Multicenter Experience with Neoadjuvant Therapy in Melanoma Highlights Heterogeneity in Contemporary Practice

Ann Surg. 2023 Jun 1;277(6):e1306-e1312. doi: 10.1097/SLA.0000000000005459. Epub 2022 Jul 7.


Objective: To determine the feasibility and impact of neoadjuvant therapy (NT) in patients who present with advanced melanoma amenable to surgical resection.

Summary background data: Given current effective systemic therapy for melanoma, the use of NT is being explored in patients with advanced melanoma with disease amenable to surgical resection.

Methods: Prospective data from 3 institutions was obtained in patients with clinically evident Stage III/IV melanoma who underwent NT. The primary objective was to compare recurrence-free survival between patients who had pathologic complete response (pCR) to those with persistent disease.

Results: NT was offered to 45 patients, with 43 patients initiating various NT regimens including PD-1 antagonist (PD-1) therapy (N = 16), PD-1 plus ipilimumab (N = 10), BRAF/MEK inhibitor therapy (N = 14), a combination of those three (N = 1), and talimogene laherparepvec (TVEC) (N = 2). Thirty-two (74.1%) patients underwent surgery whereas 11 patients did not undergo surgery for these reasons: clinical CR (N = 7), progressive disease not amenable to resection (N = 3), and ongoing therapy (N = 1). 12 of 32 patients (37.5%) had pCR with these therapies: PD-1 (N = 4), PD-1 plus ipilimumab (N = 2), BRAF/MEK (N = 4), combination (N = 1), and TVEC (N = 1). At median follow-up of 16.4 months there was only 1 recurrence in the pCR group and patients with a pCR had significantly improved recurrence-free survival compared to patients without pCR (p = 0.004).

Conclusions: Despite variability in NT regimens across institutions, NT for melanoma is feasible and associated with improved prognosis in patients who achieve a pCR. Maximizing rates of pCR could improve prognosis for patients with advanced melanoma.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Humans
  • Ipilimumab / therapeutic use
  • Melanoma* / drug therapy
  • Melanoma, Cutaneous Malignant
  • Mitogen-Activated Protein Kinase Kinases / therapeutic use
  • Neoadjuvant Therapy
  • Oncolytic Virotherapy*
  • Programmed Cell Death 1 Receptor / therapeutic use
  • Prospective Studies
  • Proto-Oncogene Proteins B-raf / genetics
  • Skin Neoplasms* / drug therapy


  • Ipilimumab
  • Mitogen-Activated Protein Kinase Kinases
  • Programmed Cell Death 1 Receptor
  • Proto-Oncogene Proteins B-raf