From Control to Conversion: Optimizing Systemic Therapy for Curative-Intent Conversion Surgery in Metastatic Gastric Cancer

Abstract

Conversion therapy enables curative-intent resection in patients with initially unresectable or metastatic cancers after effective systemic therapy. Recently, advances in systemic therapy with molecular targeted agents and immune checkpoint inhibitors (ICIs) have renewed clinical and research interest in this approach, particularly for metastatic gastric cancer (GC). This review aimed to summarize the international guidelines and expert consensus informed by contemporary evidence on conversion therapy for metastatic GC, emphasizing the central role of systemic therapy, the emergence of biomarker-driven strategies, and the optimal timing for surgical intervention. Key consensus statements (Bertinoro, OMEC, and KINGCA WEEK 2024) and pivotal studies covering the cytotoxic, targeted, and immunotherapy eras were reviewed, focusing on regimen selection, treatment duration, and prognostic determinants associated with surgical outcomes. According to global guidelines, conversion surgery is not yet standard of care but may be considered for biologically and clinically selected patients demonstrating a major response to systemic therapy. Retrospective and prospective studies have reported a median overall survival of 24-36 months in the cytotoxic era and >48 months in the ICI/targeted era among patients who underwent R0 resection. Emerging evidence supports approximately 6 months of preoperative systemic therapy, followed by R0 resection, and up to one year of postoperative maintenance therapy. Therefore, conversion surgery should be viewed as the culmination of effective systemic therapy rather than as a substitute. A biology-driven, multidisciplinary strategy integrating treatment response assessment and prognostic factor evaluation represents the next frontier in potentially curative management of metastatic GC.