Skip to main content

Advertisement

SpringerLink
Log in

Short-Course Radiation Therapy Versus Long-Course Chemoradiation in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer: New Insights from Randomized Trials

  • Radiation Therapy and Radiation Therapy Innovations in Colorectal Cancer (JY Wo, Section Editor)
  • Published:
Current Colorectal Cancer Reports

Abstract

Purpose of Review

Examine prospective evidence supporting preoperative short-course radiotherapy (SCRT) and long-course chemoradiotherapy (LCRT) for locally advanced rectal cancer and discuss recently published data that are helping to clarify the utility of SCRT.

Recent Findings

SCRT with early surgery results in lower pCR rates, lower severe acute toxicities, no difference in late toxicities, and no apparent difference in local control, DFS, and OS when compared with LCRT. When surgery is delayed after SCRT, cancer outcomes appear equivalent, including pCR rates. The addition of full-dose systemic therapy with SCRT prior to surgery is attractive to further downstage patients, particularly in patients at high risk of distant relapse.

Summary

Increasing randomized evidence is accumulating to support the use of SCRT as an acceptable preoperative treatment approach for locally advanced rectal cancer. Increasing the interval from SCRT to surgery and/or adding systemic doses of chemotherapy may mitigate potential concerns related to SCRT. More mature data and future results of ongoing randomized trials will help clarify the oncologic equivalence and safety of SCRT followed by preoperative chemotherapy.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

APR:

Abdominoperineal resection

CAPOX:

Capecitabine-oxaliplatin

CRM:

Circumferential resection margin

DFS:

Disease-free survival

EORTC:

European Organization for Research and Treatment of Cancer

FOLFOX:

Fluorouracil-leucovorin-oxaliplatin

FU:

Fluorouracil

LCRT:

Long-course chemoradiotherapy

LR:

Local recurrence

MRI:

Magnetic resonance imaging

NR:

Not reported

NSABP:

National Surgical Adjuvant Breast and Bowel Project

OS:

Overall survival

pCR:

Pathologic complete response

SCRT:

Short-course radiotherapy

TROG:

Trans-Tasman Radiation Oncology Group

References

Papers of particular interest, published recently have been highlighted as: • Of importance •• Of major importance

  1. 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(9666):811–20.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Stephens RJ, Thompson LC, Quirke P, 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. 2010;28(27):4233–9.

    Article  PubMed  Google Scholar 

  3. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, 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;72(1):15–24.

    Article  CAS  PubMed  Google Scholar 

  4. 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(10):1215–23.

    Article  CAS  PubMed  Google Scholar 

  5. Pietrzak L, Bujko K, Nowacki MP, et al. Quality of life, anorectal and sexual functions after preoperative radiotherapy for rectal cancer: report of a randomised trial. Radiother Oncol. 2007;84(3):217–25.

    Article  PubMed  Google Scholar 

  6. Ansari N, Solomon MJ, Fisher RJ, et al. Acute Adverse Events and Postoperative Complications in a Randomized Trial of Preoperative Short-course Radiotherapy Versus Long-course Chemoradiotherapy for T3 Adenocarcinoma of the Rectum: Trans-Tasman Radiation Oncology Group Trial (TROG 01.04). Ann Surg 2016.

  7. •• 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(31):3827–33. The TROG trial randomized trial of SCRT vs. LCRT showing overall oncologic equivalence of both approaches, with caveats discussed in the text.

    Article  PubMed  Google Scholar 

  8. McLachlan SA, Fisher RJ, Zalcberg J, et al. The impact on health-related quality of life in the first 12 months: a randomised comparison of preoperative short-course radiation versus long-course chemoradiation for T3 rectal cancer (trans-Tasman radiation oncology group trial 01.04). Eur J Cancer. 2016;55:15–26.

    Article  PubMed  Google Scholar 

  9. Eitta MA, El-Wahidi GF, Fouda MA, El-Hak NG, Abo El-Naga EM. Preoperative radiotherapy in resectable rectal cancer: a prospective randomized study of two different approaches. J Egypt Natl Canc Inst. 2010;22(3):155–64.

    PubMed  Google Scholar 

  10. Vironen J, Juhola M, Kairaluoma M, Jantunen I, Kellokumpu I. Tumour regression grading in the evaluation of tumour response after different preoperative radiotherapy treatments for rectal carcinoma. Int J Colorectal Dis. 2005;20(5):440–5.

    Article  CAS  PubMed  Google Scholar 

  11. Siegel R, Burock S, Wernecke KD, 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  PubMed  PubMed Central  Google Scholar 

  12. ISCRTN56463377. http://www.isrctn.com/ISRCTN56463377 (accessed 12/15/2016.

  13. Marijnen CA, Nagtegaal ID, Klein Kranenbarg E, et al. No downstaging after short-term preoperative radiotherapy in rectal cancer patients. J Clin Oncol. 2001;19(7):1976–84.

    Article  CAS  PubMed  Google Scholar 

  14. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731–40.

    Article  CAS  PubMed  Google Scholar 

  15. Gérard JP, Conroy T, Bonnetain F, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24(28):4620–5.

    Article  PubMed  Google Scholar 

  16. Bosset JF, Collette L, Calais G, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114–23.

    Article  CAS  PubMed  Google Scholar 

  17. Theodoropoulos G, Wise WE, Padmanabhan A, et al. T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence and improved disease-free survival. Dis Colon Rectum. 2002;45(7):895–903.

    Article  PubMed  Google Scholar 

  18. Valentini V, Coco C, Cellini N, et al. Ten years of preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, and sphincter preservation in three consecutive studies. Int J Radiat Oncol Biol Phys. 2001;51(2):371–83.

    Article  CAS  PubMed  Google Scholar 

  19. Valentini V, Coco C, Picciocchi A, et al. Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients. Int J Radiat Oncol Biol Phys. 2002;53(3):664–74.

    Article  PubMed  Google Scholar 

  20. Pettersson D, Cedermark B, Holm T, et al. Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Br J Surg. 2010;97(4):580–7.

    Article  CAS  PubMed  Google Scholar 

  21. Pettersson D, Lörinc E, Holm T, et al. Tumour regression in the randomized Stockholm III trial of radiotherapy regimens for rectal cancer. Br J Surg. 2015;102(8):972–8.

  22. Latkauskas T, Pauzas H, Gineikiene I, et al. Initial results of a randomized controlled trial comparing clinical and pathological downstaging of rectal cancer after preoperative short-course radiotherapy or long-term chemoradiotherapy, both with delayed surgery. Colorectal Dis. 2012;14(3):294–8.

    Article  CAS  PubMed  Google Scholar 

  23. André T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350(23):2343–51.

    Article  PubMed  Google Scholar 

  24. Fernández-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(5):859–65.

    Article  PubMed  Google Scholar 

  25. 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(4):668–74.

    Article  CAS  PubMed  Google Scholar 

  26. •• Bujko K, Wyrwicz L, Rutkowski A, et al. Long-course oxaliplatin-based preoperative chemoradiation versus 5 × 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. Ann Oncol. 2016;27(5):834–42. Recently published randomized trial of SCRT plus sequential chemotherapy vs. LCRT a benefit in overall survival with the SCRT arm. However, cancer-specific outcomes were not different between arms.

    Article  CAS  PubMed  Google Scholar 

  27. • Myerson RJ, Tan B, Hunt S, et al. Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer. Int J Radiat Oncol Biol Phys. 2014;88(4):829–36. Single institution phase III trial of SCRT plus sequential chemotherapy that describes a modern approach to deliver SCRT using a two-tiered simultaneous integrated boost intensity-modulated radiation therapy technique.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kim KH, Shin SJ, Cho MS, et al. A phase II study of preoperative mFOLFOX6 with short-course radiotherapy in patients with locally advanced rectal cancer and liver-only metastasis. Radiother Oncol. 2016;118(2):369–74.

    Article  CAS  PubMed  Google Scholar 

  29. van Dijk TH, Tamas K, Beukema JC, et al. Evaluation of short-course radiotherapy followed by neoadjuvant bevacizumab, capecitabine, and oxaliplatin and subsequent radical surgical treatment in primary stage IV rectal cancer. Ann Oncol. 2013;24(7):1762–9.

    Article  PubMed  Google Scholar 

  30. Jin J, Tang Y, Li S, et al. The initial results for a phase III study of short-term radiotherapy plus chemotherapy vs long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR trial). Journal of Clinical Oncology, 2016. http://meetinglibrary.asco.org/content/167543-176 (accessed 12/11/2016)

  31. Nilsson PJ, van Etten B, Hospers GA, et al. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer--the RAPIDO trial. BMC Cancer. 2013;13:279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wibe A, Møller B, Norstein J, et al. A national strategic change in treatment policy for rectal cancer--implementation of total mesorectal excision as routine treatment in Norway. A national audit. Dis Colon Rectum. 2002;45(7):857–66.

    Article  PubMed  Google Scholar 

  33. Wibe A, Syse A, Andersen E, et al. Oncological outcomes after total mesorectal excision for cure for cancer of the lower rectum: anterior vs. Abdominoperineal resection. Dis Colon Rectum. 2004;47(1):48–58.

    Article  PubMed  Google Scholar 

  34. Marijnen CA, Nagtegaal ID, Kapiteijn E, et al. Radiotherapy does not compensate for positive resection margins in rectal cancer patients: report of a multicenter randomized trial. Int J Radiat Oncol Biol Phys. 2003;55(5):1311–20.

    Article  CAS  PubMed  Google Scholar 

  35. Kusters M, Marijnen CA, van de Velde CJ, et al. Patterns of local recurrence in rectal cancer; a study of the Dutch TME trial. Eur J Surg Oncol. 2010;36(5):470–6.

    Article  CAS  PubMed  Google Scholar 

  36. Fokas E, Liersch T, Fietkau R, et al. Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial. J Clin Oncol. 2014;32(15):1554–62.

    Article  PubMed  Google Scholar 

  37. Ngan SY. Preoperative treatment of locally advanced rectal cancer: assets and drawbacks of short course and long course in clinical practice. Semin Radiat Oncol. 2016;26(3):186–92.

    Article  PubMed  Google Scholar 

  38. Battersby NJ, How P, Moran B, et al. Prospective validation of a Low rectal cancer magnetic resonance imaging staging system and development of a local recurrence risk stratification model: the MERCURY II study. Ann Surg. 2016;263(4):751–60.

    Article  PubMed  Google Scholar 

  39. Birgisson H, Påhlman L, Gunnarsson U, Glimelius B. Late adverse effects of radiation therapy for rectal cancer - a systematic overview. Acta Oncol. 2007;46(4):504–16.

    Article  PubMed  Google Scholar 

  40. Cox JD, Stetz J, Pajak TF. Toxicity criteria of the radiation therapy oncology group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys. 1995;31(5):1341–6.

    Article  CAS  PubMed  Google Scholar 

  41. LENT SOMA Tables. Radiother Oncol. 1995;35(1):17–60.

  42. Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish rectal cancer trial. N Engl J Med. 1997;336(14):980–7.

    Article  Google Scholar 

  43. 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(9):638–46.

    Article  CAS  PubMed  Google Scholar 

  44. Viani GA, Stefano EJ, Soares FV, Afonso SL. Evaluation of biologic effective dose and schedule of fractionation for preoperative radiotherapy for rectal cancer: meta-analyses and meta-regression. Int J Radiat Oncol Biol Phys. 2011;80(4):985–91.

    Article  PubMed  Google Scholar 

  45. Fowler JF. The linear-quadratic formula and progress in fractionated radiotherapy. Br J Radiol. 1989;62(740):679–94.

    Article  CAS  PubMed  Google Scholar 

  46. Bosset JF, Calais G, Mineur L, 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.

    Article  CAS  PubMed  Google Scholar 

  47. Kim IY, You SH, Kim YW. Neutrophil-lymphocyte ratio predicts pathologic tumor response and survival after preoperative chemoradiation for rectal cancer. BMC Surg. 2014;14:94.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Napolitano M, D’Alterio C, Cardone E, et al. Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients. Oncotarget. 2015;6(10):8261–70.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Sineshaw HM, Jemal A, Thomas CR, Mitin T. Changes in treatment patterns for patients with locally advanced rectal cancer in the united states over the past decade: an analysis from the national cancer data base. Cancer. 2016;122(13):1996–2003.

    Article  PubMed  Google Scholar 

  50. • Mowery YM, Salama JK, Zafar SY, et al. Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States. Cancer. 2016. doi:10.1002/cncr.30461. Survey-based study that details biases and opinions of radiation oncologists in the US regarding SCRT.

    PubMed  Google Scholar 

  51. Elliot AH, Martling A, Glimelius B, Nordenvall C, Johansson H, Nilsson PJ. Preoperative treatment selection in rectal cancer: a population-based cohort study. Eur J Surg Oncol. 2014;40(12):1782–8.

    Article  CAS  PubMed  Google Scholar 

  52. van den Broek CB, van Gijn W, Bastiaannet E, et al. Differences in pre-operative treatment for rectal cancer between Norway, Sweden, Denmark, Belgium and the Netherlands. Eur J Surg Oncol. 2014;40(12):1789–96.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of Washington, 1959 NE Pacific Street, Box 356043, Seattle, WA, 98195-6043, USA

    Thomas D. Mullen, Edward Y. Kim & Smith Apisarnthanarax

Authors
  1. Thomas D. Mullen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Edward Y. Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Smith Apisarnthanarax
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Smith Apisarnthanarax.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Topical Collection on Radiation Therapy and Radiation Therapy Innovations in Colorectal Cancer

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mullen, T.D., Kim, E.Y. & Apisarnthanarax, S. Short-Course Radiation Therapy Versus Long-Course Chemoradiation in the Neoadjuvant Treatment of Locally Advanced Rectal Cancer: New Insights from Randomized Trials. Curr Colorectal Cancer Rep 13, 165–174 (2017). https://doi.org/10.1007/s11888-017-0359-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11888-017-0359-4

Keywords

Search

Navigation