Imatinib-resistant gastrointestinal stromal tumors in the era of second- and third-line tyrosine kinase inhibitors: Does surgical resection have a role?

BACKGROUND: Imatinib resistance is associated with a poor prognosis in patients with gastrointestinal stromal tumors. Although novel tyrosine kinase inhibitors have improved outcomes in imatinib-resistant gastrointestinal stromal tumors, the role of resection remains unclear. We sought to investigate factors predictive of overall and progression-free survival in patients with imatinib-resistant gastrointestinal stromal tumors. METHODS: A query of our prospectively maintained Comprehensive Cancer Center registry was performed from 2003 to 2019 for patients with imatinib-resistant gastrointestinal stromal tumors. Clinicopathologic characteristics and medical and surgical treatments were collected; overall survival and progression-free survival after imatinib-resistance were analyzed with Kaplan-Meier and Cox proportional hazards modeling. RESULTS: A total of 84 patients developed imatinib resistance at a median age of 59 years. Median time to imatinib resistance after diagnosis and overall survival after imatinib resistance was 50 and 51 months, respectively. After being diagnosed with imatinib resistance, 17 (20%) patients underwent resection. On multivariable analysis, resection after imatinib resistance was independently associated with improved progression-free survival (hazard ratio 0.50; P = .027) but not overall survival (hazard ratio 0.62; P = .215). Similar findings were found on subgroup analysis of patients treated with second-line sunitinib (n = 71). CONCLUSION: Long-term survival can be achieved in patients who develop imatinib-resistant gastrointestinal stromal tumors. Surgical resection of imatinib-resistant gastrointestinal stromal tumors is associated with improved progression-free survival and should be considered in selected patients.