MRD Test Predicts Chemotherapy Survival Benefit in Colorectal Liver Metastases

Postsurgical molecular residual disease (MRD) status, as measured by the Signatera test, predicted which patients with resected colorectal liver metastases derived an overall survival (OS) benefit from adjuvant chemotherapy, according to data from the CIRCULATE-Japan GALAXY study (UMIN000039205)published in JAMA Oncology and a news release from Natera, Inc.^1,2 The findings were also presented as an oral presentation at the 2026 European Society for Medical Oncology Gastrointestinal (ESMO GI) Congress.

The liver is the most common site of distant metastasis in colorectal cancer, and colorectal liver metastases is a major cause of cancer-related mortality. Although the role of adjuvant chemotherapy after curative-intent hepatectomy has remained a matter of debate for more than 2 decades, this analysis is the first in a large cohort to demonstrate that MRD status can predict an OS benefit, rather than only a disease-free survival (DFS) benefit, from adjuvant chemotherapy in this population.

What did the study find about MRD status and chemotherapy benefit?

Among patients who underwent upfront surgery without neoadjuvant chemotherapy, those with MRD positivity who received adjuvant chemotherapy had improved OS (adjusted HR, 0.27; 95% CI, 0.08-0.88; P = .03) and DFS (adjusted HR, 0.07; 95% CI, 0.02-0.24; P <.001) compared with observation. At 48 months, OS was 65.3% (95% CI, 30.8%-85.7%) with adjuvant chemotherapy vs 32.9% (95% CI, 17.4%-49.3%) with observation. Patients with MRD negativity had favorable outcomes and showed no significant OS or DFS benefit from adjuvant chemothearpy.

How was MRD status associated with survival outcomes overall?

Postsurgical MRD positivity at 2 to 10 weeks after surgery was strongly prognostic across both cohorts. In the frontline surgery cohort, MRD positivity was associated with worse DFS (HR, 4.14; 95% CI, 2.69-6.36; P <.001) and OS (HR, 9.13; 95% CI, 4.44-18.78; P <.001) compared with MRD negativity. In patients who received neoadjuvant chemotherapy before surgery, MRD positivity was similarly associated with inferior DFS (HR, 4.82; 95% CI, 2.92-7.97; P <.001) and OS (HR, 9.43; 95% CI, 2.78-31.96; P <.001).

“For patients with colorectal liver metastases, the benefit of [adjuvant chemotherapy] after curative-intent surgery has remained uncertain,” stated Kozo Kataoka, MD, PhD, researcher in the Division of Lower GI, Department of Gastroenterological Surgery at Hyogo Medical University, and senior author of the study, in the press release.¹ “Importantly, this is the largest analysis to show that post-surgical MRD status may help identify which patients benefit from [adjuvant chemotherapy] in patients who underwent upfront surgery.”

What was the design of the GALAXY study?

CIRCULATE-Japan GALAXY was a prospective, observational registry study conducted between May 2020 and July 2024. The retrospective subset analysis included 298 patients with resected colorectal liver metastases without extrahepatic disease. They also had available MRD status 2 to 10 weeks after curative-intent hepatectomy. Patients were classified into an upfront surgery cohort (n = 191) or a neoadjuvant chemotherapy cohort (n = 107); analyses were landmarked at 70 days postsurgery to account for immortal time bias. The median follow-up was 43.2 months (range, 1-68). The median age of patients was 67 years (range, 33-85) and 64.4% were male.

What is Signatera and how does it work?

Signatera is a personalized, tumor-informed MRD test that uses whole-exome sequencing of a patient's tumor tissue to identify patient-specific somatic variants, which are then tracked in blood plasma using multiplex polymerase chain reaction–based next-generation sequencing. MRD positivity is defined as detection of at least 2 tumor-specific variants above a predefined threshold.

“This analysis adds important [OS] data in resected colorectal liver metastases, a setting where clinicians have historically had limited tools to determine who is most likely to benefit from ACT,” added Adham Jurdi, MD, senior medical director of oncology at Natera, in the press release.¹ “It further reinforces how Signatera can help tailor treatment to each patient.”

References

1. Signatera™ MRD test predicted overall survival benefit from chemotherapy in resected metastatic colorectal cancer. News release. Natera, Inc. July 6, 2026. Accessed July 6, 2026. https://tinyurl.com/mr6wz85z
2. Kataoka K, Ito K, Nakamura Y, et al. Circulating tumor DNA status and adjuvant chemotherapy in resected colorectal liver metastases. JAMA Oncol. Published online July 3, 2026. doi:10.1001/jamaoncol.2026.2191