ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of cutaneous malignant melanoma
L. M. Jost
Oncology, Medical University Clinic, Kantonsspital, Bruderholz, Switzerland
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Incidence
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- The crude incidence of malignant melanoma in the European Union is 9 cases/100 000 per year. The incidence increases with latitude, i.e. with increasing prevalence of less-pigmented skin types, from 35 cases/100 000 per year in Mediterranean countries to 1217/100 000 per year in Nordic countries. The mortality is 2.3 cases/100 000 per year with a lesser variation with geography. Increased ultraviolet B-ray exposure seems responsible for an ongoing increase in incidence during recent decades.
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Diagnosis
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- Suspicious lesions are characterized by asymmetry, border irregularities, color heterogeneity, diameter >6 mm, and evolution of color, elevation or size in recent months (ABCDE rule).
Diagnosis should always be based on a full-thickness excisional biopsy with a recommended margin of 2 mm of normal skin around the lesion. Processing by an experienced pathology institute is mandatory.
The histology report should follow the WHO classification and include the maximum thickness in millimeters (Breslow), the level of invasion (Clark level IV), the clearance of the surgical margins, the presence of ulceration and the presence and extent of regression.
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Staging and risk assessment
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- Staging and risk assessment is by physical examination with special attention to tumor satellites, in-transit metastases, regional lymph node and systemic metastases [V, D].
To exclude metastatic disease, a chest X-ray and blood count, LDH and alkaline phosphatase measurements are recommended [V, D].
Sonography of the abdomen and regional lymph nodes is recommended only in patients with melanoma of >1 mm thickness or suspicious clinical findings. Further radiological tests should be only as clinically indicated [V, D]. PET scanning is not useful for initial staging of clinically localized melanoma [III].
Risk assessment according to the new AJCC system (2002) may guide therapeutic decisions and is based on Breslow levels of the primary tumor and the presence of ulceration and of locoregional or systemic metastases as follows (Table 1).
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Treatment for localized disease
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- Wide excision of primary tumors with a normal skin margin of 0.5 cm for in situ melanoma, or 1 cm for tumors with a Breslow thickness of 12 mm and 2 cm for thicker tumors is mandatory [IIIII, A]. Modifications may be needed for preservation of function in melanomas of the fingers and toes or those of the ear.
Routine elective lymphadenectomy or irradiation to the regional lymph nodes is not recommended [II, B].
Sentinel lymph node biopsy with selective complete clearance of regional lymph nodes if the sentinel node was found positive may be useful but should be performed only by skilled teams in experienced centers.
There is no standard adjuvant therapy to date for patients with high-risk melanoma. Adjuvant immunotherapy with high-dose interferon results in a significant prolongation only of disease-free survival but not of overall survival. This result has to be balanced against the toxicity of this treatment [III]. Adjuvant chemotherapy is ineffective and not recommended. Adjuvant immunotherapy with other cytokines including interleukin-2, tumor vaccination and immunochemotherapy is controversial [III] and not to be used outside of protocols.
Radiotherapy should be considered in cases of inadequate resection margins of primary when re-excision is not feasible, such as in head and neck melanoma.
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Treatment for locoregional metastatic disease
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- Complete resection of positive regional lymph nodes must be conducted for all patients tolerating surgery [IIIII, C].
In-transit metastases or inoperable primary tumors of the limbs may be treated with isolated limb perfusion using, for example, melphalan and tumor necrosis factor [IIIII, C]. However, such treatment requires major surgery and should be restricted to a few experienced centers. Radiation therapy may be used instead [V, D].
Adjuvant systemic therapy after complete resection as mentioned above. There is no standard adjuvant therapy.
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Treatment for systemic metastatic disease
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- There is no proof that systemic treatment results in a significant prolongation of survival. Palliative chemotherapy with single agents (e.g. dacarbazine, vindesine, temozolomide) may be given to patients with preserved performance status [II, C], otherwise best-supportive care should be considered. Combination chemo- or chemo-/immunotherapy has not been proven superior to dacarbazine.
Surgery of visceral metastases may be appropriate for selected cases with good performance status and isolated tumor manifestation.
Palliative radiotherapy should be considered especially for symptomatic brain or localized bone metastases.
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Follow-up for localized or locoregional disease
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- There is currently no consensus on the frequency of follow-up and recommendations for surveillance testing. There are insufficient data to recommend regular blood tests or radiological examinations including ultrasound or PET scanning outside adjuvant treatment or follow-up protocols in patients able and willing to undergo experimental therapy. The following recommendations were judged adequate for most patients by the experts and ESMO faculty: (i) patients with sporadic or familial dysplastic nevus syndrome have a high risk and should be followed for life; (ii) sunburn during childhood and unprotected ultraviolet exposure (solar or artificial UV-B rays) are additional risk factors; (iii) follow-up for 5 years for localized melanoma of <1.5 mm Breslow thickness and for 10 years for others is deemed sufficient despite the rare occurrence of later relapses; (iv) history, physical examination including regional lymph nodes, skin inspection and palpation of primary tumor location every 3 months for 2 years and every 612 months thereafter are recommended; (v) the patients should be instructed in avoidance of sunburn, extended unprotected solar or artificial ultraviolet exposure and in lifelong regular self-examination of the skin and peripheral lymph nodes.
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Note
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Levels of Evidence [IV] and Grades of Recommendation [AD] as used by the American Society of Clinical Oncology are given in square brackets. Statements without grading were considered justified standard clinical practice by the expert authors and the ESMO faculty.
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Literature
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Coordinating author for the ESMO Guidelines Task Force: L. M. Jost, Oncology, Medical University Clinic, Kantonsspital, Bruderholz, Switzerland.
Approved by the ESMO Guidelines Task Force: August 2002.
Correspondence to:
ESMO Guidelines Task Force
ESMO Head Office
Via La Santa 7
CH-6962 Viganello-Lugano
Switzerland
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References
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1. National Institutes of Health Consensus Conference. Diagnosis and treatment of early melanoma. J Am Med Assoc 1992; 288: 13141319.
2. Wagner JD, Schauwecker DS, Davidson D et al. Prospective study of FDG-PET imaging of lymph node basins in melanoma patients undergoing sentinel node biopsy. J Clin Oncol 1999; 17: 15081515.[Abstract/Free Full Text]
3. Balch CM, Buzaid AC, Soong SJ et al. Final version of the AJCC staging system for cutaneous melanoma. J Clin Oncol 2001; 19: 36353648.[Abstract/Free Full Text]
4. Cascinelli N, Morabito A, Santinami M et al. Immediate or delayed dissection of regional nodes in patients with melanoma of the trunk: a randomised trial. WHO Melanoma Programme. Lancet 1998; 351: 793796.[CrossRef][ISI][Medline]
5. Kirkwood JM, Strawderman MH, Ernstoff MS et al. Interferon-
-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST-1684. J Clin Oncol 1996; 14: 717.[Abstract]
6. Lienard D, Eggermont AM, Koops HS et al. Isolated limb perfusion with tumor necrosis factor-alpha and melphalan with or without interferon-gamma for the treatment of in-transit melanoma metastases: a multicentre randomized phase II study. Melanoma Res 1999; 9: 491502.[ISI][Medline]
7. Middleton MR, Grob JJ, Aaronson N et al. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol 2000; 18: 158166.[Abstract/Free Full Text]
8. Shumate CR, Urist MM, Maddoy WA. Melanoma recurrence surveillance. Patient or physician based? Ann Surg 1995; 221: 566571.[ISI][Medline]
9. Punt CJ, Eggermont AM. Adjuvant interferon-alpha for melanoma revisited: news from old and new studies. Ann Oncol 2001; 12: 16631666.[Abstract]