Understanding the Prognosis of Metastatic Melanoma

Michael A. Davies, MD, PhD:This is the case of a 52-year-old woman who presented with a pigmented lesion. She had no symptoms and no other abnormal findings on physical exam. She presented to a local dermatologist, who did a biopsy. The biopsy was consistent with a primary melanoma, with a Breslow thickness of 2.3 mm. The patient underwent a sentinel lymph node biopsy, which confirmed the presence of microscopic disease in the sentinel lymph node. The patient subsequently underwent a completion lymph node dissection, which failed to find evidence of melanoma in additional lymph nodes. At that time, the patient underwent radiographic studies. These showed multiple abnormalities in the lungs consistent with metastatic disease, with no evidence of disease in other sites of the body, including the brain.

A core needle biopsy was done on 1 of the lung metastases, which confirmed the diagnosis of metastatic melanoma. Of note, the largest lung metastasis was 5 mm in diameter. Molecular testing was performed on the biopsy and confirmed the presence of aBRAF V600Emutation in the metastatic tumor. Additional workup of the patient showed no laboratory abnormalities, with normal renal function, normal liver function, and normal serum LDH value. The patient was started on systemic therapy for metastatic melanoma with targeted therapy with dabrafenib 150 mg twice every day and trametinib 2 mg once a day.

This is an interesting case that is actually relatively rare of a patient presenting with newly diagnosed metastatic melanoma as their initial presentation of disease. The majority of patients with melanoma present with clinically localized disease, undergo removal of the primary tumor, and subsequently progress with regional and, ultimately, distant metastases. However, a small number of patients like this one present de novo with stage 4 metastatic melanoma.

For patients with stage 4 melanoma, a number of factors are known to correlate with prognosis. First would be the extent of disease. This is a patient who has M1B disease with evidence of involvement of the lungs, but no other organs including the brain, and a normal serum LDH value. This patient would be expected to have a prognosis that is worse than patients who have involvement of only the skin or lymph nodes, but better than patients who have involvement of other organs for an elevated serum LDH level.

There are evidence-based guidelines to guide the appropriate wide local excision margins for patients who present with clinically localized disease. For patients who have melanomas of 2-mm thickness or less, the appropriate excision margins are approximately 1 cm. For patients with thicker primary tumors, the recommended margins are at least 2 cm. These data are based on evidence showing that these margins correlate with decreased risk of local relapse or recurrence. Notably, in this patient who actually presented with stage 4 disease, her ultimate outcomes are really determined by the extent and treatment of her metastatic disease as opposed to the management of her primary tumor.

The normal pattern of progression of melanoma is from clinically localized disease in the skin to, most commonly, regional lymph nodes. As a result, assessment of lymph node involvement is a standard consideration in patients who present with clinically localized disease without clinical evidence of lymph node involvement. For patients who present with a primary tumor with a Breslow thickness of at least 1 mm in depth, it is standard of care for patients to undergo a sentinel lymph node biopsy. If that demonstrates evidence of lymph node involvement, proceed to complete lymph node dissection to fully evaluate the extent of lymph node involvement.

We also consider the sentinel lymph node biopsy for patients who have thinner melanomas, but who also have the presence of high-risk features, such as primary tumor ulceration. Notably, it’s unclear if sentinel lymph node biopsy or the subsequent completion lymph node dissection has a significant impact on overall survival, but they provide very important information about risk stratification of patients, which can be used to guide appropriate therapies with patients.

Transcript edited for clarity.

April 2017

• A 52-year-old female presented to her dermatologist with a pigmented lesion which had recently become darker; she had it removed for cosmetic reasons
  • Pathology revealed a melanoma with a depth of 2.3 mm
  • Genetic testing;BRAF V600mutation-positive
• LDH, WNL (174 UI/L)
• She underwent wide local excision and sentinel node mapping; staining is positive for melanoma in the right axillary node
• Complete dissection of the right axilla reveals no additional involved nodes
• CT of the chest, abdomen, and pelvis showed multiple masses in both lungs, the largest being 5 mm
• She underwent core-needle biopsy of the largest lung lesion
  • Pathology revealed metastatic melanoma
  • Mutation testing:BRAF-positive
• The patient is started on dabrafenib 150 mg bid and trametinib 2 mg qd