Clinical performance of tumor-informed versus tumor-agnostic ctDNA assays for colorectal cancer recurrence: A systematic review and diagnostic accuracy meta-analysis
Daniel G. Camblor, B. Martínez-Castedo, Jorge Martín-Arana, Francisco Gimeno-Valiente, Blanca García-Micó, Francisco Martínez-Picó, Víctor Seguí, M. García-Bartolomé, Diego González, Alejandro Guimera, Marisol Huerta, Susana Roselló, Valentina Gambardella, Desamparados Roda, Leontios Pappas, Aparna Parikh, Juan Antonio Carbonell‐Asins, Andrés Cervantes, Noelia Tarazona
Abstract
In patients with early-stage colorectal cancer (CRC), circulating tumor DNA (ctDNA) testing is increasingly used to detect minimal residual disease (MRD) after curative-intent surgery. This information can guide decisions on adjuvant chemotherapy and surveillance. Two main approaches exist, tumor-informed (TI) and tumor-agnostic (TA), however, their diagnostic accuracy in clinical practice remains unclear. We conducted a bivariate diagnostic meta-analysis to compare sensitivity and specificity of TI versus TA ctDNA assays for detecting recurrence in patients with resected CRC. Subgroup analyses were performed based on landmark versus serial sampling strategies. In the serial-sampling setting, TI assays demonstrated markedly higher sensitivity than TA assays (0.88 vs. 0.59; p = 0.001), with no significant differences in false-positive rates. The landmark analyses did not show statistically significant differences between approaches. The results underscore the importance of sampling strategy when selecting a ctDNA test. When longitudinal monitoring is feasible, TI assays provide the most reliable detection of recurrence. This meta-analysis supports tailoring ctDNA testing to the clinical context, prioritizing TI approaches for serial surveillance to better guide adjuvant decision-making and improve patient outcomes.