Next questions on gastrointestinal stromal tumors: unresolved challenges and future directions.

Purpose of review: Despite remarkable progress in the management of gastrointestinal stromal tumors (GISTs), critical challenges persist. Key aspects such as risk stratification, the optimal duration of adjuvant therapy, and strategies to enhance the efficacy of first-line treatment remain subjects of ongoing debate. This review explores emerging concepts and innovative approaches aimed at refining patient selection and optimizing therapeutic decision-making to further improve clinical outcomes.

Recent findings: Molecular and genomic parameters have the potential to enhance traditional risk models, enabling more precise stratification of high-risk patients. Innovations in artificial intelligence and liquid biopsy are emerging as powerful tools for refining predictions of recurrence and treatment response. Meanwhile, the definition and prognostic significance of tumor rupture remain pivotal challenges that influence both risk assessment and adjuvant therapy decisions. Furthermore, transcriptomic and multiomic analyses have unveiled distinct GIST subtypes with significant prognostic and therapeutic implications, paving the way for more tailored treatment strategies.

Summary: Integrating molecular features into clinical decision making may refine risk assessment and personalize the treatment in patients with GIST. Future research should focus on validating these tools and redefine clinical trial designs to accelerate drug development for this rare disease.