1):49–55.

    Article  Google Scholar 

  38. Gérard A, Buyse M, Nordlinger B, Loygue J, Pène F, Kempf P, et al. Preoperative radiotherapy as adjuvant treatment in rectal cancer. Final results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC). Ann Surg. 1988;208:606–14.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Goldberg PA, Nicholls RJ, Porter NH, Love S, Grimsey JE. Long-term results of a randomised trial of short-course low-dose adjuvant pre-operative radiotherapy for rectal cancer: reduction in local treatment failure. Eur J Cancer. 1994;30A:1602–6.

    Article  CAS  PubMed  Google Scholar 

  40. Jones DJ, Zaloudik J, James RD, Haboubi N, Moore M, Schofield PF. Predicting local recurrence of carcinoma of the rectum after preoperative radiotherapy and surgery. Br J Surg. 1989;76:1172–5.

    Article  CAS  PubMed  Google Scholar 

  41. Horn A, Halvorsen JF, Dahl O. Preoperative radiotherapy in operable rectal cancer. Dis Colon Rectum. 1990;33:823–8.

    Article  CAS  PubMed  Google Scholar 

  42. Rider WD, Palmer JA, Mahoney LJ, Robertson CT. Preoperative irradiation in operable cancer of the rectum: report of the Toronto trial. Can J Surg. 1977;20:335–8.

    CAS  PubMed  Google Scholar 

  43. 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. 1988;80:21–9.

    Article  CAS  PubMed  Google Scholar 

  44. Balslev I, Pedersen M, Teglbjaerg PS, Hanberg-Soerensen F, Bone J, Jacobsen NO, et al. Postoperative radiotherapy in Dukes’ B and C carcinoma of the rectum and rectosigmoid. A randomized multicenter study. Cancer. 1986;58:22–8.

    Article  CAS  PubMed  Google Scholar 

  45. Gastrointestinal Tumor Study Group. Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med. 1985;312:1465–72.

    Article  Google Scholar 

  46. 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. 1991;324:709–15.

    Article  CAS  PubMed  Google Scholar 

  47. Glimelius B, Isacsson U, Jung B, Påhlman L. Radiotherapy in addition to radical surgery in rectal cancer: evidence for a dose-response effect favoring preoperative treatment. Int J Radiat Oncol Biol Phys. 1997;37:281–7.

    Article  CAS  PubMed  Google Scholar 

  48. Påhlman L, Glimelius B. The value of adjuvant radio(chemo)therapy for rectal cancer. Eur J Cancer. 1995;31A:1347–50.

    Article  PubMed  Google Scholar 

  49. Siegel R, Burock S, Wernecke K-D, Kretzschmar A, Dietel M, Loy V, et al. Preoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society. BMC Cancer. 2009;9:50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Cedermark B, Johansson H, Rutqvist LE, Wilking N. The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Colorectal Cancer Study Group. Cancer. 1995;75:2269–75.

    Article  CAS  PubMed  Google Scholar 

  51. Martling A, Holm T, Johansson H, Rutqvist LE, Cedermark B. The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: long-term follow-up of a population-based study. Cancer. 2001;92:896–902.

    Article  CAS  PubMed  Google Scholar 

  52. 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. 2001;345:638–46.

    Article  CAS  PubMed  Google Scholar 

  53. Kusters M, Marijnen CAM, van de Velde CJH, Rutten HJT, Lahaye MJ, Kim JH, et al. Patterns of local recurrence in rectal cancer; a study of the Dutch TME trial. Eur J Surg Oncol. 2010;36:470–6.

    Article  CAS  PubMed  Google Scholar 

  54. Roels S, Duthoy W, Haustermans K, Penninckx F, Vandecaveye V, Boterberg T, et al. Definition and delineation of the clinical target volume for rectal cancer. Int J Radiat Oncol Biol Phys. 2006;65:1129–42.

    Article  PubMed  Google Scholar 

  55. Swedish Rectal Cancer Trial, Cedermark B, Dahlberg M, Glimelius B, Påhlman L, Rutqvist LE, Wilking N. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997;336:980–7.

    Article  Google Scholar 

  56. MacFarlane JK, Ryall RD, Heald RJ. Mesorectal excision for rectal cancer. Lancet (London, England). 1993;341:457–60.

    Article  CAS  Google Scholar 

  57. ASCO Annual Meeting 2013. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: first results of the PETACC-6 randomized phase III trial. In: 2013 ASCO Annual Meeting. Abstracts. 2013.

    Google Scholar 

  58. [no authors listed]. Radiation therapy and fluorouracil with or without semustine for the treatment of patients with surgical adjuvant adenocarcinoma of the rectum. Gastrointestinal Tumor Study Group. J Clin Oncol. 1992;10:549–57.

    Article  Google Scholar 

  59. 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. 2012;30:1926–33.

    Article  CAS  PubMed  Google Scholar 

  60. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.

    Article  CAS  PubMed  Google Scholar 

  61. Roh MS, Colangelo LH, O’Connell MJ, Yothers G, Deutsch M, Allegra CJ, et al. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol. 2009;27:5124–30.

    Article  PubMed  PubMed Central  Google Scholar 

  62. 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. 2006;93:1215–23.

    Article  CAS  PubMed  Google Scholar 

  63. 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. 2012;30:3827–33.

    Article  PubMed  Google Scholar 

  64. Thomas PR, Lindblad AS. Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a review of the Gastrointestinal Tumor Study Group experience. Radiother Oncol. 1988;13:245–52.

    Article  CAS  PubMed  Google Scholar 

  65. Wolmark N, Wieand HS, Hyams DM, Colangelo L, Dimitrov NV, Romond EH, et al. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: national surgical adjuvant breast and bowel project protocol R-02. J Natl Cancer Inst. 2000;92:388–96.

    Article  CAS  PubMed  Google Scholar 

  66. 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. 2009;373:811–20.

    Article  PubMed  PubMed Central  Google Scholar 

  67. ASCO Annual Meeting 2015. A phase II single arm feasibility trial of neoadjuvant chemotherapy (NAC) with oxaliplatin/fluorouracil (OxMdG) then short-course preoperative radiotherapy (SCPRT) then immediate surgery in operable rectal cancer (ORC): COPERNICUS (NCT01263171). AS 2015.

    Google Scholar 

  68. Deng Y, Chi P, Lan P, Wang L, Cui L, Chen D, et al. A multi-center randomized controlled trial of mFOLFOX6 with or without radiation in neoadjuvant treatment of local advanced rectal cancer (FOWARC study): preliminary results. In: 2015 ASCO Annual Meeting, Abstracts, Meeting Library. 2015.

    Google Scholar 

  69. Frykholm GJ, Påhlman L, Glimelius B. Combined chemo- and radiotherapy vs. radiotherapy alone in the treatment of primary, nonresectable adenocarcinoma of the rectum. Int J Radiat Oncol Biol Phys. 2001;50:427–34.

    Article  CAS  PubMed  Google Scholar 

  70. Pettersson D, Cedermark B, Holm T, Radu C, Påhlman L, Glimelius B, et al. Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Br J Surg. 2010;97:580–7.

    Article  CAS  PubMed  Google Scholar 

  71. Allegra CJ, Yothers G, O’Connell MJ, Roh MS, Beart RW, Petrelli NJ, et al. Neoadjuvant therapy for rectal cancer: mature results from NSABP protocol R-04. 2014 Gastrointestinal Cancers Symposium, Abstracts, Meeting Library 2014. J Clin Oncol. 2014;32 (suppl 3; abstr 390).

    Article  Google Scholar 

  72. Roh MS, Yothers GA, O’Connell MJ, Beart RW, Pitot HC, Shields AF, et al. The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04. ASCO Meet Abstr. 2011;29(15_suppl):3503.

    Google Scholar 

  73. Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, et al. German Rectal Cancer Study Group. 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. 2015;16(8):979–89.

    Article  CAS  PubMed  Google Scholar 

  74. Jung M, Shin SJ, Koom WS, Jung I, Keum KC, Hur H, et al. A randomized phase 2 study of neoadjuvant chemoradiaton therapy with 5-Fluorouracil/Leucovorin or Irinotecan/S-1 in patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2015;93(5):1015–22.

    Article  CAS  PubMed  Google Scholar 

  75. 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 

  76. Helbling D, Bodoky G, Gautschi O, Sun H, Bosman F, Gloor B, et al. Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07. Ann Oncol. 2013;24(3):718–25.

    Article  CAS  PubMed  Google Scholar 

  77. Mohiuddin M, Regine WF, John WJ, Hagihara PF, McGrath PC, Kenady DE, et al. Preoperative chemoradiation in fixed distal rectal cancer: dose time factors for pathological complete response. Int J Radiat Oncol Biol Phys. 2000;46:883–8.

    Article  CAS  PubMed  Google Scholar 

  78. Rödel 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. 2012;13:679–87.

    Article  CAS  PubMed  Google Scholar 

  79. Mohiuddin M, Winter K, Mitchell E, Hanna N, Yuen A, Nichols C, et al. Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012. J Clin Oncol. 2006;24:650–5.

    Article  CAS  PubMed  Google Scholar 

  80. Wong SJ, Winter K, Meropol NJ, Anne PR, Kachnic L, Rashid A, et al. Radiation Therapy Oncology Group 0247: a randomized phase II study of neoadjuvant capecitabine and irinotecan or capecitabine and oxaliplatin with concurrent radiotherapy for patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2012;82:1367–75.

    Article  CAS  PubMed  Google Scholar 

  81. 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. 2014;32:513–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. NCT01515787 CT. PROSPECT: chemotherapy alone or chemotherapy plus radiation therapy in treating patients with locally advanced rectal cancer undergoing surgery. https://clinicaltrials.gov/ct2/show/NCT01515787 Accessed 13 June 2018.

  83. Hong TS, Kachnic LA. Preoperative chemoradiotherapy in the management of localized rectal cancer: the new standard. Gastrointest Cancer Res. 2007;1:49–56.

    PubMed  PubMed Central  Google Scholar 

  84. Trakarnsanga A. Treatment of locally advanced rectal cancer: controversies and questions. World J Gastroenterol. 2012;18:5521.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Van Cutsem E, Köhne C-H, Hitre E, Zaluski J, Chang Chien C-R, Makhson A, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17.

    Article  PubMed  Google Scholar 

  86. Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009;27:663–71.

    Article  CAS  PubMed  Google Scholar 

  87. Eisterer W, De Vries A, Öfner D, Rabl H, Koplmüller R, Greil R, et al. Preoperative treatment with capecitabine, cetuximab and radiotherapy for primary locally advanced rectal cancer–a phase II clinical trial. Anticancer Res. 2014;34:6767–73.

    CAS  PubMed  Google Scholar 

  88. Leichman CG, McDonough SL, Smalley SR, Billingsley KG, Lenz H-J, Beldner MA, et al. S0713: a phase II study of cetuximab (CET) added to induction chemotherapy (ICT) of oxaliplatin (OX) and capecitabine (CAP), followed by neoadjuvant chemoradiation (NACR) for locally advanced rectal cancer (LARC). 2015 ASCO Annual Meeting, Abstracts. J Clin Oncol. 2015;33 (Suppl; Abstr 3516).

    Article  Google Scholar 

  89. Williams KJ, Telfer BA, Stratford IJ, Wedge SR. ZD1839 (“Iressa”), a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft model. Br J Cancer. 2002;86:1157–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Valentini V, De Paoli A, Gambacorta MA, Mantini G, Ratto C, Vecchio FM, et al. Infusional 5-fluorouracil and ZD1839 (Gefitinib-Iressa) in combination with preoperative radiotherapy in patients with locally advanced rectal cancer: a phase I and II trial (1839IL/0092). Int J Radiat Oncol Biol Phys. 2008;72:644–9.

    Article  CAS  PubMed  Google Scholar 

  91. Allal AS, Roth AD, Franzetti-Pellanda A, Bonet M, Gervaz P, Bieri S. Phase I/II study of Gefitinib and concomitant preoperative radiotherapy in patients with locally advanced rectal cancer. J Cancer Ther. 2012;3:970–6.

    Article  CAS  Google Scholar 

  92. Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007;25:1658–64.

    Article  CAS  PubMed  Google Scholar 

  93. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:1626–34.

    Article  CAS  PubMed  Google Scholar 

  94. Kabbinavar FF, Hurwitz HI, Yi J, Sarkar S, Rosen O. Addition of bevacizumab to fluorouracil-based first-line treatment of metastatic colorectal cancer: pooled analysis of cohorts of older patients from two randomized clinical trials. J Clin Oncol. 2009;27:199–205.

    Article  CAS  PubMed  Google Scholar 

  95. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.

    Article  CAS  PubMed  Google Scholar 

  96. Nogué M, Salud A, Vicente P, Arriví A, Roca JM, Losa F, et al. Addition of bevacizumab to XELOX induction therapy plus concomitant capecitabine-based chemoradiotherapy in magnetic resonance imaging-defined poor-prognosis locally advanced rectal cancer: the AVACROSS study. Oncologist. 2011;16:614–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Fernández-Martos C, Pericay C, Aparicio J, Salud A, Safont M, Massuti B, et al. Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, l. J Clin Oncol. 2010;28:859–65.

    Article  CAS  PubMed  Google Scholar 

  98. Acs P, Thompson DS, Hemphill M., Wenk D, Bendell J., Kennedy A. A phase II study of 5-fluorouracil (5-FU), ziv-aflibercept, and radiation for the preoperative and adjuvant treatment of patients (pts) with stage II/III rectal cancer. 2015 ASCO Annual Meeting, Abstracts, Meeting Library. J Clin Oncol. 2015;33 (Suppl; Abstr 3607).

    Article  Google Scholar 

  99. Chau I. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol. 2006;24:668–74.

    Article  CAS  PubMed  Google Scholar 

  100. Hofheinz R-D, 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. 2012;13:579–88.

    Article  CAS  PubMed  Google Scholar 

  101. Geva R, Itzkovich E, Shamai S, Shacham-Shmueli E, Soyfer V, Klausner JM, et al. Is there a role for adjuvant chemotherapy in pathological complete response rectal cancer tumors following neoadjuvant chemoradiotherapy? J Cancer Res Clin Oncol. 2014;140:1489–94.

    Article  CAS  PubMed  Google Scholar 

  102. 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. 1994;331:502–7.

    Article  PubMed  Google Scholar 

  103. Smalley SR. Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol. 2006;24:3542–7.

    Article  CAS  PubMed  Google Scholar 

  104. Tepper JE, O’Connell M, Niedzwiecki D, Hollis DR, Benson AB, Cummings B, et al. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control–final report of intergroup 0114. J Clin Oncol. 2002;20:1744–50.

    Article  CAS  PubMed  Google Scholar 

  105. Gunderson LL, Sargent DJ, Tepper JE, Wolmark N, O’Connell MJ, Begovic M, et al. Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol. 2004;22:1785–96.

    Article  PubMed  Google Scholar 

  106. Benson AB, Venook AP, Bekaii-Saab T, Chan E, Chen Y-J, Cooper HS, et al. Rectal cancer, version 2.2015. J Natl Compr Cancer Netw. 2015;13:719–28; quiz 728.

    Article  Google Scholar 

  107. Gunderson LL, Sargent DJ, Tepper JE, O’Connell MJ, Allmer C, Smalley SR, et al. Impact of T and N substage on survival and disease relapse in adjuvant rectal cancer: a pooled analysis. Int J Radiat Oncol Biol Phys. 2002;54(2):386–96.

    Article  PubMed  Google Scholar 

  108. Dattani M, Heald RJ, Goussous G, Broadhurst J, São Julião GP, Habr-Gama A, et al. Oncological and survival outcomes in watch and wait patients with a clinical complete response after neoadjuvant chemoradiotherapy for rectal cancer: a systematic review and pooled analysis. Ann Surg. 2018;268:955–67. (Epub ahead of print).

    Article  PubMed  Google Scholar 

  109. Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U, Silva e Sousa AH, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240:711–-8.

    PubMed  PubMed Central  Google Scholar 

  110. Smith J, Chow O, Eaton A, Widman M, Nash G, Temple LKF, et al. Organ preservation in patients with rectal cancer with clinical complete response after neoadjuvant therapy. | 2015 Gastrointestinal Cancers Symposium, Abstracts, Meeting Library. J Clin Oncol. 2015;33 (Suppl 3; Abstr 509).

    Article  Google Scholar 

  111. Habr-Gama A, São Julião GP, Vailati BB, Sabbaga J, Aguilar PB, Fernandez LM, et al. Organ preservation in cT2N0 rectal cancer after neoadjuvant chemoradiation therapy: the impact of radiation therapy dose-escalation and consolidation chemotherapy. Ann Surg. 2017;24:102–7. (Epub ahead of print).

    Google Scholar 

  112. Bernier L, Balyasnikova S, Tait D, Brown G. Watch-and-wait as a therapeutic strategy in rectal cancer. Curr Colorectal Cancer Rep. 2018;14(2):37–55.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Glimelius B, Tiret E, Cervantes A, Arnold D. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24:vi81–8.

    Article  PubMed  Google Scholar 

  114. Guillem JG, Ruby JA, Leibold T, Akhurst TJ, Yeung HW, Gollub MJ, et al. Neither FDG-PET Nor CT can distinguish between a pathological complete response and an incomplete response after neoadjuvant chemoradiation in locally advanced rectal cancer: a prospective study. Ann Surg. 2013;258(2):289–95.

    Article  PubMed  Google Scholar 

  115. Patel UB, Taylor F, Blomqvist L, George C, Evans H, Tekkis P, et al. Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. J Clin Oncol. 2011;29(28):3753–60.

    Article  PubMed  Google Scholar 

  116. Duldulao MP, Lee W, Streja L, Chu P, Li W, Chen Z, et al. Distribution of residual cancer cells in the bowel wall after neoadjuvant chemoradiation in patients with rectal cancer. Dis Colon Rectum. 2013;56(2):142–9.

    Article  PubMed  PubMed Central  Google Scholar 

  117. Dossa F, Chesney TR, Acuna SA, Baxter NN. A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2017;2(7):501–13.

    Article  PubMed  Google Scholar 

  118. Kong JC, Guerra GR, Warrier SK, Ramsay RG, Heriot AG. Outcome and salvage surgery following “watch and wait” for rectal cancer after neoadjuvant therapy: a systematic review. Dis Colon Rectum. 2017;60(3):335–45.

    PubMed  Google Scholar 

  119. van der Valk M. The International Watch & Wait database (IWWD) for rectal cancer: an update. J Clin Oncol. 2017;35(4_suppl):521.

    Article  Google Scholar 

  120. Battersby NJ, Dattani M, Rao S, Cunningham D, Tait D, Adams R, et al. A rectal cancer feasibility study with an embedded phase III trial design assessing magnetic resonance tumour regression grade (mrTRG) as a novel biomarker to stratify management by good and poor response to chemoradiotherapy (TRIGGER): study protocol for a randomised controlled trial. Trials. 2017;18(1):394.

    Article  PubMed  PubMed Central  Google Scholar 

  121. 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. 2014;113(2):223–9.

    Article  PubMed  Google Scholar 

  122. Ludmir EB, Palta M, Willett CG, Czito BG. Total neoadjuvant therapy for rectal cancer: an emerging option. Cancer. 2017;123(9):1497–506.

    Article  PubMed  Google Scholar 

  123. Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, et al. Timing of rectal cancer response to chemoradiation consortium. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015;16(8):957–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Necmettin Erbakan University, Meram Medical Faculty, Konya, Turkey

    Mehmet Artaç

  2. Clinical Research, Department of Hematology and Medical Oncology, Emory University School of Medicine/Winship Cancer Institute of Emory University, Atlanta, GA, USA

    Bassel F. El-Rayes

  3. Department of Internal Medicine, Division of Medical Oncology, Hacettepe University School of Medicine, Institute of Cancer, Altındağ, Ankara, Turkey

    Suayib Yalcin

  4. Department of Oncology, Department of Pharmacology, Wayne State University, Karmanos Cancer Institute, Hudson-Webber Cancer Research Center, Detroit, MI, USA

    Philip A. Philip

Authors
  1. Mehmet Artaç
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bassel F. El-Rayes
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Suayib Yalcin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Philip A. Philip
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bassel F. El-Rayes .

Editor information

Editors and Affiliations

  1. Department of Medical Oncology, Hacettepe University Institute of Cancer, Sihhiye, Ankara, Turkey

    Suayib Yalcin

  2. Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA

    Philip A. Philip

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

Artaç, M., El-Rayes, B.F., Yalcin, S., Philip, P.A. (2019). Treatment of Rectal Cancer. In: Yalcin, S., Philip, P. (eds) Textbook of Gastrointestinal Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-18890-0_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-18890-0_9

  • 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

Search

Navigation