Practical Implementation and Tissue Tropism Considerations

Dr. Weinberg addresses practical workflows for ctDNA-positive, imaging-negative patients, noting no current standard of care exists despite NCCN guidelines addressing elevated CEA management.

His approach begins with imaging escalation: obtaining recent CT scans of chest, abdomen, and pelvis if not already performed, then escalating to PET scans and potentially liver MRI, particularly for patients with fatty liver where small-volume metastatic disease might be missed.

He introduces the concept of tissue tropism, explaining that tumor-informed testing sensitivity varies significantly by metastatic site.

Liver metastasis detection is quite sensitive, giving him confidence that ctDNA clearance to zero after liver surgery may indicate cure.

However, lung and peritoneal metastases, representing a long-standing challenge across gastrointestinal cancers, show lower sensitivity, representing an area where improved blood-based detection would be particularly valuable given current limitations of standard imaging and laparoscopy.

Dr. Weinberg describes his Georgetown trial testing atezolizumab and bevacizumab for ctDNA-positive, no-evidence-of-disease patients across multiple gastrointestinal cancer cohorts, modeled after the INTERCEPT program, with ongoing efforts through the Colorectal Cancer Alliance to develop a platform study specifically for colorectal cancer patients completing curative-intent treatment.

Regarding barriers to trial enrollment, he identifies the need for reproducible assays providing near-real-time results, since ctDNA monitoring requires tracking clearance over time rather than single-timepoint decisions.

He highlights that patients with MSI-high colorectal cancer receiving immunotherapy as a population deriving exceptional ctDNA monitoring benefit, where rapid early clearance indicates treatment efficacy and can help interpret ambiguous early scans showing pseudoprogression, sharing an example of a patient achieving pathologic complete response despite a concerning initial scan.