The intuition makes sense. Reduce tumor burden, let systemic therapy finish the job. But intuition has a poor track record in oncology. ORCHESTRA just published in JAMA. Phase 3 RCT, 382 patients, multiorgan mCRC. The bar for entry was high. You had to be able to take out more than 80% of disease burden across all sites before randomization. These are the best-case patients. Response or stable disease after 3-4 cycles of CAPOX or FOLFOX, then chemotherapy alone versus chemo plus debulking. Median OS: 27.5 months versus 30.0 months. HR 0.88, 95% CI 0.70-1.10. p = 0.26. PFS essentially identical, 10.4 versus 10.5 months. Serious adverse events significantly higher in the debulking arm, 53% versus 39%. That said, this isn’t the whole story. Symptomatic Krukenberg tumors, oligometastatic disease with curative intent, isolated liver-only disease. Those conversations should still be had. The cytoreductive surgery literature gave us hints this was coming, but the use cases that make biological sense still stand. What changes now? At minimum, “we can get more than 80% of it” is not a sufficient reason on its own. Except in NETs, NETs are weird. jamanetwork.com/journals/jam… @gutonclab @oncoalert