Clinical Review

Early Identification of Pancreatic Cancer

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Because of the delayed presentation of definitive signs and symptoms of pancreatic cancer and the anatomic location of the pancreas, pancreatic tumors are rarely detected early. Typically in an advanced stage by the time of presentation, pancreatic cancer is associated with an extremely poor survival rate. It is important for clinicians to maintain an awareness of pancreatic cancer, including patient risk factors, diagnosis through appropriate imaging studies and laboratory testing, clinical presentation, and optimal treatment and management.



In the United States in the year 2012, it has been estimated that some 43,920 patients will receive a new diagnosis of pancreatic cancer, and about 37,390 will die of the disease.1 Although it represents less than 2% of new cancer diagnoses, pancreatic cancer is the fourth leading cause of cancer-related deaths in both women and men.2,3 Because the anatomic location of the pancreas makes the disease difficult to diagnose at an early stage, pancreatic cancer has a median survival of less than six months after diagnosis, and a 4.6% survival rate at 5 years.2 The current focus on pancreatic cancer is to improve survival through earlier diagnosis—before the tumor has reached an advanced stage.4

The incidence and mortality rates for pancreatic cancer have changed only minimally during the past 30 years. In recent decades, as reported in 2011 by the National Comprehensive Cancer Network (NCCN),5 the incidence of pancreatic cancer has increased steadily. Prevalence is greater in men than in women, and African-Americans have an increased incidence of pancreatic cancer, compared with whites. In the United States alone, the approximate medical costs associated with pancreatic cancer in 2006 amounted to nearly $1.9 billion.6

According to data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database,7 derived from cases reported from 17 SEER regions between 1975 and 2009, the median patient age for a diagnosis of pancreatic cancer between 2004 and 2008 was 72 years. Prevalence of pancreatic cancer was greatest (28.6%) between ages 75 and 84, and age-adjusted incidence was reported at 12.0 per 100,000 men and women per year.7

The US median age for pancreatic cancer–associated mortality between 2004 and 2008, as reported by SEER, was 73.7 Patients in the 75-to-84 age-group accounted for 30.5% of pancreatic cancer–related deaths. In terms of all patient deaths reported in the US between 2004 and 2008, the overall pancreatic cancer–­associated age-adjusted death rate was 10.8 per 100,000 men and women per year.7

In most cases, pancreatic cancer has a very unfavorable prognosis. It is estimated that 52% of all patients diagnosed with pancreatic cancer already have distant disease at the time of diagnosis; in 26%, cancer has already metastasized. According to data from the NCCN,5 survival rates for pancreatic cancer are 24% at one year after diagnosis, and 5% at five years. Treatment options eventually narrow down to palliative care.

Nevertheless, it is important for clinicians to be knowledgeable about pancreatic cancer, with an appreciation for the complexity of this disease. A clinical understanding of patients who are at high risk for pancreatic cancer may afford clinicians the opportunity to identify and treat pancreatic cancer earlier in the disease process.


The progression from normal ductal epithelium to pancreatic ductal adenocarcinomas occurs through noninvasive precursor lesions (usually pancreatic intraepithelial neoplasias [PanINs]) that undergo clonally chosen genetic and epigenetic changes in the process.8-10Intraductal papillary mucinous neoplasms and mucinous cystic neoplasms also play a role in the development of pancreatic cancers.8,11,12

PanINs represent the most commonly identified neoplastic precursor to invasive ductal adenocarcinomas,8,13 which account for at least 90% of all pancreatic tumors and are considered one of the most lethal among all solid malignancies.13-15 PanINs measure less than 5.0 mm in diameter and cannot ordinarily be detected on pancreatic imaging.8 PanINs can store somatic genetic changes identified in invasive pancreatic cancers; these changes increase at the same rate that cytologic and architectural atypia develop in the precursor lesions.8,10 The genetic and epigenetic variations associated with pancreatic cancer may help explain the rapid progression of the tumor to an advanced stage.8

Pancreatic Cancer and Diabetes

The correlation between diabetes mellitus and pancreatic cancer has been acknowledged for many years; patients with type 1 or type 2 diabetes have an increased risk for pancreatic cancer—by 40% to 100% in patients with long-term diabetes.16 In nearly one-third of patients who develop “late-onset diabetes,” this condition may be an effect (and thus, a “harbinger”16) of pancreatic cancer. In the recently diagnosed diabetic patient, the risk for pancreatic cancer is increased by four- to sevenfold, and 1% to 2% of patients diagnosed with diabetes at age 50 or older will develop pancreatic cancer within three years.16,17

Pancreatic cancer should not be ruled out in the differential diagnosis in a patient who receives a new diagnosis of diabetes, despite an absence of risk factors for diabetes, after age 70.3


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