Increasing age, neural invasion, extramural vascular invasion, and short-course radiotherapy in locally advanced rectal cancer are associated with decreased tumor regression: a retrospective cohort study

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BACKGROUND: We investigated factors associated with pathologic complete response (pCR) and tumor regression grade (TRG) on the basis of clinical and pathological variables and their impact on cancer-free survival (CFS) after surgery for locally advanced rectal cancer (LARC). METHODS: All patients with LARC undergoing neoadjuvant treatment before curative total mesorectal excision surgery were included in a prospective institutional database connected to the National Mortality Registry. One-way analysis of variance and Pearson's chi-squared test were utilized to compare TRG groups. The Kaplan-Meier method and regression models were used to evaluate CFS, radiation modality, and staging factors. RESULTS: Of 700 patients operated on for rectal cancer between 2014 and 2024, 159 (22.7%) had LARC without known systemic cancer. Twenty-seven patients had pCR (TRG 0, 17.0%), 46 TRG 1 (29.0%), 70 TRG 2 (44.0%), and 16 TRG 3 (10%). Poor tumor regression was associated with increasing age (p = 0.009), vascular (p < 0.001) and neural invasion (p = 0.005), less differentiated tumors (p < 0.001), short-course 5 Gy × 5 (p < 0.001) rather than long-course 2 Gy × 25 radiotherapy, and omission of neoadjuvant chemotherapy (p < 0.001). Older age was a predictor of short-course radiotherapy and omission of chemotherapy (p < 0.001). Follow-up time was 46.6 months (IQR 20-80.3 months). No differences were found in CFS between TRG groups 0-3 (p = 0.18), however pCR was associated with improved CFS (p = 0.047). CONCLUSIONS: Decreased tumor regression was associated with reduced radiotherapy and chemotherapy, neural and vascular invasion, poor differentiation, and increasing age. The latter may reflect reduced application of neoadjuvant treatment in older patients. Complete responders experienced increased cancer-free survival.