Gastrointestinal Stromal Tumor Treatment Landscape

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NCCN guidelines provide evidence-based treatment recommendations for metastatic gastrointestinal stromal tumors (GISTs), establishing a clear sequential approach based on randomized controlled trials. First-line treatment with imatinib remains the gold standard, followed by sunitinib in second-line, regorafenib in third-line, and ripretinib in fourth-line settings. Recent guideline updates include considerations for ripretinib in the second line for patients intolerant to sunitinib, based on quality-of-life improvements demonstrated in the INTRIGUE study, and potential dose escalation strategies for ripretinib upon progression.

Recent NCCN guideline updates reflect evolving evidence regarding adjuvant imatinib therapy duration for patients with high-risk resected GIST. The standard 3-year adjuvant treatment period has been extended to 6 years based on improved recurrence-free survival data, though overall survival benefits remain under investigation. This extension represents a significant shift in postsurgical management strategies for localized high-risk disease, emphasizing the importance of long-term kinase inhibitor exposure in preventing disease recurrence and optimizing patient outcomes.

Molecular testing remains essential for optimal GIST management, typically performed on tumor tissue through next-generation sequencing to identify primary driver mutations and additional alterations relevant for clinical trials. When tissue sampling is challenging or insufficient, circulating tumor DNA liquid biopsy offers an alternative approach, though it requires an adequate tumor burden for reliable detection. The choice between tissue-based and liquid biopsy approaches depends on clinical circumstances, disease burden, and accessibility, with both methods providing crucial information for treatment selection and monitoring.