Could Upfront Chemotherapy Substitute Preoperative Radiochemotherapy?

  • Arvind Dasari
  • Prajnan Das


In patients with locally advanced, resectable rectal adenocarcinoma, preoperative long course chemoradiation or short-course radiation are currently considered the standards of care. Neoadjuvant radiotherapy, along with improvements in surgical techniques and imaging have dramatically reduced the risk of local recurrence. Disappointingly, these advances have not translated into reduction of risk of distant relapse or improvement in overall survival for these patients. Furthermore, pelvic radiation may be associated with several toxicities, both short and long-term. Recent data suggest that not all patients may need neoadjuvant radiotherapy, and that advances in systemic chemotherapy could be leveraged in the neoadjuvant setting to improve risk of both local and distant relapse. Based on these emerging data, several, ongoing, randomized trials are evaluating neoadjuvant approaches limiting the role of radiotherapy. In this chapter, we summarize the current state of knowledge and ongoing trials in this area. We propose that until the results of these trials are available, neoadjuvant chemotherapy without radiation should be considered investigational or only limited to those with clear contraindications to pelvic radiation. We believe these trials will likely show that preoperative chemoradiation may be more appropriate for certain groups of patients, while preoperative chemotherapy may be appropriate for other groups of patients.


  1. 1.
    Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740CrossRefPubMedGoogle Scholar
  2. 2.
    Hofheinz RD, Wenz F, Post S et al (2012) Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol 13:579–588CrossRefPubMedGoogle Scholar
  3. 3.
    O’Connell MJ, Colangelo LH, Beart RW et al (2014) 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 32:1927–1934CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Peeters KC, Marijnen CA, Nagtegaal ID et al (2007) 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 246:693–701CrossRefPubMedGoogle Scholar
  5. 5.
    Sebag-Montefiore D, Stephens RJ, Steele R et al (2009) Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet 373:811–820CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Birgisson H, Pahlman L, Gunnarsson U et al (2005) Adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the Swedish Rectal Cancer Trial. J Clin Oncol 23:8697–8705CrossRefPubMedGoogle Scholar
  7. 7.
    Meta-analysis Group In C, Piedbois P, Rougier P et al (1998) Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 16:301–308CrossRefGoogle Scholar
  8. 8.
    Buroker TR, O’Connell MJ, Wieand HS et al (1994) Randomized comparison of two schedules of fluorouracil and leucovorin in the treatment of advanced colorectal cancer. J Clin Oncol 12:14–20CrossRefPubMedGoogle Scholar
  9. 9.
    Benson AB 3rd, Venook AP, Bekaii-Saab T et al (2014) Colon cancer, version 3.2014. J Natl Compr Cancer Netw 12:1028–1059CrossRefGoogle Scholar
  10. 10.
    Karoui M, Koubaa W, Delbaldo C et al (2008) Chemotherapy has also an effect on primary tumor in colon carcinoma. Ann Surg Oncol 15:3440–3446CrossRefPubMedGoogle Scholar
  11. 11.
    Suarez J, Amat I, Vera R et al (2011) Pathologic response of primary rectal cancer to oxaliplatin-based chemotherapy. Clin Colon Rectal Surg 24:119–124CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Foxtrot Collaborative G (2012) Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol 13:1152–1160CrossRefGoogle Scholar
  13. 13.
    Bensignor T, Brouquet A, Dariane C et al (2014) Pathologic response of locally advanced rectal cancer to preoperative chemotherapy without pelvic irradiation. Colorectal Dis 17(6):491–498CrossRefGoogle Scholar
  14. 14.
    Ishii Y, Hasegawa H, Endo T et al (2010) Medium-term results of neoadjuvant systemic chemotherapy using irinotecan, 5-fluorouracil, and leucovorin in patients with locally advanced rectal cancer. Eur J Surg Oncol 36:1061–1065CrossRefPubMedGoogle Scholar
  15. 15.
    Fuchs CS, Marshall J, Mitchell E et al (2007) Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C study. J Clin Oncol 25:4779–4786CrossRefPubMedGoogle Scholar
  16. 16.
    Uehara K, Hiramatsu K, Maeda A et al (2013) Neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy for poor-risk rectal cancer: N-SOG 03 phase II trial. Jpn J Clin Oncol 43:964–971CrossRefPubMedGoogle Scholar
  17. 17.
    Chau I, Brown G, Cunningham D et al (2006) Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol 24:668–674CrossRefPubMedGoogle Scholar
  18. 18.
    Chua YJ, Barbachano Y, Cunningham D et al (2010) Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol 11:241–248CrossRefPubMedGoogle Scholar
  19. 19.
    Dewdney A, Cunningham D, Tabernero J et al (2012) 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 30:1620–1627CrossRefPubMedGoogle Scholar
  20. 20.
    Bosset JF, Collette L, Calais G et al (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114–1123CrossRefPubMedGoogle Scholar
  21. 21.
    Fernandez-Martos C, Pericay C, Aparicio J et al (2010) 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 28:859–865CrossRefPubMedGoogle Scholar
  22. 22.
    Schrag D, Weiser MR, Goodman KA et al (2014) Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol 32:513–518CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Gollub MJ, Gultekin DH, Akin O et al (2012) Dynamic contrast enhanced-MRI for the detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer. Eur Radiol 22:821–831CrossRefPubMedGoogle Scholar
  24. 24.
    Deng Y, Chi P, Wang L et al (2015) A multi-center randomized controlled trial of mFOLFOX6 with or without radiation in neoadjuvant treatment of local advanced rectal cancer (FOWARC study): Preliminary results. J Clin Oncol 33:Abstr 3500CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2018

Authors and Affiliations

  1. 1.Department of Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Radiation OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

Personalised recommendations