This is a great read on watch & wait in rectal cancer. B/c patients with local regrowth after WW have higher rates of distant mets, there has been an intuitive fear that regrowth is causal (i.e delaying TME permits metastatic seeding hence WW risky). The authors here argue (and I agree) that regrowth/metastases are manifestations of intrinsic aggressive tumor biology because: 1) no difference in time to surgery in patients w pCR/regrowth who developed mets vs. those who didn't (if delay were causal, would expect longer delay in patients who developed M1). 2) in OPRA secondary analysis, patients with cCR underwent least surgery/longest observation while those with incomplete response had surgery most frequently/immediately. But outcomes still tracked with response phenotype not timing of surgery (i.e. cCR did best). 3) tumor response itself is prognostic (i.e. even when all pts undergo TME, more regression after neoadjuvant therapy --> better DFS/DM). 4) modern tumor evolution data suggest metastatic spread mostly happens early. 5) chemo/radioresistance appears to be linked to metastatic potential (i.e. regrowth is a marker of aggressive biology not the mechanism itself). IMO a persuasive argument against hypothesis that regrowth seeds metastasis, but rather biology=dominant driver. @OncoAlert