Prognostic and predictive value of desmoplastic reaction in colorectal cancer: a multicenter retrospective study

Abstract

Abstract Background Desmoplastic reaction (DR) is a part of tumor-host reactions reflecting the maturity of tumor stroma. It is confirmed a promising prognostic factor in colorectal cancer (CRC) but further validation in large multicenter samples is needed, and the predictive value of DR type in adjuvant therapy (ACT) in CRC is still unclear. Methods A total of 2225 CRC patients from five independent institutions were divided into primary (N = 1012, from two centers) and validation (N = 1213, from three centers) cohorts. DR types were classified as immature, middle, or mature depending on the presence of hyalinized collagen bundles and myxoid stroma at the invasive front of the primary tumor. The overall survival among diverse DR types were compared using survival analysis. The correlation of DR types with tumor infiltrating lymphocytes (TILs) within stroma was analyzed using artificial intelligence-based method. Results In primary cohort, patients with mature DR had the highest 5-year survival rate (85.5% [mature], 75.3% [middle], 65.2% [immature]; hazard ratio for immature vs mature 3.01; 95% CI 2.24–4.04; P < 0.001). These findings were confirmed in validation cohort. Additionally, for stage II CRC, patients classified as non-mature DR would benefit from ACT compared with surgery alone (P = 0.035). Furthermore, immature and middle DR were associated with less distribution of TILs within stroma compared to mature (P < 0.0001). Conclusions DR type reflecting the maturity of tumor stroma is a strong independent prognosis factor for CRC patients. For stage II CRC patients, non-mature DR could be a potential marker for recognizing high-risk patients who may be benefited from ACT.