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Clinical Practice Guidelines

Clinical Practice Guidelines for Melanoma

Douglas Reintgen, MD, et al
H. Lee Moffitt Cancer Center & Research Institute

These clinical practice guidelines for melanoma have been developed at H. Lee Moffitt Cancer Center & Research Institute under the direction of Douglas Reintgen, MD, Program Leader of the Cutaneous Oncology Program, and the following program members: Frank Glass, MD; Neil Fenske, MD; C. Wayne Cruse, MD; David Rapaport, MD; Jane Messina, MD; Karen E. Wells, MD; Ronald DeConti, MD, and Jan Marshburn, MPH. Algorithms are provided for melanoma screening and diagnosis, staging, stage III and IV management, and recurrence. Follow-up guidelines are also included.

Melanoma Screening and Diagnosis

Individuals with a personal or family history of melanoma or dysplastic nevi have a 10- to 100-fold increased relative risk of melanoma1 and are eligible for screening. Those with skin phenotypes I and II (fair skin, blond or red hair, blue eyes, freckles), those raised in the sunbelt, and those with a past history of other skin cancers also have an increased relative risk of melanoma.2 Patients with a family or personal history of dysplastic nevus, with early-onset melanoma, or who are members of a melanoma-prone family are screened for the dysplastic nevus syndrome3 and/or the p16 gene mutation.4 The initial screening for the p16 gene mutation will occur in the proband identified with melanoma. If the mutation is found, screening will be offered to family members. A total body skin examination performed by trained personnel identifies 90% of melanomas.5

An excisional biopsy technique is used for suspicious lesions, and an incisional biopsy technique of the most nodular part of the lesion is used for lesions greater than 2 cm in diameter. Lesions that are found to be benign and dysplastic are followed, if the margins of excision are clear. The diagnosis of melanoma requires wide local excision (WLE), depending on the size.

Melanoma Staging

In order to ensure agreement with the diagnosis and depth of the melanoma, a formal pathology review is required for patients who present with a diagnosis of melanoma. This review has resulted in the remicrostaging of 5% of the melanomas reviewed. If the regional nodes are palpable and suspicious for tumor, fine needle aspiration (FNA) is performed. Those with a positive regional nodal FNA have stage III disease, and management is described in the stage III algorithm.

Patients with melanomas less than 1 mm in tumor thickness are treated with a 1-cm WLE per the World Health Organization trial,6 followed by observation. Those with melanomas equal to or greater than 1 mm in thickness are treated with a 2-cm WLE as dictated by the Intergroup Melanoma Trial.7 For tumors greater than 4 mm in thickness, our policy is to use 2-cm margins of excision. Physicians have leeway in the size of the margin of excision for their patients with melanoma in cosmetic-concerned areas of the body (eg, the face) or functional areas of the body (eg, palms and fingers). Clear margins must be obtained.

Patients are offered three choices for the management of the regional nodal basin: (1) observation of the nodes, (2) sentinel node biopsy of all basins at risk for disease,8,9 or (3) the NCI-sponsored Multicenter Selective Lymphadenectomy Trial,10 which randomizes patients between WLE of the primary site plus observation of their nodes vs WLE of the primary site, lymphatic mapping, and sentinel lymph node biopsy. If lymphatic mapping is not possible, patients are managed with either observation or elective node dissection.11 If the biopsy of the sentinel lymph node is positive, the patient has stage III disease and is treated according to the stage III algorithm.

Stage III and Stage IV Disease

A chest radiograph and computed tomography (CT) scan of the abdomen are obtained for patients with proven metastatic melanoma. Magnetic resonance imaging of the head is performed for those with central nervous system symptoms, and a CT scan of the pelvis is obtained for patients with lower extremity or lower abdomen primary sites that demonstrate cutaneous drainage to the groin.12

Patients with documented stage III disease and no demonstrable systemic disease undergo therapeutic regional node dissection if the disease is deemed resectable. Unresectable lesions are debulked if possible. Patients with positive margins or extranodal disease following the debulking process or a therapeutic node dissection are considered for adjuvant radiation therapy according to Radiation Therapy Oncology Group protocols.13 These patients are at risk for systemic recurrence and also are candidates for adjuvant or unresectable stage III protocols.

Patients with stage III disease that has been resected are candidates for adjuvant interferon alfa-2b according to the Eastern Cooperative Oncology Group (ECOG) Trial 1684.14 Those with stage IV disease with solitary metastases after staging are candidates for surgical resection and adjuvant therapy on research protocols. Patients with a positive resection margin of stage IV disease are candidates for radiation. Those with solitary and isolated metastases to the central nervous system are candidates for corticosteroids, resection, radiation therapy, and perhaps systemic therapy.15 Patients with solitary metastases also may be treated on stage IVresearch protocols using DTIC (dacarbazine), the Dartmouth regimen,16 BOLD (bleomycin, oncovin, lomustine, dacarbazine) chemotherapy,17 or interferon alfa-2b. Patients with unresectable solitary metastases may be candidates for radiation therapy and/or systemic therapies. Spine metastases are treated with radiation therapy followed by chemotherapy.

Patients with multiple metastases or multiple sites of metastases who are ECOG status 1 and 2 are candidates for stage IV research protocols using interferon alfa-2b plus DTIC, the Dartmouth regimen,16 or BOLD chemotherapy.17 Patients with an ECOG performance status worse than 2 receive palliative care.

Recurrence

Local and/or intransit recurrences of extremity melanoma that are confined to the extremity are treated with resection for clear margins and hyperthermic, isolated limb perfusion.18 If the tumor cannot be completely resected, a hyperthermic isolated limb perfusion is performed for palliation.

Distant cutaneous or soft-tissue recurrence can be resected. Positive margins can be radiated, or patients can be treated with stage IV protocols or systemic therapies.

Follow-up

Follow-up guidelines for patients with melanoma are presented in the Table. Those with melanoma in situ or thin melanomas are followed with a complete skin examination to detect a second melanoma, which will occur in 5% of the population.19 Those with intermediate-size melanoma undergo a baseline liver function and a chest radiograph; they are then followed with a physical examination of the local-regional distribution, a complete skin examination, and an evaluation of any symptom that could be a sign of systemic disease. The local-regional physical examination is expected to find 80% of all melanoma recurrences, with the remainder being marked by the appearance of systemic symptoms.20

Patients with thick stage II and stage III disease have baseline liver function tests, a chest radiograph, and CT scan of the abdomen for staging. A CT scan of the pelvis is performed for those with metastatic disease to the groin. Patients are followed with a local-regional physical examination, a complete skin examination, and questions for systemic symptoms. Follow-up of patients with unresectable stage III and stage IV disease is guided by research or in-house protocols.

References

  1. Garbe C, Buttner P, Weiss J, et al. Risk factors for developing cutaneous melanoma and criteria for identifying persons at risk: multicenter case-control study of the Central Malignant Melanoma Registry of the German Dermatological Society. J Invest Dermatol. 1994;102:695-699.
  2. Kopf A, Marghoob A, Slade J, et al. Basal and squamous cell carcinomas: risk factors for cutaneous malignant melanoma. Presented at the Sixth World Congress on Cancers of the Skin; September 16-17, 1885; Buenos Aires, Argentina.
  3. Elder DE, Goldman LI, Goldman SC, et al. Dysplastic nevus syndrome: a phenotypic association of sporadic cutaneous melanoma. Cancer. 1980;46:1787-1794.
  4. Kamb A, Shattuck-Eidens D, Eeles R, et al. Analysis of the p16 gene (CDKN2) as a candidate for the chromosome 9p melanoma susceptibility locus. Nat Genet. 1994;8:23-26.
  5. Rigel DS, Friedman R, Kopf A, et al. Importance of complete skin exam for the detection of malignant melanoma. J Am Acad Dermatol. 1986;14:857-860.
  6. Veronesi U, Cascinelli N. Narrow excision (1-cm margin): a safe procedure for thin cutaneous melanoma. Arch Surg. 1991;126:438-441.
  7. Balch CH, Urist MM, Karakousis CP, et al. Efficacy of 2-cm surgical margins for intermediate-thickness melanoma (1 to 4 mm): results of a multi-institutional randomized surgical trial. Ann Surg. 1993;218:267-269.
  8. Norman J, Cruse CW, Espinosa C, et al. Redefinition of cutaneous lymphatic drainage with the use of lymphoscintigraphy for malignant melanoma. Am J Surg. 1991;162:432-437.
  9. Reintgen DS, Cruse CW, Wells K, et al. The orderly progression of melanoma nodal metastases. Ann Surg. 1994;220:759-767.
  10. Multicenter Selective Lymphadenectomy Trial. National Cancer Institute Grant No. PO1 CA29605-12.
  11. Balch CM, Soong SJ, Bartolucci A, et al. Efficacy of an elective lymph node dissection of 1 to 4 mm thick melanomas for patients 60 years of age and younger. Ann Surg. 1996;224:255-266.
  12. Buzaid AC, Tinoco L, Ross M, et al. Role of CT scans in the staging of melanoma patients with local-regional disease. Proc Annu Meet Am Soc Clin Oncol. 1995;14:411. Abstract A1303.
  13. Ang KK, Byers RM, Peters LJ, et al. Regional radiotherapy as adjuvant treatment for head and neck malignancy melanoma. Arch Otolaryngol Head Neck Surg. 1990;116:169-172.
  14. Kirkwood JM, Strawderman MH, Ernstoff MS, et al. Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial 1684. J Clin Oncol. 1996;14:7-17.
  15. Amer MH, Al-Sarraf M, Baker LH, et al. Malignant melanoma and central nervous system metastases: incidence, diagnosis, treatment and survival. Cancer. 1978;42:660-668.
  16. Del Prete SA, Maurer LH, O'Donnell J, et al. Combination chemotherapy with cisplatin, carmustine, dacarbazine, and tamoxifen in metastatic melanoma. Cancer Treat Rep. 1984;68:1403-1405.
  17. Seigler HF, Lucas VS Jr, Pickett NJ, et al. DTIC, CCNU, bleomycin and vincristine (BOLD) in metastatic melanoma. Cancer. 1980;46:2346-2348.
  18. Krementz ET, Ryan RF, Muchmore JH, et al. Hyperthermic regional perfusion for melanoma of the limbs. In: Balch CM, Houghton AN, Milton GW, et al, eds. Cutaneous Melanoma. 2nd ed. Philadelphia, Pa: JB Lippincott; 1992:403.
  19. Brobeil A, Rapaport D, Wells K, et al. Multiple primary melanomas: implications for screening and follow-up programs for melanoma. Ann Surg Oncol. 1997;4:19-23.
  20. Reintgen DS, Vollmer R, Tso CY, et al. Prognosis for recurrent stage I malignant melanoma. Arch Surg. 1987;122:1338-1342.

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