Prognostic value of desmoplastic reaction characterisation in stage II colon cancer: prospective validation in a Phase 3 study (SACURA Trial)

Abstract

Background The characterisation of desmoplastic reaction (DR) has emerged as a new, independent prognostic determinant in colorectal cancer. Herein, we report the validation of its prognostic value in a randomised controlled study (SACURA trial). Methods The study included 991 stage II colon cancer patients. DR was classified by the central review as Mature, Intermediate or Immature based on the presence of hyalinised collagen bundles and myxoid stroma at the desmoplastic front. All clinical and pathological data, including DR characterisations, were prospectively recorded and analysed 5 years after the completion of the registration. Results The five-year relapse-free survival (RFS) rate was the highest in the Mature group (N = 638), followed by the Intermediate (N = 294) and Immature groups (N = 59). Multivariate analysis revealed that DR classification was an independent prognostic factor, and based on Harrell’s C-index, the Cox model for predicting RFS was significantly improved by including DR. In the conditional inference tree analysis, DR categorisation was the first split factor for predicting RFS, followed by T-stage, microsatellite instability status and budding. Conclusions Histological categorisation of DR provides important prognostic information that could contribute to the efficient selection of stage II colon cancer patients who would benefit from postoperative adjuvant therapy.

Histopathological atlas of desmoplastic reaction characterization in colorectal cancer

“…The prognostic value of the DR characterization was also assessed in the prospective randomized SACURA (surgical adjuvant chemotherapy with UFT for curatively resected stage II colon cancer) trial ( 9 ). As a result, the DR classification was demonstrated to play an essential role in a prognostic model predicting relapse-free survival (RFS), and this factor was identified as the best single discriminator of RFS events, followed by T-stage, microsatellite instability status and budding ( 10 ).…”

Expression Patterns of Microenvironmental Factors and Tenascin-C at the Invasive Front of Stage II And III Colorectal Cancer: Novel Tumor Prognostic Markers

“…Para n embedded tissues were well preserved, medical records were complete and patient status had been followed up, including overall survival and disease-free survival data that were con rmed through telephone interviews and by the mail. In addition, cases with invasion beyond the proper muscular layer were included for determination of the desmoplastic reaction [9]. Finally, patients who underwent preoperative chemoradiotherapy and emergency surgery were excluded.…”

“…The variables were recorded according to the General Rules for Management of the Japanese Colorectal Cancer Association (Table 1) [14]. In addition, DR classi cation was determined based on Ueno's classi cation [9]. This study was approved by the local ethics committee of Iwate Medical University (approval number MH2020-070), and all patients provided informed consent.…”

“…Additionally, novel and promising prognostic biomarkers are listed in the WHO classi cation 2019 [5]. There are 2 histological processes that are present within the tumor microenvironment at the invasive front of CRC: tumor budding and the desmoplastic reaction (DR) [6][7][8][9]. Tumor budding is de ned as single cells or clusters of up to four tumor cells at the invasion front of CRC [6][7][8].…”

“…It is closely associated with both local and distant metastases and is therefore a histological biomarker of tumor progression and a poor prognosis [6][7][8]. The classi cation of the DR was recently proposed by Ueno et al as a prognostic histological marker [9]. A pronounced desmoplastic stromal reaction in the microenvironment involves complex cellular interactions at the invasive front [10].…”