CPC13 BRAF mutations in melanoma: testing patterns, demographic associations and survival implications

Abstract BRAF mutation status is a critical biomarker in melanoma management, influencing prognosis and therapeutic response. Inadequate testing for BRAF status results in delayed access to systemic therapy, potentially compromising patient outcomes. National guidelines prioritize BRAF testing for advanced-stage melanoma. However, the relationship between BRAF mutations, patient demographics, tumour characteristics and survival outcomes remains poorly understood, with few national datasets available globally. This retrospective, national cohort study utilized population-based data from the National Disease Registration Service to identify all new melanomas and molecular BRAF testing performed in England from 2016 to 2021. We report only molecular testing for BRAF status, as it was not possible to routinely extract immunohistochemistry (IHC) results from pathology reports. A review of 650 randomly selected pathology reports without molecular results identified that 36 cases (5.5%) had undergone BRAF V600E IHC testing. Multivariate logistic regression was used to examine associations between BRAF testing and BRAF genotype with patient and tumour characteristics. Age-standardized net survival and a Cox proportional hazards model were used to evaluate the impact of BRAF status on survival outcomes. From 2016 to 2021, 14.4% (13 138 of 91 415) of cases of melanoma in England had a BRAF test recorded, with 34.0% (4424 of 13 012) of successfully tested tumours identified as BRAF mutated. The proportions of successfully tested stage I and II cutaneous melanomas were 2.6% (1366 of 52 353) and 26.4% (4441 of 16 844), respectively, compared with 52.2% (4558 of 8731) for stage III and IV tumours. Female patients were less likely to undergo BRAF testing [odds ratio (OR) 0.82, 95% confidence interval (CI) 0.79–0.86], as were patients aged ≥ 80 years (OR 0.88, 95% CI 0.83–0.93). BRAF mutations were associated with being female (OR 1.14, 95% CI 1.05–1.24), younger age (OR 0.97, 95% CI 0.97–0.97) and tumours on the trunk (OR 1.91, 95% CI 1.74–2.10). Among patients with BRAF mutations, 58.1% (2497 of 4298) received systemic anticancer therapy (SACT), of whom 56.7% (1417 of 2497) received targeted therapy as first line. In contrast, among patients who were BRAF wildtype, 43.1% (3367 of 7821) received SACT. Patients with BRAF mutations had significantly lower 5-year net survival than patients who had wildtype BRAF (mutated: 55.9%, 95% CI 52.7–59.2 vs. wildtype: 66.5%, 95% CI 62.1–70.1). This was particularly so in male patients and those with stage II melanoma. Among patients with BRAF mutations treated with SACT, those receiving first-line immunotherapy had improved survival compared with those treated with first-line targeted therapy, and patients who received both targeted and immunotherapy had the worst outcomes. We present the largest dataset on melanoma BRAF status in England. These findings underscore the importance of incorporating BRAF testing into ­early-stage melanoma care, ensuring early and accurate testing to guide treatment and improve understanding of patient prognosis.