Screening for hereditary pancreatic cancer – pro
The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening for pancreatic cancer in asymptomatic adults using abdominal palpation, ultrasonography, or serologic markers. The USPSTF found no evidence that screening for pancreatic cancer is effective in reducing mortality. There is a potential for significant harm due to the very low prevalence of pancreatic cancer, limited accuracy of available screening tests, the invasive nature of diagnostic tests, and the poor outcomes of treatment. As a result, the USPSTF concluded that the harms of screening for pancreatic cancer exceed any potential benefits.
There are some special groups in which screening may be reasonable. These include hereditary pancreatitism chronic pancreatitits and thos with a strong family history.
An individual’s risk of developing pancreatic cancer increases with the number of affected first-degree relatives, and it is estimated that hereditary factors account for at least 5% of pancreatic cancers.2 Familial pancreatic cancer (FPC) is inherited in an autosomal dominant manner, with variable penetrance. In order to diagnose FPC, it is necessary to obtain an accurate and thorough family history with particular emphasis on the oncologic history. While it is important to ascertain any family history of pancreatic cancer, it is also important to screen for a personal and family history of extrapancreatic malignancies, and to obtain a family cancer history beyond first-degree relatives, if possible. The family history allows the clinician to determine if prior cases of pancreatic cancer in relatives are more likely to be familial or sporadic.
If a diagnosis of FPC is made in conjunction with a family history of extrapancreatic malignancies, consideration should also be given to a syndromic FPC. Hereditary pancreatic cancer has been associated with colorectal cancer in the Lynch syndrome II variety of hereditary nonpolyposis colorectal cancer (HNPCC), with breast and ovarian cancer (breast–ovarian cancer syndrome), Peutz–Jeghers syndrome, and melanomas in the familial atypical multiple mole melanoma (FAMMM) syndrome. A family history of early pancreatitis suggestive of hereditary pancreatitis is also an important risk factor for subsequent pancreatic adenocarcinoma.
Although there are no consensus guidelines on what defines FPC, an assessment of the risk of developing pancreatic cancer according to the number of affected relatives is useful in clinical practice. Genetic testing might be a useful adjunct in the management of a patient with FPC, but should be performed only after appropriate genetic counseling. Many important genes that have at least a partial role in FPC, both syndrome-associated and nonsyndromic, have been identified. In a multicenter study, 40% of patients with a history of hereditary pancreatitis developed pancreatic adenocarcinoma by 70 years of age.6 Testing for the cationic trypsinogen gene (PRSS1), which is associated with hereditary pancreatitis, is available. The FAMMM syndrome, described in 1975, is associated with a germline mutation of the p16 tumor suppressor gene (CDKN2A). Testing for p16 mutations helps identify those patients at risk for pancreatic malignancy in families with a history of melanomas and pancreatic cancer. The majority of FPC cases, however, are nonsyndromic.
CT scanning, while critical in the management of pancreatic adenocarcinoma, has not proven to be of definitive benefit in screening for pancreatic malignancy in FPC, mainly because of a lack of adequate resolution to detect dysplasia. For CT scanning to exert a benefit in terms of mortality, it must detect either premalignant changes or early malignancy, so that curative surgery can be performed.
In conclusion, genetic counselling should precede radiological screening, an attempt to better define a familial syndrome should be made before screening, and there is no evidence that any screening is supror to another or to no screening at all. There is little evidence for CT scan based screening.
U.S. Preventive Services Task Force (USPSTF). Screening for pancreatic cancer: recommendation statement. Rockville (MD): Agency for Healthcare Research and Quality (AHRQ); 2004 Feb. 3 p. [4 references]
Ulrich CD; Consensus Committees of the European Registry of Hereditary Pancreatic Diseases, Midwest Multi-Center Pancreatic Study Group, International Association of Pancreatology.Pancreatic cancer in hereditary pancreatitis: consensus guidelines for prevention, screening and treatment.Pancreatology. 2001;1(5):416-22
Ellis I, Lerch MM, Whitcomb DC; Consensus Committees of the European Registry of Hereditary Pancreatic Diseases, Midwest Multi-Center Pancreatic Study Group, International Association of Pancreatology. Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues.
Pancreatology. 2001;1(5):405-15
Rajesh N Keswani, Amy Noffsinger and Irving Waxman A family history of pancreatic cancer, Nature Clinical Practice Gastroenterology & Hepatology (2006) 3, 586-591
Kanjeekal S, Biagi J, Walker-Dilks C. PET imaging in pancreatic cancer: recommendations. Toronto (ON): Cancer Care Ontario (CCO); 2009 Jan 19. 20 p. (Recommendation report – PET; no. 5). [34 references]