Marked regional and demographic variations persist in melanoma BRAF testing, and patients with BRAF-mutated tumours – particularly those with stage 2 disease – experience poorer five-year survival, according to a large national cohort study from England.

BRAF mutations are the most important known oncogenic drivers in melanoma and are predictive of response to targeted therapies and immunotherapy. However, incomplete or delayed BRAF testing can restrict access to systemic treatment.

Before the 2022 update to the National Institute for Health and Care Excellence guidance for melanoma, national recommendations on BRAF testing in England were limited. Little was known about real-world testing patterns, relevant patient and tumour characteristics, or associated survival outcomes at a national level.

This retrospective national cohort study sought to address this evidence gap using data from the National Disease Registration Service. The researchers included 91,415 new melanoma diagnoses in England between 2016 and 2021.

Molecular BRAF testing was performed in 14% of cases (13,138 patients), with 13,012 successfully tested tumours included in genotype analyses. Among the tested tumours, 34% were BRAF-mutated.

The dataset captured detailed demographic, pathological, treatment and survival data, enabling assessment of testing patterns, treatment use and melanoma-specific outcomes.

Regional BRAF testing gaps linked to survival differences

Testing rates varied widely by region, from 23% in the West Midlands to 11% in Yorkshire and the Humber. Female patients and those aged 80 years or older were less likely to be tested.

BRAF mutations were more common in younger patients, females and tumours located on the trunk and were less frequent in head and neck melanomas.

Survival analyses showed that patients with BRAF-mutated tumours had worse outcomes, with a five-year net survival of 55.9% compared with 66.5% in BRAF wild-type melanoma.

Stage 2 disease was associated with poorer survival, with five-year survival of 55.5% for BRAF-mutated tumours versus 66.8% for wild-type. First-line immunotherapy was associated with lower melanoma-specific mortality than first-line targeted therapy among patients with advanced disease who received systemic therapy.

Data limitations and implications for practice

The researchers cautioned that national datasets might not fully represent all BRAF testing, especially immunohistochemistry-based assays, and that regional differences in data submission could affect reported testing rates.

Furthermore, evolving testing practices and changes in treatment options over the study period, along with limitations in staging and recurrence data, complicate the interpretation of long-term outcomes.

Looking ahead, the researchers suggested that implementing updated guidance, along with broader access to genomic testing, should help to reduce variation in BRAF testing across England. They also emphasised the importance of ongoing audit and regular updates of national policy as melanoma diagnostics and treatments continue to advance.

Overall, the findings highlight the impact of BRAF mutations on survival and underscore the need for early, accurate and consistent testing to support prognostication, guide treatment decisions and promote equitable access to systemic therapies nationwide.

Reference
Mistry K et al. A national cohort study of melanoma BRAF status, testing patterns, patient and tumour characteristics, treatment and survival in England from 2016 to 2021. Br J Dermatol 2025;193:1146–54.