Recommended Follow-up for Recurrent Metastatic Melanoma

Michael A. Davies, MD. PhD:Our first case is the case of a 73-year-old Caucasian gentleman who presented initially in June of 2010 with a primary melanoma of the right pre-auricular region. His primary melanoma was 8 mm in depth and was ulcerated, consistent with a stage IB melanoma. The patient was notable for having had prior resection of 1 kidney, causing him to have chronic renal insufficiency. However, other than that, he had normal activities of daily living and was fully independent.

In June 2016, the patient presented for routine follow-up. His laboratory values were significant for an elevated LDH and an elevated creatinine, but he had normal liver function tests. Imaging studies demonstrated the presence of opacities in both the lungs and liver, and MRI for the brain was negative for any metastases. The patient underwent a core needle biopsy of 1 of the lung lesions, which confirmed the presence of metastatic melanoma. This lesion was referred for metastatic testing for aBRAFmutation and was negative for the presence of aBRAF V600mutation.

So, this is a patient who is presenting with recurrent metastatic melanoma with a wild-typeBRAFgenotype. The patient is in his 70s, but has good activity status. In terms of medical comorbidities, it’s noted that he has abnormal renal function, but otherwise appears to be very healthy. The other tests are significant for the fact that he has no symptoms and good performance status, but he does have an elevated LDH, which is a known negative prognostic factor in patients with metastatic melanoma.

For patients with metastatic melanoma, comorbidities present a significant variable to consider in choosing therapies for patients. In addition, the extent of disease—and particularly the serum LDH—can help guide therapeutic decisions in regard to estimating patients’ prognosis and the aggressiveness of disease. Finally, the standard of care at this point in time is to test metastatic melanoma lesions for the presence of aBRAFmutation. This is due to the availability of multiple therapies that are affective in patients with aBRAFmutation, but which are ineffective in patients who have a wild-typeBRAFgene as this patient does.

This patient initially presented with a stage 1B melanoma that was 8-mm thick and ulcerated. One of the questions about this case is whether the patient should have undergone a sentinel lymph node biopsy. While, in general, sentinel lymph node biopsy is recommended for patients with Breslow thickness of 1 mm or greater, this patient had a relatively thick primary melanoma (8 mm) and, in addition, had a high-risk feature present with the presence of ulceration, a known prognostic factor in patients with primary disease. Therefore, it would have been reasonable to consider a sentinel lymph node biopsy for this patient at initial presentation. For patients who have no lymph nodes, but no distant metastatic disease, patients are usually seen for the first 2 to 3 years every 3 to 4 months, with restaging studies. However, this patient did not undergo a sentinel lymph node biopsy and therefore had stage I disease. He probably should have been followed every 3 to 6 months, primarily with physical exams, a dermatologic exam, and perhaps a chest x-ray. However, in retrospect, perhaps it would have been appropriate for this patient to have undergone evaluation of his lymph nodes via sentinel lymph node biopsy to help guide what his follow-up should have been.

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