Neoadjuvant Imatinib Therapy in Rectal Gastrointestinal Stromal Tumors: A Comprehensive Narrative Review of Tumor Downsizing, Sphincter Preservation, Transanal Surgical Platforms, Functional Outcomes, and Survival.
Raja Naga Praneeth NP, Kandagari Nagapavani N
Rectal gastrointestinal stromal tumors (GISTs) represent approximately 5-8.5% of all GISTs and pose unique surgical challenges due to the confined pelvic anatomy and proximity to the anal sphincter complex. Historically, radical surgery - including abdominoperineal resection (APR) or pelvic exenteration - was frequently required for complete tumor clearance, resulting in permanent colostomy and significant functional morbidity. The introduction of imatinib mesylate, a selective tyrosine kinase inhibitor (TKI) targeting KIT and PDGFRA, has fundamentally transformed the management of rectal GIST. Neoadjuvant imatinib therapy achieves significant tumor downsizing (25-46% reduction), reduces mitotic activity, and enables sphincter-preserving surgery in patients who would otherwise require radical resection. The concurrent evolution of transanal endoscopic platforms - including transanal endoscopic microsurgery (TEM), transanal minimally invasive surgery (TAMIS), and robotic TAMIS (R-TAMIS) - has further expanded the possibilities for organ preservation, achieving R0 resection rates of 89-100% with favorable functional outcomes and preserved fecal continence. Emerging evidence also suggests improvements in distant recurrence-free survival, disease-specific survival, and overall survival compared with upfront surgery. This comprehensive narrative review examines the rationale, efficacy, response assessment, surgical implications, the role of transanal surgical platforms, functional outcomes, quality of life, survival outcomes, and current guideline recommendations for neoadjuvant imatinib in rectal GIST.