Evolving Molecular Profiling and Liquid Biopsy Practices Guide First-Line CRC Therapy Decisions: With Chandler Park, MD; and Midhun Malla, MD

In this episode of MedNews Week's Oncology Unplugged, host Chandler Park, MD, a medical oncologist at Norton Cancer Institute in Louisville, Kentucky, was joined by Midhun Malla, MD, a gastrointestinal oncologist and associate professor of medicine—hematology & oncology at the University of Alabama at Birmingham School of Medicine, to discuss evolving approaches to colorectal cancer (CRC) management, with a focus on circulating tumor DNA (ctDNA), adjuvant therapy decision-making, and molecular profiling in metastatic disease.

Drs Park and Malla began by talking through the clinical utility of ctDNA in patients with stage II and III colon cancer. Dr Malla referenced the DYNAMIC (ACTRN12615000381583) and observational BESPOKE CRC (NCT04264702) trials, noting that ctDNA serves as a prognostic biomarker for recurrence and is increasingly used to guide post-surgical surveillance.

They also addressed clinical nuances in managing stage II T4 tumors, which Dr Malla identified as being at high risk for peritoneal spread—an anatomical site less likely to shed detectable ctDNA. For such patients, he supports offering adjuvant chemotherapy irrespective of ctDNA results. When the discussion turned to stage III disease, Dr Malla drew on evidence from the IDEA collaboration to recommend 3 months of capecitabine and oxaliplatin for low-risk patients, including those who are elderly but have preserved performance status.

In the metastatic setting, Drs Park and Malla highlighted the expanding role of next-generation sequencing and liquid biopsy. Dr Malla advocated for dual tissue-based and plasma-based testing to capture tumor heterogeneity and accelerate actionable insights. He emphasized the importance of rapid molecular profiling in guiding first-line therapy decisions, particularly in patients with BRAF V600E–mutant tumors.