Detecting BRAF mutations in colorectal cancer in clinical practice: an Italian experts' position paper.

Abstract

BRAF p.V600E exon 15 hotspot mutation can identify a molecular subgroup of metastatic colorectal cancer (mCRC) patients exhibiting poor prognosis under the conventional chemotherapy regimen. Recently, the chemotherapy-free combination of encorafenib and cetuximab has been approved as the standard of care for previously treated BRAF p.V600E mCRC patients, and genomic testing for BRAF mutations at the time of mCRC diagnosis is currently recommended. In clinical practice, BRAF mutation testing strategies are dramatically impacted by a lack of harmonization and standardization, both in the pre-analytical and analytical phases, which can result in BRAF-mutated patients not receiving the most appropriate therapy at recurrence. This paper proposes nine statements providing practical and concise advice on BRAF mutation testing in CRC, derived from collegial discussion and analysis of a multidisciplinary team of experts, including referral Italian oncologists and pathologists. The statements overview pivotal aspects implied in the detection, treatment and management of BRAF-mutated patients and have been drafted to represent a valuable tool for healthcare professionals committed to mCRC patient management. In addition, they represent a platform for implementing diagnostic-therapeutic workflows that can adapt to the variability of local resources while respecting the high-quality standards required by modern precision oncology.