Role of Operative Therapy in Treatment of Metastatic and/or Recurrent Gastrointestinal Stromal Tumors

Abstract

Introduction: Operative resection of metastatic and recurrent gastrointestinal stromal tumor (GIST) is controversial. Current treatment strategies rely on response to systemic tyrosine kinase inhibitor therapies with individualized utilization of operative intervention. We investigated the role of operative therapy in patients with metastatic and/or recurrent GIST. Methods: This retrospective cohort study included all consecutive patients treated for metastatic and/or recurrent GIST between January 2002 and June 2011. Patients were stratified by use of operative therapy and by disease response to tyrosine kinase inhibitor (partial response; stable disease; progressive disease). Kaplan-Meier survival analyses with log-rank comparisons tested the effects of operative therapy and response to targeted systemic therapy on survival. Results: of 438 patients treated for GIST during the study period, 87 patients (mean age 60±14 years, 55% male) had metastatic and/or recurrent GIST (84% metastatic, 3% recurrent, 13% metastatic and recurrent). Half of these patients (n=43) had metastatic disease at the time of original diagnosis. Median time to development of metastases/recurrence in the other 44 patients was 29 months (IQR: 13-61 months). 54 of the 87 patients (62%) underwent operative exploration. Peri-operative mortality was zero. R2 subtotal resections for palliative debulking were performed in 19 patients (22%); 35 patients had gross total resections. Operative intervention was associated with improved disease-specific survival compared to systemic therapy alone (1-year: 98% vs. 80%; 5-year: 65% vs. 11%, p<0.001). One- and five year disease-specific survival after R2 resections (95% and 26%, respectively) did not differ from those patients treated non-operatively (p=0.190). A tyrosine kinase inhibitor was used before resection in 32 patients (59%) for a median of 7 months (IQR: 3-13 months): disease response was partial in 13 patients, stable in 10, and progressive in 9. One- and five year disease-specific survival was strongly associated with preoperative disease response to tyrosine kinase inhibitor (partial response: 100% and 100%; stable disease: 100% and 42%; progressive disease: 89% and 11%, respectively, p<0.001). Patients selected for metastasectomy (n=22) without preoperative tyrosine kinase therapy had similar disease-specific 1- and 5- year survival (95% and 87%, respectively) to patients with partial response (p=0.695) and better disease-specific survival than patients with stable disease (p=0.022). Conclusions: Patients with partial response or stable disease with tyrosine kinase inhibitor therapy demonstrate improved survival associated with operative treatment of recurrent or metastatic GIST. There is no survival benefit among patients who develop progressive disease on tyrosine kinase inhibitor or patients undergoing R2 resection.