Oligometastatic GIST: Impact of Treatment Modalities and Metastatic Distribution on Overall Survival

Background/Objectives: Oligometastatic GIST, defined in this study as five or fewer metastatic lesions confined to a single organ, represents a distinct subset with a lower metastatic burden than widely metastatic disease and may have different prognostic and therapeutic considerations. Methods: We reviewed biopsy-proven oligometastatic GIST diagnosed between August 1998 and June 2025 from a prospectively maintained institutional database, collecting genomic, metastatic, treatment, ethnicity, and survival data. Overall survival (OS), calculated from diagnosis of oligometastatic disease, was estimated by Kaplan-Meier analysis and compared using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Results: Of 525 subjects with GIST in our database, 96 (18.3%) had oligometastatic GIST (median age: 54 years; median OS from diagnosis of oligometastatic disease: 9.77 years). Most tested tumors were KIT-positive (91.6%), predominantly harboring KIT exon 11 alterations (69.5%). The most common metastatic sites were the liver (n = 44) and peritoneum (n = 37). Overall, 58 patients underwent surgery, including 55 cytoreductive procedures and 3 emergent operations for bleeding or obstruction. Among the cytoreductive procedures, indications included multifocal disease after tyrosine kinase inhibitor (TKI) response (n = 21), unifocal disease after TKI response (n = 18), unifocal progression on TKI (n = 13), and equivocal or undocumented TKI response (n = 3). Overall survival did not differ by liver versus peritoneal metastases (HR: 1.27; 95% CI, 0.59-2.70; p = 0.540) or Hispanic versus non-Hispanic ethnicity (HR: 0.81; 95% CI, 0.34-1.90; p = 0.624). Cytoreductive surgery combined with systemic therapy was associated with longer overall survival than systemic therapy alone (10.8 vs. 7.4 years; HR: 0.44; 95% CI, 0.22-0.89; p = 0.019). Conclusions: In this retrospective cohort, cytoreductive surgery combined with systemic therapy was associated with longer overall survival than systemic therapy alone.