Depression as a potential early indicator of pancreatic cancer: a systematic review of prevalence, mechanisms, and temporal associations.

BACKGROUND Pancreatic cancer (PC) remains one of the most lethal malignancies, with a five-year survival rate of only 12%, largely due to late diagnosis. Depression is frequently reported in PC and may precede its onset, yet underlying mechanisms remain unclear. AIMS This systematic review examined (1) the prevalence of depression in PC, (2) potential psychological, clinical, and biological mechanisms, and (3) the temporality of depressive symptoms relative to PC diagnosis. METHODS Following PRISMA guidelines, EMBASE, MEDLINE, Web of Science, and Cochrane were searched through February 2025 (PROSPERO: CRD42022378830). Studies including adults with PC assessing depression or related biomarkers were analyzed. RESULTS Twenty-six studies met inclusion criteria. Depression prevalence ranged 3.5-51.8%. Six studies reported depressive symptoms often preceding diagnosis by 3-6 months. Biomarker studies identified elevated IL-6, CRP, and kynurenine-tryptophan pathway alterations. CONCLUSIONS Depression may represent a paraneoplastic or early manifestation of PC. Further prospective, mechanistic studies are warranted.