Sites of metastases before systemic treatment influence progression patterns and survival in stage IV melanoma patients.

A highly significant association between an increase in number of lesions in the brain and PFS was observed (HR1.13, 95% CI 1.06-1.21, adjusted P < 0.005).

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In patients with BRAF/MEKi as first-line treatment administered immediately after the first metastatic event ( n = 169), the total number of metastatic sites at baseline was borderline significant in its association with PFS (HR 1.14, 95% CI 1-1.29, P = 0.045), whereas the association of total number of lesions at baseline with PFS was highly significant (HR 1.06, 95% CI 1.02-1.10, P = 0.002).

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Only the presence of SST disease at baseline (HR 1.74, 95% CI 1.18-2.58, adjusted P = 0.05) was borderline significantly associated with PFS, whereas an increase in the number of brain lesions showed a trend of association that did not achieve statistical significance (HR 1.18, 95% CI 1.05-1.33, adjusted P = 0.06) ( Supplementary Table S10 , available at https://doi.org/10.1016/j.iotech.2025.101078 ).

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Despite this trend, pairwise differences in PFS between patients with more than three brain lesions at baseline versus those with one to three brain lesions at baseline ( P = 0.1) and no brain lesions at baseline ( P = 0.07) did not reach statistical significance.

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