In rectal cancer, the type of desmoplastic response after preoperative chemoradiotherapy is associated with prognosis

Although the essential contribution of the desmoplastic reaction (DR) to aggressive tumor behavior is increasingly recognized, its prognostic value has not been investigated in rectal cancer after preoperative chemoradiotherapy. We retrospectively analyzed 101 consecutive patients with rectal cancer treated with short-course chemoradiotherapy followed by surgery (2001–2007). The DR in the resected primary tumor was pathologically classified into three patterns on the basis of products of cancer-associated fibroblasts (CAFs): mature (multilayered fibrotic), intermediate (keloid-like hyalinized), and immature (mostly myxoid). We classified 46 tumors as mature, 30 as intermediate, and 25 as immature DR. In addition, immunostaining of CD8⁺ and FoxP3⁺ cells was performed to characterize the immune response accompanying DR. Mature DR correlated with higher density of CD8⁺ and FoxP3⁺ cells in both resected surgical and pretreatment biopsy specimens. A significant association with DR category was observed for T stage, lymphatic invasion, and venous invasion (P ≤ 0.0001–0.0006). Mature DR was significantly associated with higher grade of pathological response (P = 0.0350). The 5-year disease-free survival (DFS) rates were 82, 72, and 47 % for mature, intermediate, and immature DR, respectively (P = 0.0055). On multivariate analysis, DR category and ypN were independently predictive of DFS. The pattern of the DR in rectal cancers after chemoradiotherapy treatment might have a prognostic value, as it likely reflects pretreatment desmoplastic environment.