This study evaluates the efficacy and safety of surgical intervention in patients with focally progressive GISTs after imatinib treatment. The enrolled patients will be randomized to receive surgery following imatinib 400 milligram per day (MG/d) or only tyrosine kinase inhibitor (Imatinib 600 MG/d or Sunitinib 37.5 MG/d).

Imatinib is the first-line treatment for advanced GIST with a satisfactory response rate, but complete remission rarely happens. Besides, drug resistance can occur during the treatment and the median time of drug resistance is about 20-24 months. Once drug resistance occurs, the patient's condition will progress rapidly. As a salvage treatment, the effect of increasing the dose of imatinib or switching to sunitinib is very limited. Progress after imatinib treatment usually involves two conditions, focal progression and extensive progression. For local progression, all resistant lesions can be completely resected; extensive progression refers to resistance progression in multiple sites, and progressive lesions cannot be completely removed. The present study is aimed to assess the benefits of surgical resection of imatinib-resistant lesions in patients with localized disease.

Inclusion Criteria:

1. Patients whose pathology is clearly diagnosed as recurrent/metastatic GIST, have undergone standardized imatinib treatment, and the disease progresses during the treatment;
2. The lesions with progress are confined to one organ, and the number is ≤3; after evaluation by relevant professional surgeons or multidisciplinary team discussion, it is considered that the progressive lesions can be completely and safely removed without affecting the organ function;
3. Age: 18 years old ≤ age ≤ 75 years old;
4. No other malignant tumors occurred within five years;
5. Eastern Cooperative Oncology Group (ECOG) physical status score <2 points;
6. American Society of Anesthesiologists (ASA) score <3 points;
7. There are no restrictions on gender and race;
8. Patients with informed consent.

Exclusion Criteria:

1. The patient has other serious comorbidities and cannot tolerate surgery: such as severe cardiopulmonary disease, cardiac function in grade 2 or lower, pulmonary infection, moderate to severe chronic obstructive pulmonary disease (COPD), etc., combined with severe diabetes and/or kidney Insufficient function, combined with severe hepatitis and/or functional Child-pugh grade C or a grade B that is clearly difficult to correct, combined with severe malnutrition;
2. Patients with extensive disease progress;
3. Imatinib primary resistant patients;
4. Patients with other diseases requiring simultaneous surgical intervention, such as gallstones; inguinal hernia;
5. Disease-related complications such as bleeding, perforation, and obstruction;
6. Pregnant or lactating women;
7. The patient has a serious mental illness;
8. Patients with other malignant tumors within five years;
9. The patient has participated in or is participating in other clinical studies or is using other tyrosinekinase inhibitors.