Neoadjuvant immunotherapy could slash recurrence in stage IIB/IIC melanoma — what the data show

Education and decision-support only — not a medical device or personalised advice. Always discuss your specific situation with your specialist team.

Recent analysis of patients with clinical stage IIB/IIC melanoma showed that many experience recurrence within five years after surgery alone, underscoring a high risk of disease return ¹. Could delivering immunotherapy before the operation lower that risk? This post draws on that 2026 study and on early‑phase trials that are testing pembrolizumab or nivolumab as a pre‑operative strategy. The evidence is still early, and most data come from small cohorts.

Does giving immunotherapy before surgery lower recurrence risk?

The 2026 cohort highlighted that patients with bulky nodal disease or ulcerated primary tumors tended to have the shortest disease‑free intervals, suggesting a potential window for early systemic therapy ¹. Early‑phase trials of neoadjuvant checkpoint inhibitors have reported pathological responses that correlate with longer disease‑free periods, although these findings are based on limited numbers and surrogate endpoints ¹. Some registry data have not shown a clear overall‑survival advantage when neoadjuvant therapy is compared with standard adjuvant treatment, likely because follow‑up remains short ¹. Together, the data hint that pre‑operative immunotherapy could reduce recurrence, but the signal is modest and requires confirmation in larger studies.

Which tumor features help decide who might benefit most from a pre‑operative approach?

The same 2026 analysis identified ulceration, a high mitotic rate, and involvement of more than three lymph nodes as factors linked to early recurrence ¹. Emerging biomarker work in neoadjuvant studies suggests that tumors with higher tumor‑mutational burden or stronger PD‑L1 expression may respond better to checkpoint blockade, although these observations are drawn from small subsets and need validation ¹. Because the predictive value of these markers is not yet established, clinicians often rely first on the clinical risk factors described above while awaiting stronger biomarker data.

What are the risks and trade‑offs of receiving immunotherapy before the tumor is removed?

Neoadjuvant checkpoint inhibitors can cause immune‑related adverse events such as colitis, hepatitis, or skin rash, and severe (grade 3) events have been reported in a minority of patients, sometimes delaying surgery ¹. On the other hand, early tumor shrinkage may allow less extensive surgery and better cosmetic outcomes. A matched analysis did not find higher rates of wound‑healing complications in patients who received neoadjuvant therapy versus those who received it after surgery, but the sample size was small ¹. Weighing the potential for improved disease control against the chance of treatment‑related toxicity is essential when discussing options.

Neoadjuvant immunotherapy offers a promising way to address high‑risk stage IIB/IIC melanoma before it spreads, but the evidence remains early and largely based on small studies. Patients with ulcerated or bulky disease may stand to gain the most, while biomarker testing could help refine selection as more data emerge. Discuss trial options, biomarker results, and how a pre‑operative strategy fits into your overall care plan with your dermatologist and oncology team. Always discuss any changes to your care or screening plan with a qualified dermatologist.

TL;DR

• Recurrence after surgery alone is common in stage IIB/IIC melanoma.
• Neoadjuvant immunotherapy is being tested and may improve disease‑free outcomes, but data are early.
• Benefit appears strongest in ulcerated or bulky nodal disease.
• Ask about trial enrollment and biomarker testing before choosing pre‑operative therapy.
• Discuss with your dermatologist how a neoadjuvant approach fits your overall care plan.

Additional references

[2] Luke JJ, Rutkowski P, Queirolo P, et al. Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial. Lancet. 2022;399(10336):1718–1729. PMID 35367007

[3] Long GV, Menzies AM, Scolyer RA. Neoadjuvant Checkpoint Immunotherapy and Melanoma: The Time Is Now. J Clin Oncol. 2023;41(12):2204–2213. PMID 37104746

Questions to ask your specialist

If your oncologist or surgeon mentions neoadjuvant immunotherapy, here are questions to guide the conversation:

1. Am I a candidate for neoadjuvant (pre-surgery) immunotherapy? (Stage IIB–III with resectable disease is the typical setting.)
2. What is my expected risk of pathological complete response (pCR)? Patients who achieve pCR have substantially better long-term outcomes — ask what factors in my tumour predict this.
3. How long would the neoadjuvant course delay my surgery? (Typically 6–12 weeks — ask whether this delay carries any risk in my specific case.)
4. What happens if the neoadjuvant therapy does not shrink the tumour? (Understand the plan B — surgery is still performed; what are the adjuvant options?)
5. Is there a clinical trial for neoadjuvant approaches that I should consider? Some trials combine neoadjuvant immunotherapy with novel agents. Ask before starting standard treatment.
6. Will I need adjuvant therapy after surgery even if I have a response? (Current data suggest some patients may not need continued systemic therapy after a deep response — ask about the latest evidence.)

See our Clinical Trial Finder and Getting specialist care for further support.