The Role of Multiagent Chemoradiation in the Management and Prognosis of Anal Squamous Cell Carcinoma

  • Paolo Goffredo
  • Alan F. Utria
  • Jennifer E. Hrabe
  • Irena Gribovskaja-Rupp
  • Muneera R. Kapadia
  • Imran HassanEmail author
2018 SSAT Quick Shot Presentation



The standard treatment for anal squamous cell carcinoma (ASCC) is multiagent chemotherapy with radiation (CRT). This is based on several randomized trials demonstrating lower recurrence and colostomy-free survival rates with multiagent CRT; however, these studies could not confirm an overall survival (OS) benefit. We hypothesized that the lack of improved OS was due to limited sample sizes and follow-up, and that multiagent CRT is associated with higher OS.


The National Cancer Database was queried for patients diagnosed with stages I, II, and II ASCC and received between 45 and 59.4 Gy of radiation between 2004 and 2015. OS of patients receiving multiagent CRT compared to monoagent CRT and radiation alone was analyzed across stages.


A total of 10,438 patients received multiagent CRT, 1163 had monoagent CRT and 446 received radiation alone. Compared to the other two groups, patients receiving multiagent CRT were younger, had fewer comorbidities, and more advanced disease (all p < 0.001). After adjusting for available confounders, multiagent CRT remained independently associated with higher OS for stages II and III ASCC. A subset analysis of patients ≥ 70 years demonstrated similar survival between monoagent versus multiagent CRT across all stages.


Multiagent CRT is associated with an OS benefit compared to monoagent CRT or radiation alone for stages II and III, but not stage I ASCC. Monoagent CRT may represent an adequate treatment for selected patients ≥ 70 years. The benefit of multiagent CRT should be balanced against treatment-related toxicities depending on disease stage and patient physiology.


Anal squamous cell carcinoma Chemotherapy Radiation Survival 



We would like to thank Timothy Ginader from the University of Iowa Biostatistics Core Alliance for his statistical support.

Author Contribution

Each Author meets the International Committee of Medical Journal Editors (ICMJE), including:

- Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work;

- Drafting the work or revising it critically for important intellectual content;

- Final approval of the version to be published; and

- Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Compliance with Ethical Standards


None to report. The data used in the study are derived from a de-identified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology employed, or the conclusions drawn from these data by the investigator.


  1. 1.
    NIH. Cancer Stat Facts: Anal Cancer. Accessed 1 August 1st 2018.
  2. 2.
    Benson AB, 3rd, Venook AP, Al-Hawary MM, Cederquist L, Chen YJ, Ciombor KK et al. Anal Carcinoma, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN. 2018;16(7):852–71. doi: Scholar
  3. 3.
    Nigro ND, Vaitkevicius VK, Considine B, Jr. Combined therapy for cancer of the anal canal: a preliminary report. Diseases of the colon and rectum. 1974;17(3):354–6.Google Scholar
  4. 4.
    Leichman L, Nigro N, Vaitkevicius VK, Considine B, Buroker T, Bradley G et al. Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy. The American journal of medicine. 1985;78(2):211–5.Google Scholar
  5. 5.
    Shridhar R, Shibata D, Chan E, Thomas CR. Anal cancer: current standards in care and recent changes in practice. CA: a cancer journal for clinicians. 2015;65(2):139–62. doi: Scholar
  6. 6.
    Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol. 1997;15(5):2040–9. doi: Scholar
  7. 7.
    Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet. 1996;348(9034):1049–54.Google Scholar
  8. 8.
    Flam M, John M, Pajak TF, Petrelli N, Myerson R, Doggett S et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1996;14(9):2527–39. doi: Scholar
  9. 9.
    National Cancer Database 2018. Accessed March 2018.Google Scholar
  10. 10.
    Fritz ACP, A Jack, K Shanmugarathnam, L Sobin, DM Parkin, S Whelan. International Classification of Disease for Oncology. 3rd ed. Geneva: World Health Organization; 2000.Google Scholar
  11. 11.
    National Comprehensive Cancer Network 2017. Accessed May 2017.
  12. 12.
    Northover J, Glynne-Jones R, Sebag-Montefiore D, James R, Meadows H, Wan S et al. Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). British journal of cancer. 2010;102(7):1123–8. doi: Scholar
  13. 13.
    Ludmir EB, Kachnic LA, Czito BG. Evolution and Management of Treatment-Related Toxicity in Anal Cancer. Surgical oncology clinics of North America. 2017;26(1):91–113. doi: Scholar
  14. 14.
    Yeung R, McConnell Y, Roxin G, Banerjee R, Urgoiti GB, MacLean AR et al. One compared with two cycles of mitomycin C in chemoradiotherapy for anal cancer: analysis of outcomes and toxicity. Current oncology (Toronto, Ont). 2014;21(3):e449–56. doi: Scholar
  15. 15.
    Kachnic LA, Winter K, Myerson RJ, Goodyear MD, Willins J, Esthappan J et al. RTOG 0529: a phase 2 evaluation of dose-painted intensity modulated radiation therapy in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal. International journal of radiation oncology, biology, physics. 2013;86(1):27–33. doi: Scholar
  16. 16.
    Gunderson LL, Winter KA, Ajani JA, Pedersen JE, Moughan J, Benson AB, 3rd et al. Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012;30(35):4344–51. doi: Scholar
  17. 17.
    James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP et al. Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 x 2 factorial trial. The Lancet Oncology. 2013;14(6):516–24. doi: Scholar
  18. 18.
    Peiffert D, Tournier-Rangeard L, Gerard JP, Lemanski C, Francois E, Giovannini M et al. Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012;30(16):1941–8. doi: Scholar
  19. 19.
    Buckstein M, Arens Y, Wisnivesky J, Gaisa M, Goldstone S, Sigel K. A Population-Based Cohort Analysis of Chemoradiation Versus Radiation Alone for Definitive Treatment of Stage I Anal Cancer in Older Patients. Diseases of the colon and rectum. 2018;61(7):787–94. doi: Scholar
  20. 20.
    Geltzeiler CB, Tsikitis VL, Kim JS, Thomas CR, Jr., Herzig DO, Lu KC. Variation in the Use of Chemoradiotherapy for Stage II and III Anal Cancer: Analysis of the National Cancer Data Base. Annals of surgical oncology. 2016;23(12):3934–40. doi: Scholar
  21. 21.
    Winchester DP, Stewart AK, Phillips JL, Ward EE. The national cancer data base: past, present, and future. Annals of surgical oncology. 2010;17(1):4–7. doi: Scholar
  22. 22.
    Bilimoria KY, Stewart AK, Winchester DP, Ko CY. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Annals of surgical oncology. 2008;15(3):683–90. doi: Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2019

Authors and Affiliations

  • Paolo Goffredo
    • 1
  • Alan F. Utria
    • 1
  • Jennifer E. Hrabe
    • 1
  • Irena Gribovskaja-Rupp
    • 1
  • Muneera R. Kapadia
    • 1
  • Imran Hassan
    • 1
    Email author
  1. 1.Department of SurgeryUniversity of Iowa Hospitals & ClinicsIowa CityUSA

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