The administration of neoadjuvant chemoradiotherapy (nCRT) followed by total mesorrectal excision (TME) and selective use of adjuvant chemotherapy can still be considered the standard of care in locally advanced rectal cancer (LARC). However, avoiding sequelae of TME and entering a narrow follow-up program of watch and wait (W&W), in select cases that achieve a comparable clinical complete response (cCR) to nCRT, is now very attractive to both patients and clinicians. Many advances based on well-designed studies and long-term data coming from big multicenter cohorts have drawn some important conclusions and warnings regarding this strategy. In order to safely implement W&W, it is important consider proper selection of cases, best treatment options, surveillance strategy and the attitudes towards near complete responses or even tumor regrowth. The present review offers a comprehensive overview of W&W strategy from its origins to the most current literature, from a practical point of view focused on daily clinical practice, without losing sight of the most important future prospects in this area.

PURPOSE: Organ preservation has become an attractive alternative to surgery (total mesorectal excision [TME]) among patients with rectal cancer after neoadjuvant therapy who achieve a clinical complete response (cCR). Nearly 30% of these patients will develop local regrowth (LR). Although salvage resection is frequently feasible, there may be an increased risk for development of subsequent distant metastases (DM). The aim of this study is to compare the risk of DM between patients with LR after Watch and Wait (WW) and patients with near-complete pathologic response (nPCR) managed by TME at the time of reassessment of response. METHODS: Data from patients enrolled in the International Watch & Wait Database (IWWD) with cCR managed by WW and subsequent LR were compared with patients managed by TME (with ≤10% cancer cells—nPCR) from the Spanish Rectal Cancer Project (VIKINGO project). The primary end point was DM-free survival at 3 years from decision to WW or TME. The secondary end point was possible risk factors associated with DM. RESULTS: Five hundred and eight patients with LR were compared with 893 patients with near-complete response after TME. Overall, DM rate was significantly higher among LRs (22.8% v 10.2%; P ≤ .001). Independent risk factors for DM included LR ( v TME at reassessment; P = .001), ypT3-4 status ( P = .016), and ypN+ status ( P = .001) at the time of surgery. 3-year DM-free survival was significantly worse for patients with LR (75% v 87%; P = .001). When stratified for pathologic stage, patients with LR did significantly worse through all stages ( P ≤ .009). CONCLUSION: Patients with LR appear to have a higher risk for subsequent DM development than patients with nPCR managed by TME at restaging irrespective of final pathology. Leaving the primary undetectable tumor in situ until development of LR may result in worse oncologic outcomes.