Fig. 3

Stage III N1b-3 (AJCC 7th)/Stage IIIB-D (AJCC 8th) melanoma immunotherapy treatment algorithm. The consensus of the panel was to separate Stage III N1a (based on AJCC 7th edition) and Stage IIIA (AJCC 8th) from other Stage III subsets based on lower risk of metastatic potential. However, a minority (30%) felt that all Stage III subsets should be treated similarly. All treatment options shown may be appropriate and final selection of therapy should be individualized based on patient eligibility and treatment availability at the physician’s discretion. These algorithms represent consensus sequencing suggestions by the panel. (1) There are limited data on the role of adjuvant therapy following sentinel lymphadenectomy alone. (2) After evaluation by multi-disciplinary team with surgical oncology, if complete resection is possible patients should undergo resection followed by adjuvant therapy listed. If the tumor is considered unresectable, a different treatment paradigm should be followed. (3) In patients with Stage IIIB-IV resected melanoma, there is Level A evidence supporting the use of nivolumab over ipilimumab and pembrolizumab over placebo for stage IIIB-C and IIA patients with micrometastases > 1 mm. Accordingly, nivolumab or pembrolizumab were supported by 46% of the panel. (4) Ipilimumab at 3 mg/kg was supported by a minority of panelists (8.3%). (5) There is Level A evidence to support the use the combination of dabrafenib and trametinib in patients with BRAF V600E/K mutant, Stage III melanoma. (6) While there are Level A data that 1 year interferon-α2b is associated with improvement in RFS, no panelists recommended considering this therapy for this patient population. (7) Overall, the majority of panelists recommended a clinical trial, if available. (8) The majority of the panelists have had experience with T-VEC, and half of respondents said they would recommend T-VEC for first-line treatment for limited disease burden, and a significant minority (39%) would consider T-VEC for patients with locoregional disease. (9) Unresectable disease could be managed by options available for stage IV patients (see Fig. 4). Abbreviations: CR, complete response; LDH, lactate dehydrogenase; NCCN, National Comprehensive Cancer Network; PD, progressive disease; RFS, recurrence-free survival, TVEC, talimogene laherparepvec