Threshold association analysis between residual tumour size and distant metastasis risk after neoadjuvant therapy for rectal cancer: A multicentre retrospective study

PURPOSE: This study aimed to perform a threshold analysis of residual tumour size (RTS) to identify the critical threshold influencing distant metastasis (DM), thereby enabling more precise risk stratification. METHODS: This multicentre retrospective cohort study included patients with locally advanced rectal cancer who underwent radical surgery following neoadjuvant chemoradiotherapy (nCRT). Kaplan-Meier survival curves were plotted and compared using the log-rank test. Multivariable Cox proportional hazards models were used to identify independent prognostic factors. The threshold-effect analysis was performed to determine the potential critical point of RTS. RESULTS: In this multi-institutional study, threshold-effect analysis identified a significant inflection point at 3 cm for the association between RTS and DM risk. Below this threshold, each 1-cm increase was associated with a markedly higher risk (HR = 1.70, p = 0.015), whereas no significant association was observed above 3 cm (p = 0.692). Patients with an RTS ≥3 cm exhibited significantly poorer early (≤ 24 months) recurrence-free survival (RFS) and disease-free survival (DFS). After 24 months, the pattern was reversed. RTS ≥3 cm was an independent risk factor for both worse RFS (HR = 1.45, p = 0.033) and DM. Subgroup analyses confirmed the consistent negative prognostic impact of RTS ≥3 cm across most strata. CONCLUSIONS: This study established an objective prognostic threshold for RTS following nCRT. This marks a shift in the understanding of this indicator-from a static association between 'risk and size' to a dynamic association between 'risk and time'.