New Melanoma Treatments Do Not Supplant Surgery as First-Line Therapy

By Will Boggs MD

November 13, 2018

NEW YORK (Reuters Health) - Although several new melanoma treatments have shown promise, none replaces surgery as the primary therapy yet, according to updated guidelines from the American Academy of Dermatology (AAD).

"Surgery remains the cornerstone of cutaneous melanoma treatment," Dr. Susan M. Swetter from Stanford University Medical Center and Cancer Institute and Veterans Affairs Palo Alto Health Care System in California told Reuters Health. "Non-surgical approaches (imiquimod and traditional forms of radiation therapy) should only be considered if surgery is impractical or contraindicated, and only for melanoma in situ, lentigo maligna type, as cure rates are lower."

Dr. Swetter and colleagues in the multidisciplinary AAD work group updated and expanded on the previously published 2011 melanoma clinical practice guideline. They based their update/expansion on available evidence published since that guideline.

Diagnosis, which is also the first stage of treatment, should include a narrow excisional/complete biopsy with 1- to 3-mm margins that encompass the entire breadth of the lesion and is of sufficient depth to prevent transection at the base, according to the guideline.

Both for primary cutaneous melanoma and for melanoma in situ, surgical excision with histologically negative margins is recommended. Surgical margins should be wider for cutaneous melanoma (1-2 cm) than for melanoma in situ (0.5-1 cm).

Sentinel lymph node biopsy should be performed before wide excision of the primary tumor but in the same operative setting where possible.

"Mohs micrographic surgery and other staged excision techniques can provide exhaustive peripheral margin histologic assessment for melanoma in situ, lentigo maligna type and tissue sparing in anatomically constrained sites," Dr. Swetter said. "Current data are insufficient to recommend Mohs surgery for invasive cutaneous melanoma, in which the use of surgical margins less than 1 cm has not been adequately studied."

Until further information is available, routine molecular testing is discouraged, and testing of the primary cutaneous melanoma for oncogenic mutations (including BRAF and NRAS) is recommended only in the presence of metastatic disease.

Topical imiquimod may be appropriate as second-line treatment for melanoma in situ, lentigo maligna type when surgery is not possible or after optimal surgery. For this diagnosis, radiation therapy may also be used as second-line therapy for nonsurgical candidates.

Depending on the stage of the melanoma, follow-up is recommended every three to 12 months for the first one to two years, every six to 12 months through year five, and at least annually thereafter.

The guideline includes new recommendations for the management of cutaneous malignancy in pregnancy. A tailored, multidisciplinary approach is generally recommended. A prolonged waiting period before subsequent pregnancy is not recommended for women with a history of cutaneous melanoma.

Genetic counseling is now recommended for certain patients.

The guideline recommends ongoing assessment for early identification of dermatologic toxicities associated with newer drugs for advanced cutaneous melanoma.

Because of various gaps in knowledge, some recommendations are based on consensus expert opinion rather than on high-level evidence, so, as a general rule, management should always be tailored to meet the needs of the individual patient.

"Over the last decade, treatment options for metastatic melanoma have greatly improved, including in the adjuvant setting," Dr. Swetter said. "The use of adjuvant anti-PD-1 monotherapy and BRAF/MEK inhibition has been associated with improved disease-free and overall survival. As such, accurate staging of patients with cutaneous melanoma is critical and currently incorporates sentinel lymph node biopsy to pathologically stage the regional lymph nodes in appropriate patients."

"Only in the last year have effective, more tolerable adjuvant therapies been FDA-approved for patients with resected stage III melanoma, including patients with regional lymph node disease detected via sentinel lymph node biopsy," she said. "The hope is that less invasive procedures for melanoma will be performed in the future, and replaced by better drugs and techniques."

"Already, fewer completion lymph node dissections are being done following a positive sentinel lymph node biopsy, although regional nodal ultrasound is important for surveillance in this setting," she said. "Multidisciplinary collaboration among dermatologists, surgeons, and medical oncologists is recommended for patients at higher risk of disease recurrence."

"Further investigation of molecular techniques may improve identification of those patients at highest risk of disease relapse and death, so that appropriate interventions can be made," Dr. Swetter concluded.

The comprehensive document appears in the November 1st Journal of the American Academy of Dermatology.


J Am Acad Dermatol 2018.


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