Diagnostic Workup for Recurrent Metastatic Melanoma

Michael A. Davies, MD, PhD:So, one of the questions we often get asked is about the appropriate diagnostic and staging workup for patients who present with primary melanoma. For patients who present with a primary melanoma that is at least 1-mm thick without clinical evidence of lymph node involvement, we generally recommend that patients undergo a sentinel lymph node biopsy to determine if there is microscopic lymph node involvement. We also consider sentinel lymph node biopsy for patients with thinner primary melanomas, but with high-risk features, such as the evidence of tumor ulceration. For patients who undergo a sentinel lymph node biopsy that does confirm metastatic involvement to the lymph nodes, we often recommend complete lymph node dissection, as it can actually be very informative, in terms of the patient’s subsequent risk, to know if other lymph nodes are involved. Notably, it’s unclear at this point if the completion lymph node dissection actually has therapeutic benefit for patients, and hopefully, we’ll have data in the near future in those regards.

For patients who have lymph node involvement, it is routine for us to evaluate whether the patient has evidence of distant metastatic disease with imaging of the body, either by CAT scans of the chest, abdomen, and pelvis or potentially by PET/CT, particularly for patients who aren’t amenable to IV contrast studies. In addition, melanoma is a disease that has high risk of metastasis to the brain, and therefore, we usually include an initial baseline MRI of the brain in the evaluation of any new patient with regional involvement.

For patients who present with metastatic, or stage 4 melanoma, it’s very important to perform certain baseline evaluations to help guide appropriate patient management. Those include initial radiographic studies to determine the extent of the disease, including MRI of the brain, and also imaging of the body, either by CAT scans or by PET/CTs. In addition, it is the standard of care for patients who undergo molecular testing of their tumors for theBRAF V600mutation. This mutation is detected in approximately 50% of cutaneous melanomas. And notably, theBRAFmutations are essentially 100% concordant between primary tumors and metastases. So, that molecular testing can be performed on primary tumors or biopsies of metastatic lesions.

While it is not necessarily the standard of care, at many centers, we also do extended molecular testing for other known oncogenic mutations in this disease, includingNRASmutations, which are present in approximately 20% of the patients, and also mutations in thec-KIToncogene. Mutations inc-KITare actually rare in patients with cutaneous melanoma—having a prevalence of about 1% to 2%—but they’re much more common in other melanoma subtypes, including acral lentiginous melanomas and mucosal melanomas. And notably, patients who have an activatingc-KITmutation may respond to c-KIT inhibitors.

One of the emerging areas of research is the immunohistochemistry test for PD-L1 protein. In certain cancers, like lung cancer, testing for PD-L1 is actually required in order for patients to be treated with PD-1 antibodies. That is actually not a requirement in patients with metastatic melanoma. However, there is growing evidence that the PD-L1 test may help in making therapeutic decisions for patients.

Transcript edited for clarity.

June 2010

• A 73-year-old Caucasian male presented to his physician with a right pre-auricular pigmented lesion, 8 mm-diameter
• PMH: arterial hypertension, dyslipidemia, hyperuricemia and hypothyroidism, for which he has been medically treated
• He is a non-drinker and a former smoker
• In 2002, he had undergone a right nephrectomy for a spontaneous retroperitoneal hematoma. Consequently, he has chronic renal insufficiency
  • Creatinine, 1.8 mg/dL
  • GFR, 40 mL/min
• He otherwise maintains full autonomy in his daily activities and personal care
• He subsequently underwent surgical resection. Pathologic assessment revealed an ulcerated melanoma
  • Breslow index 0.8 mm
  • Clark level of III (pT1b, Stage IB)
• Since his surgery, he remains active and continues golfing 3 times per week

June 2016

• On routine follow-up, the patient presents with moderate asthenia that limited his daily activity, without other relevant clinical symptoms (ECOG PS 1)
• Physical examination did not detect any relevant findings
• Remarkable laboratory findings: Urea, 70 mg/dL; Creatinine 1.76 mg/dL; AST, 59 UI/L; ALT 52 UI/L; GGT 363 UI/L; Alk Phos, 204; LDH, 820 UI/L
• Full-body CT scan revealed the presence of pulmonary and hepatic nodules, no evidence of brain metastases
• He underwent core-needle biopsy of the largest hepatic lesion in segment IVb without any complications
  • Pathology revealed metastatic melanoma
  • Mutation testing:BRAF-negative