What are the treatment recommendations for stage III malignant melanoma?

Updated: May 05, 2020
  • Author: Winston W Tan, MD, FACP; Chief Editor: Dirk M Elston, MD  more...
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Stage III [2, 1] :

  • For stage III (clinically positive nodes), surgical excision is recommended with complete lymph node dissection; adjuvant therapy includes clinical trials, observation, or biologic therapy; pembrolizumab or nivolumab are currently favored for biologic therapy, as they have a better toxicity profile than interferon or ipilumimab.

  • Consider radiation therapy to nodal basin for stage IIIC disease with multiple nodes involved or macroscopic extranodal extension

  • Biologic therapy for stage III melanoma is selected on the basis of the toxicity profile and results of randomized trials

  • PD-1 inhibitors are commonly used today rather than ipilumimab and interferon formulations due to lesser toxicity with these agents.

  • Pembrolizumab is indicated for adjuvant treatment of resected, high-risk stage 3 melanoma; level one evidence showed pembrolizumab (200 mg q3wk for 1 year) had a significantly prolonged 1-year recurrence-free survival compared with placebo (75.4% vs 61%; P < 0.001) In April 2020, FDA approved additional dosing of 400 mg q6wk for up to 1 year. [3] [4]

  • Nivolumab is indicated for adjuvant treatment of resected stage III or IV melanoma; level one evidence shows that recurrence-free survival is better with nivolumab (3 mg/kg q2wk for 1 year) than with ipilimumab [5]

  • Ipilimumab is indicated for the adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes >1 mm who have undergone complete resection, including total lymphadenectomy; the recommended regimen is 10 mg/kg IV q3wk for 4 doses followed by 10 mg/kg q12wk for up to 3 years [6]

  • Peginterferon alfa-2b has been approved for adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 d of definitive surgical resection including complete lymphadenectomy; dosing recommendations are 6 μg/kg/wk SC for eight doses followed by 3 μg/kg/wk SC for up to 5 years

  • Interferon alfa-2b (20 million IU/m2 IV five times weekly for 4 wk, then 10 million IU/m2 SC three times weekly for 48 wk; treat for a total of 1 year) [7]

For patients with stage III in-transit disease, primary treatment options include the following:

  • Complete resection (preferred, if feasible)

  • SLNB for resectable disease

  • Hyperthermic perfusion/infusion with melphalan for localized multiple lesions in a single extremity or recurrent lesions in a single limb

  • Talimogene laherparepvec is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrence after initial surgery [8] It is administered by injection into cutaneous, subcutaneous, and/or nodal lesions that are visible, palpable, or detectable by ultrasound guidance. Dosage and volume of the injection(s) depend on whether it is the initial dose, second dose, or subsequent doses and by lesion size.

  • Clinical trial

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