Melanoma Outcomes, Immunotherapy Advances, and Gene Expression Profiling Guidelines

Conclusions

• Melanoma incidence remains high, but survival is excellent for localized disease and has improved substantially for advanced disease over the last decade.
• Checkpoint immunotherapy, especially anti-PD-1 and anti-CTLA-4 combinations, has driven major gains in metastatic melanoma survival.
• Neoadjuvant immunotherapy before surgery appears to improve outcomes for resectable advanced melanoma compared with surgery followed by adjuvant therapy alone.
• Gene expression profiling should not replace standard pathologic staging, but it may help select a small subset of lower-risk T1b/T2a patients for sentinel node biopsy decisions.
• Prospective, blinded, multicenter validation is essential before gene expression profiling tests should be widely adopted for clinical decision-making.
• The MERLIN_001 CP-GEP test identified patients with less than 10% sentinel node positivity risk, but it did not reliably identify a group below 5% risk overall.
• A high-risk CP-GEP result was associated with substantially higher sentinel node positivity than a low-risk result, supporting some predictive value.
• CP-GEP appears to add value beyond clinicopathologic nomograms in some threshold ranges, but its advantage is modest and context dependent.
• Current clinical “high-risk” features alone do not reliably identify T1a patients with sufficiently high nodal risk to justify routine sentinel node biopsy.
• The 31-gene i31-GEP test may identify low- and high-risk groups, but much of its apparent prognostic value may overlap with already favorable or unfavorable tumor features.
• There is still not enough prospective evidence that high-risk GEP results should guide more intensive surveillance or additional treatment.
• More frequent CT or PET-CT surveillance has not improved outcomes and may be associated with worse survival and higher costs.
• Overall, these tests may be useful for carefully selected patients, but their routine use for surveillance or treatment escalation remains unproven.