Multicenter randomized trial of tumor debulking with chemotherapy in multiorgan metastatic colorectal cancer

Local therapy, including surgery, radiation, and ablation, is increasingly used in patients with multiorgan metastatic colorectal cancer (mCRC). However, prospective evidence for a survival benefit of tumor debulking is lacking. The randomized ORCHESTRA trial, at 27 centers in The Netherlands and one center in the UK, evaluated tumor debulking in adult patients with multiorgan mCRC in whom more than 80% tumor debulking was deemed feasible by local therapy. After achieving objective response or stable disease to induction chemotherapy with or without bevacizumab, patients were randomized 1:1 to receive chemotherapy alone (standard care group; n=192) or tumor debulking followed by chemotherapy (tumor debulking group; n=190). The primary endpoint was overall survival (OS). After a median follow-up of 32.3 months, median OS was 27.5 months in the standard care group versus 30.0 months in the tumor debulking group (aHR 0.88; p=0.26) whereas the median progression-free survival was 10.4 months versus 10.5 months (aHR 0.83; p=0.08). Serious adverse events were more frequent in the tumor debulking group (39% versus 53%’ p=0.006). The authors conclude that tumor debulking added to first-line palliative systemic treatment failed to significantly improve OS and should not be considered standard care.