Short-Course Radiation Versus Long-Course Chemoradiation for Rectal Cancer

View More View Less
  • a From the Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Radiotherapy and Oncology, Johann Wolfgang Goethe-Universität, Frankfurt, Germany; and Department of Radiotherapy, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Rome, Italy.
Restricted access

The 2 broad approaches to preoperative therapy for rectal cancer are chemoradiation and short-course radiation. The outcomes of these 2 approaches reported in nonrandomized trials are not comparable because patients selected for treatment with short-course radiotherapy included those with cT1–3 disease, whereas patients selected for chemoradiation included those with T3 and/or N+ disease. However, more recent trials of short-course radiation have included patients with cT3 and/or N+ disease who also underwent sequential or postoperative chemotherapy, allowing a more relevant comparison with chemoradiation. This article compares the 2 preoperative approaches and addresses their emerging roles.

Correspondence: Bruce D. Minsky, MD, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 97, Room B2.4562, Houston, TX 77030. E-mail: bminsky@mdanderson.org
  • 1

    Sauer R, Becker H, Hohenberger P. Preoperative chemoradiotherapy as compared with postoperative chemoradiotherapy for locally advanced rectal cancer. N Engl J Med 2004;351:1120.

    • Search Google Scholar
    • Export Citation
  • 2

    Sauer R, Liersch T, Merkel S. 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;30:19261933.

    • Search Google Scholar
    • Export Citation
  • 3

    Kapiteijn E, Marijnen CA, Nagtegaal ID. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345:638646.

    • Search Google Scholar
    • Export Citation
  • 4

    Marijnen CA, Kapiteijn E, van de Velde CJ. Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol 2002;20:817825.

    • Search Google Scholar
    • Export Citation
  • 5

    Braendengen M, Tveit KM, Berglund A. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol 2008;22:36873694.

    • Search Google Scholar
    • Export Citation
  • 6

    Braendengen M, Tveit KM, Bruheim K. Late patient-reported toxicity after preoperative radiotherapy or chemoradiotherapy in nonresectable rectal cancer: results from a randomized phase III study. Int J Radiat Oncol Biol Phys 2012;81:10171024.

    • Search Google Scholar
    • Export Citation
  • 7

    Arbea L, Martinez-Monge R, Diaz-Gonzalez J. Four-week neoadjuvant intensity-modulated radiation therapy with concurrent capecitabine and oxaliplatin in locally advanced rectal cancer patients: a validation phase II trial. Int J Radiat Oncol Biol Phys 2012;83:587593.

    • Search Google Scholar
    • Export Citation
  • 8

    Samuelian JM, Callister MD, Ashman JB. Reduced acute bowel toxicity in patients treated with intensity modulated radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 2012;82:19811987.

    • Search Google Scholar
    • Export Citation
  • 9

    Callister MD, Ezzell GA, Gunderson LL. IMRT reduces the dose to small bowel and other pelvic organs in the preoperative treatment of rectal cancer [abstract]. Int J Radiat Oncol Biol Phys 2006;66(Suppl):Abstract s290.

    • Search Google Scholar
    • Export Citation
  • 10

    Aristu JJ, Arbea L, Rodriguez J. Phase I-II trial of concurrent capecitabine and oxaliplatin with preoperative intensity modulated radiotherapy in patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2008;71:748755.

    • Search Google Scholar
    • Export Citation
  • 11

    Roh MS, Yothers GA, O’Connell MJ. The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04 [abstract]. J Clin Oncol 2011;29(Suppl):Abstract 221s.

    • Search Google Scholar
    • Export Citation
  • 12

    Hofheinz RD, Wenz F, Post S. Chemoradiotherapy with capecitibine versus fluorouracil for locally advanced rectal cancer: a randomized, multicentre, non-inferiority phase III trial. Lancet Oncol 2012;13:579588.

    • Search Google Scholar
    • Export Citation
  • 13

    Aschele C, Cionini L, Lonardi S. 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;29:27732780.

    • Search Google Scholar
    • Export Citation
  • 14

    Gerard JP, Azria D, Gourgou-Bourgade S. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III ACCORD 12/0405 PRODIGE 2. J Clin Oncol 2010;28:16381644.

    • Search Google Scholar
    • Export Citation
  • 15

    Gerard JP, Azria D, Gourgou-Bourgade S. Clinical results at 3 years of the ACCORD 12 randomized trial in rectal cancer [abstract]. J Clin Oncol 2012;30(Suppl):Abstract 389.

    • Search Google Scholar
    • Export Citation
  • 16

    Roedel C, Becker H, Fietkau R. Preoperative chemoradiotherapy and postoperative chemotherapy with 5-fluorouracil and oxaliplatin versus 5-fluorouracil alone in locally advanced rectal cancer: first results of the German CAO/ARO/AIO-04 randomized phase III trial [abstract]. J Clin Oncol 2011;29(Supp):Abstract 222s.

    • Search Google Scholar
    • Export Citation
  • 17

    Willett CG, Duda D, di Tomaso E. Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol 2009;27:30203026.

    • Search Google Scholar
    • Export Citation
  • 18

    Crane CH, Eng C, Feig BW. Phase II trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2008;76:824830.

    • Search Google Scholar
    • Export Citation
  • 19

    Dipetrillo T, Pricolo V, Lagares-Garcia J. Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation for rectal cancer. Int J Radiat Oncol Biol Phys 2012;82:124129.

    • Search Google Scholar
    • Export Citation
  • 20

    Resch G, DeVries A, Ofner D. Preoperative treatment with capecitabine, bevacizumab and radiotherapy for primary locally advanced rectal cancer - a two stage phase II clinical trial. Radiother Oncol 2012;102:1013.

    • Search Google Scholar
    • Export Citation
  • 21

    Allegra CJ, Yothers G, O’Connel MJ. Phase III trial assessing Bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol 2011;29:1116.

    • Search Google Scholar
    • Export Citation
  • 22

    van Cutsem E, Lang I, D’haens G. KRAS status and efficacy in the first-line treatment of patients with metastatic colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab: the CRYSTA experience [abstract]. J Clin Oncol 2008;26(Suppl):Abstract 1006s.

    • Search Google Scholar
    • Export Citation
  • 23

    Dewdney A, Cunningham D, Tabernero J. 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;30:16201627.

    • Search Google Scholar
    • Export Citation
  • 24

    Goldberg RM, Sargent DJ, Thibodeau SN. Adjuvant mFOLFOX6 plus or minus cetuximab (Cmab) in patients (pts) with KRAS mutant (m) resected stage III colon cancer (CC): NCCTG Intergroup phase III trial N0147 [abstract]. J Clin Oncol 2012;28(Suppl):Abstract 3508.

    • Search Google Scholar
    • Export Citation
  • 25

    Schrag D, Weiser MR, Goodman KA. Neoadjuvant FOLFOX-bev, without radiation, for locally advanced rectal cancer [abstract]. J Clin Oncol 2010;28(Suppl):Abstract 3551.

    • Search Google Scholar
    • Export Citation
  • 26

    Skibber JM, Hoff PM, Minsky BD. Cancer of the rectum. In: DeVita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology, 6th ed. Philadelphia, PA: Lippincott Williams and Wilkeins; 2001:12711318.

    • Search Google Scholar
    • Export Citation
  • 27

    Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997;336:980987.

    • Search Google Scholar
    • Export Citation
  • 28

    Camma C, Giunta M, Fiorica F. Preoperative radiotherapy for resectable rectal cancer. A meta-analysis. JAMA 2000;284:10081015.

  • 29

    Colorectal Cancer Collaborative Group. Adjuvant radiotherapy for rectal cancer: a systematic overview of 22 randomised trials involving 8507 patients. Lancet 2001;358:12911304.

    • Search Google Scholar
    • Export Citation
  • 30

    Birgisson H, Pahlman L, Glimelius B. Adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the Swedish Rectal Cancer Trial. J Clin Oncol 2005;23:86978705.

    • Search Google Scholar
    • Export Citation
  • 31

    van Gijn W, Marijnen CA, Nagtegaal ID. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 2011;12:575582.

    • Search Google Scholar
    • Export Citation
  • 32

    Stephens RJ, Thompson LC, Quirke P. Impact of short-course preoperative radiotherapy for rectal cancer on patient’s 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 2010;27:42334239.

    • Search Google Scholar
    • Export Citation
  • 33

    Fernandez-Martos C, Pericay C, Aparicio J. 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 Cáncer de Recto 3 Study. J Clin Oncol 2010;28:859865.

    • Search Google Scholar
    • Export Citation
  • 34

    Garcia-Aguilar J, Smith DD, Avila K. Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial. Ann Surg 2011;254:97102.

    • Search Google Scholar
    • Export Citation
  • 35

    van Dijk TH, Havenga K, Beukema J. Short-course radiation therapy, neoadjuvant bevacizumab, capecitabine and oxaliplatin, and radical resection of primary tumor and metastasis in primary stage IV rectal cancer: a phase II multicenter study of the Dutch Colorectal Cancer Group [abstract]. J Clin Oncol 2010;28(Suppl):Abstract 295s.

    • Search Google Scholar
    • Export Citation
  • 36

    Myerson RJ, Parikh PJ, Tan B. A single institution phase II trial of five fractions of radiotherapy followed by four courses of FOLFOX chemotherapy as preoperative therapy for rectal adenocarcinoma [abstract]. J Clin Oncol 2012;30(Suppl):Abstract 553.

    • Search Google Scholar
    • Export Citation
  • 37

    Sebag-Montefiore D, Stephens RJ, Steele R. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicenter, randomised trial. Lancet 2009;373:811820.

    • Search Google Scholar
    • Export Citation
  • 38

    Bujko K, Nowacki MP, Nasierowska-Guttmejer A. Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomized trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiother Oncol 2004;72:1524.

    • Search Google Scholar
    • Export Citation
  • 39

    Bujko K, Nowacki MP, Nasierowska-Guttmejer A. Long term results of a randomized trial comparing preoperative short-course radiotherapy with preperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg 2006;93:12151223.

    • Search Google Scholar
    • Export Citation
  • 40

    Ngan S, Fischer R, Goldstein D. A randomized trial comparing local recurrence (LR) rates between short course (SC) and long course (LC) radiotherapy (RT) for clinical T3 rectal cancer: an Intergroup trial (TROG, AGITG, CSSANZ, RACS) [abstract]. J Clin Oncol 2010;28(Suppl):Abstract 15s.

    • Search Google Scholar
    • Export Citation
  • 41

    Sargent D, Yothers G, van Cutsem E. Use of two-year disease-free survival (DFS) as a primary endpoint in stage III adjuvant colon cancer trials with fluoropyrimidines with or without oxaliplatin or irinotecan: new data from 12,676 patients from MOSAIC, X-ACT, PETACC-3, NSABP C-06 and C-07, and C89803 [abstract]. J Clin Oncol 2009;27(Suppl):Abstract 170s.

    • Search Google Scholar
    • Export Citation
  • 42

    Tepper JE, O’Connell MJ, Niedzwiecki D. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control—final report of Intergroup 0114. J Clin Oncol 2002;20:17441750.

    • Search Google Scholar
    • Export Citation
  • 43

    Peeters KC, Marijnen CA, Nagtegaal ID. 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 2007;246:693701.

    • Search Google Scholar
    • Export Citation
  • 44

    Bosset JF, Collette L, Bardet E. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 2006;355:11141123.

  • 45

    Gerard JP, Conroy T, Bonnetain F. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 2006;28:46204625.

    • Search Google Scholar
    • Export Citation
  • 46

    Bonnetain F, Bosset JF, Gerard JP. An analysis of preoperative chemoradiotherapy with 5FU/leucovorin for T3-4 rectal cancer on survival in a pooled analysis of EORTC 22921 and FFCD 9203 trials: surrogacy in question? [abstract]. J Clin Oncol 2011;29(Suppl):Abstract 222s.

    • Search Google Scholar
    • Export Citation
  • 47

    Khrizman P, Niland JC, ter Veer A. Postoperative adjuvant chemotherapy (CTX) use in patients (Pts) with stage II/III rectal cancer treated with neoadjuvant therapy: a National Comprehensive Cancer Network (NCCN) analysis [abstract]. J Clin Oncol 2011;29(Supp):Abstract 224s.

    • Search Google Scholar
    • Export Citation
  • 48

    Beets GL, Mass M, Nelemans PJ. Evaluation of response after chemoradiation for rectal cancer as a predictive factor for the benefit of adjuvant chemotherapy: a pooled analysis of 2724 individual patients [abstract]. J Clin Oncol 2011;29(Suppl 4):Abstract 139.

    • Search Google Scholar
    • Export Citation
  • 49

    Valentini V, van Stiphout RG, Lammering G. Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: results of a phase II study. J Clin Oncol 2011;29:31633172.

    • Search Google Scholar
    • Export Citation
  • 50

    Valentini V, Aristei C, Glimelius B. Multidisciplinary rectal cancer management: 2nd European Rectal Cancer Consensus Conference. Radiother Oncol 2009;92:148163.

    • Search Google Scholar
    • Export Citation
  • 51

    Guillem JG, Diaz-Gonzalez J, Minsky BD. cT3N0 rectal cancer: potential overtreatment with preoperative chemoradiotherapy is warranted. J Clin Oncol 2008;26:368373.

    • Search Google Scholar
    • Export Citation
  • 52

    Sauer R, Roedel C. The author’s reply. N Engl J Med 2005;352:510511.

  • 53

    Nash GM, Weiss A, Dasgupta R. Close distal margin and rectal cancer recurrence after sphincter-preserving rectal resection. Dis Colon Rectum 2010;53:13651373.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 384 254 23
PDF Downloads 84 52 4
EPUB Downloads 0 0 0