Prognostic stratification of resected pancreatic ductal adenocarcinoma: Past, present, and future

Pancreatic ductal adenocarcinoma (PDAC) is the digestive cancer with the poorest prognosis, with a 5-year overall survival rate of 7%. Complete surgical resection followed by adjuvant chemotherapy is the only treatment with curative intent. However, many patients with an apparently localized disease who may undergo primary tumor resection already have micro-metastatic disease and will promptly develop metastases. Considering the significant rate of morbidity and mortality upon pancreatic surgery, the pre-operative identification of patients with an aggressive disease is therefore a major clinical issue. Although tumor size, differentiation, margins, and lymph node invasion are the main "classical" prognostic factors, they are not sufficient to fully predict early disease recurrence. In the last decade, multi-omics high-throughput analyses have provided a new insight into PDAC biology and have led to the description of multiple molecular subtypes, with a significant prognostic value for most of them, but that have not yet been transposed to routine clinical practice, mainly due to poor availability of tumor tissue material prior to surgical resection. In this review, we provide an overview of the current status of clinico-pathological and molecular biomarkers (tumor and blood) to predict early recurrence, and their implications for clinical practice and future research development.