Key Takeaways and Future Questions in Perioperative GC/GEJC

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The key clinical takeaways from MATTERHORN center on establishing D-FLOT as the new standard perioperative chemotherapy for gastric and gastroesophageal (GEJ) adenocarcinomas, replacing historical chemoradiation approaches and FLOT monotherapy. Critical to successful implementation is appropriate patient staging, particularly laparoscopic staging, which remains underutilized despite being recommended in NCCN guidelines and proving essential for accurate disease assessment and treatment planning. Multidisciplinary evaluation and risk stratification early in the diagnostic process are fundamental to delivering optimal care and avoiding treatment of patients with more advanced disease than initially appreciated.

The application of D-FLOT extends logically to esophageal adenocarcinomas, representing a comfortable extrapolation given the biological similarity between distal esophageal, GEJ, and proximal gastric cancers (GC). From a medical oncology perspective, these represent the same disease process despite requiring different surgical approaches and involving different surgical specialists depending on tumor location above or below the GEJ. This biological similarity, combined with the superior outcomes demonstrated by FLOT over chemoradiation in previous trials, supports the broad application of D-FLOT across the spectrum of esophagogastric adenocarcinomas.

Looking forward, several important questions remain open for investigation, including the potential for nonoperative approaches in patients achieving complete pathologic responses, particularly given the approximately 20% complete response rate observed with D-FLOT. However, organ preservation should remain within clinical trial settings for microsatellite-stable patients until appropriate assessment tools are validated. The continued challenge of poorly differentiated, signet ring cell tumors that show limited response to current therapies represents an important area needing focused research attention. Future development will likely emphasize increasingly personalized approaches incorporating targeted therapies, improved biomarker utilization, and potentially novel treatment sequencing strategies to further improve outcomes beyond the significant advancement represented by MATTERHORN.