In neoadjuvant settings, ctDNA monitoring allows for real-time therapy adjustment. Data from the iSpy platform shows 80% of hormone-positive patients clear ctDNA with half the chemotherapy, enabling de-escalation, while the remaining 20% can be identified for escalated treatment.

A key conceptual shift is viewing ctDNA not as a statistical risk marker, but as direct detection of molecular residual disease (MRD). This framing, similar to how a CT scan identifies metastases, explains its high positive predictive value and justifies its use in making critical treatment decisions.

For colorectal cancer patients in surveillance, serial ctDNA testing offers profound reassurance. Data shows that after achieving one year of consistently negative results, the probability of a future recurrence drops to just 0.9%, providing a level of confidence previously unattainable with other methods.

A positive ctDNA test indicating minimal residual disease is strongly linked to recurrence. This expert argues clinicians have an obligation to act on this information, even without definitive guidelines. Framing inaction as unacceptable challenges the passive "wait-and-see" approach.

In neoadjuvant therapy, a patient's long-term outcome is better predicted by stopping tumor DNA shedding (ctDNA clearance) than by achieving pathologic complete response (pCR), the traditional gold standard. This redefines what constitutes a successful treatment response before surgery.

The practice-changing DYNAMIC trial showed that a ctDNA-guided strategy for stage II colorectal cancer reduces adjuvant chemotherapy use by 50%. Despite this significant de-escalation of treatment, patient outcomes and survival rates were identical to the standard-of-care approach.

The InVigor11 study was the first to show that detecting recurrence via a ctDNA test before it's visible on scans is not just a prognostic sign, but an actionable clinical state. Intervening with therapy at this early stage was proven to improve patient outcomes, establishing a new paradigm for cancer surveillance.

Observational data from the BESPOKE study showed that the survival benefit from adjuvant chemotherapy was only seen in patients who tested positive for ctDNA post-surgery. In contrast, ctDNA-negative patients had overlapping survival curves whether they received chemotherapy or not, questioning its utility for that group.

The interpretation of ctDNA is context-dependent. Unlike in the adjuvant setting, in the neoadjuvant setting, remaining ctDNA positive post-treatment signifies that the current therapy has failed. These high-risk patients need a different therapeutic approach, not an extension of the ineffective one.