Know the Facts

PCC-EDC Surveillance protocol for patients “at risk”(lower risk) for pancreatic cancer

Lower risk patients (tend to have the following features):

Age (Pancreatic cancer incidence increases with age. At age 70, risk of pancreatic cancer is 1%, based on achieving age 70 alone. In patients with index lesions, age is also an indirect reflection of the duration in years of anticipated surveillance, (i.e., the younger age = greater total number of years of anticipated surveillance and correspondingly greater cumulative risk of malignancy).

No symptoms attributable to pancreas

No worrisome radiographic features

Absence of high grade atypia on biopsy

Molecular pancreatic fluid profile <1 mutations and no increased DNA quantity/quality

No abnormalities of serum Amylase, Lipase, Alkaline Phosphatase, CA 19-9, CEA, HGB A1C or AST (or clear alternative explanation of demonstrated abnormality)

Absence of tobacco use

Lifestyle characterized by absence of obesity/fatty diet/sedentary activity level

Family history of pancreatic cancer without an index lesion (e.g., IPMN) in the person being screened

• <= 1 first degree relative (FDR) with pancreatic cancer

Family history of IPMN

• <= 1 FDR with IPMN

Screening Recommendations:

Baseline Testing: History/physical, MRI-MRCP, EUS-FNA of “cyst” of MPC for cytopathologic, biochemical and molecular analyses (cysts >10 mm or MPD>4mm), serum Amylase, Lipase, Alkaline Phosphatase, CA 19-9, CEA, HGB A1C, AST and C-Peptide.

Annual Surveillance Testing

History/physical

*MRI-MRCP (or CT if MRI-MRCP contraindicated)

Serum Amylase, Lipase, Alkaline Phosphatase, CA 19-9, CEA, HGB A1C, AST and C-Peptide (Consider labs 2-4 times per year ​especially if history of concerning trends or abnormalities)

Every 3-5 years Surveillance Testing

Upper EUS (endoscopic ultrasound)**

Upper EUS-FNA of “cyst” or MPD for cytopathologic, biochemical and molecular analyses (cysts >10mm or MPD>4m)

Consider EGD (endoscopic retrograde examination) with secretin and collection of duodenal aspirate for cytopathologic, biochemical and molecular analyses (cysts <10mm or MPD <4mm)

PCC-EDC Surveillance protocol for patients “at risk” (higher) for pancreatic cancer

Higher risk patients: (if fit, many of these will be offered surgery; if unfit or surgery averse, they will be offered close interval surveillance and/or endoscopic cyst ablation)

High Risk:

Age >=70, or anticipated prolonged (i.e., multiple decades) of surveillance (Pancreatic cancer incidence increases with age. At age 70, risk of pancreatic cancer is 1%, based on achieving age 70 alone. In patients with index lesions, age is also an indirect reflection of number of years of anticipated surveillance (i.e., the younger age = greater number of years of anticipated surveillance and the greater risk of malignancy over time).
Symptoms attributable to pancreas (sp. steatorrhea, weight loss, diabetes, jaundice, pancreatitis; but less so abdominal/back pain)

Worrisome radiographic features

• Main duct dilation >6mm
• ***Main duct diameter increasea during surveillance 6 month visit (e.g., progression from 5mm to 7mm)
• Mural nodule(s) or thick (>2mm) septae
• Associated mass
• Pancreatic duct stricture or cutoff with upstream main pancreatic duct dilation
• Quantity of cysts so numerous that surveillance is unreliable
• Size >3cm (unproven; insufficient as single risk factor; but still recommend high risk protocol for surveillance)
• Greatest diameter increase by >5mm for lesions >1cm since last surveillance 6 month visit (unproven; but still recommend high risk protocol for surveillance)
• Doubling of size for lesions <1cm since last surveillance visit (unproven; but still recommend high risk protocol for surveillance)
• New IPMN in previously negative pancreatic remnant (prior resection)

Worrisome pathology, pancreatic fluid or serum markers

• ***Cytopathology: Moderate or High grade atypia
• Surgical pathology (prior resection): High grade dysplasia

Worrisome pancreatic fluid

• DNA/cyst fluid molecular analysis (>1 of the following: increased DNA quantity/quality, KRas mutation, LOH mutation)

Worrisome serum markers

• ***Rising/abnormal serum CA19-9 and/or CEA
• Rising/abnormal serum Alkaline Phosphatase, Bilirubin or AST
• Rising/abnormal serum HGB A1C (+/-) especially with lowering of C-Peptide and loss of weight
• Abnormal Amylase, Lipase (elevated or suppressed above/below patient’s established baseline)

Family history of pancreatic cancer (or other relevant hereditary cancer syndrome) without an index pancreas lesion (e.g., IPMN) in the person being screened

• 2 FDR with pancreatic cancer (20 fold)
• 2 FDR with IPMN
• 1 FDR with pancreatic cancer and one with IPMN
• ***>2 FDR with pancreatic cancer (17-38.5% lifetime risk “LTR” by age 70)
• ***FAMM (CDKN2A mutation: 17% LTR by age 70)
• ***HP (PRSS1 mutation: 30-55% LTR by age 70))
• ***PJ (STK11 mutation: 11-60% LTR by age 70)
• ***HBOS (BRCA2: 2% LTR by age 70) Most common inherited mutation

Family history of pancreatic cancer with an index pancreas lesion (e.g., IPMN) in person being screened

• >=1 first degree relative with pancreatic cancer
• >=1 first degree relative with IPMN
• >=1 first degree relative with pancreatic cancer and one with IPMN

Tobacco use
Lifestyle characterized by obesity/fatty diet/sedentary activity level

Baseline Testing: History/physical, MRI-MRCP, EUS-FNA, cytopathologic, biochemical and molecular analyses, serum Amylase, Lipase, Alkaline Phosphatase, CA 19-9, CEA, HGB A1C and AST.

Annual Surveillance Testing

EUS

EUS-FNA, cytopathologic, biochemical and molecular analysis semi-annually or annually (BD >=10mm or MPD>=4mm)

EGD/ER (endoscopic retrograde examination) with secretin and collection of duodenal aspirate for cytopathologic, biochemical and molecular analyses (cysts <=10mm or MPD <=4mm)

Semi-Annual Surveillance Testing

History/physical

MRI-MRCP (or CT if MRI-MRCP contraindicated)

Serum Amylase, Lipase, Alkaline Phosphatase, CA 19-9, CEA, HGB A1C and AST (Consider labs 3-4 times a year especially if history of concerning trends or abnormalities)

Every 1-3 years Surveillance Testing

Upper EUS

Upper EUS-FNA, cytopathologic, biochemical, and molecular analysis semi-annually or annually (BD >=10mm or MPD>=4mm)

Consider EGD with secretin and collection of duodenal aspirate for cytopathologic, biochemical, and molecular analyses (cysts <=10mm or MPD <=4mm)

* Patients with current (within last 3 months) benign molecular pancreatic fluid profile (no mutations and no increased DNA quantity/quality) who are negative for any of the other 8 risk criteria (age, symptoms/signs, x-rays, biopsies, blood tests, family history of pancreatic cysts/cancer, tobacco, and obesity/fatty diet) could forego annual cross sectional imaging for a 2 year interval. We strongly recommend the patients still return annually to PCC-EDC, however, for education, H&P and serum tumor marker labs. There is a high rate of attrition of patients who are not followed at least annually.

** Patients in the “lower risk” group undergoing Upper EUS surveillance need not undergo cross-sectional imaging (MRI-MRCP or CT) in the same visit unless this is desired as a roadmap b the EUS physician or there are anticipated “blind spots” that need cross sectional imaging review.

*** These patients in the “higher risk” group may require even higher intensity of surveillance, i.e., H&P, serum tumor markers, cross sectional imaging 3-4 times per year and EUS-FNA, cytopathologic, biochemical and molecular analysis semi-annually.