#ESMO26 | INTerpath-001: My Personal Perspective Ahead of the Presidential Session This innovation deserves recognition: a groundbreaking result for personalized cancer vaccines. However, in patients with macroscopic stage III melanoma who are eligible for neoadjuvant IO, this trial does not establish the added value over contemporary perioperative strategies. Neoadjuvant treatment can produce substantial responses while allowing some patients to avoid adjuvant therapy. The trial design I would prioritize is: Neoadjuvant IO → surgery → standard adjuvant therapy ± a personalized vaccine in patients without a major pathological response. Here, “failure to achieve a major pathological response” is a more appropriate selection criterion than “any residual disease.” Patients with minimal residual viable tumor who still achieve a major pathological response should not automatically receive additional treatment. This approach would direct treatment intensification toward patients at higher risk of recurrence. The key biological uncertainty, however, is that IO-resistant residual disease is not necessarily vaccine-sensitive. Whether vaccination can overcome that resistance needs to be demonstrated. This criticism should remain specific to that population: INTerpath-001 retains distinct clinical value for patients with stage IIB/IIC disease and those who underwent surgery without neoadjuvant therapy.