Advertisement

Principles of Adjuvant and Neoadjuvant Therapy for Locally Advanced Rectal Cancer

  • Sepehr Khorasani
  • Arun Nagarajan
  • Timothy Nguyen
  • Sami A. ChadiEmail author
Chapter

Abstract

More than half the patients with rectal cancer present with locally advanced rectal disease at diagnosis with a high risk of recurrence. Preoperative chemoradiotherapy and standardized radical surgery with total mesorectal excision have been established as the ‘gold standard’ for treating these patients. Pathological staging using the ypTNM classification system to decide on adjuvant chemotherapy (ACT) is widely used in clinical practice, but the delivery of ACT is still controversial, as many discrepancies persist in the conclusions of different trials, due to heterogeneity of the inclusion criteria between studies, lack of statistical power, and variations in preoperative and adjuvant regimens. In 2014, a meta-analysis of four randomized phase-III trials (EORTC 22921, I-CNR-RT, PROCTOR-SCRIPT, CHRONICLE) failed to demonstrate any statistical efficacy of fluorouracil (5FU)-based ACT. Three recent randomized trials aimed to compare 5FU with 5FU plus oxaliplatin-based chemotherapy. Two of them (ADORE, CAO/ARO/AIO-04) appeared to find a disease-free survival benefit for patients treated with the combination therapy. Thus, while awaiting new data, it can be said that, as of 2015, patients with yp stage I tumors or histological complete response derived no benefit from adjuvant therapy. On the other hand, the FOLFOX chemotherapy regimen should be proposed for yp stage III patients, and may be considered for yp stage II tumors in fit patients with high-risk factors. Nevertheless, well-designed and sufficiently powered clinical trials dedicated to adjuvant treatments for rectal cancer.

Keywords

Adjuvant therapy Neoadjuvant therapy Locally advanced rectal cancer Chemoradiotherapy Recurrence Total mesorectal excision Pathological staging Randomized trials Tumor staging 

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2006;66:7–30.CrossRefGoogle Scholar
  2. 2.
    Quah HM, Chou JF, Gonen M, et al. Pathologic stage is most prognostic of disease-free survival in locally advanced rectal cancer patients after preoperative chemoradiation. Cancer. 2008;113:57–64.PubMedCrossRefGoogle Scholar
  3. 3.
    Bufalari A, Boselli C, Giustozzi G, et al. Locally advanced rectal cancer: a multivariate analysis of outcome risk factors. J Surg Oncol. 2000;74:2–10.PubMedCrossRefGoogle Scholar
  4. 4.
    Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986;1:1479–82.CrossRefGoogle Scholar
  5. 5.
    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(16):1926–33.PubMedCrossRefGoogle Scholar
  6. 6.
    Millard T, Kunk PR, Ramsdale E, Rahma OE. Current debate in the oncological management of rectal cancer. World J Gastrointest Oncol. 2016;8(10):715–24.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Benson AB, Venook AP, Bekaii-Saab T, et al. Rectal cancer, version 2.2015. J Natl Compr Cancer Netw. 2015;13:719–28. quiz 728, 2015CrossRefGoogle Scholar
  8. 8.
    Glimelius B, Tiret E, Cervantes A, et al. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(suppl6):vi81–8.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Khrizman P, Niland JC, ter Veer A, et al. Postoperative adjuvant chemotherapy use in patients with stage II/III rectal cancer treated with neo- adjuvant therapy: A National Comprehensive Cancer Network analysis. J Clin Oncol. 2013;31:30–8.PubMedCrossRefGoogle Scholar
  10. 10.
    van Gijn W, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mes- orectal excision for resectable rectal cancer: 12-year ollow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011;12:575–82.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Netter J, Douard R, Durdux C, Landi B, Berger A, Taieb J. Advances in management of adjuvant chemotherapy in rectal cancer: consequences for clinical practice. Clin Res Hepatol Gastroenterol. 2016;40:546–52.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Wanebo HJ, Koness RJ, Vezeridis MP, Cohen SI, Wrobleski DE. Pelvic resection of recurrent rectal cancer. Ann Surg. 1994;220(4):586–95. discussion 595–7PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Chadi SA, Berho M, Wexner SD. Surgeon perspectives on the use and effects of neoadjuvant chemoradiation in the treatment of rectal cancer: a comprehensive review of the literature. Langenbeck's Arch Surg. 2015;400:661–73.CrossRefGoogle Scholar
  14. 14.
    Stewart DB, Dietz DW. Total mesorectal excision: what are we doing? Clin Colon Rectal Surg. 2007;20(3):190–202.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Heald RJ, Husband EM, Ryall RD. Themesorectum in rectal cancer surgery-the clue to pelvic recurrence? Br J Surg. 1982;69(10):613–6.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision. Lancet. 1986;2(8514):996–9.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Quirke P. Training and quality assurance for rectal cancer: 20 years of data is enough. Lancet Oncol. 2003;4(11):695–702.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Trimble EL, Ungerleider RS, Abrams JA, Kaplan RS, Feigal EG, Smith MA, Carter CL, Friedman MA. Neoadjuvant therapy in cancer treatment. Cancer Suppl. 1993;72(11):3515.CrossRefGoogle Scholar
  19. 19.
    Cecil TD, Sexton R, Moran BJ, et al. Total mesorectal excision results in low local recurrence rates in lymph node-positive rectal cancer. Dis Colon Rectum. 2004;47:1145–50.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Faerden AE, Naimy N, Wiik P, et al. Total mesorectal excision for rectal cancer: difference in outcome for low and high rectal cancer. Dis Colon Rectum. 2005;48:2224–31.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    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(11):1114–23.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    O’Connell MJ, Martenson JA, Wieand HS, 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.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Patel SA, Ryan DP, Hong TS. Combined modality therapy for rectal cancer. Cancer J. 2016;22(3):211–7.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    O’Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014;32:1927–34.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012;13:579–88.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    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(26):2696–704.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    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(31):5124–30.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, François E, de La Roche G, Bouché O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahé MA, Bécouarn Y, Dupuis O, Lledo G, Montoto-Grillot C, Conroy T. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Schmoll HJ, Haustermans K, Price TJ, Nordlinger B, Hofheinz R, Daisne JF, Janssens J, Brenner B, Schmidt P, Reinel H, Hollerbach S, Caca K, Fauth F, Hannig C, Zalcberg JR, Tebbutt NC, Mauer ME, Messina C, Manfred P. 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(suppl):abstr 3501.Google Scholar
  31. 31.
    Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska- Lange A, Folprecht G, Sauer R. 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.PubMedCrossRefGoogle Scholar
  32. 32.
    Rodel C, Liersch T, Fietkau R, Hohenberger W, Graeven U, Hothorn T, Arnold D, Raab H-R, Wittekind C, Hess CF, Staib L, Becker H, Sauer R, German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with 5-fluorouracil and oxaliplatin versus 5-fluorouracil alone in locally advanced rectal cancer: Results of the German CAO/ARO/AIO-04 randomized phase III trial. J Clin Oncol. 2014;32:3500.CrossRefGoogle Scholar
  33. 33.
    Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Lin X, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese fowarc multicenter, open-label, randomized three-arm phase III trial. J Clin Oncol. 2016;34(27):3300–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Kusters M, Marijnen CA, van de Velde CJ, Rutten HJ, Lahaye MJ, Kim JH, Beets-Tan RG, Beets GL. Patterns of local recurrence in rectal cancer; a study of the Dutch TME trial. Eur J Surg Oncol. 2010;36:470–6.CrossRefGoogle Scholar
  35. 35.
    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(17):1731–40. PubMedCrossRefGoogle Scholar
  36. 36.
    Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Pudełko M, et al. Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiother Oncol. 2004;2(1):15–24.CrossRefGoogle Scholar
  37. 37.
    Birgisson H, Påhlman L, Gunnarsson U, Glimelius B. Swedish rectal cancer trial group. adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the swedish rectal cancer trial. J Clin Oncol Am Soc Clin Oncol. 2005;23(34):8697–705.CrossRefGoogle Scholar
  38. 38.
    Bujko K, Nowacki MP, Nasierowska-Guttmejer A, et al. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Ngan SY, Burmeister B, Fisher RJ, 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.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Zhou Z-R, Liu S-X, Zhang T-S, Chen L-X, Xia J, Hu Z-D, et al. Short-course preoperative radiotherapy with immediate sur- gery versus long-course chemoradiation with delayed surgery in the treatment of rectal cancer: a systematic review and meta-analysis. Surg Oncol. 2014;23(4):211–21.PubMedCrossRefGoogle Scholar
  41. 41.
    Pettersson D, Cedermark B, Holm T, Radu C, Pahlman L, Glimelius B, Martling A. Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Br J Surg. 2010;97:580–7.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Pettersson D, Lörinc E, Holm T, Iversen H, Cedermark B, Glimelius B, Martling A. Tumour regression in the randomized Stockholm III Trial of radiotherapy regimens for rectal cancer. BJS. 2015;102:972–8.CrossRefGoogle Scholar
  43. 43.
    Joshua Smith J, Garcia-Aguilar J. Advances and challenges in treatment of locally advanced rectal cancer. J Clin Oncol. 2015;33(16):1797–808.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Gunderson LL. Past, present, and future of intraoperative irradiation for colorectal cancer. Int J Radiat Oncol Biol Phys. 1996;34(3):741–4.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Holman FA, Haddock MG, Gunderson LL, Kusters M, Nieuwenhuijzen GAP, van den Berg HA, Nelson H, Rutten HJT. Results of intraoperative electron beam radiotherapy containing multimodality treatment for locally unresectable T4 rectal cancer: a pooled analysis of the Mayo Clinic Rochester and Catharina Hospital Eindhoven. J Gastrointest Oncol. 2016;7(6):903–16.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Kusters M, Valentini V, Calvo FA, Krempien R, Nieuwenhuijzen GA, Martijn H, Doglietto GB, del Valle E, Roeder F, Buchler MW, van de Velde CJH, Rutten HJT. Results of European pooled analysis of IORT-containing multimodality treatment for locally advanced rectal cancer: adjuvant chemotherapy prevents local recurrence rather than distant metastases. Ann Oncol. 2010;21:1279–84.PubMedCrossRefGoogle Scholar
  47. 47.
    Dubois JB, Bussieres E, Richaud P, et al. Intra-operative radiotherapy of rectal cancer: results of the French multi-institutional randomized study. Radiother Oncol. 2011;98:298–303.PubMedCrossRefGoogle Scholar
  48. 48.
    Mirnezami R, Chang GJ, Das P, et al. Intraoperative radiotherapy in colorectal cancer: systematic review and meta-analysis of techniques, long-term outcomes, and complications. Surg Oncol. 2013;22:22–35.PubMedCrossRefGoogle Scholar
  49. 49.
    Diaz-Gonzalez JA, Calvo FA, Cortes J, et al. Prognostic factors for disease-free survival in patients with T3-4 or N+ rectal cancer treated with preoperative chemoradiation therapy, surgery, and intraoperative irradiation. Int J Radiat Oncol Biol Phys. 2006;64:1122–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Ferenschild FT, Vermaas M, Verhoef C, Dwarkasing RS, Eggermont AM, de Wilt JH. Abdominosacral resection for locally advanced and recurrent rectal cancer. Br J Surg. 2009;96(11):1341–7.  https://doi.org/10.1002/bjs.6695.CrossRefPubMedGoogle Scholar
  51. 51.
    Valentini V, Coco C, Rizzo G, et al. Outcomes of clinical T4M0 extra-peritoneal rectal cancer treated with preoperative radiochemotherapy and surgery: a prospective evaluation of a single institutional experience. Surgery. 2009;145:486–94.PubMedCrossRefGoogle Scholar
  52. 52.
    Patel SA, Wo JY, Hong TS. Advancing techniques of radiation therapy for rectal cancer. Semin Radiat Oncol. 2016;26:220–5.PubMedCrossRefGoogle Scholar
  53. 53.
    Kusunoki M, Yanagi H, et al. Anoabdominal rectal resection and colonic J pouch-analanastomosis:10 years’ experience. Br J Surg. 1997;84:1277–80.PubMedCrossRefGoogle Scholar
  54. 54.
    Appelt AL, Vogelius IR, et al. Long-termresults of a randomized trialin locally advanced rectal cancer: no benefit from adding a brachytherapy boost. Int J Radiat Oncol Biol Phys. 2014;90:110–8.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Evans J, Tait D, Swift I, Pennert K, Tekkis P, Wotherspoon A, Chau I, Cunningham D, Brown G. Timing of surgery following preoperative therapy in rectal cancer: the need for a prospective randomized trial? Dis Colon Rectum. 2011;54(10):1251–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Francois Y, Nemoz CJ, Baulieux J, Vignal J, Grandjean JP, Partensky C, et al. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol. 1999;17(8):2396.PubMedCrossRefGoogle Scholar
  57. 57.
    Tulchinsky H, Shmueli E, Figer A, et al. An interval 7 weeks between neoadjuvant therapy and surgery improves pathologic complete response and disease-free survival in patients with locally advanced rectal cancer. Ann Surg Oncol. 2008;15:2661–7.PubMedCrossRefGoogle Scholar
  58. 58.
    Kalady MF, de Campos-Lobato LF, Stocchi L, et al. Predictive factors of pathologic complete re- sponse after neoadjuvant chemoradiation for rectal cancer. Ann Surg. 2009;250:582–9.PubMedGoogle Scholar
  59. 59.
    Petrelli F, Coinu A, Lonati V, et al. Asystematic review and meta-analysis of adjuvant chemotherapy after neoadjuvant treatment and surgery for rectal cancer. Int J Color Dis. 2015;30:447–57.CrossRefGoogle Scholar
  60. 60.
    Probst CP, Becerra AZ, Aquina CT, Tejani MA, Wexner SD, Garcia-Aguilar J, Remzi FH, David W Dietz MD, Monson JRT, Fleming FJ. Extended intervals after neoadjuvant therapy in locally advanced rectal cancer: the key to improved tumor response and potential organ preservation. J Am Coll Surg. 2015;221(2):430–40.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Lefevre JH, Mineur L, Kotti S, et al. Effect of interval (7 or 11 weeks) between neoadjuvant radiochemotherapy and surgery on complete pathologic response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6). J Clin Oncol. 2016;34(31):3773–80.PubMedCrossRefGoogle Scholar
  62. 62.
    Temple LK, Romanus D, Niland J, Veer AT, Weiser MR, Skibber J, et al. Factors associated with sphincter-preserving surgery for rectal cancer at national comprehensive cancer network centers. Ann Surg. 2009;250(2):260–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Gérard J-P, Azria D, Gourgou-Bourgade S, Martel-Lafay I, Hennequin C, Etienne P-L, et al. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol Am Soc Clin Oncol. 2012;30(36):4558–65.CrossRefGoogle Scholar
  64. 64.
    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: path- ologic results of the STAR-01 randomized phase III trial. J Clin Oncol. 2011;29(20):2773–80.PubMedCrossRefGoogle Scholar
  65. 65.
    Gérard J-P, Rostom Y, Gal J, Benchimol D, Ortholan C, Aschele C, et al. Can we increase the chance of sphincter saving surgery in rectal cancer with neoadjuvant treatments: lessons from a systematic review of recent randomized trials. Crit Rev Oncol Hematol. 2012;81(1):21–8.PubMedCrossRefGoogle Scholar
  66. 66.
    McCarthy K, Pearson K, Fulton R, Hewitt J. Pre-operative chemoradiation for non-metastatic locally advanced rectal cancer. Cochrane Database Syst Rev. 2012;12:CD008368.PubMedGoogle Scholar
  67. 67.
    Jestin P, Påhlman L, Gunnarsson U. Risk factors for anastomotic leakage after rectal cancer surgery: a case-control study. Color Dis. 2008;10(7):715–21.CrossRefGoogle Scholar
  68. 68.
    Warschkow R, Steffen T, Thierbach J, Bruckner T, Lange J, Tarantino I. Risk factors for anastomotic leakage after rectal cancer resection and reconstruction with colorectostomy. A retrospective study with bootstrap analysis. Ann Surg Oncol. 2011;18(10):2772–82.PubMedCrossRefGoogle Scholar
  69. 69.
    Lee W-S, Yun SH, Roh Y-N, Yun H-R, Lee WY, Cho YB, et al. Risk factors and clinical outcome for anastomotic leakage after total mesorectal excision for rectal cancer. World J Surg. 2008;32(6):1124–9.PubMedCrossRefGoogle Scholar
  70. 70.
    Qin C, Ren X, Xu K, Chen Z, He Y, Song X. Does preoper- ative radio(chemo)therapy increase anastomotic leakage in rectal cancer surgery? A meta-analysis of randomized controlled trials. Gastroenterol Res Pract. 2014;2014(2):910956–7.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Peeters KCMJ. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients—a Dutch colorectal cancer group study. J Clin Oncol. 2005;23(25):6199–206.PubMedCrossRefGoogle Scholar
  72. 72.
    Marijnen CAM, van de Velde CJH, Putter H, van den Brink M, Maas CP, Martijn H, et al. Impact of short-term preoperative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol. 2005;23(9):1847–58.PubMedCrossRefGoogle Scholar
  73. 73.
    Stephens RJ, Thompson LC, Quirke P, Steele R, Grieve R, Couture J, et al. Impact of short-course preoperative radiotherapy for rectal cancer on patients’ quality of life: data from the Medical Research Council CR07/National Cancer Institute of Canada Clinical Trials Group C016 randomized clinical trial. J Clin Oncol Am Soc Clin Oncol. 2010;28(27):4233–9.CrossRefGoogle Scholar
  74. 74.
    Loos M, Quentmeier P, Schuster T, Nitsche U, Gertler R, Keerl A, et al. Effect of preoperative radio(chemo)therapy on long- term functional outcome in rectal cancer patients: a systematic re- view and meta-analysis. Ann Surg Oncol. 2013;20(6):1816–28.PubMedCrossRefGoogle Scholar
  75. 75.
    Glimelius BLG. The role of preoperative and postoperative radiotherapy in rectal cancer. Clin Colorectal Cancer. 2002;2(2):82–92.PubMedCrossRefGoogle Scholar
  76. 76.
    Påhlman L, Glimelius B, Graffman S. Pre-versus postoper-ative radiotherapy in rectal carcinoma: an interim report from a randomized multicentre trial. Br J Surg. 1985;72(12):961–6.PubMedCrossRefGoogle Scholar
  77. 77.
    De Caluwé L, Van Nieuwenhove Y, Ceelen WP. Preoperative chemoradiation versus radiation alone for stage II and III resectable rectal cancer. Cochrane Database Syst Rev. 2013;2:CD006041.Google Scholar
  78. 78.
    Dronkers JJ, Lamberts H, Reutelingsperger IMMD, Naber RH, Dronkers-Landman CM, Veldman A, et al. Preoperative ther- apeutic programme for elderly patients scheduled for elective abdominal oncological surgery: a randomized controlled pilot study. Clin Rehabil. 2010;24(7):614–22.PubMedCrossRefGoogle Scholar
  79. 79.
    Li C, Carli F, Lee L, Charlebois P, Stein B, Liberman AS, et al. Impact of a trimodal prehabilitation program on functional recovery after colorectal cancer surgery: a pilot study. Surg Endosc. 2013;27(4):1072–82.PubMedCrossRefGoogle Scholar
  80. 80.
    Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, Calvo FA, García-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W, Suárez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11:835–44.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Park IJ, Eng C, You YN, et al. Exploratory analysis of adjuvant chemotherapy benefits after preoperative chemoradiotherapy and radical resection for rectal cancer. J Clin Oncol. 2012;30:21.Google Scholar
  82. 82.
    Habr-Gama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240:711–7.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Habr-Gama A, Perez RO, Proscurshim I, et al. Patterns of failure and survival for nonoperative treatment of stage c0 distal rectal cancer following neoadjuvant chemoradiation therapy. J Gastrointest Surg. 2006;10:1319–28.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Habr-Gama A, Gama-Rodrigues J, São Julião GP, et al. Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: Impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys. 2014;88:822–8.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Maas M, Beets-Tan RG, Lambregts DM, et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol. 2011;29:4633–40.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Smith JD, Ruby JA, Goodman KA, et al. Nonoperative management of rectal cancer with complete clinical response after neoadjuvant therapy. Ann Surg. 2012;256:965–72.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, et al. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990;322:352–8.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Petersen SH, Harling H, Kirkeby LT, Wille-Jorgensen P, Mocellin S. Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database Syst Rev. 2012;3:CD004078.Google Scholar
  89. 89.
    Biagi JJ, Raphael MJ, Mackillop WJ, Kong W, King WD, Booth CM. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer. A systematic review and meta-analysis. JAMA. 2011;305:2335e2342.CrossRefGoogle Scholar
  90. 90.
    NCCN: National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology (NCCN Guidelines). Rectal cancer; 2015.Google Scholar
  91. 91.
    Oncoline. Dutch Colorectal Cancer Guideline (version 3.0). Utrecht: Association of Comprehensive Cancer Centres. Available at: http://www.oncoline.nl/colorectaalcarcinoom; 2014.
  92. 92.
    Poulsen LO, Qvortrup C, Pfeiffer P, Yilmaz M, Falkmer U, Sorbye H. Review on adjuvant chemotherapy for rectal cancer e why do treatment guidelines differ so much. Acta Oncol. 2015;54:437–46.PubMedCrossRefPubMedCentralGoogle Scholar
  93. 93.
    Bosset J-F, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun R-J, et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014;15(2):184–90.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    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 neoad- juvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control. Ann Oncol. 2014;25(7):1356–62.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Breugom AJ, van Gijn W, Muller EW, Berglund A, van den Broek CBM, 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) randomised phase III trial. Ann Oncol. 2015;26(4):696–701.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Breugom AJ, Swets M, Bosset J-F, Collette L, Sainato A, Cionini L, et al. Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data. Lancet Oncol. 2015;16(2):200–7.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Sainato A, Cernusco Luna Nunzia V, Valentini V, De Paoli A, Mau-rizi ER, Lupattelli M, et al. No benefit of adjuvant fluorouracilleucovorin chemotherapy after neoadjuvant chemoradiother-apy in locally advanced cancer of the rectum (LARC): longterm results of a randomized trial (I-CNR-RT). Radiother Oncol. 2014;113(2):223–9.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Petrelli F, Coinu A, Lonati V, Barni S. A systematic review and meta-analysis of adjuvant chemotherapy after neoad- juvant treatment and surgery for rectal cancer. Int J Color Dis. 2015;30(4):447–57.CrossRefGoogle Scholar
  99. 99.
    Bujko K, Glimelius B, Valentini V, Michalski W, Spalek M. Postoperative chemotherapy in patients with rectal cancer receiving preoperative radio(chemo)therapy: a meta-analysis of randomized trials comparing surgery ± a fluoropyrimidine and surgery + a fluoropyrimidine ± oxaliplatin. Eur J Surg Oncol. 2015;41(6):713–23.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    André 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. 2009;27:3109–16.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Yothers G, O’Connell MJ, Allegra CJ, et al. Oxaliplatin as adjuvant for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol. 2011;29(28):3768–74.Google Scholar
  102. 102.
    Schmoll H-J, Cartwright T, Tabernero J, Nowacki MP, Figer A, Maroun J, et al. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1864 patients. J Clin Oncol. 2007;25(1):102–9.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, et al. Oxaliplatin added to fluorouracil-based preop- erative 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.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Glynne-Jones R, Grainger J, Harrison M, et al. Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in rectal cancer: should we be more cautious? Br J Cancer. 2006;94:363–71.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Chau I, Brown G, Cunningham D, et al. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Fernandez-Martos C, Pericay C, Aparicio J, 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, locally advanced rectal cancer: Grupo Cancer de Recto 3 Study. J Clin Oncol. 2010;28:859–65.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Garcia-Aguilar J, Smith DD, Avila K, et al. Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial. Ann Surg. 2011;254:97–102.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Garcia-Aguilar J, Marcet J, Coutsoftides T, et al. Impact of neoadjuvant chemotherapy following chemoradiation on tumor response, adverse events, and surgical complications in patients with advanced rectal cancer treated with TME. J Clin Oncol. 2011;224s:29.Google Scholar
  109. 109.
    Glynne-Jones R, Hughes R. Critical appraisal of the ‘wait and see’ approach in rectal cancer for clinical complete responders after chemoradiation. Br J Surg. 2012;99:897–909.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    García-Albéniz X, Gallego R, Hofheinz RD, Fernández-Esparrach G, Ayuso- Colella JR, Bombí JA, et al. Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation. World J Gastroenterol. 2014;20:15820–9.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Dossa F, Acuna SA, Rickles AS, Berho M, Wexner SD, Quereshy FA, Baxter NN, Chadi SA. Association between adjuvant chemotherapy and overall survival in patients with rectal cancer and pathological complete response after neoadjuvant chemotherapy and resection. JAMA Oncol. 2018;4(7):930–7.PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Kainthla R, Huerta S. Adjuvant chemotherapy for ypT0N0M0 rectal cancer following chemoradiotherapy and total mesorectal excision. Anti-Cancer Drugs. 2016;27:819–23.PubMedCrossRefGoogle Scholar
  113. 113.
    Glynne-Jones R, Counsell N, Quirke P, 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. 2014;25:1356–62.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Xu Z, Gupta Mohile S, Tejani MA, Becerra AZ, Probst CP, Aquina CT, Hensley BJ, Arsalanizadeh R, Noyes K, Monson JRT, Fleming FJ. Poor compliance with adjuvant chemotherapy use associated with poorer survival in patients with rectal cancer: an NCDB analysis. Cancer. 2016;123(1):52–61.PubMedCrossRefGoogle Scholar
  115. 115.
    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(11):709–15.PubMedCrossRefGoogle Scholar
  116. 116.
    Tveit KM, Guldvog I, Hagen S, Trondsen E, Harbitz T, Nygaard K, Norwegian Adjuvant Rectal Cancer Project Group, et al. Randomized controlled trial of postoperative radiotherapy and short-term time-scheduled 5-fluorouracil against surgery alone in the treatment of Dukes B and C rectal cancer. Br J Surg. 1997;84(8):1130–5.PubMedCrossRefGoogle Scholar
  117. 117.
    Wood CB, Gillis CR, Blumgart LH. A retrospective study of the natural history of patients with liver metastases from colorectal cancer. Clin Oncol. 1976;2:285–8.PubMedGoogle Scholar
  118. 118.
    Kornprat P, Jarnagin WR, Gonen M, et al. Outcome after hepatectomy for multiple (four or more) colorectal metastases in the era of effective chemotherapy. Ann Surg Oncol. 2007;14:1151–60.PubMedCrossRefGoogle Scholar
  119. 119.
    Cummings L, Payes JD, Cooper GS. Survival after hepatic resection in metastatic colorectal cancer: a population-based study. Cancer. 2007;109:718–26.PubMedCrossRefGoogle Scholar
  120. 120.
    Nathan H, de Jong MC, Pulitano C, et al. Conditional survival after surgical resection of colorectal liver metastasis: an international multi-institutional analysis of 949 patients. J Am Coll Surg. 2010;210:755–66.PubMedCrossRefGoogle Scholar
  121. 121.
    Scheele J, Stangl R, Altendorf-Hofmann A. Hepatic metastases from colorectal carcinoma: impact of surgical resection on the natural his- tory. Br J Surg. 1990;77:1241–6.PubMedCrossRefGoogle Scholar
  122. 122.
    Adam R, Delvart V, Pascal G, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004;240:644–57. discussion 657e8PubMedPubMedCentralCrossRefGoogle Scholar
  123. 123.
    Morris EJA, Forman D, Thomas JD, et al. Surgical management and outcomes of colorectal cancer liver metastases. Br J Surg. 2010;97:1110–8.PubMedCrossRefPubMedCentralGoogle Scholar
  124. 124.
    Schmoll HJ, Büchele T, Grothey A, Dempke W. Where do we stand with 5-fluorouracil? Semin Oncol. 1999;26:589–605.PubMedPubMedCentralGoogle Scholar
  125. 125.
    Ohhara Y, Fukuda N, Takeuchi S, Honma R, Shimizu Y, Kinoshita I, Hirotoshi DA. Role of targeted therapy in metastatic colorectal cancer. World J Gastrointest Oncol. 2016;8(9):642–55.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Lièvre A, Bachet JB, Le Corre D, Boige V, Landi B, Emile JF, Côté JF, Tomasic G, Penna C, Ducreux M, Rougier P, Penault- Llorca F, Laurent-Puig P. KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer. Cancer Res. 2006;66:3992–5.PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359:1757–65.PubMedCrossRefPubMedCentralGoogle Scholar
  128. 128.
    Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:1626–34.PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345:638–46.PubMedCrossRefPubMedCentralGoogle Scholar
  130. 130.
    Sebag-Montefiore D, Stephens RJ, Steele R, 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.PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Cameron MG, Kersten C, Vistad I, Sophie Foss Å, Guren MG. Palliative pelvic radiotherapy of symptomatic incurable rectal cancer – a systematic review. Acta Oncol. 2014;53:164–73.PubMedCrossRefPubMedCentralGoogle Scholar
  132. 132.
    Glimelius B. Recurrent rectal cancer. The pre-irradiated primary tumour: can more radiotherapy be given? Color Dis. 2003;5:501–3.CrossRefGoogle Scholar
  133. 133.
    Guren MG, Undseth C, Rekstad BL, Brændengen M, Dueland S, Spindler K-LG, Glynne-Jones R, Tveit KM. Reirradiation of locally recurrent rectal cancer: a systematic review. Radiother Oncol. 2014;113:151–7.PubMedCrossRefGoogle Scholar
  134. 134.
    van der Meij W, Rombouts AJM, Rütten H, Bremers AJA, de Wilt JHW. Treatment of locally recurrent rectal carcinoma in previously (chemo) irradiated patients: a review. Dis Colon Rectum. 2016;59(2):148–56.PubMedCrossRefGoogle Scholar
  135. 135.
    Wexner SD, Berho ME. The rationale for and reality of the new national accreditation program for rectal cancer. Dis Colon Rectum. 2017;60(6):595–602.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2019

Authors and Affiliations

  • Sepehr Khorasani
    • 1
  • Arun Nagarajan
    • 2
  • Timothy Nguyen
    • 3
  • Sami A. Chadi
    • 1
    Email author
  1. 1.Department of SurgeryUniversity Health Network, University of TorontoTorontoCanada
  2. 2.Department of Radiation OncologyCleveland Clinic FloridaWestonUSA
  3. 3.Department of Hematology/OncologyCleveland Clinic FloridaWestonUSA

Personalised recommendations