Prognostic Significance of Desmoplastic Reaction After Neoadjuvant Chemoradiotherapy in Advanced Rectal Cancer

BACKGROUND: Desmoplastic reaction is recognized as a prognostic factor in colorectal cancer. However, its significance in locally advanced rectal cancer following neoadjuvant chemoradiotherapy remains underexplored. OBJECTIVE: To assess the prognostic value of desmoplastic reaction in specimens from patients with advanced rectal cancer after chemoradiotherapy. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at a single comprehensive cancer center. PATIENTS: The study included 255 patients with advanced rectal cancer who underwent fluoropyrimidine-based chemoradiotherapy followed by total mesorectal excision from 2005 to 2014. Desmoplastic reaction was classified into mature, intermediate, and immature categories based on histological analysis. MAIN OUTCOMES: The primary outcomes were recurrence-free survival and overall survival. RESULTS: Desmoplastic reaction was classified as mature (69.0%), intermediate (5.5%), or immature (25.5%). The mature group had a higher percentage of good responders (34.1%) compared with the intermediate (0%) and immature (4.6%) groups ( p < 0.0001). The mature group correlated with better outcomes, with a higher 5-year recurrence-free survival (85.4%) and overall survival (93.0%) as compared with intermediate (45.1% and 76.2%, respectively) and immature (65.8% and 88.8%, respectively) groups. In the multivariable analysis, intermediate/immature desmoplastic reaction was significantly associated with poorer recurrence-free survival ( p = 0.03). Among poor responders, intermediate/immature desmoplastic reaction was associated with poorer recurrence-free survival ( p = 0.03). Adjuvant chemotherapy did not significantly improve the 5-year recurrence-free survival rate for the mature group (adjuvant chemotherapy vs. no chemotherapy, 86.4% vs. 84.8%; p = 0.64), with worse trends observed in the intermediate/immature combined group (55.9% vs. 69.4%, respectively, p = 0.27). LIMITATIONS: The limitations include the subjective nature of desmoplastic reaction assessment and the study's retrospective design. CONCLUSIONS: Desmoplastic reaction in surgical specimens post-chemoradiotherapy is associated with responses to chemoradiotherapy and serves as a significant prognostic factor in advanced rectal cancer, particularly for those responding poorly to chemoradiotherapy. See Video Abstract .