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.