Modern approaches to pancreatic cancer treatment (based on the 56th meeting of the European Pancreatic Club, Santiago de Compostela, Spain, June 26–29, 2024)

The article provides a brief summary of the main statements of lectures, scientific reports, and discussions that took place within the framework of the 56th meeting of the European Pancreatic Club (Santiago de Compostela, Spain, June 26–29, 2024). The paper presents eight reports that highlight the most intriguing aspects of contemporary therapeutic and diagnostic approaches to pancreatic ductal carcinoma. In his lecture, S. Crippa (Milan, Italy) first noted that a unified understanding of the definition of oligometastatic disease in pancreatic ductal carcinoma needs further development. The lecturer recommended performing surgery after a long course of polychemotherapy, stabilizing the disease, and a significant period of follow-up, while fully informing the patient about the possibility of treatment failure and poor prognosis. In her report, G. Gasparini (Milan, Italy) identified the parameters influencing the futility of radical surgical intervention, including the ASA class, tumor size, and CA 19-9 level. Stratification according to these criteria will help to avoid early mortality and recurrence of pancreatic ductal carcinoma, as well as start treatment of patients at high risk of primary surgical treatment with neoadjuvant polychemotherapy. The lecture by A. Rodríguez-Ariza (Madrid, Spain) characterizes the “liquid biopsy” and identifies new promising markers for non-invasive diagnosis of tumor progression. According to modern research, a multiparametric “liquid biopsy” determines circulating tumor DNA, KRAS mutations, aberrant methylation, loss of heterozygosity, and microsatellite instability for prognostic stratification in patients with metastatic ductal carcinoma of the pancreas, thereby serving as a potential tool for decision-making and personalized treatment of pancreatic cancer patients. In his lecture, T. Henk (Heidelberg, Germany) noted that personalized therapy at the modern level is very problematic, and the only hope for the survival of patients lies in surgical treatment, which improves its quality year after year. Simultaneously, a personalized RNA vaccine that stimulates T-cell immunity holds enormous promise. L. Guyvanyuk (Kyiv, Ukraine) and K. Gorgulu (Munich, Germany) engaged in a discussion among young scientists. On the one hand, they highlighted the significance of BRCA 1/2 and PALB 1 mutations, which affect 20% of patients, and suggested treatment with platinum and/or PARP inhibitors. They also demonstrated a significant difference in the median overall survival, nearly a year, among patients who adhered to the recommendations of molecular studies. On the other hand, researchers emphasize that pancreatic ductal carcinoma possesses a unique set of features, including a combination of mutations that determine the metabolic “flexibility” of cancer cells and tumor markers that identify immunoinvasiveness and resistance mechanisms. At the same time, because of the tumor’s heterogeneity, there are doubts that a biopsy will yield a truly representative proportion of the tumor. The author demonstrated that not only genetic markers are important, but also markers of other types, such as the fluidity of tumor cell membranes. K. Labori (Oslo, Norway) presented the current state of the problem of neoadjuvant treatment of primary resectable pancreatic ductal carcinoma, as well as the results of the NorPACT-1 trial. The histopathological response (R0 status) was better in the neoadjuvant polychemotherapy group, but this did not affect the patients’ survival. According to the study, primary surgical treatment had a statistically significant advantage in overall survival at 38.5 months, compared to 25.1 in the neoadjuvant treatment group. Around 20% of patients worldwide initially receive a diagnosis of locally advanced pancreatic ductal carcinoma, according to K. Takaori (Kyoto, Japan). A Japanese study demonstrated that surgery could effectively treat about 40% of patients with locally advanced pancreatic ductal carcinoma. Many randomized controlled trials have also shown a median overall survival of 21.8 to 40 months, although this is a small and carefully selected group of patients after a good response to neoadjuvant polychemotherapy. This review may primarily interest oncologists and oncosurgeons who specialize in pancreatic pathology, as well as surgeons and general practitioners.