Detectable ctDNA Potential Predictor of Gastroesophageal, Esophageal Cancer Recurrence

Can circulating tumor DNA (ctDNA) detect cancer recurrence in patients being treated for esophageal cancer or gastroesophageal (GE) cancer earlier than traditional clinical or radiographic methods? Investigators presenting new research at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium believe this to be a distinct possibility.1,2 The method is considered minimally invasive and highly sensitive, with an overall better ability to detect cancer recurrence earlier.2

Their findings show that among patients treated with curative intent through surgery or chemoradiation, there are positive correlations between detectable ctDNA and predictive ability of cancer recurrence, making the method a potentially valuable tool for posttreatment surveillance and molecular residual disease (MRD) detection. Both studies utilized the Signatera assay, which can be customized for each patient and incorporated at the neoadjuvant, adjuvant, surveillance, and metastatic treatment phases, with promising results seen for bladder, breast, colon, lung, and ovarian cancers.3

ctDNA in Gastroesophageal Cancer1

This retrospective analysis incorporated electronic health record data from 2022 to 2025 from 24 adult patients who had 51 ctDNA results from 1 of 5 periods: baseline (2%); between 1 and 60 days after neoadjuvant therapy, either chemotherapy or chemoradiation (2%); between 1 and 90 days after surgical resection, the MRD detection window (27%); after adjuvant therapy (4%); and any time during the 2-year surveillance period after curative-intent treatment (65%). These patients did not have other active cancers when they were being treated for their GE cancer.

Adenocarcinoma was the cancer subtype in all cases (gastric cancer, n = 11; esophageal cancer, n = 13). At diagnosis, 18 cases were locally advanced (gastric, n = 8; esophageal/GE junction [GEJ], n = 10) and 6 cases were metastatic (gastric, n = 3; esophageal/GEJ, n = 3). Treatment regimens comprised perioperative chemotherapy and surgical resection; perioperative chemotherapy, neoadjuvant chemoradiation, and surgical resection; neoadjuvant chemoradiation and surgical resection; and chemoradiation only. Following treatment, there were 12 cases of recurrent disease among patients who at diagnosis had locally advanced esophageal/GEJ (n = 5) or gastric (n = 4) cancer and metastatic esophageal/GEJ (n = 1) or gastric (n = 2) cancer and no evidence of disease/active surveillance among patients who at diagnosis had locally advanced esophageal/GEJ (n = 6) or gastric (n = 4) cancer and metastatic esophageal/GEJ (n = 1) or gastric (n = 1) cancer.

Concentrating on the results from the MRD window and the 2-year surveillance period (n = 14), the investigators saw these results:

• 50% each of cases were MRD-positive or -negative
• Of the patients who were MRD-positive, recurrence occurred in 100%
• Of the patients who were MRD-negative, recurrence occurred in 28.6%

ctDNA is considered a minimally invasive and highly sensitive procedure, with an overall better ability to detect cancer recurrence earlier. | Image Credit: © ArtemisDiana-stock.adobe.com

Noting that most of the patients with detectable ctDNA eventually experienced disease recurrence, the authors noted a likely promising association between these outcomes—but also that more information is needed to confirm this relationship.

ctDNA in Esophageal Cancer2

The ctDNA of patients in this prospective observational study (N = 14) was collected at 3 time points: pretreatment, on-treatment, and post treatment. The surveillance window for the primary end point of recurrence/death from any cause/end of follow-up with event-free survival (EFS) was the 12 weeks after conclusion of definitive treatment or 2 weeks after the end of additional treatment. The median patient age was 71 years (range, 46-81), and adenocarcinoma was the dominant subtype (93%; n = 13); squamous cell carcinoma was the remaining single case. Most patients (79%) had stage III disease, but all patients had stage II or III disease. Eighty-six percent were male patients.

Patients underwent definitive chemoradiation (64%; n = 9) or neoadjuvant chemoradiation and surgery (35%; n = 5). Over the median follow-up of 6.2 months (range, 1.9-27.6), the ctDNA positivity rate dropped from 100% during the pretreatment period to 70% in the surveillance window; during this time, patients had a median of 2 (range, 1-5) ctDNA analyses performed. RFS was significantly inferior in the patients who were ctDNA positive (HR, 28.3; 95% CI, 3.1-3767.7; P = .001), with disease recurrence or death seen in 85% of this group. In contrast, there were no cases of disease recurrence in any of the patients who continuously had ctDNA-negative results—although 1 of these patients did die from a noncancer cause.

Overall, the study investigators found that among the patients with ctDNA-positive results who underwent definitive treatment, disease recurrence via clinical or radiographic evaluation occurred within a median of 4.1 months (range, 0.7-7.3); however, their data also show that patients underwent imaging earlier because of their ctDNA results.

The authors highlight the consistent results from their investigation, explaining the high rate of identification for those at high risk of disease recurrence through ctDNA monitoring and that positive results from this biomarker assay have a strong correlation with worsened EFS. Like the authors of the first study, too, they recommend validation, especially regarding how these data could guide surveillance and treatment decisions.

References

1. Silva KW, Cohen SA, Shankaran V, et al. Examining the role of circulating tumor DNA in gastroesophageal cancers treated with curative intent. Presented at: American Society of Clinical Oncology Gastrointestinal Cancers Symposium; January 8-10, 2026; San Francisco, CA. Abstract 437.
2. Sedigh SF, Antatamian A, Khayat MM, et al. Tumor-informed ctDNA monitoring during surveillance for early detection of recurrence in patients with stage II/III esophageal cancer treated with chemoradiation. Presented at: American Society of Clinical Oncology Gastrointestinal Cancers Symposium; January 8-10, 2026; San Francisco, CA. Abstract 440.
3. Signatera. Natera. Accessed January 8, 2026. https://www.natera.com/oncology/signatera-advanced-cancer-detection/