Treatment of Primary Tumor and Locoregional Disease

  • Dirk Schadendorf
  • Corinna Kochs
  • Elisabeth Livingstone


After the initial excision of the primary tumor with a narrow resection margin and pathologic confirmation of cutaneous melanoma, the subsequent standard treatment is wide surgical excision to remove melanoma cells that may be present in the adjacent tissue. The pathological examination of the specimen should confirm the completeness of the tumor excision and check for satellite metastases, as surgery can be curative especially in tumors with low thicknesses and in the absence of metastatic spread and can reduce the risk of local recurrence.


Sentinel Lymph Node Cutaneous Melanoma Wide Local Excision Isolate Limb Perfusion Isolate Limb Infusion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Sladden MJ, Balch C, Barzilai DA, et al. Surgical excision margins for primary cutaneous melanoma. Cochrane Database Syst Rev. 2009;4:CD004835.Google Scholar
  2. 2.
    Mocellin S, Pasquali S, Nitti D. The impact of surgery on survival of patients with cutaneous melanoma: revisiting the role of primary tumor excision margins. Ann Surg. 2011;253:238-243.Google Scholar
  3. 3.
    Malignes melanom: diagnostik, therapie und nachsorge. Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF). Accessed June 20, 2013.
  4. 4.
    Kenady DE, Brown BW, McBride CM. Excision of underlying fascia with a primary malignant melanoma: effect on recurrence and survival rates. Surgery. 1982;92:615-618.Google Scholar
  5. 5.
    Mohrle M. Micrographic controlled surgery (3D-histology) in cutaneous melanoma. J Dtsch Dermatol Ges. 2003:1:869-875.Google Scholar
  6. 6.
    Thomas RM, Amonette RA. Mohs micrographic surgery. Am Fam Physician. 1988;37:135-142.Google Scholar
  7. 7.
    Chang KH, Dufresne R Jr, Cruz A, Rogers GS. The operative management of melanoma: where does Mohs surgery fit in? Dermatol Surg. 2011;37:1069-1079.Google Scholar
  8. 8.
    Farshad A, Burg G, Panizzon R, Dummer R. A retrospective study of 150 patients with lentigo maligna and lentigo maligna melanoma and the efficacy of radiotherapy using Grenz or soft X-rays. Br J Dermatol. 2002;146:1042-1046.Google Scholar
  9. 9.
    Storper IS, Lee SP, Abemayor E, Juillard G. The role of radiation therapy in the treatment of head and neck cutaneous melanoma. Am J Otolaryngol. 1993;14:426-431.Google Scholar
  10. 10.
    Vongtama R, Safa A, Gallardo D, Calcaterra T, Juillard G. Efficacy of radiation therapy in the local control of desmoplastic malignant melanoma. Head Neck. 2003;25:423-428.Google Scholar
  11. 11.
    Ellis LZ, Cohen JL, High W, Stewart L. Melanoma in situ treated successfully using imiquimod after nonclearance with surgery: review of the literature. Dermatol Surg. 2012;38:937-946.Google Scholar
  12. 12.
    Hauschild A, Gogas H, Tarhini A, et al. Practical guidelines for the management of interferon-α-2b side effects in patients receiving adjuvant treatment for melanoma. Cancer. 2008;112:982-994.Google Scholar
  13. 13.
    Mocellin S, Pasquali S, Rossi CR, Nitti D. Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis. J Natl Cancer Inst. 2010;102:493-501.Google Scholar
  14. 14.
    Wheatley K, Ives N, Hancock B, Gore M, Eggermont A, Suciu S. Does adjuvant interferon-α for high-risk melanoma provide a worthwhile benefit? A meta-analysis of the randomised trials. Cancer Treat Rev. 2003;29:241-252.Google Scholar
  15. 15.
    Pirard D, Heenen M, Melot C, Vereecken P. Interferon alpha as adjuvant postsurgical treatment of melanoma: a meta-analysis. Dermatology. 2004;208:43-48.Google Scholar
  16. 16.
    Eggermont AMM, Suciu S, Santinami M, et al; EORTC Melanoma Group. Adjuvant therapy with pegylated interferon alfa-2b versus observation alone in resected stage III melanoma: final results of EORTC 18991, a randomised phase III trial. Lancet. 2008;372:117-126.Google Scholar
  17. 17.
    Eggermont AMM, Suciu S, Testori A, et al. Ulceration and stage are predictive of interferon efficacy in melanoma: results of the phase III adjuvant trials EORTC 18952 and EORTC 18991. Eur J Cancer. 2012;48:218-225.Google Scholar
  18. 18.
    Australian Cancer Network Melanoma Guidelines Revision Working Party. Clinical Practice Guidelines for the Management of Melanoma in Australia and New Zealand: Evidence-Based Best Practice Guidelines. Wellington, New Zealand: Cancer Council Australia and Australian Cancer Network and the Sydney and New Zealand Guidelines Group; 2008.Google Scholar
  19. 19.
    National Institute for Health and Clinical Excellence. Improving Outcomes for People with Skin Tumours including Melanoma: The Manual. London, UK; 2006.Google Scholar
  20. 20.
    Jradi Z, Eigentler TK, Garbe C. Adjuvante therapie des malignen melanoms. Arzneimitteltherapie. 2012;30:46-52.Google Scholar
  21. 21.
    Kirkwood JM, Ibrahim JG, Sondak VK, et al. High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol. 2000;18:2444-2458.Google Scholar
  22. 22.
    Loquai C, Schmidtmann I, Beutel M, et al. Quality of life in melanoma patients during adjuvant treatment with pegylated interferon-α2b: patients’ and doctors’ views. Eur J Dermatol. 2011;21:976-984.Google Scholar
  23. 23.
    National Cancer Institute. Protocol Development. CTCAE v4.0 Open Comment Period. ctep. Last update March 20, 2013. Accessed June 20, 2013.Google Scholar
  24. 24.
    Veronesi U, Adamus J, Aubert C, et al. A randomized trial of adjuvant chemotherapy and immunotherapy in cutaneous melanoma. N Engl J Med. 1982;307:913-916.Google Scholar
  25. 25.
    Hill GJ 2nd, Moss SE, Golomb FM, et al. DTIC and combination therapy for melanoma: III. DTIC (NSC 45388) Surgical Adjuvant Study COG PROTOCOL 7040. Cancer. 1981;47:2556-2562.Google Scholar
  26. 26.
    Loutfi A, Shakr A, Jerry M, Hanley J, Shibata HR. Double blind randomized prospective trial of levamisole/placebo in stage I cutaneous malignant melanoma. Clin Invest Med. 1987;10:325-328.Google Scholar
  27. 27.
    Cayabyab MJ, Macovei L, Campos-Neto A. Current and novel approaches to vaccine development against tuberculosis. Front Cell Infect Microbiol. 2012;2:154.Google Scholar
  28. 28.
    Agarwala SS, Neuberg D, Park Y, Kirkwood JM. Mature results of a phase III randomized trial of bacillus Calmette-Guerin (BCG) versus observation and BCG plus dacarbazine versus BCG in the adjuvant therapy of American Joint Committee on Cancer Stage I-III melanoma (E1673): a trial of the Eastern Cooperative Oncology Group. Cancer. 2004;100:1692-1698.Google Scholar
  29. 29.
    Kleeberg UR, Suciu S, Brocker EB, et al; EORTC Melanoma Group in cooperation with the German Cancer Society (DKG). Final results of the EORTC 18871/DKG 80-1 randomised phase III trial. rIFN-α2b versus rIFN-γ versus ISCADOR MR versus observation after surgery in melanoma patients with either high-risk primary (thickness > 3 mm) or regional lymph node metastasis. Eur J Cancer. 2004;40:390-402.Google Scholar
  30. 30.
    Lens MB, Dawes M, Goodacre T, Newton-Bishop JA. Elective lymph node dissection in patients with melanoma: systematic review and meta-analysis of randomized controlled trials. Arch Surg. 2002;137:458-461.Google Scholar
  31. 31.
    Koops HS, Vaglini M, Suciu S, et al. Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593. J Clin Oncol. 1998;16:2906-2912.Google Scholar
  32. 32.
    Meier F, Will S, Ellwanger U, et al. Metastatic pathways and time courses in the orderly progression of cutaneous melanoma. Br J Dermatol. 2002;147:62-70.Google Scholar
  33. 33.
    Morton DL, Wanek L, Nizze JA, Elashoff RM, Wong JH. Improved long-term survival after lymphadenectomy of melanoma metastatic to regional nodes. Analysis of prognostic factors in 1134 patients from the John Wayne Cancer Clinic. Ann Surg. 1991;214:491-501.Google Scholar
  34. 34.
    van der Ploeg AP, van Akkooi AC, Rutkowski P, et al; European Organization for Research and Treatment of Cancer Melanoma Group. Prognosis in patients with sentinel node-positive melanoma without immediate completion lymph node dissection. Br J Surg. 2012;99:1396-1405.Google Scholar
  35. 35.
    Davis PG, Serpell JW, Kelly JW, Paul E. Axillary lymph node dissection for malignant melanoma. ANZ J Surg. 2011;81:462-466.Google Scholar
  36. 36.
    Ul-Mulk J, Holmich LR. Lymph node dissection in patients with malignant melanoma is associated with high risk of morbidity. Dan Med J. 2012;59:A4441.Google Scholar
  37. 37.
    Starritt EC, Joseph D, McKinnon JG, Lo SK, de Wilt JHW, Thompson JF. Lymphedema after complete axillary node dissection for melanoma: assessment using a new, objective definition. Ann Surg. 2004;240:866-874.Google Scholar
  38. 38.
    Balch CM, Gershenwald JE, Soong S-J, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27:6199-6206.Google Scholar
  39. 39.
    van Akkooi AC, et al. Expert opinion in melanoma: the sentinel node; EORTC Melanoma Group recommendations on practical methodology of the measurement of the microanatomic location of metastases and metastatic tumour burden. Eur J Cancer. 2009:45:2736-2742.Google Scholar
  40. 40.
    van der Ploeg IM, Kroon BBR, Antonini N, Valdes Olmos RA, Nieweg OE. Comparison of three micromorphometric pathology classifications of melanoma metastases in the sentinel node. Ann Surg. 2009;250:301-304.Google Scholar
  41. 41.
    Meier A, Satzger I, Volker B, Kapp A, Gutzmer R. Comparison of classification systems in melanoma sentinel lymph nodes—an analysis of 697 patients from a single center. Cancer. 2010;116:3178-3188.Google Scholar
  42. 42.
    Agrawal S, Kane JM III, Guadagnolo BA, Kraybill WG, Ballo MT. The benefits of adjuvant radiation therapy after therapeutic lymphadenectomy for clinically advanced, high-risk, lymph node-metastatic melanoma. Cancer. 2009;115:5836-5844.Google Scholar
  43. 43.
    Gojkovič-Horvat A, Jančer B, Blas M, et al. Adjuvant radiotherapy for palpable melanoma metastases to the groin: when to irradiate? Int J Radiation Oncol Biol Phys. 2011;83:310-316.Google Scholar
  44. 44.
    Strojan P, Jančer B, Čemažar M, Perme MP, Hočevar M. Melanoma metastases to the neck nodes: role of adjuvant irradiation. Int J Radiation Oncol Biol Phys. 2010;77:1039-1045.Google Scholar
  45. 45.
    Negrier S, Saiag P, Guillot B, et al; National Federation of Cancer Campaign Centers; French Dermatology Society. Guidelines for clinical practice: standards, options and recommendations 2005 for the management of adult patients exhibiting an M0 cutaneous melanoma, full report. National Federation of Cancer Campaign Centers. French Dermatology Society. Update of the 1995 Consensus Conference and the 1998 Standards, Options, and Recommendations. Ann Dermatol Venereol. 2005;132:10S3-10S85.Google Scholar
  46. 46.
    Radny P, Caroli UM, Bauer J, et al. Phase II trial of intralesional therapy with interleukin-2 in softtissue melanoma metastases. Br J Cancer. 2003;89:1620-1626.Google Scholar
  47. 47.
    Weide B, Eigentler TK, Pflugfelder A, et al. Survival after intratumoral interleukin-2 treatment of 72 melanoma patients and response upon the first chemotherapy during follow-up. Cancer Immunol Immunother. 2011;60:487-493.Google Scholar
  48. 48.
    Strobbe LJ, Hart AA, Rumke P, Israels SP, Nieweg OE, Kroon BB. Topical dinitrochlorobenzene combined with systemic dacarbazine in the treatment of recurrent melanoma. Melanoma Res. 1997;7:507-512.Google Scholar
  49. 49.
    Terheyden P, Kortum A-K, Schulze H-J, et al. Chemoimmunotherapy for cutaneous melanoma with dacarbazine and epifocal contact sensitizers: results of a nationwide survey of the German Dermatologic Co-operative Oncology Group. J Cancer Res Clin Oncol. 2007;133:437-444.Google Scholar
  50. 50.
    Von Wussow P, Block B, Hartmann F, Deicher H. Intralesional interferon-alpha therapy in advanced malignant melanoma. Cancer. 1988;61:1071-1074.Google Scholar
  51. 51.
    Fierlbeck G, d’Hoedt B, Stroebel W, Stutte H, Bogenschutz O, Rassner G. Intralesional therapy of melanoma metastases with recombinant interferon-beta. Hautarzt. 1992;43:16-21.Google Scholar
  52. 52.
    Tan JK, Ho VC. Pooled analysis of the efficacy of bacille Calmette-Guerin (BCG) immunotherapy in malignant melanoma. J Dermatol Surg Oncol. 1993;19:985-990.Google Scholar
  53. 53.
    Wolf IH, Richtig E, Kopera D, Kerl H. Locoregional cutaneous metastases of malignant melanoma and their management. Dermatol Surg. 2004;30:244-247.Google Scholar
  54. 54.
    Sersa G, Štabuc B, Čemažar M, Miklavčič D, Rudolf Z. Electrochemotherapy with cisplatin: clinical experience in malignant melanoma patients. Clin Cancer Res. 2000;6:863-867.Google Scholar
  55. 55.
    Gaudy C, Richard MA, Folchetti G, Bonerandi JJ, Grob JJ. Randomized controlled study of electrochemotherapy in the local treatment of skin metastases of melanoma. J Cutan Med Surgery. 2006;10:115-121.Google Scholar
  56. 56.
    Cornett WR, McCall LM, Petersen RP, et al. Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020. J Clin Oncol. 2006;24:4196-4201.Google Scholar
  57. 57.
    Ashton KS. Nursing care of patients undergoing isolated limb procedures for recurrent melanoma of the extremity. J P erianesth Nurs. 2012;27:94-109.Google Scholar
  58. 58.
    Moreno-Ramirez D, de la Cruz-Merino L, Ferrandiz L, Villegas-Portero R, Nieto-Garcia A. Isolated limb perfusion for malignant melanoma: systematic review on effectiveness and safety. Oncologist. 2010;15:416-427.Google Scholar
  59. 59.
    Noorda EM, Takkenberg B, Vrouenraets BC, et al. Isolated limb perfusion prolongs the limb recurrence-free interval after several episodes of excisional surgery for locoregional recurrent melanoma. Ann Surg Oncol. 2004;11:491-499.Google Scholar
  60. 60.
    Raymond AK, Beasley GM, Broadwater G, et al. Current trends in regional therapy for melanoma: lessons learned from 225 regional chemotherapy treatments between 1995 and 2010 at a single institution. J Am Coll Surg. 2011;213:306-316.Google Scholar
  61. 61.
    Gimbel MI, Delman KA, Zager JS. Therapy for unresectable recurrent and in-transit extremity melanoma. Cancer Control. 2008;15:225-232.Google Scholar
  62. 62.
    Overgaard J, Gonzalez Gonzalez D, Hulshof MCCH, et al. Hyperthermia as an adjuvant to radiation therapy of recurrent or metastatic malignant melanoma. A multicentre randomized trial by the European Society for Hyperthermic Oncology. 1996. Int J Hypertherm. 2009;25:323-334.Google Scholar
  63. 63.
    Seegenschmiedt MH, Keilholz L, Altendorf-Hofmann A, et al. Palliative radiotherapy for recurrent and metastatic malignant melanoma: prognostic factors for tumor response and long-term outcome: a 20-year experience. Int J Radiation Oncol Biol Phys. 1999;44:607-618.Google Scholar

Copyright information

© Springer Healthcare 2013

Authors and Affiliations

  • Dirk Schadendorf
    • 1
  • Corinna Kochs
    • 2
  • Elisabeth Livingstone
    • 2
  1. 1.Dermatology Venereology and AllergologyUniversity Hospital EssenEssenGermany
  2. 2.Department for DermatologyUniversity Hospital EssenEssenGermany

Personalised recommendations