Neoadjuvant Immunotherapy for Melanoma: Five-Year Survival of About 98% in Patients With a Major Pathological Response

For patients with melanoma who can undergo surgery, whether treatment should continue after tumor removal is a question that affects both recurrence risk and the burden of medication. An international analysis published in *Nature Medicine* on October 1 linked pathological changes in tumors after neoadjuvant treatment to long-term survival: patients who received immunotherapy and achieved a major pathological response had an estimated five-year overall survival rate of about 98%.

Led by Georgina Long, with participation from the International Neoadjuvant Melanoma Consortium, the study retrospectively pooled data from 26 centers on 1,038 patients with resectable stage IIIB–IV cutaneous melanoma, including acral melanoma. The study included cases from clinical trials and routine clinical practice; 735 patients received immune checkpoint inhibitors, while the remainder received targeted therapy or immunotherapy combined with targeted therapy, so not all patients belonged to the same treatment group.

A major pathological response means that examination of tumor tissue after surgery shows complete or near-complete regression of cancer cells. Among patients who achieved this response, estimated five-year overall survival was 98.8% for those receiving PD-1 monotherapy and 97.9% for those receiving PD-1 therapy combined with other immuno-oncology drugs. These figures describe patients who responded well and cannot be applied to everyone receiving neoadjuvant immunotherapy. They also do not mean that patients remained entirely free of recurrence for five years.

Another finding concerns treatment duration. Melanoma Institute Australia noted that patients who achieved a major pathological response appeared to gain no additional benefit from continuing immunotherapy after surgery. If future trials can confirm which patients are suitable for shorter treatment courses, unnecessary treatment and toxicity could potentially be reduced. For now, this remains a direction requiring validation and does not support assuming that postoperative medication can be omitted for everyone.

The value of these data lies in the inclusion of experience from both trials and routine clinical practice, but the pooled analysis also has limitations. Different therapies were not randomly assigned across the entire dataset, and patient characteristics and postoperative management may have influenced the results. Comparisons between groups alone cannot establish which regimen is superior. Median follow-up for the overall population was 2.6 years, and the five-year survival rates are statistical estimates; they do not mean that every patient had been followed for a full five years. Longer follow-up would still help confirm the durability of the results.

The next challenge is to translate a good pathological response into reliable treatment choices while finding other options for patients with an insufficient response. The institute mentioned that the NeoIRENIE trial is exploring personalized strategies of this kind. This analysis provides evidence for adjusting treatment according to response, while whether reducing treatment is safe and how to continue treatment for patients with drug resistance are questions that the next phase of research will need to answer.