Prevention of Pancreatic Cancer

Objective
To make recommendations about screening for and prevention of pancreatic cancer, specifically adenocarcinoma, among asymptomatic persons in Canada.

Burden of Suffering
Cancer of the pancreas is the fourth leading cause of cancer deaths in Canada in both men and women, accounting for 2,611 deaths in 1990 and an estimated 36,000 potential years of life lost. For 1993 it was estimated that there would be 2,750 new cases of pancreatic cancer and 2,900 deaths from the disease in Canada. In contrast with many other parts of the world, the age-specific mortality rates in Canada appear to have been dropping over the last 35 years. This cancer is more common in men and older persons (the majority of cases being diagnosed between ages 60 and 80).

Symptoms of pancreatic cancer (PC) are usually nonspecific (e.g., abdominal pain, weight loss) and frequently disregarded, resulting in late detection in 80-90% of patients. In Ontario only 8% of patients live more than five years after diagnosis. Although alcohol has not been established as a risk factor, smoking has shown a consistent association with an increased risk of PC, with numerous cohort and case-control studies reporting a relative risk of 2 to 5. Positive associations have also been found between PC and dietary factors such as meat, eggs, carbohydrates, refined sugar, cholesterol, fat and total calorie intake, as well as negative (protective) associations with intake of vegetables and fruits. However, study results are inconsistent.

An association between pancreatic carcinoma and diabetes mellitushas been suggested. However, it has not been adequately determined whether diabetes is a result of the cancer, or whether it might just increase the risk for pancreatic carcinoma.

Options
Screening measures considered were abdominal examination, magnetic resonance imaging (MRI), computerized tomography (CT), endoscopic retrograde cholangio-pancreatography (ERCP), endoscopic ultrasound, abdominal ultrasound, and serologic markers (CA19-9, peanut agglutinin, pancreatic oncofetal antigen, DU-PAN-2, carcinoembryonic antigen, alpha-fetoprotein, CA-50, SPan-1, tissue polypeptide antigen) (p863-4). Treatment approaches were surgery and surgery followed by external beam and/or intraoperative radiotherapy (p865).

Outcomes
Sensitivity and specificity of screening tests. Primary measures of effectiveness of prevention and treatment were 5-year survival rates, and procedure-associated adverse effects (p864).

Evidence
This guideline was adapted from a report prepared for the 1989 U.S. Preventive Services Task Force. MEDLINE was searched for English-language articles published from 1988 to October 1992 using the keywords pancreatic neoplasms, epidemiology, United States, Europe and Canada, smoking, risk factors, primary prevention, diet therapy, monoclonal antibodies, diagnosis, sensitivity and specificity, mass screening, false positive and false negative reaction and diabetes mellitus.

Values
The 13-member Task Force of experts in family medicine, geriatric medicine, pediatrics, psychiatry and epidemiology used an evidence-based method for evaluating the effectiveness of preventive health care interventions. Recommendations were not based on cost-effectiveness of options. Patient preferences were not discussed.

Background papers providing critical appraisal of the evidence and tentative recommendations prepared by the chapter author were pre-circulated to the members. Evidence for this topic was presented and deliberated upon in 1- to 2-day meetings, 2 to 3 times per year from January 1993 to June 1993. Consensus was reached on final recommendations.

Benefits, Harms, and Costs
There are no reliable screening tests to detect adenocarcinoma in asymptomatic individuals. The deep anatomic location of the pancreas makes palpation of small localized tumours unlikely. MRI and CT are expensive. ERCP and endoscopic ultrasound are invasive procedures, and therefore not appropriate for screening purposes (p863).

Studies of abdominal ultrasound in symptomatic patients with suspected disease report sensitivities of 40% to 98% and specificities up to 90% to 94%. The procedure is limited by visualization difficulties due to patient obesity, bowel gas and the 2-3 cm range of resolution (p863)

Serologic tumour markers are not tumour- or organ-specific. CA19-9 is the most widely accepted serodiagnostic test for pancreatic cancer. Among asymptomatic persons, specificities of 94% to 99% are reported. Due to the low prevalence of the disease, there is a large proportion of false positives. In a cohort study, over 10,000 asymptomatic persons were screened using ultrasound alone or CA19-9 + elastase-1. The likelihood of pancreatic cancer given a positive result was 0.5%, and only 1 of the 4 cancers detected could be curably resected.

Evidence on the effectiveness of early treatment by surgical resection and adjuvant radiotherapy is inconclusive. However, the 5-year survival of localized disease appears to be poor (p866).

In cohort and case control studies, smoking is consistently associated with an increased risk for developing pancreatic cancer, with relative risks ranging from 2 to 5 (p862). Also, former smokers have reduced risk when compared with current smokers. There is good evidence from RCTs that smoking cessation strategies are effective for reducing the risk of pancreatic cancer (p864).

Recommendations
Recommendation grade [A, B, C, D, E]  and level of evidence [I, II-1, II-2, II-3, III] are indicated after each recommendation. Citations in support of individual recommendations are identified in the guideline text.

• There is fair evidence to exclude routine screening for pancreatic cancer, specifically adenocarcinoma (from the PHE) using abdominal palpation, ultrasound or serologic tumour markers [D, II-2]
• There is fair evidence to consider smoking cessation counselling as a strategy to prevent pancreatic cancer [B, I, II-2].

Source Document
Morrison BJ. Prevention of pancreatic cancer. In: Canadian Task Force on the Periodic Health Examination. Canadian Guide to Clinical Preventive Health Care. Ottawa: Health Canada, 1994; 850-59.