Long-term results achieved by guideline-based stage-dependent management of anal cancer in a non-HIV population

A Correction to this article is available

This article has been updated

Abstract

Purpose

Therapy of anal cancer follows national and international guidelines that are mainly derived from randomized trials. This study aimed to analyze long-term results of stage-dependent treatment of anal cancer in a non-selected patient cohort.

Patients and method

All consecutive patients treated for anal cancer between 2000 and 2015 were retrieved from a prospective database. Risk-dependent screening for human immunodeficiency virus showed no infection. Main outcome measure was overall survival with respect to tumor site and treatment. Secondary endpoints were cause-specific survival, stoma free survival, and the rate of salvage operations.

Results

In total, 106 patients were treated for anal cancer. Of those, 69 (65.1%) suffered from anal canal cancer and 37 (34.9%) from anal margin cancer. Three patients with synchronous distant metastases were excluded from analysis. The majority of patients (n = 79, 76.7%) were treated by chemoradiotherapy in curative intention. Twenty-two patients underwent local surgery. Five-year overall survival was 73.1% and cause-specific survival at 5 years was 87.4%. Overall, 14 patients (13.6%) needed salvage surgery. Their 5-year cause-specific survival was 57.7%. A permanent ostomy was avoided in 77.7%.

Conclusions

Treatment of anal cancer results in low rates of salvage surgery and permanent ostomies, when therapy was determined by a multidisciplinary team following national and international guidelines.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Change history

  • 20 August 2020

    The authors of the article mentioned above found out errors on the Table 4 concerning the number and survival rates of patients with incomplete radiotherapy.

References

  1. 1.

    Alfa-Wali M, Dalla Pria A, Nelson M, Tekkis P, Bower M (2016) Surgical excision alone for stage T1 anal verge cancers in people living with HIV. Eur J Surg Oncol 42:813–816

    CAS  Article  Google Scholar 

  2. 2.

    Garrett K, Kalady MF (2010) Anal neoplasms. Surg Clin N Am 90:147–161

    Article  Google Scholar 

  3. 3.

    Glynne-Jones R, Nilsson PJ, Aschele C, Goh V, Peiffert D, Cervantes A, Arnold D (2014) Anal cancer: ESMO-ESSO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 25(Suppl 3):iii 10–iii 20

    Article  Google Scholar 

  4. 4.

    Gimenez F, Costa-e-Silva IT, Daumas A, Araujo J, Medeiros SG, Ferreira L (2011) The value of high-resolution anoscopy in the diagnosis of anal cancer precursor lesions in HIV-positive patients. Arq Gastroenterol 48:136–145

    Article  Google Scholar 

  5. 5.

    Wilkinson JR, Morris EJ, Downing A, Aravani A, Thomas JD, Sebag-Montefiore D (2014) The rising incidence of anal cancer in England 1990-2010: a population-based study. Color Dis 16:O234–O239

    CAS  Article  Google Scholar 

  6. 6.

    Salati SA, Al Kadi A (2012) Anal cancer—a review. Int J Health Sci (Qassim) 6:206–230

    Article  Google Scholar 

  7. 7.

    Nigro ND, Vaitkevicius VK, Considine B Jr (1974) Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum 17:354–356

    CAS  Article  Google Scholar 

  8. 8.

    Glynne-Jones R, Saleem W, Harrison M, Mawdsley S, Hall M (2016) Background and current treatment of squamous cell carcinoma of the anus. Oncol Ther 4:135–172

    Article  Google Scholar 

  9. 9.

    Aggarwal A, Duke S, Glynne-Jones R (2013) Anal cancer: are we making progress? Curr Oncol Rep 15:170–181

    Article  Google Scholar 

  10. 10.

    National Comprehensive Cancer Network NCCN (2016) Clinical practice guidelines in oncology, anal carcinoma. Version I.2017. http://www.nccn.org. Accessed 25 May 2018

  11. 11.

    Schmitt-Reisser B (2004) In: Krebsgesellschaft D (ed) Kurzgefasste interdisziplinäre Leitlinien 2004. Diagnostik und Therapie maligner Erkrankungen, 4th edn. Zuckschwerdt, München, pp 190–198

    Google Scholar 

  12. 12.

    Deutsche Aids-Gesellschaft e.V. (DAIG) (2013) Deutsch-Österreichische Leitlinie: Anale Dysplasien und Analkarzinome bei HIV-Infizierten: Prävention, Diagnostik, Therapie. http://www.awmf.org/uploads/tx_szleitlinien/055-007l_S1k_Anale_Dysplasien_Analkarzinom_HIV_infizierten_09-2013__01.pdf. Accessed 15 Nov 2018

  13. 13.

    Brierley JD, Gospodarowicz MK, Wittekind C (2016) Anal canal and perianal skin. In: Brierley JD, Gospodarowicz MK, Wittekind C (eds) TNM classification of malignant tumors, 8th edn. Wiley-Blackwell, Chichester, pp 77–80

    Google Scholar 

  14. 14.

    Geltzeiler CB, Nabavizadeh N, Kim J, Kim CL, Billingsley KG, Thomas CR, Herzig DO, Tsikitis VL (2014) Chemoradiotherapy with a radiation boost for anal cancer decreases the risk for salvage abdominoperineal resection: analysis from the national cancer data base. Ann Surg Oncol 21:3616–3620

    Article  Google Scholar 

  15. 15.

    Alamri Y, Buchwald P, Dixon L, Dobbs B, Eglinton T, McCormick J, Wakeman C, Frizelle FA (2016) Salvage surgery in patients with recurrent or residual squamous cell carcinoma of the anus. Eur J Surg Oncol 42:1687–1692

    CAS  Article  Google Scholar 

  16. 16.

    Glynne-Jones R, Sebag-Montefiore D, Adams R, Gollins S, Harrison M, Meadows HM, Jitlal M (2013) Prognostic factors for recurrence and survival in anal cancer: generating hypotheses from the mature outcomes of the first United Kingdom Coordinating Committee on Cancer Research Anal Cancer Trial (ACT I). Cancer 119:748–755

    CAS  Article  Google Scholar 

  17. 17.

    James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS, Saunders MP, Maughan T, McDonald A, Essapen S, Leslie M, Falk S, Wilson C, Gollins S, Begum R, Ledermann J, Kadalayil L, Sebag-Montefiore D (2013) 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 × 2 factorial trial. Lancet Oncol 14:516–524

    CAS  Article  Google Scholar 

  18. 18.

    Gunderson LL, Winter KA, Ajani JA, Pedersen JE, Moughan J, Benson AB 3rd, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA, Willett CG (2012) 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. J Clin Oncol 30:4344–4351

    CAS  Article  Google Scholar 

  19. 19.

    Peiffert D, Tournier-Rangeard L, Gérard JP, Lemanski C, François E, Giovannini M, Cvitkovic F, Mirabel X, Bouché O, Luporsi E, Conroy T, Montoto-Grillot C, Mornex F, Lusinchi A, Hannoun-Lévi JM, Seitz JF, Adenis A, Hennequin C, Denis B, Ducreux M (2012) Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 trial. J Clin Oncol 30:1941–1948

    CAS  Article  Google Scholar 

  20. 20.

    Fleshner PR, Chalasani S, Chang GJ, Levien DH, Hyman NH, Buie WD, Standards Practice Task Force, American Society of Colon and Rectal Surgeons (2008) Practice parameters for anal squamous neoplasms. Dis Colon Rectum 51:2–9

    Article  Google Scholar 

  21. 21.

    Steele SR, Varma MG, Melton GB, Ross HM, Rafferty JF, Buie WD, Standards Practice Task Force of the American Society of Colon and Rectal Surgeons (2012) Practice parameters for anal squamous neoplasms. Dis Colon Rectum 55:735–749

    Article  Google Scholar 

  22. 22.

    Glynne-Jones R, Northover JMA, Cervantes A (2010) Anal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 21(Suppl 5):v87–v92

    Article  Google Scholar 

  23. 23.

    Madlung A (2019) Radiotherapy of anal and rectal cancer. Squamous cell anal carcinoma from a radiologic perspective. Coloproctology 41:255–261

    Article  Google Scholar 

  24. 24.

    Williams M, Swampillai A, Osborne M, Mawdsley S, Hughes R, Harrison M, Harvey R, Glynne-Jones R (2013) Squamous cell carcinoma antigen: a potentially useful prognostic marker in squamous cell carcinoma of the anal canal and margin. Cancer 119:2391–2398

    CAS  Article  Google Scholar 

  25. 25.

    Nelson VM, Benson AB 3rd (2017) Epidemiology of anal canal cancer. Surg Oncol Clin N Am 26:9–15

    Article  Google Scholar 

  26. 26.

    Amirian ES, Fickey PA Jr, Scheurer ME, Chiao EY (2013) Anal cancer incidence and survival: comparing the greater San-Francisco bay area to other SEER cancer registries. PLoS One 8:e58919

    Article  Google Scholar 

  27. 27.

    Statistisches Landesamt Sachsen (2017) Bevölkerung 2017. https://www.statistik.sachsen.de/html/426.htm. Accessed 01 June 2019

  28. 28.

    Robert-Koch-Institut (2018) HIV/AIDS Eckdaten https://www.rki.de/DE/Content/InfAZ/H/HIVAIDS/Eckdaten/Eckdaten.htmlHIV/AIDS in Sachsen—Eckdaten der Schätzung. Accessed 01 June 2019

  29. 29.

    Kim E, Kim JS, Choi M, Thomas CR Jr (2016) Conditional survival in anal carcinoma using the National Population-Based Survey of epidemiology and end results database (1988-2012). Dis Colon Rectum 59:291–298

    Article  Google Scholar 

  30. 30.

    Bilimoria KY, Bentrem DJ, Rock CE, Stewart AK, Ko CY, Halverson A (2009) Outcomes and prognostic factors for squamous-cell carcinoma of the anal canal: analysis of patients from the National Cancer Data Base. Dis Colon Rectum 52:624–631

    Article  Google Scholar 

  31. 31.

    Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB 3rd, Thomas CR Jr, Mayer RJ, Haddock MG, Rich TA, Willett CG (2008) Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA 299:1914–1921

    CAS  Article  Google Scholar 

  32. 32.

    Chakravarthy AB, Catalano PJ, Martenson JA, Mondschein JK, Wagner H, Mansour EG, Talamonti MS, Benson AB 3rd (2011) Long-term follow-up of a phase II trial of high-dose radiation with concurrent 5-fluorouracil and cisplatin in patients with anal cancer (ECOG E4292). Int J Radiat Oncol Biol Phys 81:e607–e613

    CAS  Article  Google Scholar 

  33. 33.

    Delhorme JB, Antoni D, Mak KS, Severac F, Freel KC, Schumacher C, Rohr S, Brigand C, Noel G (2016) Treatment that follows guidelines closely dramatically improves overall survival of patients with anal canal and margin cancers. Crit Rev Oncol Hematol 101:131–138

    Article  Google Scholar 

  34. 34.

    Harris DA, Williamson J, Davies M, Evans MD, Drew P, Beynon J (2013) Outcome of salvage surgery for anal squamous cell carcinoma. Color Dis 15:968–973

    CAS  Article  Google Scholar 

  35. 35.

    Hardt J, Mai S, Weiß C, Kienle P, Magdeburg J (2016) Abdominoperineal resection and perineal wound healing in recurrent, persistent, or primary anal carcinoma. Int J Color Dis 31:1197–1203

    CAS  Article  Google Scholar 

  36. 36.

    Mariani P, Ghanneme A, De la Rochefordière A, Girodet J, Falcou MC, Salmon RJ (2008) Abdominoperineal resection for anal cancer. Dis Colon Rectum 51:1495–1501

    CAS  Article  Google Scholar 

  37. 37.

    Hogg ME, Popowich DA, Wang EC, Kiel KD, Stryker SJ, Halverson AL (2009) HIV and anal cancer outcomes: a single institution’s experience. Dis Colon Rectum 52:891–897

    Article  Google Scholar 

  38. 38.

    Hannes S, Reinisch A, Bechstein WO, Habbe N (2016) Salvage abdominoperineal excisions in recurrent anal cancer--impact of different reconstruction techniques on outcome, morbidity, and complication rates. Int J Color Dis 31:653–659

    Article  Google Scholar 

  39. 39.

    Guerra GR, Kong JC, Bernardi MP, Ramsay RG, Phillips WA, Warrier SK, Lynch AC, Ngan SY, Heriot AG (2018) Salvage surgery for locoregional failure in anal squamous cell carcinoma. Dis Colon Rectum 61:179–186

    Article  Google Scholar 

  40. 40.

    Chai CY, Tran Cao HS, Awad S, Massarweh NN (2018) Management of stage I squamous cell carcinoma of the anal canal. JAMA 153:209–215

    Google Scholar 

  41. 41.

    Chang GJ, Welton ML (2004) Human papillomavirus, condylomata acuminata, and anal neoplasia. Clin Colon Rectal Surg 17:221–230

    Article  Google Scholar 

  42. 42.

    Mennini FS, Bonanni P, Bianic F, de Waure C, Baio G, Plazzotta G, Uhart M, Rinaldi A, Largeron N (2017) Cost-effectiveness analysis of the nine-valent HPV vaccine in Italy. Cost Eff Resour Alloc 15:11

    Article  Google Scholar 

  43. 43.

    Villa LL, Costa RL, Petta CA et al (2006) High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer 95:1459–1466

    CAS  Article  Google Scholar 

Download references

Funding

The maintenance of the database at the Coloproctologic Unit of Dresden-Friedrichstadt General Hospital is supported by a grant from the Tumor Centre Dresden.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Sigmar Stelzner.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Fankhaenel, B., Zimmer, J., Bleyl, D. et al. Long-term results achieved by guideline-based stage-dependent management of anal cancer in a non-HIV population. Int J Colorectal Dis 34, 1895–1905 (2019). https://doi.org/10.1007/s00384-019-03396-x

Download citation

Keywords

  • Anal cancer
  • Overall survival
  • Cause specific survival
  • Chemoradiotherapy
  • Salvage surgery