Pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma is a comparatively uncommon but highly lethal malignancy. GLOBOCAN 2024 estimates 531,318 new cases worldwide, ranking eleventh for incidence with an age-standardised rate of 4.7 per 100,000, against 490,786 deaths, ranking sixth for cancer mortality at 4.2 per 100,000; IARC's own cancer-type overview page separately describes it as the twelfth most common cancer, a minor internal discrepancy between two GLOBOCAN 2024 outputs. In the United States, SEER projects 67,530 new cases and 52,740 deaths for 2026, making it the third leading cause of cancer death, with an overall five-year relative survival of only 13.7% for patients diagnosed between 2016 and 2022. Survival tracks stage sharply: 43.6% at five years for the 15% of patients diagnosed with localised disease, 17.0% for the 28% with regional spread, and 3.4% for the 51% who already have distant metastases at diagnosis.

Treatment is organised around resectability. Resectable and borderline resectable disease is treated with a combination of neoadjuvant therapy, surgery and postoperative chemotherapy, though the optimal neoadjuvant regimen remains unknown and is being tested in ongoing trials; for good-performance-status patients after resection, adjuvant mFOLFIRINOX improved median overall survival to 53.5 months against 35.5 months for gemcitabine in the PRODIGE-24 trial, with a five-year overall survival of 43.2% against 31.4%, at the cost of substantially more grade 3 or 4 toxicity. Locally advanced disease that cannot be resected because of vascular involvement is treated with chemotherapy, with chemoradiation added in some patients; the LAP07 trial showed no overall-survival benefit from adding chemoradiation to gemcitabine-based induction, though that trial predates the widespread adoption of FOLFIRINOX in this setting. Metastatic disease is treated with combination chemotherapy chosen by fitness: FOLFIRINOX improved median overall survival to 11.1 months against 6.8 months for gemcitabine alone, gemcitabine plus nab-paclitaxel improved it to 8.5 against 6.7 months, and the newer NALIRIFOX regimen gave 11.1 against 9.2 months compared with gemcitabine plus nab-paclitaxel. The 4% to 8% of patients with a germline BRCA1 or BRCA2 variant are managed with platinum-based first-line chemotherapy and, if the disease has not progressed after sixteen weeks or more, olaparib maintenance, though the POLO trial that supported this approach showed a progression-free survival benefit without a statistically significant overall-survival benefit.

Nuclear medicine currently has almost no defined role in this disease. NCCN materials describe PET/CT as not a routine test, useful only as a problem-solving adjunct after a dedicated pancreatic-protocol CT in high-risk patients, such as those with borderline resectable disease, a markedly elevated CA 19-9, a large primary tumour or large regional nodes, and explicitly not a substitute for high-quality CT; ESMO guidance goes further, stating that PET/CT does not add staging information in resectable disease and cannot be recommended. No FDG-PET-based or receptor-targeted imaging role for pancreatic ductal adenocarcinoma itself was identified in any guideline reviewed. The clinical gap this leaves is large: conventional CT misjudges resectability often enough that published series report 20% to 48% of patients thought resectable on CT turning out to be unresectable at surgery, and a Cochrane meta-analysis put the median pre-test probability of unresectable disease after a resectable-looking CT at 41.4%, while no validated tumour-specific serum marker exists to help, since CA 19-9 has low specificity and a normal level does not exclude recurrence. That combination, a common and morbid staging failure with no molecular imaging tool aimed at it, is the opportunity that fibroblast activation protein imaging is intended to address.