Updates in the diagnosis and management of ductal adenocarcinoma of the pancreas

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by high aggressiveness, poor prognosis, and unsatisfactory survival rates. The incidence of PDAC is increasing annually, and thus, the number of deaths due to PDAC is increasing worldwide. Modern imaging modalities, including multidetector computed tomography, magnetic resonance imaging-cholangiopancreatography, endoscopic retrograde cholangiopancreatography, positron emission tomography-computed tomography, endoscopic ultrasound and tumor markers, have made significant contributions to the diagnosis of pancreatic cancer. However, early diagnosis remains challenging despite progress in liquid biopsy (tumor DNA, tumor parts or cells), miRNAs, genomic analysis, MTA (metastasis-associated) proteins or circulating cancer-derived exosomes. Early diagnosis and radical surgical excision offer a unique chance of long-term survival in patients with an otherwise poor prognosis. However, surgery alone is insufficient, and multimodal treatment is needed. Novel treatment modalities, i.e., immunotherapy, vaccines, targeted gene therapy, extracellular vesicles (particularly exosomes), new chemotherapy, novel radiotherapy and angiogenesis-restricting biological agents, were applied with promising outcomes. It seems that the biological mechanisms underlying the disease determine the effectiveness of any therapeutic effort. Thus, further research at the molecular level must focus on novel treatments to prevent the growth, invasion, and spread of cancer cells.

Keywords: Artificial intelligence-driven diagnostics; Circulating tumor DNA; Immunotherapy; Liquid biopsy; Pancreatectomy; Pancreatic ductal adenocarcinoma; Targeted therapy; Tumor microenvironment.

Figure 1

Pancreatic ductal adenocarcinoma. A: Scheme of diagnostic approach for pancreatic ductal adenocarcinoma (PDAC) in order of priority; B: Scheme of criteria for local borderline resectable PDAC; C: Scheme of PDAC management. Tu: Tumor; SMV: Superior mesenteric vein; SMA: Superior mesenteric artery; PV: Portal vein; CA: Celiac axis; CHA: Common hepatic artery; PHA: Proper hepatic artery; PPD: Proximal pancreatoduodenectomy; DP: Distal pancreatectomy, TP: Total pancreatectomy; LND: Lymph node dissection; FOLFIRINOX: Leucovorin, 5-fluorouracil, irinotecan, oxaliplatin; GEMNABP: Gemcitabine + nab-paclitaxel; NALIRIFOX liposomal irinotecan, fluorouracil, leucovorin, oxaliplatin + certepetide (for chemoresistance); PDAC: Pancreatic ductal adenocarcinoma; MDCT: Multidetector computed tomography; CT: Computed tomography; MRI: Magnetic resonance imaging; MRCP: Magnetic resonance cholangiopancreatography; EUS: Endoscopic ultrasound; FNA: Fine needle aspiration; FNB: Fine-needle tissue biopsy; PET: Positron emission tomography; CA 19-9: Carbohydrate antigen.