Skip to main content

Neoadjuvant Treatment in Rectal Cancer: Do We Always Need Radiotherapy–or Can We Risk Assess Locally Advanced Rectal Cancer Better?

  • Conference paper
  • First Online:
Early Gastrointestinal Cancers

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 196))

Abstract

There is good quality evidence that preoperative radiotherapy reduces local recurrence but there is little impact on overall survival. This is not completely unexpected as radiotherapy is a localised treatment and local control may not prevent systemic failure. Optimal quality-controlled surgery for patients with operable rectal cancer in the trial setting can be associated with local recurrence rates of less than 10 % whether patients receive radiotherapy or not (Quirke et al. 2009). However, despite the reassuring results of randomised trials, concerns remain that radiotherapy increases surgical morbidity (Horisberger et al. 2008; Stelzmueller et al. 2009; Swellengrebel et al. 2011), which can compromise the delivery of postoperative adjuvant chemotherapy. There are also significant late effects from pelvic radiotherapy (Peeters et al. 2005; Lange et al. 2007) and a risk of second malignancies (Birgisson et al. 2005; van Gijn et al. 2011). If preoperative radiotherapy does not impact on survival, can it be omitted in selected cases? The answer is yes—with the proviso that we are using good quality magnetic resonance imaging and good quality TME surgery within the mesorectal plane and the predicted risk of subsequent metastatic disease justifies its use. In this case, the concept of neoadjuvant chemotherapy (NACT) is a potentially attractive alternative strategy which might have less early and long-term side effects compared to preoperative radiotherapy—particularly where the MRI predicts a high risk of metastatic disease in the context of a modest risk of local recurrence. This chapter discusses a more precise method of risk categorisation for locally advanced rectal cancer, and discusses possible options for neoadjuvant chemotherapy (NACT).

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

  • André T, Boni C, Navarro M et al (2009) 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 27(19):3109–3116

    Article  PubMed  Google Scholar 

  • Aschele C, Cionini L, Lonardi S et al (2011) 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 29(20):2773–2780

    Article  PubMed  CAS  Google Scholar 

  • Birgisson H, Pahlman L, Gunnarsson U, Glimelius B (2005) Occurrence of second cancers in patients treated with radiotherapy for rectal cancer. J Clin Oncol 23:6126–6131

    Article  PubMed  Google Scholar 

  • Birgisson H, Pahlman L, Glimelius B (2006) Adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the Swedish rectal cancer trial. J Clin Oncol 23:8697–8705

    Article  Google Scholar 

  • Bosset JF, Collette L, Calais G et al (2006) Chemoradiotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114–1123

    Article  PubMed  CAS  Google Scholar 

  • Braendengen M, Tveit KM, Berglund A et al (2008) Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol 26(22):3687–3694

    Article  PubMed  CAS  Google Scholar 

  • Bujko K, Nowacki MP, Nasierowska-Guttmejer A et al (2006) Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg 93(10):1215–1223

    Article  PubMed  CAS  Google Scholar 

  • Cecil DT, Sexton R, Moran BJ, Heald RJ (2004) Total mesorectal excision results in low local recurrence rates in lymph node-positive rectal cancer. Dis Colon Rectum 47:1145–1150

    Article  PubMed  Google Scholar 

  • Cercek A, Weiser MR, Goodman KA, et al., (2010) Complete pathological response in the primary of rectal or colon cancer treated with FOLFOX without radiation. J Clin Oncol 28:3649 (15S suppl (May 20 Supplement): 297s (abstract))

    Google Scholar 

  • Chua YJ, Barbachano Y, Cunningham D et al (2010) Neoadjuvant capecitabine and oxaliplatin before chemoradiation and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol 11(3):241–248

    Article  PubMed  CAS  Google Scholar 

  • Dirschmid K, Lang A, Mathis G et al (1996) Incidence of extramural venous invasion in colorectal carcinoma: findings with a new technique. Hum Pathol 27(11):1227–1230

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Martos C, Pericay C, Salud A (2011) Three-year outcomes of GCR-3: a phase II randomized trial comparing conventional preoperative chemoradiation (CRT) followed by surgery and postoperative adjuvant chemotherapy (CT) with induction CT followed by CRT and surgery in locally advanced rectal cancer. J Clin Oncol 29:abstr 3552 (Suppl)

    Google Scholar 

  • Fernández-Martos C, Pericay C, Aparicio J et al (2010) Phase II, Randomized study of concomitant chemoradiation followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiation and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: grupo cancer de recto 3 study. J Clin Oncol 28(5):859–865

    Article  PubMed  Google Scholar 

  • Frasson M, Garcia-Granero E, Roda D, et al (2011) Preoperative chemoradiation may not always be needed for patients with T3 and T2 N + rectal cancer. Cancer 117(14): 3118–3125. doi: 10.1002/cncr.25866

    Google Scholar 

  • Frykholm GJ, Pahlman L, Glimerlius B (2001) Combined chemo- and radiotherapy vs radiotherapy alone in the treatment of primary, nonresectable adenocarcinoma of the rectum. Int J Radiat Oncol Biol Phys 50(2):427–434

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Aguilar J, Smith DD, Avila K et al (2011) Timing of rectal cancer response to chemoradiation consortium. optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial. Ann Surg 254(1):97–102

    Article  PubMed  Google Scholar 

  • Gerard JP, Conroy T, Bonnetain F et al (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–T4 rectal cancers: results of FFCD 9203. J Clin Oncol 24:4620–4625

    Article  PubMed  Google Scholar 

  • Gerard JP, Azria D, Gourgou-Bourgade S et al (2010) 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 28:1638–1644

    Article  PubMed  CAS  Google Scholar 

  • Glynne-Jones R, Anyamene N, Moran B, Harrison M (2012) Neoadjuvant chemotherapy in MRI-staged high-risk rectal cancer in addition to or as an alternative to preoperative chemoradiation? Ann Oncol [Epub ahead of print]

    Google Scholar 

  • Herman MP, Kopetz S, Bhosale PR, Eng C, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, Delclos ME, Krishnan S, Crane CH, Das P (2009) Sacral insufficiency fractures after preoperative chemoradiation for rectal cancer: incidence, risk factors, and clinical course. Int J Radiat Oncol Biol Phys 74(3):818–823

    Article  PubMed  Google Scholar 

  • Horisberger K, Hofheinz RD, Palma P et al (2008) Tumor response to neoadjuvant chemoradiation in rectal cancer: predictor for surgical morbidity? Int J Colorectal Dis 23(3):257–264

    Article  PubMed  CAS  Google Scholar 

  • Ishii Y, Hasegawa H, Endo T et al (2010) Medium-termresults of neoadjuvant systemic chemotherapy using irinotecan, 5-fluorouracil, and leucovorin in patients with locally advanced rectal cancer. Eur J Surg Oncol 36(11):1061–1065

    Article  PubMed  CAS  Google Scholar 

  • Kuebler JP, Wieand HS, O’Connell MJ et al (2007) Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol 25(16):2198–2204

    Article  PubMed  CAS  Google Scholar 

  • Kusters M, Marijnen CA, van de Velde CJ et al (2010) Patterns of local recurrence in rectal cancer; a study of the Dutch TME trial. Eur J Surg Oncol 36(5):470–476

    Article  PubMed  CAS  Google Scholar 

  • Lange MM, den Dulk M, Bossema ER et al (2007) Risk factors for faecal incontinence after rectal cancer treatment. Cooperative clinical investigators of the Dutch total mesorectal excision trial. Br J Surg 94(10):1278–1284

    Article  PubMed  CAS  Google Scholar 

  • Marijnen CA, van de Velde CJ, Putter H et al (2005) 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 23(9):1847–1858

    Article  PubMed  Google Scholar 

  • Mathis KL, Larson DW, Dozois EJ et al (2012) Outcomes following surgery without radiotherapy for rectal cancer. Br J Surg 99(1):137–143

    Article  PubMed  CAS  Google Scholar 

  • MERCURY Study Group (2007) Extramural depth of tumour invasion at thin section MR in patients with rectal cancer. Results of the MERCURY Study. Radiology 243:132–139

    Article  Google Scholar 

  • Merkel S, Mansmann U, Siassi M, Papadopoulus T, Hohenberger W, Heranek P (2001) The prognostic inhomogeneity in pT3 rectal carcinomas. Int J Colorectal Dis 16:298–304

    Article  PubMed  CAS  Google Scholar 

  • Morris E, Quirke P, Thomas JD et al (2008) Unacceptable variation in abdominoperineal excision rates for rectal cancer: time to intervene? Gut 57(12):1690–1697

    Article  PubMed  CAS  Google Scholar 

  • Ngan S, Fisher R, Goldstein D et al., (2010) TROG, AGITG, CSSANZ, and RACS.A randomized trial comparing local recurrence (LR) rates between short-course (SC) and long-course (LC) preoperative radiotherapy (RT) for clinical T3 rectal cancer: an intergroup trial (TROG, AGITG, CSSANZ, RACS). J Clin Oncol 2010 28:(15):3509 (abstract)

    Google Scholar 

  • Peeters KC, van de Velde CJ, Leer JW et al (2005) 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 23(25):6199–6206

    Article  PubMed  CAS  Google Scholar 

  • Peeters KC, Marijnen CA, Nagtegaal ID, For the Dutch Colorectal Cancer Group 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(5):693–701

    Article  PubMed  Google Scholar 

  • Pollack J, Holm T, Cedermark B et al (2006) Long-term effect of preoperative radiation therapy on anorectal function. Dis Colon Rectum 49(3):345–352

    Article  PubMed  Google Scholar 

  • Quirke P, Steele R, Monson J et al (2009) MRC CR07/NCIC-CTG CO16 trial investigators; NCRI colorectal cancer study group. Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG CO16 randomised clinical trial. Lancet 373(9666):821–828

    Article  PubMed  Google Scholar 

  • Rödel C, Liersch T, Hermann R et al (2007) Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer. J Clin Oncol 25:668–674

    Google Scholar 

  • Roh MS, Colangelo LH, O’Connell MJ et al (2009) Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP-R03. J Clin Oncol 27:5124–5130

    Article  PubMed  Google Scholar 

  • Sauer R, Becker H, Hohenberger W, German Rectal Cancer Study Group et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740

    Article  PubMed  CAS  Google Scholar 

  • Schrag D, Weiser MR, Goodman KA, et al., Neoadjuvant FOLFOX-bev, without radiation for locally advanced rectal cancer. J Clin Oncol 2010;28:3511 (15S_suppl (May 20 Supplement) 263s (abstract))

    Google Scholar 

  • 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(9666):811–820

    Article  PubMed  Google Scholar 

  • Smith N, Brown G (2008) Preoperative staging of rectal cancer. Acta Oncol 47(1):20–31

    Article  PubMed  Google Scholar 

  • Stelzmueller I, Zitt M, Aigner F et al (2009) Postoperative morbidity following chemoradiation for locally advanced low rectal cancer. J Gastrointest Surg 13(4):657–667

    Article  PubMed  Google Scholar 

  • Sternberg A, Amar M, Alfici R, Groisman G (2002) Conclusions from a study of venous invasion in stage IV colorectal adenocarcinoma. J Clin Pathol 55(1):17–21

    Article  PubMed  CAS  Google Scholar 

  • Swellengrebel HA, Marijnen CA, Verwaal VJ et al (2011) Toxicity and complications of preoperative chemoradiotherapy for locally advanced rectal cancer. Br J Surg 98(3):418–426

    Article  PubMed  CAS  Google Scholar 

  • Taylor FG, Quirke P, Heald RJ, For the MERCURY study group et al (2011) Preoperative high-resolution magnetic resonance imaging can identify good prognosis stage I, II, and III rectal cancer best managed by surgery alone: a prospective, multicenter, european study that recruited consecutive patients with rectal cancer. Ann Surg 253(4):711–719

    Article  PubMed  Google Scholar 

  • van Gijn W, Marijnen CA, Nagtegaal ID et al (2011) Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12 year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 12(6):575–582

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rob Glynne-Jones .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Glynne-Jones, R. (2012). Neoadjuvant Treatment in Rectal Cancer: Do We Always Need Radiotherapy–or Can We Risk Assess Locally Advanced Rectal Cancer Better?. In: Otto, F., Lutz, M. (eds) Early Gastrointestinal Cancers. Recent Results in Cancer Research, vol 196. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-31629-6_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-31629-6_2

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-31628-9

  • Online ISBN: 978-3-642-31629-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics