SCAC Biomarker Strategy: From PD-L1 CPS Scoring to Next-Generation Molecular Profiling

Biomarkers and Treatment Expectations

Current biomarker landscape in anal cancer remains limited, with traditional markers like PD-L1, tumor mutational burden, and mismatch repair deficiency proving unreliable for treatment selection. EGFR expression occurs at high rates in anal squamous cell carcinoma, but targeting strategies have not demonstrated meaningful clinical benefit. PIK3CA aberrations represent one of the most common mutations, with potential therapeutic targets in clinical trials, although no approved therapies currently exist.

KRAS status evaluation may inform treatment decisions, as the majority of patients are KRAS wild type, potentially making them candidates for EGFR inhibitor combinations. Limited retrospective data suggest 20% to 30% response rates with EGFR inhibitors plus chemotherapy in refractory settings, although this approach lacks guideline support. HER2 amplification occurs rarely but represents a potentially actionable target when identified through comprehensive genomic profiling.

Treatment expectation discussions must emphasize disease control rather than cure in the metastatic setting, focusing on improved survival and quality-of-life balance. The marathon vs sprint analogy helps patients understand the chronic disease management approach. Circulating tumor DNA (ctDNA) represents an emerging prognostic tool, particularly HPV ctDNA monitoring after chemoradiation, which may identify high-risk patients requiring closer surveillance or additional therapy interventions.