World Journal of Surgery

, Volume 43, Issue 7, pp 1809–1819 | Cite as

Treatment Strategies and Survival Trends for Anorectal Melanoma: Is it Time for a Change?

  • James P. Taylor
  • Miloslawa Stem
  • David Yu
  • Sophia Y. Chen
  • Sandy H. Fang
  • Susan L. Gearhart
  • Bashar Safar
  • Jonathan E. EfronEmail author
Original Scientific Report



Immunotherapy advances for the treatment of cutaneous melanoma question its efficacy in treating anorectal mucosal melanoma (ARMM). We aimed to identify the prevalence, current management, and overall survival (OS) for ARMM.


Review of patients with ARMM from 2004 to 2015 National Cancer Database. Factors associated with immunotherapy were identified using multivariable logistic regression. The primary outcome was 2- and 5-year OS. Subgroup analysis by treatment type was performed.


A total of 1331 patients were identified with a significant increase in prevalence (2004: 6.99%, 2015: 10.53%). ARMM patients were older, white, on Medicare, and from the South. The most common treatment was surgery (48.77%), followed by surgery + radiation (11.75%), surgery + immunotherapy (8.68%), and surgery + chemotherapy (8.68%). 16.93% of patients received immunotherapy, with utilization increasing (7.24%: 2004, 21.27%: 2015, p < 0.001). Patients who received immunotherapy had a significantly better 2-year OS (42.47% vs. 49.21%, p < 0.001), and other therapies did not reveal a significant difference. Adjusted analysis showed no difference in 2- and 5-year OS based on therapy type.


The prevalence of ARMM has increased. The use of immunotherapy has increased substantially. Some survival benefit with the administration of immunotherapy may exist that has yet to be revealed. A more aggressive treatment paradigm is warranted.



Mr. Edwin Lewis provided generous support to Dr. Efron’s Department of Surgery Research Fund.

Compliance with ethical standards

Conflict of interest

None of the authors of this paper have any conflicts of interest.


  1. 1.
    Chang AE, Karnell LH, Menck HR (1998) The National Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 83:1664–1678CrossRefGoogle Scholar
  2. 2.
    Bullard KM, Tuttle TM, Rothenberger DA, Madoff RD, Baxter NN, Finne CO, Spencer MP (2003) Surgical therapy for anorectal melanoma. J Am Coll Surg 196:206–211CrossRefGoogle Scholar
  3. 3.
    Meguerditchian AN, Meterissian SH, Dunn KB (2011) Anorectal melanoma: diagnosis and treatment. Dis Colon Rectum 54:638–644CrossRefGoogle Scholar
  4. 4.
    Moozar KL, Wong CS, Couture J (2003) Anorectal malignant melanoma: treatment with surgery or radiation therapy, or both. Can J Surg 46:345–349Google Scholar
  5. 5.
    Row D, Weiser MR (2009) Anorectal melanoma. Clin Colon Rectal Surg 22:120–126CrossRefGoogle Scholar
  6. 6.
    Brady MS, Kavolius JP, Quan SH (1995) Anorectal melanoma. A 64-year experience at Memorial Sloan-Kettering Cancer Center. Dis Colon Rectum 38:146–151CrossRefGoogle Scholar
  7. 7.
    Yeh JJ, Shia J, Hwu WJ, Busam KJ, Paty PB, Guillem JG, Coit DG, Wong WD, Weiser MR (2006) The role of abdominoperineal resection as surgical therapy for anorectal melanoma. Ann Surg 244:1012–1017CrossRefGoogle Scholar
  8. 8.
    Yeh JJ, Weiser MR, Shia J, Hwu WJ (2005) Response of stage IV anal mucosal melanoma to chemotherapy. Lancet Oncol 6:438–439CrossRefGoogle Scholar
  9. 9.
    Hillenbrand A, Barth TF, Henne-Bruns D, Formentini A (2008) Anorectal amelanotic melanoma. Colorectal Dis 10:612–615CrossRefGoogle Scholar
  10. 10.
    McLaughlin CC, Wu XC, Jemal A, Martin HJ, Roche LM, Chen VW (2005) Incidence of noncutaneous melanomas in the US. Cancer 103:1000–1007CrossRefGoogle Scholar
  11. 11.
    Carvajal RD, Antonescu CR, Wolchok JD, Chapman PB, Roman RA, Teitcher J, Panageas KS, Busam KJ, Chmielowski B, Lutzky J, Pavlick AC, Fusco A, Cane L, Takebe N, Vemula S, Bouvier N, Bastian BC, Schwartz GK (2011) KIT as a therapeutic target in metastatic melanoma. JAMA 305:2327–2334CrossRefGoogle Scholar
  12. 12.
    Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, Cho KH, Aiba S, Brocker EB, LeBoit PE, Pinkel D, Bastian BC (2005) Distinct sets of genetic alterations in melanoma. N Engl J Med 353:2135–2147CrossRefGoogle Scholar
  13. 13.
    Carvajal RD, Spencer SA, Lydiatt W (2012) Mucosal melanoma: a clinically and biologically unique disease entity. J Natl Compr Cancer Netw 10:345–356CrossRefGoogle Scholar
  14. 14.
    Callahan A, Anderson WF, Patel S, Barnholtz-Sloan JS, Bordeaux JS, Tucker MA, Gerstenblith MR (2016) Epidemiology of anorectal melanoma in the United States: 1992 to 2011. Dermatol Surg 42:94–99CrossRefGoogle Scholar
  15. 15.
    Kiran RP, Rottoli M, Pokala N, Fazio VW (2010) Long-term outcomes after local excision and radical surgery for anal melanoma: data from a population database. Dis Colon Rectum 53:402–408CrossRefGoogle Scholar
  16. 16.
    Pessaux P, Pocard M, Elias D, Duvillard P, Avril MF, Zimmerman P, Lasser P (2004) Surgical management of primary anorectal melanoma. Br J Surg 91:1183–1187CrossRefGoogle Scholar
  17. 17.
    Ciarrocchi A, Pietroletti R, Carlei F, Amicucci G (2017) Extensive surgery and lymphadenectomy do not improve survival in primary melanoma of the anorectum: results from analysis of a large database (SEER). Colorectal Dis 19:158–164CrossRefGoogle Scholar
  18. 18.
    Tchelebi L, Guirguis A, Ashamalla H (2016) Rectal melanoma: epidemiology, prognosis, and role of adjuvant radiation therapy. J Cancer Res Clin Oncol 142:2569–2575CrossRefGoogle Scholar
  19. 19.
    Sadozai H, Gruber T, Hunger RE, Schenk M (2017) Recent successes and future directions in immunotherapy of cutaneous melanoma. Front Immunol 8:1617CrossRefGoogle Scholar
  20. 20.
    (2017) National Cancer Database.
  21. 21.
    (2017) Census regions and divisions of the United states.
  22. 22.
    Hosmer DW Jr, Lemeshow S (2000) Applied logistic regression, 2nd edn. Wiley, New YorkCrossRefGoogle Scholar
  23. 23.
    Weinstock MA (1993) Epidemiology and prognosis of anorectal melanoma. Gastroenterology 104:174–178CrossRefGoogle Scholar
  24. 24.
    Cote TR, Sobin LH (2009) Primary melanomas of the esophagus and anorectum: epidemiologic comparison with melanoma of the skin. Melanoma Res 19:58–60CrossRefGoogle Scholar
  25. 25.
    Micu E, Juzeniene A, Moan J (2011) Comparison of the time and latitude trends of melanoma incidence in anorectal region and perianal skin with those of cutaneous malignant melanoma in Norway. J Eur Acad Dermatol Venereol 25:1444–1449CrossRefGoogle Scholar
  26. 26.
    Iddings DM, Fleisig AJ, Chen SL, Faries MB, Morton DL (2010) Practice patterns and outcomes for anorectal melanoma in the USA, reviewing three decades of treatment: is more extensive surgical resection beneficial in all patients? Ann Surg Oncol 17:40–44CrossRefGoogle Scholar
  27. 27.
    Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723CrossRefGoogle Scholar
  28. 28.
    Ku GY, Yuan J, Page DB, Schroeder SE, Panageas KS, Carvajal RD, Chapman PB, Schwartz GK, Allison JP, Wolchok JD (2010) Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival. Cancer 116:1767–1775CrossRefGoogle Scholar
  29. 29.
    Gorka E, Fabo D, Gezsi A, Czirbesz K, Fedorcsak I, Liszkay G (2018) Dabrafenib therapy in 30 patients with melanoma metastatic to the brain: a single-centre controlled retrospective study in Hungary. Pathol Oncol Res 24:401–406CrossRefGoogle Scholar
  30. 30.
    Kim KB, Eton O, Davis DW, Frazier ML, McConkey DJ, Diwan AH, Papadopoulos NE, Bedikian AY, Camacho LH, Ross MI, Cormier JN, Gershenwald JE, Lee JE, Mansfield PF, Billings LA, Ng CS, Charnsangavej C, Bar-Eli M, Johnson MM, Murgo AJ, Prieto VG (2008) Phase II trial of imatinib mesylate in patients with metastatic melanoma. Br J Cancer 99:734–740CrossRefGoogle Scholar
  31. 31.
    Ugurel S, Hildenbrand R, Zimpfer A, La Rosee P, Paschka P, Sucker A, Keikavoussi P, Becker JC, Rittgen W, Hochhaus A, Schadendorf D (2005) Lack of clinical efficacy of imatinib in metastatic melanoma. Br J Cancer 92:1398–1405CrossRefGoogle Scholar
  32. 32.
    Hodi FS, Friedlander P, Corless CL, Heinrich MC, Mac Rae S, Kruse A, Jagannathan J, Van den Abbeele AD, Velazquez EF, Demetri GD, Fisher DE (2008) Major response to imatinib mesylate in KIT-mutated melanoma. J Clin Oncol 26:2046–2051CrossRefGoogle Scholar
  33. 33.
    Lutzky J, Bauer J, Bastian BC (2008) Dose-dependent, complete response to imatinib of a metastatic mucosal melanoma with a K642E KIT mutation. Pigment Cell Melanoma Res 21:492–493CrossRefGoogle Scholar
  34. 34.
    Kluger HM, Dudek AZ, McCann C, Ritacco J, Southard N, Jilaveanu LB, Molinaro A, Sznol M (2011) A phase 2 trial of dasatinib in advanced melanoma. Cancer 117:2202–2208CrossRefGoogle Scholar
  35. 35.
    Woodman SE, Trent JC, Stemke-Hale K, Lazar AJ, Pricl S, Pavan GM, Fermeglia M, Gopal YN, Yang D, Podoloff DA, Ivan D, Kim KB, Papadopoulos N, Hwu P, Mills GB, Davies MA (2009) Activity of dasatinib against L576P KIT mutant melanoma: molecular, cellular, and clinical correlates. Mol Cancer Ther 8:2079–2085CrossRefGoogle Scholar
  36. 36.
    Zhao J, Zhu Y, Zhang C, Wang X, He H, Wang H, Wu Y, Zhou W, Shen Z (2013) Sorafenib or sunitinib as postoperative adjuvant therapy for Chinese patients with locally advanced clear cell renal cell carcinoma at high risk for disease recurrence. Urol Oncol 31:1800–1805CrossRefGoogle Scholar
  37. 37.
    Quintas-Cardama A, Lazar AJ, Woodman SE, Kim K, Ross M, Hwu P (2008) Complete response of stage IV anal mucosal melanoma expressing KIT Val560Asp to the multikinase inhibitor sorafenib. Nat Clin Pract Oncol 5:737–740CrossRefGoogle Scholar
  38. 38.
    Min L, Hodi FS (2014) Anti-PD1 following ipilimumab for mucosal melanoma: durable tumor response associated with severe hypothyroidism and rhabdomyolysis. Cancer Immunol Res 2:15–18CrossRefGoogle Scholar
  39. 39.
    Tokuhara K, Nakatani K, Tanimura H, Yoshioka K, Kiyohara T, Kon M (2017) A first reported case of metastatic anorectal amelanotic melanoma with a marked response to anti-PD-1 antibody nivolumab: a case report. Int J Surg Case Rep 31:188–192CrossRefGoogle Scholar
  40. 40.
    Faure M, Rochigneux P, Olive D, Taix S, Brenot-Rossi I, Gilabert M (2018) Hyperprogressive disease in anorectal melanoma treated by PD-1 inhibitors. Front Immunol 9:797CrossRefGoogle Scholar
  41. 41.
    Malaguarnera G, Madeddu R, Catania VE, Bertino G, Morelli L, Perrotta RE, Drago F, Malaguarnera M, Latteri S (2018) Anorectal mucosal melanoma. Oncotarget 9:8785–8800CrossRefGoogle Scholar
  42. 42.
    Kirchoff DD, Deutsch GB, Foshag LJ, Lee JH, Sim MS, Faries MB (2016) Evolving therapeutic strategies in mucosal melanoma have not improved survival over five decades. Am Surg 82:1–5Google Scholar
  43. 43.
    MacCallum C, Skandarajah A, Gibbs P, Hayes I (2018) The value of clinical colorectal cancer registries in colorectal cancer research: a systematic review. JAMA Surg 153:841–849CrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2019

Authors and Affiliations

  • James P. Taylor
    • 1
  • Miloslawa Stem
    • 1
  • David Yu
    • 1
    • 2
  • Sophia Y. Chen
    • 1
  • Sandy H. Fang
    • 1
  • Susan L. Gearhart
    • 1
  • Bashar Safar
    • 1
  • Jonathan E. Efron
    • 1
    Email author
  1. 1.Johns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Queen’s University School of MedicineKingstonCanada

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