Ultrasensitive Liquid Biopsies: A New Paradigm in Immunotherapy Monitoring and Prediction

Investigators at Vall d'Hebron Institute of Oncology report that an ultrasensitive liquid biopsy detected early immunotherapy response signals and predicted survival in advanced cancer patients enrolled in phase 1 trials—supporting earlier molecular risk stratification.

Circulating tumor DNA (ctDNA) provided earlier, molecular-level response data that complements imaging and traditional biomarkers, giving actionable biologic context before radiographic confirmation. This molecular readout can refine patient selection and strengthen correlative analyses in early‑phase immunotherapy protocols; the clinical view therefore shifts toward integrating molecular surveillance alongside standard assessments.

In broad phase 1 advanced‑cancer cohorts, investigators reported concordant endpoints for early response detection and survival associations. Serial ctDNA assessments across primary and independent validation cohorts (retrospective n=136, prospective n=66) showed treatment‑associated declines within weeks that correlated with progression‑free and overall survival—indicating molecular changes can precede or accompany imaging and inform early trial readouts.

Baseline ctDNA carried clear prognostic value: lower baseline levels associated with longer PFS and OS across studied cohorts. Main limitations remain variable tumor shedding, assay sensitivity ceilings, and persistent challenges distinguishing true progression from pseudoprogression; these caveats moderate but do not negate the platform's clinical promise.

Key Takeaways:

• Ultrasensitive ctDNA platforms detected early response signals and predicted survival in phase 1 immunotherapy cohorts.
• Serial ctDNA changes were measurable within weeks and correlated with PFS and OS, complementing imaging.
• Limitations include variable shedding, sensitivity limits, and pseudoprogression challenges, which require prospective validation.