A national cohort study of melanoma BRAF status, testing patterns, patient and tumour characteristics, treatment and survival in England from 2016 to 2021

Background: Inadequacy of testing for melanoma BRAF status results in delayed access to systemic therapy. BRAF mutations and their association with patient/tumour characteristics and survival is poorly understood.

Objectives: To report national data from England on the frequency of molecular BRAF testing; the association of patient/tumour characteristics with BRAF mutations; and the treatment and survival of patients with BRAF mutations.

Methods: This national retrospective cohort study identified all new melanomas and molecular BRAF testing in England diagnosed from 2016 to 2021 using population-based data from the National Disease Registration Service. Multivariate logistic regression determined the association between BRAF testing with patient/tumour characteristics and BRAF genotype with patient/tumour characteristics. Age-standardized net survival analysed melanoma-specific mortality by BRAF genotype.

Results: Of new cases of melanoma, 14% (n = 13 138/91 415) had a BRAF test registered. The proportion of successfully tested tumours that were BRAF-mutated was 34% (n = 4424/13 012). The West Midlands tested the highest proportion of cutaneous tumours (23%; n = 1783/7901) vs. the lowest in Yorkshire and the Humber (11%; n = 856/7760). Female patients [odds ratio (OR) 0.82, 95% confidence interval (CI) 0.79–0.86] and those aged > 80 years (OR 0.88, 95% CI 0.83–0.93) were less likely to be tested for BRAF mutations. BRAF mutations were associated with female gender (OR 1.16, 95% CI 1.07–1.26). Patients aged > 80 (OR 0.36, 95% CI 0.32–0.40) had lower odds of having BRAF-mutated tumours. Patients with BRAF mutations had a lower 5-year net survival [55.9% (95% CI 52.7–59.2) vs. BRAF wildtype 5-year net survival 66.5% (95% CI 62.1–60.1)], particularly in stage II disease.

Conclusions: This study presents the largest dataset on national melanoma BRAF status published to date. The data highlight geographical and demographic variations in BRAF testing and the impact of BRAF mutations on survival rates, particularly in patients with stage II disease. This highlights the critical role of consistent, early and accurate testing to ensure equal care, guide treatment decisions and understand prognosis.