El ADN tumoral circulante informado por el tumor estratifica el riesgo de recurrencia y la supervivencia en el...

Patients with anal squamous cell carcinoma (ASCC) who fail chemoradiation (CRT) have poor outcomes, underscoring the need for biomarkers to guide risk stratification. In a real-world two-center cohort of 84 adults with non-metastatic ASCC treated with curative-intent CRT, we prospectively evaluate a tumor-informed circulating tumor DNA (ctDNA) assay (Signatera^TM, Natera). Here we show that across 647 plasma specimens, ctDNA is positive at pre-treatment in 79% (61/77), including 89% (24/27) with stage III disease. End-of-treatment ctDNA positivity identifies patients with inferior one-year outcomes: 63% overall survival, 44% progression-free survival, and 39% locoregional failure. Conversely, patients who were ctDNA-negative at baseline or who cleared ctDNA during-treatment have 100% locoregional failure-free survival. During surveillance, ctDNA re-emergence precedes clinical or radiographic relapse in every case. These findings support the consideration of ctDNA as a dynamic, treatment-responsive biomarker warranting prospective validation for risk-adapted surveillance and adjuvant therapy in ASCC.