Prognostic Value of Circulating Tumor Dna in the Perioperative Management of Esophageal Cancer

Abstract Background There is a scarcity of prognostic biomarkers for esophageal and esophagogastric cancers. Circulating tumor DNA (ctDNA) has shown promise in several cancers as an assay capable of detecting residual disease following resection as well as recurrence during the surveillance phase. However, there is limited evidence supporting its use in the perioperative phase of care, which could be helpful in preemptively identifying patients at high risk of recurrence and improving patient selection for surgery. We aim to evaluate the prognostic value of pre- and on-treatment ctDNA detection. Methods A retrospective study was conducted on patients from a single institution with pathologically diagnosed stage Ib-IVA esophageal carcinoma who underwent definitive local therapy, including esophagectomy, endoscopic resection (ER), or definitive chemoradiotherapy (CRT), between 2022 and 2024. These patients had ctDNA analysis performed at baseline, pre-treatment, and post-treatment using a plasma-based tumor-informed assay. ctDNA detection and quantification was annotated to clinicopathologic characteristics. Results In total, 38 patients were included; 29 esophagectomy, 7 CRT, and 2 ER. Baseline ctDNA was detectable in 63% (23/38) (2.36 MTM/ml SD 5.46). 88% (14/16) achieved ctDNA clearance within a median 51 days post local control. Overall, 79% of surgical patients (23/29) had neoadjuvant therapy. Baseline ctDNA was detectable in 74% (17/23) (2.22 MTM/ml SD 5.89). 26% (6/23) had no residual disease at resection, associated with lower baseline ctDNA (0.37 MTM/ml vs. 1.70 MTM/ml, p = 0.005). Nodal metastases were found in 12 patients, associated with higher pre-treatment ctDNA levels (3.1 MTM/ml vs.1.2 MTM/ml, p 0.001). Conclusion This study highlights the potential of ctDNA as a prognostic biomarker in esophageal cancer. We’ve demonstrated that local therapy for esophageal cancer effectively clears ctDNA. Additionally, baseline ctDNA detection and post-treatment clearance were strongly associated with disease status, and higher pre-treatment ctDNA levels were observed in patients with nodal metastases. Quantitative analysis of baseline ctDNA prior to therapy may be a useful prognostic indicator for patients likely to have nodal metastases and poor treatment response at the time of surgery. These findings suggest that ctDNA may be useful for identifying high-risk patients and guiding treatment decisions in the perioperative phase.