Relapse after stage I melanoma came later, but with worse disease

Design

National registry cohort (GEM1801)

Population

365 patients with metastatic melanoma on first-line treatment, Spain, 2018–2024

Primary outcome

Overall survival by stage of original primary

Effect

Median OS 19.8 months after stage I vs 32.6–60.1 months after stage II–III

The Spanish Melanoma Registry analysed 365 patients starting first-line treatment for metastatic melanoma between 2018 and 2024, grouped by the stage of their original primary: 58 stage I, 32 IIA, 80 IIB/C and 195 stage III.

Relapse came latest after stage I — a median of 52 months, against 25–30 months for the others. But at relapse, these patients more often had three or more metastatic sites (OR 1.89), brain metastases (OR 4.02, 95% CI 2.13 to 7.58) and raised LDH (OR 2.19). Median overall survival was 19.8 months after a stage I primary, against 33–60 months for stages II and III.

One explanation is that stage I patients are discharged from surveillance and relapse is found late. Another is biology. Either way, a thin primary should not reassure anyone once systemic disease appears, and patients need to know what symptoms should bring them back years later.

• Systemic relapse after stage I melanoma is uncommon but can appear four or more years later.
• In a patient with a past thin melanoma and new neurological symptoms, consider brain imaging early.
• Teach stage I patients what to report after routine follow-up ends — new lumps, persistent headache, weight loss.
• Treat metastatic disease on its own features; a thin primary does not predict a mild course.

Why it matters

Patients with the 'best' primaries had the worst outcomes once disease spread, which challenges a common assumption.

Don't overread it

A small registry subgroup — it does not show that more intensive surveillance of stage I patients would improve survival.

The statistics, in plain English

An odds ratio of 4.02 for brain metastases means much higher odds of brain involvement at relapse after a stage I primary. The survival figure for stage I has a wide interval (12 to 55.9 months) because only 58 patients were in that group. This is registry data, so it describes patterns rather than explaining them.

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