SynthesisBJS open2026
Role of circulating tumour DNA in predicting complete clinical response and local regrowth after total neoadjuvant therapy for rectal cancer: meta-analysis.
Synthesis in BJS open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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5 authors.
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Abstract
backgroundNon-operative management after total neoadjuvant therapy (TNT) has emerged as a potential strategy for patients with locally advanced rectal cancer (LARC) achieving clinical complete response (cCR). Circulating tumour DNA (ctDNA) has been proposed as a systemic biomarker to augment response assessment, but its role in predicting cCR and local regrowth remains uncertain.
methodsA systematic review and meta-analysis were performed of studies evaluating ctDNA dynamics in patients with LARC undergoing TNT. PubMed, EMBASE, and Web of Science databases were searched from database inception to 31 March 2026. Primary outcomes were the association between post-TNT ctDNA status and cCR and sustained cCR. Pooled odds ratios (ORs) were calculated using a random-effects model.
resultsSix studies comprising 597 patients were included. ctDNA negativity following TNT was associated with higher likelihood of cCR (OR 8.01; 95% confidence interval (c.i.) 1.43 to 44.90; I2 = 27.0%). The association with sustained cCR was not statistically significant (OR 3.46; 95% c.i. 0.03 to 394.64; I2 = 59.9%). Across studies, post-TNT ctDNA positivity was associated with inferior disease-free, distant recurrence-free, and progression-free survival. ctDNA demonstrated high specificity and positive predictive value for residual disease, but low sensitivity for the detection of residual local disease and local regrowth, with a substantial proportion of patients with residual tumour remaining ctDNA negative at restaging.
conclusionPost-TNT ctDNA positivity may identify patients at increased risk of adverse oncological outcomes. However, ctDNA negativity was not consistently associated with the absence of residual local disease, limiting its utility as an independent determinant of organ preservation eligibility. ctDNA should be interpreted as a complementary tool for systemic risk stratification alongside established anatomical assessment.
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