A review of the surgical management of metastatic gastrointestinal stromal tumours (GISTs) on imatinib mesylate (Glivec™)

Gastrointestinal stromal tumours (GISTs) are defined as a group of C-KIT positive mesenchymal tumours of the gastrointestinal tract. Although they may arise throughout the gut, the commonest sites are stomach and small intestine. Over 80% of metastases are to the liver and omentum. Targeted therapy (imatinib) can inhibit C-KIT and thereby aberrant tumoural proliferation. Imatinib may induce shrinkage of lesions and cystic change. Such physical changes often correspond with reduced metabolic activity demonstrated by 18-FDGPET scans. These changes may enable metastatectomy reducing tumour pain and the risk of haemorrhage and rupture in the short term. In the long term, resection may lessen the risk of recurrence by removing potentially resistant clones. The precise role of palliative resection for GIST metastases on imatinib remains unclear. Imatinib has changed the natural history of metastatic GISTs, with increased survival times. Surgery remains an important management strategy in the metastatic setting because complete pathological responses are rare with imatinib. Surgery is likely to provide the best palliation, greatest reduction in tumour burden and eliminate resistant clones. A multidisciplinary team approach with expertise concentrated in a few centres specialising in the management of these rare tumours is vital to the successful outcome. Future issues regarding the management of differential response of the metastases to imatinib are highlighted. With the emergence of techniques enabling identification of the precise mutational status of the C-KIT oncogene, the imatinib/surgery sequence could be tailored to the type of C-KIT mutation.