[Association between gross tumor regression patterns, distal resection margin distance, and local recurrence in...

Objective: To investigate the associations of macroscopic tumor regression patterns and distal resection margin (DRM) distance with local recurrence in patients with rectal cancer after neoadjuvant chemoradiotherapy (nCRT), and to provide evidence for surgical decision-making and intraoperative assessment of the distal resection extent. Methods: This single-center retrospective cohort study used data from the prospective MONT-R registry. A total of 410 patients with mid-to-low locally advanced rectal cancer who underwent nCRT followed by radical surgery at Peking Union Medical College Hospital between December 2017 and September 2022 were included. Of these, 276 patients were male (67.3%), and the median age was 60 years (interquartile range [IQR], 51-67 years). According to the gross appearance of postoperative specimens, tumors were classified as scar-like, ulcerative, or protruding mass-type patterns. Clinicopathological characteristics, DRM distance, and the incidence of inadequate DRM, defined as DRM ≤0.5 cm, were compared among groups. Disease-free survival (DFS) and local recurrence-free survival (LRFS) were analyzed using the Kaplan-Meier method. Results: Of the 410 patients, 42 (10.2%) had scar-like tumors, 360 (87.8%) had ulcerative tumors, and 8 (2.0%) had protruding mass-type tumors. The lymph node metastasis rate differed significantly among groups (χ²=8.63, P=0.013), with no lymph node metastasis observed in the scar-like group, compared with 17.2% (62/360) in the ulcerative group and 1/8 in the protruding mass-type group. Pathological tumor diameter also differed significantly among groups (H=11.82, P=0.003) , with the mass-type showing the largest diameter [median (Q1, Q3): 2.9 (2.3, 4.0) cm], whereas no obvious difference was observed between the ulcerative type [2.0 (1.3, 2.5) cm] and the scar-like type [1.5 (1.2, 2.0) cm]. The distributions of ypT stage, perineural invasion, and lymphovascular invasion did not differ significantly among groups (all P>0.05). Only 4 patients had a positive circumferential resection margin; all of whom were in the ulcerative group. The proportions of CAP 0-1 tumor regression and pathological complete response were higher in the scar-type group than in the other groups, but the differences were not statistically significant (P=0.098 and P=0.081, respectively). The median DRM distances in the scar-type, ulcerative-type, and protruding mass-type groups were 1.15 (0.20, 2.00) cm, 1.70 (1.00, 2.75) cm, and 2.55 (1.38, 3.62) cm, respectively, with a significant difference among groups (H=9.67, P=0.008). The incidence of inadequate DRM was significantly higher in the scar-type group than in the ulcerative-type and protruding mass-type groups [38.1% (16/42) vs. 15.3% (55/360) vs. 1/8; χ²=13.67, P=0.001]. During a median follow-up of 51 months (IQR, 36-64 months), no significant differences were observed in DFS (P=0.947) or LRFS (P=0.175) among the three groups. Similarly, DFS (P=0.731) and LRFS (P=0.131) did not differ significantly between patients with inadequate and adequate distal resection margins. Conclusions: After nCRT for rectal cancer, patients with a scar-like macroscopic tumor regression pattern had a lower risk of lymph node metastasis and a shorter DRM. However, in the setting of standardized total mesorectal excision, a shorter DRM was not associated with adverse survival outcomes.