The investigators' goal is to conduct a prospective multicenter study to evaluate the yield and outcomes of screening of pancreas cancer in individuals who are at-risk for pancreatic cancer. We plan to use International Cancer of the Pancreas Screening (CAPS3) Consortium recommendations to standardize study population, screening methodology, and study outcomes.

Methods The investigators' goal is to conduct a prospective multicenter study to evaluate the yield and outcomes of pancreas cancer screening in high-risk individuals. High-risk patients who are undergoing pancreatic cancer screening in accordance with national guidelines at participating study centers will be eligible for the study. Information regarding patient characteristics, findings at screening examination, and patient outcomes will be collected.

Primary Outcome (Primary Aim):

To identify the proportion of patients who meet International Cancer of the Pancreas Screening Consortium screening criteria 3rd update (CAPS Jan 2020), or more updated national guidelines, who are found at the screening to have high-risk pancreatic lesions amenable to treatment (definition of "high-risk lesions amenable to treatment" is provided under the section on study outcomes).

Secondary outcomes (Secondary Aims) will include (details are provided under the section on study outcomes):

1. Proportion of patients diagnosed with any stage pancreatic cancer
2. proportion of patients undergoing pancreatic surgery
3. Cancer-related outcome, defined as a cancer-related death
4. proportion of patients experience harms, defined as any complications/adverse event due to screen related procedures
5. Comparison of cancer outcome, defined cancer-related death, in screen-detected cancer with cancer outcomes reported by the SEERs population-based registry. Study overview Study type: a prospective observational cohort. High-risk patients who meet study inclusion criteria at study centers will be identified.

Screening and patient follow-up will be performed at individual study centers per standard clinical practice. Patient characteristics, screening performed and screening results, clinical outcome data will be collected by individual study centers. This data will be stored and analyzed at central study REDCap located at Beth Israel Deaconess Medical Center (BIDMC)

Inclusion Criteria:

• Inclusion criteria 1-3 are indications for pancreatic cancer screening as defined by the CAPS3 guidelines or updated national pancreatic cancer screening guidelines. Patients who do not meet these guidelines but are undergoing pancreatic cancer screening at the discretion of their treating physician at participating study centers will also be included in the study. Based upon the indication for screening, patients will be categorized as either meeting CAPS3 screening criteria, or not meeting CAPS3 screening criteria.

  1. Familial Pancreatic cancer kindred. This is defined as family history of pancreas cancer that meet the criteria listed below.

     1. If at least two affected relatives who are First degree relatives (FDR) to each other, of whom at least one is an FDR to the individual considered for surveillance
     2. If at least three affected relatives on the same side of the family, of whom at least one is an FDR to the individual considered for surveillance
     3. If at least two affected relatives on the same side of the family, of whom at least one is an FDR to the individual considered for surveillance Screening is usually initialed at age 50 years or 10 years younger than the youngest family member with pancreatic cancer

  2. Patients with genetic susceptibility to pancreas cancer

     1. Patients with Peutz-Jeghers syndrome diagnosed with using clinical criteria or with a deleterious mutation in liver kinase B1/Serine/threonine kinase 11 (LKB1/STK11). Screening is usually initiated at age 40 years or later.
     2. Patients with Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM syndrome), diagnosed using clinical criteria or CDKN2A p16 mutation.

Screening is usually initiated at age 45 years or 10 years younger than the youngest family member with pancreatic cancer.

1. Hereditary Breast and Ovarian Cancer syndrome: diagnosed using clinical criteria or deleterious Breast Cancer gene 1 (BRCA1), Breast Cancer gene 2 (BRCA2), Partner and Localizer of BRCA2 (PALB2). The usual indication for screening is:

   • BRCA1 mutation and at least one affected first-degree relative with pancreatic cancer
   • BRCA 2 mutation and at least one affected first-degree relative, or at least two relatives of any degree with pancreatic cancer
   • PALB2 mutation and at least one affected first-degree relative with pancreatic cancer Screening is usually initiated at age 45 or 10 years younger than the youngest family member with pancreatic cancer; or per updated national screening guidelines

2. Lynch syndrome or Ataxia Telangiectasia Mutated (ATM) mutations with at least one affected first-degree relative (FDR). Lynch syndrome could be diagnosed either by using clinical criteria or Mutator L homolog 1 (MLH1), Mutator S homolog 2 (MSH2), Mutator S homolog 6 (MSH6), Postmeiotic Segregation Increased, S. Cerevisiae, 2 (PMS2) or EPCAM mutation.

   Screening to be initiated at age 45 or 10 years younger than the youngest family member with pancreatic cancer.

3. Patients with hereditary pancreatitis diagnosed using clinical criteria or deleterious Serine Protease 1 (PRSS1) mutation. Screening is usually initiated at age 40 years or 10 years younger than the youngest family member with pancreatic cancer 3. New-onset diabetes, age > 50 years with weight loss. 4. Patients who do not meet these CAPS screening criteria but are determined by the site principal investigator to be high-risk for pancreatic cancer based upon family history or other risk factors, and are undergoing pancreatic cancer screening will also be included in the study. Indication for pancreatic cancer screening and age at which screening was initiated will be recorded.

Exclusion Criteria:

• Patients presenting with symptoms suggestive of pancreatic cancer who are undergoing diagnostic EUS or MRCP e.g. acute recurrent pancreatitis, abnormal imaging

Any patient who meets the eligibility criteria exposed above based on CAPS3 or updated national pancreatic screening guidelines criteria at BIDMC and collaboration centers part of the study in the time frame of 2020 to 2027 (which is the end of enrollment)