The Selective Use of Radiation Therapy in Rectal Cancer Patients

  • Andrew Martella
  • Christopher Willett
  • Manisha Palta
  • Brian Czito
Gastrointestinal Cancers (J Meyer, Section Editor)
  • 90 Downloads
Part of the following topical collections:
  1. Topical Collection on Gastrointestinal Cancers

Abstract

Purpose of Review

Colorectal cancer has a high global incidence, and standard treatment employs a multimodality approach. In addition to cure, minimizing treatment-related toxicity and improving the therapeutic ratio is a common goal. The following article addresses the potential of omitting radiotherapy in select rectal cancer patients.

Recent Findings

Omission of radiotherapy in rectal cancer is analyzed in the context of historical findings, as well as more recent data describing risk stratification of stage II–III disease, surgical optimization, imaging limitations, improvement in systemic chemotherapeutic agents, and contemporary studies evaluating selective omission of radiotherapy.

Summary

A subset of rectal cancer patients exists that may be considered low to intermediate risk for locoregional recurrence. With appropriate staging, surgical technique, and possibly improved systemic therapy, it may be feasible to selectively omit radiotherapy in these patients. Current imaging limitations as well as evidence of increased locoregional recurrence following radiotherapy omission lend us to continue supporting the standard treatment of approach of neoadjuvant chemoradiation therapy followed by surgical resection until additional improvements and prospective evidence can support otherwise.

Keywords

Radiotherapy omission Rectal cancer Risk stratification rectal cancer Imaging rectal cancer Minimizing toxicity Prognostic factors rectal cancer 

Notes

Compliance with Ethical Standards

Conflict of Interest

Andrew Martella declares that he has no conflict of interest.

Christopher Willett declares that he has no conflict of interest.

Manisha Palta has received research support from Merck and honoraria from Oakstone CME and UpToDate.

Brian Czito declares that he has 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.

References

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

  1. 1.
    Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiol Biomark Prev. 2016;25(1):16–27.  https://doi.org/10.1158/1055-9965.EPI-15-0578.CrossRefGoogle Scholar
  2. 2.
    Li Y, Wang J, Ma X, Tan L, Yan Y, Xue C, et al. A review of neoadjuvant chemoradiotherapy for locally advanced rectal cancer. Int J Biol Sci. 2016;12(8):1022–31.  https://doi.org/10.7150/ijbs.15438.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Gunderson LL, Sosin H. Areas of failure found at reoperation (second or symptomatic look) following "curative surgery" for adenocarcinoma of the rectum. Clinicopathologic correlation and implications for adjuvant therapy. Cancer. 1974;34(4):1278–92.CrossRefPubMedGoogle Scholar
  4. 4.
    Willett CG, Tepper JE, Cohen AM, Orlow E, Welch CE. Failure patterns following curative resection of colonic carcinoma. Ann Surg. 1984;200(6):685–90.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Wolmark N, Wieand HS, Hyams DM, Colangelo L, Dimitrov NV, Romond EH, et al. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst. 2000;92(5):388–96.CrossRefPubMedGoogle Scholar
  6. 6.
    Cedermark B, Johansson H, Rutqvist LE, Wilking N. The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Colorectal Cancer Study Group. Cancer. 1995;75(9):2269–75.CrossRefPubMedGoogle Scholar
  7. 7.
    Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst. 1988;80(1):21–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005;23(24):5644–50.  https://doi.org/10.1200/JCO.2005.08.144.CrossRefPubMedGoogle Scholar
  9. 9.
    Gastrointestinal Tumor Study G. Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med. 1985;312(23):1465–72.  https://doi.org/10.1056/NEJM198506063122301.CrossRefGoogle Scholar
  10. 10.
    Gerard A, Buyse M, Nordlinger B, Loygue J, Pene F, Kempf P, et al. Preoperative radiotherapy as adjuvant treatment in rectal cancer. Final results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC). Ann Surg. 1988;208(5):606–14.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Pahlman L, Glimelius B. Pre- or postoperative radiotherapy in rectal and rectosigmoid carcinoma. Report from a randomized multicenter trial. Ann Surg. 1990;211(2):187–95.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Lai LL, Fuller CD, Kachnic LA, Thomas CR Jr. Can pelvic radiotherapy be omitted in select patients with rectal cancer? Semin Oncol. 2006;33(6 Suppl 11):S70–4.  https://doi.org/10.1053/j.seminoncol.2006.10.019.CrossRefPubMedGoogle Scholar
  13. 13.
    Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, et al. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control—final report of intergroup 0114. J Clin Oncol. 2002;20(7):1744–50.  https://doi.org/10.1200/JCO.2002.07.132.CrossRefPubMedGoogle Scholar
  14. 14.
    Gunderson LL, Sargent DJ, Tepper JE, Wolmark N, O'Connell MJ, Begovic M, et al. Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol. 2004;22(10):1785–96.  https://doi.org/10.1200/JCO.2004.08.173.CrossRefPubMedGoogle Scholar
  15. 15.
    Willett CG, Badizadegan K, Ancukiewicz M, Shellito PC. Prognostic factors in stage T3N0 rectal cancer: do all patients require postoperative pelvic irradiation and chemotherapy? Dis Colon Rectum. 1999;42(2):167–73.CrossRefPubMedGoogle 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.CrossRefPubMedGoogle Scholar
  17. 17.
    Heald RJ, Husband EM, Ryall RD. The mesorectum in rectal cancer surgery—the clue to pelvic recurrence? Br J Surg. 1982;69(10):613–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Cecil TD, Sexton R, Moran BJ, Heald RJ. Total mesorectal excision results in low local recurrence rates in lymph node-positive rectal cancer. Dis Colon Rectum. 2004;47(7):1145–9; discussion 9-50.  https://doi.org/10.1007/s10350-004-0086-6.CrossRefPubMedGoogle Scholar
  19. 19.
    Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638–46.  https://doi.org/10.1056/NEJMoa010580.CrossRefPubMedGoogle Scholar
  20. 20.
    Group MS. Extramural depth of tumor invasion at thin-section MR in patients with rectal cancer: results of the MERCURY study. Radiology. 2007;243(1):132–9.  https://doi.org/10.1148/radiol.2431051825.CrossRefGoogle Scholar
  21. 21.
    Bipat S, Glas AS, Slors FJ, Zwinderman AH, Bossuyt PM, Stoker J. Rectal cancer: local staging and assessment of lymph node involvement with endoluminal US, CT, and MR imaging--a meta-analysis. Radiology. 2004;232(3):773–83.  https://doi.org/10.1148/radiol.2323031368.CrossRefPubMedGoogle Scholar
  22. 22.
    Guillem JG, Diaz-Gonzalez JA, Minsky BD, Valentini V, Jeong SY, Rodriguez-Bigas MA, et al. cT3N0 rectal cancer: potential overtreatment with preoperative chemoradiotherapy is warranted. J Clin Oncol. 2008;26(3):368–73.  https://doi.org/10.1200/JCO.2007.13.5434.CrossRefPubMedGoogle Scholar
  23. 23.
    Minsky BD, Conti JA, Huang Y, Knopf K. Relationship of acute gastrointestinal toxicity and the volume of irradiated small bowel in patients receiving combined modality therapy for rectal cancer. J Clin Oncol. 1995;13(6):1409–16.  https://doi.org/10.1200/JCO.1995.13.6.1409.CrossRefPubMedGoogle Scholar
  24. 24.
    Birgisson H, Pahlman L, Gunnarsson U, Glimelius B. Occurrence of second cancers in patients treated with radiotherapy for rectal cancer. J Clin Oncol. 2005;23(25):6126–31.  https://doi.org/10.1200/JCO.2005.02.543.CrossRefPubMedGoogle Scholar
  25. 25.
    Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, 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.  https://doi.org/10.1016/S0140-6736(09)60484-0.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    • Harris DA, Thorne K, Hutchings H, Islam S, Holland G, Hatcher O, et al. Protocol for a multicentre randomised feasibility trial evaluating early surgery alone in LOw rectal cancer (SAILOR). BMJ Open. 2016;6(11):e012496.  https://doi.org/10.1136/bmjopen-2016-012496. This is a feasibility study that will help guide future trials evaluating surgery alone in the treatment of rectal cancer. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Glynne-Jones R, Chau I. Neoadjuvant therapy before surgical treatment. EJC Suppl. 2013;11(2):45–59.  https://doi.org/10.1016/j.ejcsup.2013.07.032.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    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.  https://doi.org/10.1200/JCO.2011.40.1836.CrossRefPubMedGoogle Scholar
  29. 29.
    • Schrag D, Weiser MR, Goodman KA, Gonen M, Hollywood E, Cercek A, et al. Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol. 2014;32(6):513–8.  https://doi.org/10.1200/JCO.2013.51.7904. Contemporary pilot trial providing feasibility evidence for the use of chemotherapy without radiotherapy to support necessary larger randomized trials. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Ishii Y, Hasegawa H, Endo T, Okabayashi K, Ochiai H, Moritani K, et al. Medium-term results of neoadjuvant systemic chemotherapy using irinotecan, 5-fluorouracil, and leucovorin in patients with locally advanced rectal cancer. Eur J Surg Oncol. 2010;36(11):1061–5.  https://doi.org/10.1016/j.ejso.2010.05.017.CrossRefPubMedGoogle Scholar
  31. 31.
    Glynne-Jones R. Neoadjuvant treatment in rectal cancer: do we always need radiotherapy-or can we risk assess locally advanced rectal cancer better? Recent Results Cancer Res. 2012;196:21–36.  https://doi.org/10.1007/978-3-642-31629-6_2.CrossRefPubMedGoogle Scholar
  32. 32.
    •• Fernandez-Martos C, Brown G, Estevan R, Salud A, Montagut C, Maurel J, et al. Preoperative chemotherapy in patients with intermediate-risk rectal adenocarcinoma selected by high-resolution magnetic resonance imaging: the GEMCAD 0801 phase II multicenter trial. Oncologist. 2014;19(10):1042–3.  https://doi.org/10.1634/theoncologist.2014-0233. Highlights the need for imaging to keep pace with changing treatment approaches, and allows us to make more personalized decisions regarding treatment. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    •• Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, et al. 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.  https://doi.org/10.1200/JCO.2016.66.6198. Provides evidence of efficacy and feasibility of using modified chemotherapeutic regimens that can obtain similar downstaging but inferior pathological response rates to a radiation-based approach. Highlights the importance that these new regimens must maintain appropriate degree of efficacy without additional toxicity. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Andrew Martella
    • 1
  • Christopher Willett
    • 1
  • Manisha Palta
    • 1
  • Brian Czito
    • 1
  1. 1.Duke Cancer Center, Medicine CircleDuke University HospitalDurhamUSA

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