Pancreatic Cancer: Complete Guide

Written by: Amanda Foster, MD

Reviewed by: Dr. Richard Kim, Pancreatic Oncologist

Last reviewed: January 24, 2026

Quick Facts

Fourth leading cause of cancer death
5-year survival rate: 12% overall
Often diagnosed at advanced stage (80% unresectable)
Median age at diagnosis: 70 years
Slightly more common in men than women
Smoking increases risk by 2-3 fold
Only 20% of patients are surgical candidates at diagnosis
Rapid progression and early metastasis common

What is Pancreatic Cancer?

Pancreatic cancer begins when cells in the pancreas develop mutations in their DNA and grow uncontrollably. The pancreas is a 6-inch long organ located behind the stomach that produces enzymes for digestion and hormones (including insulin) that regulate blood sugar.

Key Points

Most pancreatic cancers (90%) are exocrine tumors (adenocarcinomas)
Often called a "silent disease" due to lack of early symptoms
Aggressive cancer with tendency for early spread
Difficult to detect early due to pancreas location deep in abdomen
Treatment advances are improving outcomes for some patients

Pancreas Anatomy

The pancreas has three main parts:

Head: Widest part, near duodenum (60-70% of cancers)
Body: Middle section (15-20% of cancers)
Tail: Narrow end near spleen (5-10% of cancers)

The pancreas has two main functions:

Exocrine function: Produces digestive enzymes
Endocrine function: Produces hormones like insulin and glucagon

Types of Pancreatic Cancer

Exocrine Tumors (95%)

Pancreatic Adenocarcinoma (90%)

Most common type
Arises from ductal cells
Also called pancreatic ductal adenocarcinoma (PDAC)
Aggressive with poor prognosis

Other Exocrine Tumors

Acinar cell carcinoma: 1-2% of cases, slightly better prognosis
Adenosquamous carcinoma: Very rare and aggressive
Colloid carcinoma: From IPMN, better prognosis
Hepatoid carcinoma: Extremely rare
Signet ring cell carcinoma: Very rare, poor prognosis
Undifferentiated carcinoma: Very aggressive

Neuroendocrine Tumors (5%)

Pancreatic neuroendocrine tumors (PNETs): Better prognosis than adenocarcinoma
Functional tumors: Produce hormones
- Insulinomas (most common)
- Gastrinomas
- Glucagonomas
- VIPomas
- Somatostatinomas
Non-functional tumors: Don't produce hormones

Cystic Tumors

Intraductal papillary mucinous neoplasms (IPMNs): Can become malignant
Mucinous cystic neoplasms (MCNs): Primarily in women, can progress to cancer
Serous cystadenomas: Usually benign
Solid pseudopapillary neoplasms: Rare, mostly in young women

Signs and Symptoms

Early Symptoms (Often Vague)

Abdominal pain that radiates to back
Loss of appetite
Unexplained weight loss
Fatigue
New-onset diabetes or worsening blood sugar control
Digestive problems

Advanced Symptoms

Head of Pancreas Tumors

Jaundice: Yellowing of skin and eyes (70% of head tumors)
- Dark urine
- Light-colored or greasy stools
- Itchy skin
Pain in upper abdomen or mid-back
Nausea and vomiting
Enlarged gallbladder (Courvoisier's sign)

Body/Tail Tumors

Pain (more common presentation)
Weight loss
Often no jaundice
May present later with larger tumors

Paraneoplastic Syndromes

Trousseau syndrome: Blood clots (10% of patients)
Depression: May precede diagnosis
Panniculitis: Fat necrosis causing skin nodules

⚠️ Red Flag Symptoms

Seek immediate medical evaluation for:

Painless jaundice
Unexplained weight loss >10% body weight
New-onset diabetes after age 50
Persistent upper abdominal pain
Sudden worsening of chronic pancreatitis symptoms

⚠️ Medical Emergency

Seek immediate care for:

Severe abdominal pain with fever (possible infection)
Signs of blood clot (leg swelling, chest pain, shortness of breath)
Severe jaundice with confusion
Uncontrolled vomiting

Causes and Risk Factors

Modifiable Risk Factors

Smoking:
- Doubles risk
- Accounts for 20-30% of cases
- Risk decreases after quitting
Obesity: BMI ≥30 increases risk by 20%
Diet: High in red/processed meat, low in fruits/vegetables
Alcohol: Heavy consumption (>3 drinks/day)
Occupational exposures: Pesticides, dyes, chemicals

Non-Modifiable Risk Factors

Age:
- Average age at diagnosis: 70
- Rare before age 45
Gender: Slightly more common in men
Race: Higher incidence in African Americans
Family history: 5-10% have familial component
Genetic syndromes (5-10%):
- BRCA1/BRCA2 mutations
- Lynch syndrome
- Familial atypical multiple mole melanoma (FAMMM)
- Peutz-Jeghers syndrome
- Hereditary pancreatitis
- Li-Fraumeni syndrome
- Ataxia-telangiectasia

Medical Conditions

Chronic pancreatitis: 5% lifetime risk
Diabetes:
- Long-standing: 2x risk
- New-onset: May be early sign
Cystic lesions: IPMNs, MCNs
H. pylori infection: Possible increased risk
Hepatitis B: Possible association

Diagnosis

Initial Evaluation

Complete medical history
Physical examination
Blood tests:
- Complete blood count
- Comprehensive metabolic panel
- Liver function tests
- Bilirubin levels

Tumor Markers

CA 19-9:
- Elevated in 80-85% of cases
- Not specific (can be elevated in other conditions)
- Useful for monitoring treatment response
- Very high levels (>1000 U/mL) suggest advanced disease
CEA: Less sensitive than CA 19-9
CA 125: May be elevated

Imaging Studies

CT Scan (Pancreatic Protocol)

Triple-phase with thin slices
Assesses tumor size and vascular involvement
Evaluates for metastases
Determines resectability

MRI/MRCP

Better for cystic lesions
Evaluates bile duct and pancreatic duct
Alternative when CT contraindicated

Endoscopic Ultrasound (EUS)

Most sensitive for small tumors
Allows fine-needle aspiration (FNA) biopsy
Evaluates vascular invasion
Assesses lymph nodes

PET/CT

Detects distant metastases
Not routine but helpful in select cases

Tissue Diagnosis

EUS-FNA: Preferred method, 85-95% sensitivity
CT-guided biopsy: For larger masses
ERCP with brushings: For strictures
Laparoscopy: Detects peritoneal disease (20-30% of cases)

⚠️ Note on Biopsy

Tissue diagnosis not always required before surgery if:

Classic imaging findings
Resectable disease
No evidence of metastases

Staging

TNM Staging (8th Edition)

Stage	T	N	M	Description
Stage IA	T1	N0	M0	Tumor ≤2 cm, confined to pancreas
Stage IB	T2	N0	M0	Tumor >2 cm but ≤4 cm
Stage IIA	T3	N0	M0	Tumor >4 cm
Stage IIB	T1-3	N1	M0	1-3 positive lymph nodes
Stage III	T1-3	N2	M0	≥4 positive lymph nodes
	T4	Any N	M0	Involves celiac axis, SMA, or common hepatic artery
Stage IV	Any T	Any N	M1	Distant metastasis

Resectability Status

Resectable (15-20%)

No distant metastases
No arterial involvement (celiac, SMA, hepatic)
No SMV/portal vein involvement or <180° involvement without irregularity

Borderline Resectable (10%)

No distant metastases
Venous involvement potentially reconstructable
Arterial abutment <180° without stenosis
Consider neoadjuvant therapy

Locally Advanced (30%)

No distant metastases
>180° arterial encasement
Unreconstructable venous occlusion

Metastatic (40-50%)

Distant organ metastases
Most common: liver, peritoneum, lungs

Treatment Options

Treatment by Stage

Resectable Disease

Surgery (see surgical procedures section)
Adjuvant chemotherapy (standard):
- mFOLFIRINOX (preferred if fit)
- Gemcitabine + capecitabine
- Gemcitabine monotherapy
- 5-FU/leucovorin (if cannot tolerate above)
Consider clinical trials

Borderline Resectable

Neoadjuvant therapy:
- FOLFIRINOX (preferred)
- Gemcitabine + nab-paclitaxel
- Consider radiation (controversial)
Restaging
Surgery if resectable
Adjuvant therapy

Locally Advanced

Systemic chemotherapy (4-6 months)
Restaging - consider surgery if converted to resectable
Chemoradiation or SBRT (selected patients)
Maintenance therapy

Metastatic Disease

First-line chemotherapy:
- FOLFIRINOX (fit patients, ECOG 0-1)
- Gemcitabine + nab-paclitaxel
- Gemcitabine monotherapy (poor performance status)
Second-line options:
- Gemcitabine-based if prior FOLFIRINOX
- 5-FU-based if prior gemcitabine
- Liposomal irinotecan + 5-FU/leucovorin

Chemotherapy Regimens

FOLFIRINOX

5-FU + leucovorin + irinotecan + oxaliplatin
Median OS: 11.1 months (metastatic)
High toxicity - requires good performance status
Modified versions with dose reductions often used

Gemcitabine + nab-paclitaxel

Median OS: 8.5 months (metastatic)
Better tolerated than FOLFIRINOX
Peripheral neuropathy common

Targeted Therapy

Erlotinib: Modest benefit with gemcitabine (historical)
Olaparib: BRCA-mutated, maintenance after platinum
Larotrectinib/Entrectinib: NTRK fusion-positive (rare)
Pembrolizumab: MSI-H/dMMR tumors (1-2%)

Radiation Therapy

Role controversial and evolving
Options:
- Conventional fractionation with chemotherapy
- SBRT (stereotactic body radiation)
- Proton therapy (investigational)
May be used for:
- Borderline resectable (neoadjuvant)
- Positive margins after surgery
- Locally advanced disease
- Palliation of pain or bleeding

Supportive Care

Pain management: Often requires opioids, celiac plexus block
Pancreatic enzymes: For exocrine insufficiency
Diabetes management: May need insulin
Nutritional support: Dietitian consultation essential
Biliary drainage: Stenting for obstruction
Anticoagulation: Consider for thrombosis risk
Palliative care: Early integration improves outcomes

Surgical Procedures

Pancreaticoduodenectomy (Whipple Procedure)

For tumors in head of pancreas:

Removes:
- Head of pancreas
- Duodenum
- Gallbladder
- Common bile duct
- Part of stomach (classic) or pylorus-preserving
Reconstructs digestive tract
Mortality: <2% at high-volume centers
Morbidity: 30-40%
Complications:
- Pancreatic fistula (10-20%)
- Delayed gastric emptying (15-20%)
- Wound infection
- Hemorrhage

Distal Pancreatectomy

For body/tail tumors:

Removes tail and body of pancreas
Usually includes splenectomy
Lower morbidity than Whipple
Risk of pancreatic fistula

Total Pancreatectomy

Removes entire pancreas
Results in diabetes and complete exocrine insufficiency
Reserved for extensive disease or IPMN

Vascular Resection

Portal vein/SMV reconstruction possible
Arterial resection controversial
Requires experienced surgeon

High-Volume Centers

Surgery should be performed at centers doing >15-20 cases/year:

Lower mortality (2% vs 10%)
Better long-term outcomes
More likely to receive appropriate adjuvant therapy

Prognosis and Survival

Overall Survival

1-year survival: 35%
5-year survival: 12%
10-year survival: <5%

By Stage

Localized (resectable): 5-year survival 40-45% with treatment
Regional (node-positive): 5-year survival 15-20%
Distant (metastatic): 5-year survival 3%

Prognostic Factors

Favorable

Complete surgical resection (R0)
Well-differentiated tumor
No lymph node involvement
CA 19-9 normalization after treatment
Good performance status
Ability to receive adjuvant therapy

Unfavorable

Positive margins (R1/R2)
Poorly differentiated
Lymph node involvement
Perineural invasion
High CA 19-9 (>1000 U/mL)
Large tumor size

Long-term Survivors

Characteristics of 5+ year survivors:

Early-stage disease at diagnosis
Complete surgical resection
Receipt of multimodality therapy
BRCA mutations (better response to platinum)
Exceptional responders to therapy (rare)

Clinical Trials and Research

Active Areas of Research

Immunotherapy combinations: Checkpoint inhibitors + vaccines
KRAS inhibitors: Targeting KRAS G12C, G12D
Stromal modification: Breaking down tumor stroma
CAR-T therapy: Engineered T cells
Liquid biopsies: Early detection and monitoring
Precision medicine: Molecular profiling for targeted therapy
Metabolic targeting: Exploiting cancer metabolism

Important Clinical Trials

Neoadjuvant therapy optimization
Maintenance therapy strategies
Novel drug combinations
Early detection biomarkers
High-risk screening protocols

Clinical Trial Participation

Consider clinical trials at all stages of disease. Benefits include:

Access to novel therapies
Close monitoring
Contributing to research
Potential for better outcomes

Living with Pancreatic Cancer

Physical Symptoms Management

Pain: Multimodal approach, consider nerve blocks
Nausea: Anti-emetics, small frequent meals
Weight loss: High-calorie supplements, appetite stimulants
Fatigue: Energy conservation, gentle exercise
Diarrhea: From fat malabsorption, needs enzyme replacement

Nutritional Support

Pancreatic enzyme replacement with meals
Small, frequent meals
Low-fat diet if steatorrhea
Vitamin supplementation (fat-soluble vitamins)
Monitor and treat diabetes
Consider nutritional supplements

Psychological Support

High rates of depression and anxiety
Individual counseling
Support groups
Family counseling
Spiritual support if desired

Advance Care Planning

Early discussions about goals of care
Advance directives
Healthcare proxy designation
Palliative care integration
Hospice referral when appropriate

Frequently Asked Questions

Why is pancreatic cancer so deadly?

Several factors contribute: late diagnosis due to lack of early symptoms, aggressive biology with early spread, location near vital structures, dense stroma limiting drug delivery, and high rate of treatment resistance.

Are there screening tests for pancreatic cancer?

No routine screening exists for average-risk individuals. High-risk individuals (strong family history, genetic syndromes) may undergo surveillance with MRI/EUS, but this is not standardized.

What are the warning signs I should watch for?

New-onset diabetes after 50, unexplained weight loss, persistent upper abdominal or back pain, jaundice, changes in stool, and loss of appetite. These symptoms warrant medical evaluation.

Is pancreatic cancer hereditary?

About 5-10% have hereditary component. Risk increases with family history: 2x risk with one affected relative, 6x with two, 32x with three. Genetic testing may be recommended.

What is the Whipple procedure?

Major surgery removing head of pancreas, duodenum, gallbladder, and part of stomach. It's the standard surgery for head of pancreas tumors. Recovery takes 6-8 weeks.

Can pancreatic cancer be prevented?

While not entirely preventable, risk can be reduced by not smoking, maintaining healthy weight, limiting alcohol, and managing diabetes. High-risk individuals may benefit from surveillance.

What is CA 19-9?

A blood marker often elevated in pancreatic cancer but not specific. Used to monitor treatment response and detect recurrence. Not reliable for screening as it can be normal in early disease.

Should I seek a second opinion?

Yes, particularly for treatment planning. Pancreatic cancer is complex, and treatment at high-volume centers improves outcomes. Second opinions are standard practice.

What about alternative treatments?

No alternative treatments have proven effective against pancreatic cancer. Some complementary therapies may help with symptoms. Always discuss with your oncologist to avoid interactions.

Are there long-term survivors?

Yes, though uncommon. About 10% of resected patients survive 5+ years. Some patients with favorable biology or exceptional treatment response become long-term survivors.

Sources

National Cancer Institute. Pancreatic Cancer Treatment (PDQ) - Health Professional Version. Updated January 2026.
American Cancer Society. Pancreatic Cancer Statistics. 2026.
NCCN Clinical Practice Guidelines. Pancreatic Adenocarcinoma. Version 1.2026.
Mizrahi JD, et al. Pancreatic cancer. Lancet. 2025.
ASCO Clinical Practice Guidelines. Metastatic Pancreatic Cancer. 2025 Update.
Tempero MA. NCCN Guidelines Insights: Pancreatic Adenocarcinoma. J Natl Compr Canc Netw. 2025.
Park W, et al. Pancreatic Cancer: Review of Epidemiology, Diagnosis, and Treatment. JAMA. 2025.