Interpreting Endpoints and Pathologic Response: Applying EFS, PCR, and Biomarkers in Perioperative Decision Making

This segment examines how event-free survival, overall survival, and pathologic response measures inform clinical interpretation of the MATTERHORN trial. The discussion begins with an overview of the study’s statistical hierarchy and alpha allocations, providing context for how efficacy signals were evaluated. The panel considers whether EFS is an appropriate primary endpoint in locally advanced, resectable disease, noting that while OS remains the definitive measure of benefit, EFS also reflects meaningful clinical outcomes by capturing recurrence, progression, and surgical complications that directly affect patient experience. The conversation then explores how pathologic complete response serves as an early indicator of favorable prognosis and can influence discussions about postoperative therapy, even though PCR does not fully replace long-term survival data. The panel describes how they counsel patients on PCR, R0 resection, and nodal status after surgery and how biomarkers, including ctDNA, PD-L1, MSI/MMR, HER2, and CLDN18.2, may eventually guide duration of adjuvant immunotherapy. The segment highlights ongoing uncertainty about whether all patients require a full year of postoperative treatment, especially those with deep responses or toxicity concerns.