# Pancreatic ductal adenocarcinoma

Source: https://nuclide.cc/indications/pancreatic-cancer/  
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## TL;DR

Pancreatic cancer is one of the deadliest common cancers because it is usually found only after it has already grown into nearby structures or spread elsewhere. Surgery can cure it, but scans before the operation often cannot tell whether the tumour is truly removable, so some patients are opened up only to find the cancer has already spread too far.

## Summary

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.

## Fields

- Kind: Indication
- Last checked: 2026-09-23
- Also known as: pancreatic cancer; PDAC; pancreatic adenocarcinoma
- Tags: gastrointestinal; staging; unresectability
- Group: gastrointestinal
- Burden: GLOBOCAN 2024 estimates 531,318 new cases of pancreatic cancer worldwide, ranking eleventh for incidence with an age-standardised rate of 4.7 per 100,000, and 490,786 deaths, ranking sixth for cancer mortality at 4.2 per 100,000 (IARC's cancer-type overview page separately describes it as the twelfth most common cancer). SEER projects 67,530 new US cases and 52,740 US deaths in 2026, the third leading cause of cancer death in the United States, against an overall five-year relative survival of only 13.7%.
- Subtypes: Resectable disease, tumours without vascular involvement; Borderline resectable disease, with vascular or local structural involvement carrying a high risk of an R1 resection; Locally advanced (unresectable) disease, with local vessel impingement or invasion precluding surgery; Metastatic disease; Germline BRCA1/BRCA2-mutated disease, present in 4% to 8% of patients with pancreatic adenocarcinoma
- Biomarkers: CA 19-9 in serum, used to track response and progression during and after treatment despite low specificity and no tumour-specific role; Germline BRCA1/BRCA2 status, which identifies candidates for platinum-based chemotherapy and, on sustained response, olaparib maintenance; Peritoneal cytology obtained at staging laparoscopy, with a positive predictive value of 94% and specificity of 98% for unresectability, though sensitivity is only 25%

## Standard of care

- Resectable or borderline resectable disease: Neoadjuvant therapy (chemotherapy with or without chemoradiation), surgery, and postoperative chemotherapy or chemoradiation; the optimal neoadjuvant regimen is unknown. After resection, adjuvant mFOLFIRINOX is preferred for good performance status, giving a median overall survival of 53.5 months against 35.5 months for gemcitabine (PRODIGE-24), at higher toxicity.
- Locally advanced (unresectable) disease: Chemotherapy with or without targeted therapy, or chemotherapy followed by chemoradiation in patients without metastases; the LAP07 trial found no overall-survival benefit from adding chemoradiation to gemcitabine-based induction, though FOLFIRINOX has since been widely adopted in this setting.
- Metastatic disease, first line: FOLFIRINOX (median overall survival 11.1 versus 6.8 months for gemcitabine), gemcitabine plus nab-paclitaxel (8.5 versus 6.7 months), or NALIRIFOX (11.1 versus 9.2 months against gemcitabine plus nab-paclitaxel), chosen by performance status.
- Metastatic disease, germline BRCA1/BRCA2-mutated: First-line platinum-based chemotherapy; olaparib maintenance can be considered after at least sixteen weeks without progression, based on the POLO trial, which showed a progression-free survival benefit (7.4 versus 3.8 months) without a statistically significant overall-survival benefit.

## State of the art

- Adjuvant chemotherapy intensity now clearly changes outcomes after resection: PRODIGE-24 showed mFOLFIRINOX gave a median overall survival of 53.5 months and a five-year overall survival of 43.2%, against 35.5 months and 31.4% for gemcitabine, though 75.9% of FOLFIRINOX patients had grade 3 or 4 toxicity compared with 52.9% on gemcitabine.
- In metastatic disease, regimen choice has continued to improve median overall survival incrementally, from 6.8 months on gemcitabine alone, to 11.1 months with FOLFIRINOX, to 11.1 months with the newer NALIRIFOX regimen against 9.2 months for gemcitabine plus nab-paclitaxel in the NAPOLI 3 trial.
- Biomarker-selected therapy has entered the metastatic setting for the small germline BRCA1/BRCA2-mutated subgroup, but the benefit is confined to progression-free survival; NCI's own commentary on the POLO trial notes that without a proven overall-survival benefit the result lays groundwork for future combination studies rather than establishing olaparib as a standard of care on its own.
- PET/CT remains a problem-solving adjunct rather than a staging tool, reserved by NCCN-derived guidance for high-risk patients such as those with borderline resectable disease or a markedly elevated CA 19-9, explicitly not a substitute for a dedicated pancreatic-protocol CT.

## Open problems

- Conventional CT misjudges resectability often enough to be a clinical problem: published series report 20% to 48% of patients thought resectable on CT being found 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%.
- No validated tumour-specific serum marker exists; CA 19-9 has low specificity and a normal level does not preclude recurrence, so it cannot be used for screening or to reliably rule out disease.
- The optimal neoadjuvant chemotherapy regimen and sequencing for borderline resectable disease is unresolved, with multiple trials (including ALLIANCE, PREOPANC-3, PANACHE-01-PRODIGE and NorPACT-01) still evaluating different approaches.
- Even in the biomarker-selected germline BRCA-mutated population, PARP inhibitor maintenance has not shown a statistically significant overall-survival benefit, leaving the clinical value of that selection strategy incomplete.
- Disease burden is projected to keep rising against stagnant early detection, with pancreas and liver cancers projected to surpass breast, prostate and colorectal cancers to become the second and third leading causes of cancer death by 2030.

## Sources

- IARC GLOBOCAN 2024 pancreas factsheet: https://gco.iarc.who.int/media/globocan/factsheets/cancers/13-pancreas-fact-sheet.pdf
- SEER Cancer Stat Facts: pancreatic cancer: https://seer.cancer.gov/statfacts/html/pancreas.html
- NCI PDQ: pancreatic cancer treatment, health professional version: https://www.cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq
- FDA approval letter, nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/021660Orig1s037.pdf
- ASCO Post: FDA approves olaparib for germline BRCA-mutated metastatic pancreatic cancer: https://ascopost.com/issues/january-25-2020/fda-approves-olaparib-for-patients-with-germline-brca-mutated-metastatic-pancreatic-cancer/
- Ferrari C et al., review of PET/CT guideline positions in pancreatic cancer: https://pmc.ncbi.nlm.nih.gov/articles/PMC8394552/

## Connected records

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- technologies: [FAPI PET](https://nuclide.cc/technologies/fapi-pet/), [FDG PET](https://nuclide.cc/technologies/fdg-pet/), [PET/CT](https://nuclide.cc/technologies/pet-ct/)
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