Pancreatic Cancer: Risk Factors, Symptoms, Diagnosis, and Prognosis

Pancreatic adenocarcinoma (PDAC) accounts for >90% of pancreatic cancers. It is the 3rd leading cause of cancer death in the US (5-year relative survival ~12% for all stages; ~3% for metastatic).

Risk Factors

• Non-modifiable: Age (>65), male sex, Black race, family history (2+ FDRs), genetic syndromes (BRCA2, PALB2, Lynch, FAMMM, Peutz-Jeghers), blood type A/B/AB (vs. O).
• Modifiable: Smoking (2–3× risk; 20–25% of cases), obesity (BMI >30), type 2 diabetes (long-standing; also new-onset diabetes can be a manifestation), chronic pancreatitis, heavy alcohol, occupational exposures (chlorinated hydrocarbons, metalworking).

Symptoms (Often Late)

• Epigastric/back pain (worse supine, better leaning forward).
• Unintentional weight loss, anorexia.
• Jaundice (painless, if head tumor obstructs CBD) – dark urine, pale stools, pruritus.
• New-onset diabetes (age >50, normal weight) or sudden worsening of controlled diabetes.
• Nausea, vomiting (gastric outlet obstruction).
• Steatorrhea (fat malabsorption from exocrine insufficiency).
• Thrombophlebitis migrans (Trousseau sign).

Diagnosis & Staging

• CT abdomen/pelvis with pancreatic protocol (arterial/venous phases).
• EUS-FNA (endoscopic ultrasound-guided fine-needle aspiration) for tissue.
• CA 19-9 (tumor marker; not for screening).
• Staging: Resectable, Borderline resectable, Locally advanced, Metastatic.

Treatment by Stage

• Resectable: Surgery (Whipple/distal pancreatectomy) ± neoadjuvant/adjuvant chemo (FOLFIRINOX or gemcitabine/nab-paclitaxel).
• Borderline: Neoadjuvant therapy → reassess for surgery.
• Locally advanced: Chemotherapy ± radiation; clinical trials.
• Metastatic: Systemic chemo (FOLFIRINOX or gem/nab-pac); targeted therapy (olaparib for BRCA, pembrolizumab for MSI-H); symptom control.

Early Detection

No population screening. High-risk individuals (genetic syndromes, strong family history) may enter surveillance programs (annual MRI/EUS from age 50 or 10 yrs before earliest family diagnosis).