ESCAT v2: New Version of the Precision Oncology Framework

Precision oncology has evolved significantly since the publication of ESCAT in 2018. Approvals of tumor-agnostic therapies, expansion of real-world evidence data, and recognition of genomic resistance biomarkers have demanded a review of the original framework. ESMO assembled an international panel of experts to update the ESCAT classification. The new framework, ESCAT v2, introduces substantial changes. Tier I has been restructured into three categories: proven, inferred, and extrapolated, which maintain the same clinical guideline but differ in the level of certainty of the evidence supporting them. Additionally, ESCAT v2 incorporates formal criteria for evaluating tumor-agnostic therapies through the ESMO Tumour-Agnostic Classifier and Screener (ETAC-S) ¹.

New Guidelines and Classifications

ESCAT v2 also refines Tier II into three sub-tiers, based on prospective interventional evidence, high-quality real-world or non-prospective evidence, and replicated case-level evidence. Tier X has been subdivided into changes that were tested and did not prove predictive (X-A) and biomarker-therapy combinations where the therapy does not show significant activity in the population defined by the biomarker (X-B). The new version introduces a parallel four-level resistance scale, ranging from clinically validated resistance to preclinical or computational evidence ¹.

ESCAT v2 provides a comprehensive and evidence-graded framework for interpreting actionable and resistance biomarkers in cancer. This allows for more detailed communication between clinicians, patients, regulators, and researchers, maintaining a clear guideline for action when evidence supports patient benefit. The update reflects contemporary clinical practice and supports more confident decision-making ².