Katrina S. Pedersen, MD, MS

This segment explores the rapidly evolving landscape of ctDNA assays and the challenges clinicians face in interpreting and applying these tests in CRC care. The discussion emphasizes that ctDNA technology is advancing at an unprecedented pace, with each new generation of assays differing in methodology, sensitivity, and clinical reporting. As a result, clinicians must remain vigilant about assay versioning, analytic validity, and the implications for treatment decision-making.

In this segment, the discussion centers on the evolving role of ctDNA and MRD testing in CRC, particularly in the curative-intent setting. Experts highlight how ctDNA is increasingly used as both a predictive tool for guiding adjuvant therapy and as a surveillance strategy to monitor for early recurrence. They emphasize that although ctDNA is promising, it remains optional in practice due to limited evidence supporting de-escalation of therapy in certain populations.

This segment focuses on the evolving treatment landscape for refractory mCRC, with an emphasis on how clinicians interpret and integrate new trial data, such as STELLAR-303, into clinical practice. The discussion frames this trial within the context of heavily pretreated patients, highlighting the practical challenges of sequencing therapies like TAS-102, fruquintinib, and regorafenib. The panelists use the trial as a springboard to examine broader themes in treatment decision-making, balancing efficacy, tolerability, and patient-centered considerations.

This segment centers on the practical implementation of biomarker testing in mCRC and the remaining gaps between evidence and real-world practice. The panel begins by affirming that single-gene testing alone is largely obsolete, with most institutions relying on comprehensive NGS using both tissue and liquid biopsy. However, targeted single-gene assays, such as rapid KRAS testing, still play a role in select scenarios, particularly when expedited results are needed for clinical trial eligibility.

In this segment, the panel transitions to a focused discussion of critical biomarkers in mCRC beyond MSI-H/dMMR, emphasizing how rapidly the biomarker landscape has expanded heading into 2026. Faculty underscore that comprehensive molecular testing is no longer optional, as multiple actionable alterations now meaningfully influence treatment selection and outcomes.

This segment focuses on practical decision-making for first-line systemic therapy in patients with unresectable, multi-organ mCRC, particularly those with left-sided, RAS/BRAF wild-type disease. Dr Parikh frames the discussion around ongoing controversies, including the use of triplet versus doublet chemotherapy, timing of anti-EGFR therapy, and balance between efficacy and quality-of-life considerations such as skin toxicity.

This segment transitions the discussion from MSI-H disease to the broader management of mCRC, emphasizing the importance of multidisciplinary care and individualized treatment pathways. Dr Parikh frames the conversation by noting that, unlike many other gastrointestinal malignancies, patients with stage IV CRC can experience long-term survival and, in select cases, achieve cure. As a result, surgical and local therapies remain central considerations even in the metastatic setting.

This segment focuses on best practices for MMR and MSI testing in CRC, emphasizing that biomarker assessment is a critical and “never-miss” step prior to treatment decision-making. Dr Parikh opens by describing institutional reflex testing workflows, in which all newly diagnosed colorectal carcinomas, regardless of stage, automatically undergo immunohistochemistry (IHC) for loss of MMR proteins, rather than universal PCR-based MSI testing.

This segment focuses on real-world toxicity management with immune checkpoint inhibitors, particularly nivolumab plus ipilimumab, and how increasing familiarity has shaped clinician comfort and patient outcomes in MSI-H/dMMR mCRC. The discussion opens with reflections on unexpected or rare immune-related adverse events, highligting the heterogeneous and sometimes unpredictable nature of immunotherapy toxicity. Although classic toxicities such as colitis, pneumonitis, hepatitis, and rash are well recognized, panelists note that unusual presentations can occur and require clinical vigilance.

In this segment, the panel addresses a key clinical question in MSI-H/dMMR mCRC: should dual immune checkpoint blockade with nivolumab plus ipilimumab be used universally upfront, or can clinicians safely sequence therapies and reserve CTLA-4 inhibition for later lines?

Experts discuss the evolving role of ctDNA in managing MSI-high cancer patients, emphasizing non-operative approaches and improved treatment strategies.

Experts discuss recent advancements in precision care for unresectable metastatic colorectal cancer, focusing on innovative treatment strategies and biomarker roles.

Panelists discuss how important clinical pearls include early genomic profiling, emphasizing lifestyle modifications like exercise programs that can reduce recurrence by 7%, and using olanzapine as the most effective antiemetic for delayed chemotherapy-related nausea.

Panelists discuss how immunotherapy generally provides better quality of life compared to traditional chemotherapy, particularly noting that microsatellite instability-high patients on immune checkpoint inhibitors report significantly better experiences than those on FOLFOX regimens.

Panelists discuss how they assess quality of life in clinical practice by asking simple questions like “What do you do for fun?” and “How was your week?” rather than relying solely on formal quality of life questionnaires.

Panelists discuss how they’re excited about future combination therapies, particularly TAS-102 with fruquintinib and novel immunotherapy approaches targeting patients with liver metastases who are typically checkpoint inhibitor refractory.

Panelists discuss how they approach rechallenge with chemotherapy, considering it primarily in patients who never truly progressed on oxaliplatin-based therapy or those who might benefit from EGFR antibody reintroduction after a drug holiday.

Panelists discuss how they manage fruquintinib dosing by starting at lower doses (3 to 4 mg) in patients with poor performance status or frailty, then titrating up as tolerated rather than starting at the full 5-mg dose.

Panelists discuss how they modify dosing schedules for TAS-102 (trifluridine/tipiracil), with some preferring every-other-week dosing instead of the standard 2-weeks-on schedule to reduce neutropenia and improve tolerability.

Panelists discuss how clinical trials remain the preferred option in third-line treatment, while acknowledging that regorafenib may benefit from dose reduction strategies and potential combination with immunotherapy in select patients.

Panelists discuss how 3 drugs (regorafenib, TAS-102, and fruquintinib) offer modest but meaningful survival benefits in treatment-refractory colorectal cancer, with TAS-102 plus bevacizumab being the preferred combination when tolerated.

Panelists discuss how circulating tumor DNA testing serves as the best prognostic technology available, particularly useful for identifying high-risk stage II patients who would benefit from adjuvant therapy, though surveillance strategies for positive results remain unclear.

Panelists discuss how doublet immunotherapy with ipilimumab and nivolumab provides superior outcomes compared to single-agent PD-1 therapy or chemotherapy in microsatellite instability-high colorectal cancer, supporting the “hit hard, hit early” approach.

Panelists discuss how the BREAKWATER trial demonstrates that upfront treatment with encorafenib plus cetuximab significantly improves outcomes in BRAF V600E-mutated colorectal cancer, turning a historically poor prognostic marker into a targetable opportunity.

Panelists discuss how dihydropyrimidine dehydrogenase testing remains controversial with institutions debating whether to implement universal pharmacogenomic testing given the challenges of standardization, genotype-phenotype correlation, and low incidence of severe deficiency.

John L. Marshall, MD; Marwan G. Fakih, MD; Arvind N. Dasari, MD, MS; and Katrina S. Pedersen, MD, discuss how precision medicine has transformed metastatic colorectal cancer treatment through comprehensive molecular testing, targeted therapies like BRAF/EGFR inhibition and immunotherapy combinations for microsatellite instability-high tumors, and personalized approaches to treatment sequencing and dosing modifications that balance efficacy with quality of life considerations.

Katrina S. Pedersen, MD, MS, discusses key updates in the therapeutic landscape for patients with molecularly targetable metastatic colorectal cancer.

Katrina S. Pedersen, MD, MS, discusses the evolution of the role of immunotherapy in the treatment of patients with hepatocellular carcinoma.

Katrina S. Pedersen, MD, MS, discusses the evolving use of cytoreductive surgery for patients with peritoneal carcinomatosis.

Katrina S. Pedersen, MD, MS, discusses key updates and FDA approvals from 2023 in metastatic colorectal cancer.