Systemic relapse after stage I melanoma came later but with more brain metastases and shorter survival

Design

Registry-based cohort analysis (Spanish Melanoma Registry GEM1801)

Population

365 patients with metastatic melanoma treated first line, grouped by primary stage

Primary outcome

Overall survival and features at systemic relapse by primary stage

Effect

Median OS 19.8 months after stage I vs 60.1 (IIA), 32.6 (IIB/C), 43 (III); p = 0.024

Relapse to systemic disease after stage I melanoma is uncommon, yet it accounts for close to a third of metastatic cases. This Spanish registry analysis looked at what primary stage means once melanoma has become advanced. It included 365 patients treated first line between 2018 and 2024: 58 with prior stage I, 32 with IIA, 80 with IIB/C and 195 with III.

Median time to relapse was 52 months after stage I, 30 after IIA, 27 after IIB/C and 25 after stage III. At relapse, previous stage I patients more often had three or more metastatic sites (OR 1.89, 95% CI 1.06 to 3.35), brain metastases (OR 4.02, 2.13 to 7.58) and elevated LDH (OR 2.19, 1.18 to 4.04). Median overall survival was 19.8 months after stage I, against 60.1 after IIA, 32.6 after IIB/C and 43 after III (p = 0.024).

The registry holds only patients who relapsed, so it says nothing about how likely relapse is after each stage. It does suggest that relapse after a low-risk primary is often found late and at high burden. That may be worth weighing when counselling about long-term skin checks and symptom awareness, within the follow-up schedule your guideline recommends.

• Relapse after stage I took a median of 52 months, much later than after stage III.
• At relapse, prior stage I patients had more brain metastases (OR 4.02) and raised LDH (OR 2.19).
• Median overall survival was 19.8 months after stage I against 32.6 to 60.1 months after stage II.
• Counsel stage I patients on symptoms that need prompt review, including neurological ones.
• Follow your current guideline for surveillance; this registry does not change it.

Why it matters

A low-stage primary is not a guarantee that any later relapse will be mild.

Don't overread it

The registry includes only patients who relapsed and cannot estimate relapse risk, nor does it test whether longer surveillance would improve outcomes.

The statistics, in plain English

An odds ratio of 4.02 for brain metastases with a confidence interval of 2.13 to 7.58 means patients who relapsed after stage I were roughly four times as likely as the comparison group to have brain metastases when relapse was found. The survival difference had a wide interval for stage I (12 to 55.9 months) because only 58 patients were in that group.

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