Interpreting the GALAXY and BESPOKE CRC Data: ctDNA as a Predictor for Metastases-Directed Therapy (MDT)
Experts discuss how positive ctDNA results after chemotherapy can guide timely, metastasis-directed interventions in colorectal cancer, highlighting the shift from reliance on CEA to more sensitive molecular testing—and emphasizing the need for high-quality imaging to capitalize on ctDNA’s potential for enabling curative surgical outcomes.
EP: 1.The Oncology Surgeon’s Role in Postoperative Surveillance Following CRC Resection
EP: 2.Communicating the Risk of Disease Relapse to the Patient After Curative CRC Resection
EP: 3.How Postoperative ctDNA Results Influence Treatment Decisions Following CRC Resection
EP: 4.Identifying Patients Requiring Intensive Surveillance Following CRC Resection
EP: 5.Evaluating the Clinical Value of ctDNA Testing in the Longitudinal Management of the CRC Patient
EP: 6.The Importance of Multidisciplinary Communication and Care Coordination for the Resected CRC Patient
EP: 7.ctDNA Surveillance Monitoring ESMO 2025 Abstract: Study Methods, Objectives, and Baseline Characteristics for GALAXY and BESPOKE CRC
EP: 8.Interpreting the GALAXY and BESPOKE CRC Data: Transient ctDNA Clearance and the Risk of Recurrence
EP: 9.Interpreting the GALAXY and BESPOKE CRC Data: Serially ctDNA-Negative Patients and the Risk of Recurrence
EP: 10.Interpreting the GALAXY and BESPOKE CRC Data: ctDNA as a Predictor for Metastases-Directed Therapy (MDT)
A major challenge in clinical practice is determining how to respond to a positive circulating tumor DNA (ctDNA)ctDNA result following chemotherapy. When a recurrence is suspected, identifying a visible lesion becomes crucial, particularly if surgical resection is an option. This is where ctDNA can guide metastasis-directed therapy, offering the chance to surgically remove the source of recurrence in select cases. If chemotherapy has failed to clear residual disease, surgery guided by ctDNA detection may offer the best outcome—essentially a “home run” scenario for this biomarker.
Recent pooled data from the Galaxy GALAXY and bespoke BESPOKE CRC studies illustrate how ctDNA is being used to guide localized interventions. While Although use of metastasis-directed therapy was relatively uncommon in patients with stage II/III patientsdisease, it occurred more frequently in stage IV cases, particularly when ctDNA was positive. Notably, ctDNA results prompted intervention more often than elevated carcinoembryonic antigen (CEA) levels. This underscores a broader shift in clinical reliance—from the historically entrenched but inconsistent CEA marker toward the more sensitive and actionable ctDNA testing. CEA, though still in use, is increasingly viewed as unreliable, particularly in the context of modern precision oncology.
To act effectively on a ctDNA-positive result, high-quality imaging is essential. Basic or low-resolution scans may miss small, early metastases, undermining the potential benefit of ctDNA surveillance. Thin-slice, multiphase CT or contrast-enhanced MRI should be standard when ctDNA becomes positive, especially if the goal is curative resection. The sensitivity of the molecular test must be matched by the sensitivity of imaging, or opportunities for early salvage may be lost. Ultimately, combining advanced biomarkers with high-quality diagnostics and timely surgical decision-making can shift outcomes for patients—potentially offering curative interventions earlier than was possible using traditional surveillance methods alone.
