MATTERHORN Spotlight—Shaping the Treatment Horizon for Gastric/Gastroesophageal Junction (GEJ) Cancers - Episode 2
Perioperative Therapy In GC/GEJC: Challenges and Unmet Needs
Panelists discuss how perioperative FLOT chemotherapy has simplified treatment decisions but presents toxicity challenges for patients with comorbidities, while emphasizing the critical importance of laparoscopic staging and acknowledging that current approaches still fail to cure approximately half of patients.
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Perioperative chemotherapy has become the standardized approach for gastric cancers (GC) and gastroesophageal junction cancers (GEJC), simplifying treatment decisions by eliminating the historical debate over radiation therapy inclusion. All patients with resectable gastric and GEJ tumors now receive perioperative FLOT chemotherapy as the standard approach. However, FLOT presents significant challenges as not all patients are suitable candidates due to its substantial toxicity profile and the complexity of administering this intensive regimen to patients with comorbidities. Medical oncologists require a learning curve to identify appropriate candidates and safely modify the regimen, when necessary, as the primary goal is ensuring patients reach surgery several months later while effectively treating micrometastatic disease.
Despite the implementation of effective chemotherapy and advanced surgical techniques, cure rates remain disappointingly low, with many patients still experiencing recurrence. This persistent challenge highlights the critical unmet need for more effective strategies to target micrometastatic disease and reduce recurrence rates. The heterogeneous nature of GC compounds these challenges, with different subtypes including intestinal-type and diffuse-type cancers presenting varying treatment responses and prognosis. Signet ring cell variants are particularly difficult to treat and often associated with poor outcomes.
From a surgical perspective, several unmet needs persist, including the challenge of late-stage presentation due to unreliable early symptoms and a lack of screening programs in most countries. Appropriate staging remains controversial but crucial, with laparoscopic staging being essential yet not universally performed. This staging procedure helps determine disease extent, treatment goals, and appropriate therapeutic approaches. Additionally, standardization of surgical techniques is critical, as GC operations require extended lymphadenectomy and specialized oncologic approaches that differ significantly from benign gastrectomy procedures, emphasizing the importance of high-quality cancer-specific surgical care.
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