Adjuvant treatment of gastrointestinal stromal tumors (GIST)-state of the art, controversies, and future directions.

Adjuvant treatment of gastrointestinal stromal tumors (GISTs) with imatinib has improved recurrence-free survival in patients at high risk of relapse after complete surgical resection. Nevertheless, its impact on overall survival (OS) remains limited, and optimal patient selection and treatment duration remain subjects of ongoing debate. Current risk stratification relies on tumor size, mitotic count, anatomical location, and tumor rupture, yet these factors incompletely capture the biological heterogeneity of GISTs. In particular, intermediate-risk disease represents a heterogeneous group for which the benefit of adjuvant therapy remains uncertain and requires individualized decision-making. Molecular profiling has become an essential component of GIST management. Mutations in KIT and platelet-derived growth factor receptor alpha (PDGFRA) provide important prognostic and predictive information. KIT exon 11 mutations are associated with the greatest sensitivity to imatinib, whereas exon 9 mutations and non-KIT/PDGFRA GISTs exhibit distinct biological behavior and therapeutic responses. Tumor rupture is consistently associated with a high risk of recurrence, although optimal treatment strategies are not clearly established. Three years of adjuvant imatinib is currently considered the standard of care for high-risk GISTs. Nevertheless, recurrence frequently occurs after treatment discontinuation, particularly in very high-risk patients. Emerging evidence suggests that prolonged therapy may improve progression-free survival in selected subgroups, although a clear OS benefit has not been demonstrated. Future advances in risk stratification are expected to integrate molecular, multiomics, and artificial intelligence-based approaches to better identify patients most likely to benefit from adjuvant therapy, personalize treatment duration, and minimize overtreatment in localized GISTs. A comprehensive literature review was conducted using PubMed and major oncology congress resources. The search focused on English-language studies investigating adjuvant therapy duration, risk stratification, mutational profiling, and long-term outcomes in localized GISTs. Priority was given to randomized phase II/III trials, pivotal observational studies, and current international guideline recommendations.