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.