Advancing Therapeutic Strategies for Pancreatic Cancer: A Review of Surgical, Systemic and Diagnostic Innovations

Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumors (PNETs), remains one of the deadliest malignancies in gastrointestinal oncology. PDAC is characterized by late diagnosis, rapid progression, and limited resectability, with only 20% of cases eligible for surgery at diagnosis. Standard treatments involve surgical resection and adjuvant or neoadjuvant chemotherapy, yet metabolic reprogramming and oncogene interactions contribute to treatment resistance. Surgical innovations, including minimally invasive pancreatoduodenectomy (MIPD), fluorescence-guided resection, and robotic-assisted techniques, have improved perioperative outcomes but require further validation for long-term survival benefit. The functional PNETs also demand targeted resection, whereas the management of the non-functional tumor less than 2 cm is still debatable. ICG-surgical INDO fluorescence surgery is a promising way of enhancing visualization and cytectasis, although it is not as widely standardized. Systemic treatment has evolved with regimens such as FOLFIRINOX, gemcitabine combinations, and targeted therapies for patients with BRCA or KRAS mutations. The targeting and minimization of systemic toxicity is achieved through nanoparticle-based drug delivery systems and exosomes. Non-coding RNA-targeted and immunotherapy are also being implemented to eliminate resistance and enhance efficacy. Non-resectable tumors can be treated with ablation techniques (RFA, MWA, IRE, cryoablation) and brachytherapy, whereas intraoperative radiotherapy (IORT) provides better local control. Despite the gains made, the high rates of recurrence and drug resistance still need the use of treatment strategies that combine different methods and are tailored for each patient. The future of clinical practice re-quires using fluorescence navigation, novel ablation methods, and nanomedicine. Imaging techniques, surgical methods, and molecular advancements have improved precision, which is promising for better outcomes in this potentially lethal disease. Further randomized trials are needed to refine these approaches and optimize their impact on survival and quality of life in patients with pancreatic cancer.