Dr. John Strickler from Duke Cancer Institute moderated a comprehensive discussion with Drs. Eleonora Teplinsky, Benjamin Weinberg, Petros Grivas, and Luis Raez on integrating circulating tumor DNA (ctDNA) and minimal residual disease (MRD) testing across breast, colorectal, bladder, and lung cancers. The panel established foundational concepts distinguishing tumor-informed from tumor-naïve assays, emphasizing that ctDNA positivity represents a prognostic marker across tumor types, with bladder cancer having the strongest predictive evidence following FDA approval based on the IMvigor011 trial. Discussion addressed practical challenges including reimbursement inconsistencies, patient communication strategies for asymptomatic positive results, and the treatment on molecular recurrence (TOMR) paradigm. Tumor-specific data highlighted the GALAXY and BESPOKE CRC observational studies for colorectal cancer, SURVIVE and iSPY trials for breast cancer, and emerging whole-genome sequencing approaches for lung cancer. Panelists emphasized that although de-escalation strategies show promise, particularly in stage II colorectal cancer, intensification trials have been largely disappointing. The discussion concluded with calls for prospective randomized data, clinical trial enrollment, and addressing clonal hematopoiesis as a key technical challenge requiring resolution before widespread guideline adoption.
Dr. John Strickler introduces the program on circulating tumor DNA (ctDNA) and minimal residual disease (MRD) testing across solid tumors, joined by Dr. Eleonora Teplinsky (breast and gynecologic oncology, Valley Health System), Dr. Ben Weinberg (gastrointestinal oncology, Georgetown University), Dr. Petros Grivas (genitourinary oncology, Fred Hutchinson Cancer Center), and Dr. Luis Raez (thoracic oncology, Memorial Healthcare System).
Dr. Teplinsky addresses where ctDNA and MRD testing fit within the patient care continuum, noting that value isn't uniform across disease stages or tumor types. The strongest signal currently exists in the post-treatment surveillance setting, where tumor-informed assays can identify patients at higher recurrence risk before disease becomes visible on imaging.
Dr. Weinberg explains the treatment on molecular recurrence (TOMR) concept, drawing parallels to biochemical relapse monitoring in prostate cancer. In colorectal cancer, patients with positive ctDNA after completing curative-intent surgery and adjuvant chemotherapy will experience radiographic recurrence at a median of approximately 5.5 months, representing a population potentially amenable to curative intervention through escalated imaging to identify oligometastatic disease suitable for metastasectomy, or enrollment in novel drug development trials.
Dr. Grivas confirms ctDNA integration into multidisciplinary tumor boards is increasing, describing his bladder cancer multidisciplinary clinic involving urology, medical oncology, radiation oncology, and pathology/radiology review focused on localized muscle-invasive bladder cancer.
Dr. Teplinsky discusses the evolving breast cancer surveillance paradigm, noting historical data showing routine imaging surveillance doesn't impact outcomes, though this data predates modern imaging technology.
Dr. Weinberg discusses 2 major observational datasets informing colorectal cancer ctDNA practice.
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.
Dr. Raez discusses IASLC 2025 data, now published in the Journal of Thoracic Oncology, representing important progress for lung cancer's MRD research, which has historically lagged behind gastrointestinal and genitourinary cancers.
Dr. Teplinsky, reflecting on commonalities across tumor types, notes that although the discussion focused on early-stage breast cancer, increasing ctDNA use exists in metastatic disease to identify treatment-emergent mutations guiding therapy selection, representing a different application context.
Dr. Weinberg addresses where evidence is strongest versus where the field risks getting ahead of itself.
Dr. Raez addresses choosing between tumor-informed and tumor-naïve platforms, noting no formal prospective comparison exists.
Dr. Weinberg envisions increasing ctDNA incorporation into adjuvant decision-making, anticipating that Circulate North America results will provide comfort for de-escalating ctDNA-negative patients while escalating ctDNA-positive patients.
