Failure of downregulation of survivin following neoadjuvant radiochemotherapy in rectal cancer is associated with distant metastases and shortened survival.

PURPOSE: Valid molecular markers need to be implemented in clinical trials to fulfill the demand of a risk-adapted and more individualized multimodal therapy of locally advanced primary rectal cancer. In this study, the expression of the inhibitor-of-apoptosis (IAP) protein survivin was evaluated in pretreatment biopsies and corresponding posttreatment resection specimens, and was correlated to histo-pathological tumor characteristics and clinical follow-up. PATIENTS AND METHODS: One hundred sixteen patients with stage II/III rectal cancer treated with 5-FU-based neoadjuvant radiochemotherapy (RCT) at a single university medical centre within the German Rectal Cancer Trials were investigated. Survivin expression in pretreatment biopsies and surgical resection specimens were determined by immunohistochemistry by two independent institutions and correlated with histopathologic parameters, tumor recurrences, disease-free (DFS), and overall cancer-specific survival (CSS).
RESULTS: In pretreatment biopsies, a higher survivin expression correlated with advanced ypT (P = 0.026) and ypUICC (P = 0.05) stage as well as DFS (P = 0.038) after preoperative RCT. High posttreatment survivin levels were associated with advanced ypT stage (P = 0.03) and residual lymph node metastases (P = 0.04). Moreover, neoadjuvant RCT resulted in a significant downregulation of survivin expression (P < 0.0001). A failure of RCT-induced downregulation was associated with development of distant metastases (P = 0.0056) and cancer-related death (P = 0.026), and correlated significantly with DFS (P = 0.011*/0.02**) and CSS (P = 0.0017*/0.01**) in uni-* and multivariate** analyses.
CONCLUSIONS: Survivin expression displays a marker with prognostic utility in rectal cancers. These results underline the potential of survivin to monitor individual response to RCT and encourage anti-survivin strategies in multimodal rectal cancer therapy within future randomized clinical trials. ©2010 AACR.

RCT Entities:   Population Interventions Outcomes