What are the most important prognostic factors in patients with residual rectal cancer after preoperative chemoradiotherapy?

BACKGROUND: We aimed to establish robust histoprognostic predictors on residual rectal cancer after preoperative chemoradiotherapy (CRT). METHODS: Analyzing known histoprognostic factors in 146 patients with residual disease allows associations with patient outcome to be evaluated. RESULTS: The median follow-up time was 77.8 months, during which 59 patients (40.4%) experienced recurrence and 41 (28.1%) died of rectal cancer. On univariate analysis, residual tumor size, ypT category, ypN category, ypTNM stage, downstage, tumor regression grade, lymphatic invasion, perineural invasion, venous invasion, and circumferential resection margin (CRM) were significantly associated with recurrence free survival (RFS) or/and cancer-specific survival (CSS) (all p<0.005). On multivariate analysis, higher ypTNM stage and CRM positivity were identified as independent prognostic factors for RFS (ypTNM stage, p=0.024; CRM positivity, p<0.001) and CSS (p=0.022, p=0.017, respectively). Furthermore, CRM positivity was an independent predictor of reduced RFS and CSS, irrespective of subgrouping according to downstage (non-downstage, p<0.001 and p<0.001; downstage, p=0.002 and p=0.002) or lymph node metastasis (non-metastasis, p<0.001 and p=0.001; metastasis, p<0.001 and p<0.001). CONCLUSION: CRM status may be as powerful as ypTNM stage as a prognostic indicator for patient outcome in patients with residual rectal cancer after preoperative CRT.