Surgery for metastatic gastrointestinal stromal tumor: to whom and how to?

Although imatinib is a standard treatment for metastatic or recurrent gastrointestinal stromal tumors (GISTs), acquired c-kit mutations reportedly cause secondary resistance to imatinib. Sunitinib is a tyrosine kinase inhibitor (TKI) that can be used as second-line therapy in imatinib-resistant or -intolerant GISTs. For sunitinib-resistant or -intolerant GISTs, regorafenib is a standard third-line treatment. Although TKI therapies have revolutionized the treatment of recurrent or metastatic GISTs, they cannot cure GISTs. Therefore, in the era of TKIs, role of cytoreductive surgery for recurrent or metastatic GISTs has been discussed. Retrospective studies of treatment strategies with front-line surgery prior to imatinib have shown that initial cytoreduction confers no benefit in cases of advanced or recurrent GIST, and administering imatinib is the principle treatment. Most retrospective studies report cytoreductive surgery to be feasible in patients with metastatic GIST whose disease is stable or responsive to imatinib. Cytoreductive surgery may be indicated in limited disease progression refractory to imatinib when complete resection is possible, but case selection is critical. Cytoreductive surgery for metastatic GIST treated with sunitinib seems less feasible because of high rates of incomplete resections and complications. The role of cytoreductive surgery for metastatic GISTs would be difficult to establish in a prospective study; individualized treatments need to be carefully designed based on c-kit and platelet-derived growth factor receptor alpha (PDGFRA) mutations and other factors.