Tumor-informed circulating tumor DNA stratifies recurrence risk and survival in anal squamous cell carcinoma
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<sup>TM</sup>, 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.
Authors
- N. Segal
- Aron Bercz (ORCID: https://orcid.org/0000-0002-4259-2644)
- Abraham J. Wu (ORCID: https://orcid.org/0000-0002-2597-7091)
- R. Ravella (ORCID: https://orcid.org/0000-0003-0376-5554)
- Louise C. Connell (ORCID: https://orcid.org/0000-0002-3193-4629)
- Charles P. Olinger
- Natasha Mohan
- Janet Alvarez (ORCID: https://orcid.org/0000-0001-7853-959X)
- M. Gonen
- Rona Yaeger (ORCID: https://orcid.org/0000-0002-7233-5454)
- Nathan J. Schauer (ORCID: https://orcid.org/0000-0002-3004-4923)
- Paul Bernard Romesser (ORCID: https://orcid.org/0000-0001-8268-2903)
- Devika Rao (ORCID: https://orcid.org/0000-0001-5404-8841)
- M. Zinovoy
- Jorge Marcet (ORCID: https://orcid.org/0000-0003-3728-8741)
- Angela Adames (ORCID: https://orcid.org/0000-0002-4440-6032)
- A. Cercek
- Wini Zambare (ORCID: https://orcid.org/0000-0001-7063-0700)
- Yu-Jui Ho
- Vonetta L Williams
- Jeanine Lisanti
- Marsha Reyngold
- E. Pappou
- J. Garcia-Aguilar
- V. N. Aushev
- Samuel Rivero-Hinojosa
- Philip B. Paty
- Martin R. Weiser
- John J. Cuaron
- Chris H. Crane
- Diana A. Roth O’Brien
- J. Joshua Smith
- Elisa K. Liu
- Shruti Sharma
- Meenakshi Malhotra
- Richard Tuli
- Minetta C. Liu
- Adham Jurdi
- Caroline E. Kostrzewa
Institutions
- Memorial Sloan Kettering Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of South Florida (US)
- Tampa General Hospital (US)
- Natera (United States) (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-02-26
- DOI
- https://doi.org/10.1038/s41467-026-69984-y
- Primary Topic
- Colorectal and Anal Carcinomas
- Type
- article
- Field-Weighted Citation Impact
- 0.00