Watch-and-wait approach in high-risk locally advanced rectal cancer: outcomes after complete response to total neoadjuvant therapy.

BACKGROUND: In patients with the most advanced stages of high-risk locally advanced rectal cancer (LARC), extensive resections often lead to morbidity and functional impairment. It is unclear whether these patients, despite poor prognosis, are suitable candidates for a watch-and-wait (W&W) approach in cases of a clinical complete response (cCR). METHODS: Consecutive patients with high-risk LARC who underwent total neoadjuvant therapy (TNT), followed by surgery or a W&W approach between January 2016 and February 2023, were retrospectively analysed. High-risk features included tumour invasion into the mesorectal fascia, grade 4 extramural venous invasion, enlarged lateral lymph nodes, or tumour deposits. Patients were categorized into complete response (CR) or non-CR, and stratified by W&W and surgically treated. Outcomes were regrowth, local recurrence, distant metastases (DM), regrowth-free survival, organ survival, local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), recurrence-free survival (RFS) (all death-censored), and overall survival. RESULTS: Of 135 patients, 29 (21.5%) achieved a cCR and entered W&W. A total of 103 patients (78.0%) underwent immediate surgery, including 15 (11.1%) with a pathological CR. Median follow-up was 42 months (range 9-76) for CR patients versus 42.5 months (range 7-82) for non-CR patients. Local recurrence and DM occurred in 1 (2.3%) and 7 patients (15.9%) in the CR group, respectively, versus 14 (15.9%) and 21 patients (23.9%) in the non-CR group, respectively. Three-year death-censored LRFS and DMFS rates were 97.6% and 82.7% in the CR group, respectively, versus 85.8% and 76.0% in the non-CR group, respectively (P = 0.016, P = 0.273). Five-year overall survival was 89.5% in the CR group versus 84.0% in the non-CR group (P = 0.131). Median follow-up was 44 months (range 16-71) in W&W patients and 42 months (range 7-82) in surgically treated patients. Among W&W patients, regrowth occurred in seven patients (24.1%) and the 3-year death-censored regrowth-free survival was 79.2%. Three-year death-censored RFS and 5-year overall survival were 71.9% and 90.9% in W&W patients, respectively, versus 72.3% and 84.2% in surgically treated patients, respectively (P = 0.680, P = 0.115). CONCLUSION: A W&W approach can be considered safe and feasible for patients with high-risk LARC. Achieving a CR after TNT is associated with favourable oncological outcomes.