The simple fact that the U.S. Preventive Services Task Force
(USPSTF) recommended against routine screening for pancreatic cancer in
asymptomatic adults (we discussed in the previous post), and just recently
adjusted its position, shows clearly that the screening effectiveness for
pancreatic cancer is still more than questionable, and more research is needed to
develop the cost-effective, safe, and efficient ways of the early tumor
detection. However, shift in the general attitude of the professionals’
approach allows allocating more significant amount of funds for the
investigation and trials.
Screening Tests
Accuracy
Adenocarcinoma is the principal form of pancreatic neoplasm
for which screening has been considered. So far, there are no reliable
screening tests for detecting pancreatic cancer in asymptomatic persons, which
will allow catching the problem on the early stages, when the disease is still
curable. The deep anatomic location of the pancreas makes detection of small
localized tumors extremely challenging during the routine abdominal
examination. Even in patients with confirmed pancreatic cancer, an abdominal
mass is palpable in only 15–25% of all cases.
Imaging procedures such as magnetic resonance imaging and
computed tomography are too costly to use as routine screening tests, while more
accurate tests such as endoscopic retrograde cholangiopancreatography and
endoscopic ultrasound are inappropriate for screening asymptomatic patients due
to their invasiveness. Abdominal ultrasonography is a noninvasive screening
test, but there is little information on the usefulness of abdominal ultrasound
as a screening test for pancreatic cancer in asymptomatic persons. In
symptomatic patients with suspected disease it has a reported sensitivity of 40–98%
and specificity as high as 90–94%. Conventional ultrasonography is limited by
visualization difficulties in the presence of bowel gas or obesity and by its
range of resolution (2–3 cm). Even tumors <2 cm in diameter are frequently associated
with metastatic disease, thus limiting the ability of ultrasound to detect
early disease.
Most persons with pancreatic malignancy have elevated levels
of certain serologic markers such as CA19-9, peanut agglutinin, pancreatic
oncofetal antigen, DU-PAN-2, carcinoembryonic antigen, α-fetoprotein, CA-50, SPan-1,
and tissue polypeptide antigen. None of these markers is, however, tumor specific
or organ specific; elevations of various serologic markers also occur in
significant proportions of persons with benign gastrointestinal diseases or
malignancies other than pancreatic cancer.
Most of these markers have been studied exclusively in
high-risk populations, such as symptomatic patients with suspected pancreatic
cancer. CA19-9 has probably achieved the widest acceptance as a serodiagnostic
test for pancreatic carcinoma in symptomatic patients, with an overall
sensitivity of approximately 80% (68–93%) and specificity of 90% (73–100%);
while the overall sensitivity was highest in patients with more advanced disease
stages.
Among healthy subjects, CA19-9 has good specificity (94–99%)
but nevertheless generates a large proportion of false-positive results due to
the very low prevalence of pancreatic cancer in the general population.
A study of a mass screening of more than 10,000 asymptomatic
persons for pancreatic cancer in Japan, using either ultrasonography alone or
CA19-9 plus elastase-1, found the likelihood of pancreatic cancer given a
positive screening test to be 0.5%; only one of the four cancers discovered
could be curably. The predictive value of a positive test could be improved if
a population at substantially higher risk could be identified. Diabetes mellitus
in older adult patients might be useful as a marker for a population at high risk
of having pancreatic cancer. Cohort studies have reported incidences of
pancreatic cancer among diabetic patients ranging from 51 to 166/100,000 person-years.
We will review several studies which are give hope for the
possibility of development for the efficient screening procedure for pancreatic
cancer early detection in asymptomatic population.
Northwestern University
Study, 2007
Optical technology developed by a Northwestern University with
proven efficiency dealing with the early detection of colon cancer has been
successfully used in research for early detection of pancreatic cancer as well.
Vadim Backman and Yang Liu teamed up with physicians at Evanston Northwestern
Healthcare (ENH) to confirm they could detect both early- and advanced-stage
pancreatic cancer without touching or imaging the pancreas.
The extraordinarily sensitive technique, which is minimally
invasive and takes advantage of certain light-scattering effects, can detect
abnormal changes in cells lining the duodenum even though the cells appear
normal when examined with a conventional microscope, detecting the changes which
could accurately predict the presence of cancer.
More than 30,000 people in the United States die each year
from pancreatic cancer. The overall five-year survival rate is less than 5
percent; most patients die within the first two years. If detected early, when
the tumor can be successfully removed, however, the survival rate is 100
percent if a precancerous lesion is found and 50 percent for a stage 1 cancer.
“Using endoscopy and taking biopsies of the pancreas are
extremely risky procedures that are not used on asymptomatic patients,” said
Backman. “When a patient becomes symptomatic, it is too late. This creates a
vicious cycle that we want to break.
“We have found that we can take measurements safely in the
duodenum and use a biological phenomenon called the 'field effect' to our
advantage,” he said. “If you have a precancerous or cancerous lesion in the
pancreas, even tissue that looks normal and is away from the lesion --
including in the duodenum, a different organ than the pancreas -- will have
molecular and other kinds of abnormal changes. No one can detect these changes
earlier than we can.”
“We also found that
the diagnostic performance of the technique is not compromised by risk factors
in the patients,” said Liu. “The markers don't depend on age -- the cells know
if they are old or if they are cancerous. The markers do not change if the
patient is a smoker. And the markers do not change with the location, stage or
size of the tumor in the pancreas.”
Most cancers in the pancreas originate from the main
pancreatic duct, a 10-centimeter-long duct located in the pancreas that
perforates the duodenum, the first and shortest part of the small intestine.
The pancreatic duct is difficult to reach and if attempted, it is a risky
procedure with a 20 percent chance of significant complications, including
acute pancreatitis.
In the study, biopsies of normal-looking tissue were taken
from the duodenum near the opening of the pancreatic duct for analysis. For
each sample, light is shined on the tissue. The light scatters and some of it
bounces back to sensors in the fiber-optic probe. A computer analyzes the
pattern of light scattering, looking for the “fingerprint” of carcinogenesis in
the nanoarchitecture of the cells.
The researchers found the technique identified with 100
percent accuracy each person who had a resectable (the tumor can be removed
surgically) cancerous tumor in the pancreas. Some people were identified who
did not have a tumor; it is uncertain whether this is a false finding or if it
means those people could be at risk for developing pancreatic cancer and need
to be watched closely.
The method combines two complementary technologies developed
by Backman and colleagues in his lab: four-dimensional elastic light-scattering
fingerprinting (4D-ELF) and low-coherence enhanced backscattering spectroscopy
(LEBS). The researchers found that the two combined work better than one alone
in pancreatic cancer screening.
University of
Michigan Comprehensive Cancer Center Study, 2011
Researchers at the University of Michigan Comprehensive
Cancer Center have identified a protein that shows distinct changes in structure
between pancreatic cancer, non-cancerous diseases and normal blood serum. The
protein also changes from early stage pancreatic cancer to advanced disease. The
finding suggests a blood test could serve as a potential screening tool to
detect pancreatic cancer -- which has the worst prognosis of any cancer type --
at an earlier, more treatable stage.
In this study, senior study author David M. Lubman and
colleagues looked at proteins in the blood, and identified one, haptoglobin,
that is in fairly high abundance. Haptoglobin is a type of glycoprotein, a
category of proteins that has complex chains of sugar groups attached to it.
These sugar groups are highly regulated in normal cells but develop a different
structure in cancer cells.
Because haptoglobin appears in abundance in serum, it is
easy to pull out and isolate from the blood serum with an antibody. The
researchers could then look at the structure of the sugar groups from the
haptoglobin in the serum using a mass spectrometer, which is a device that
separates and identifies molecules based on their molecular weight. They found
it was easy to see the changes in the structure of the sugar groups from serum
samples of pancreatic cancer versus non-cancerous disease, with distinct
changes in structure or the amount of each structure present for each stage of
pancreatic cancer versus pancreatitis, diabetes or normal samples.
Researchers are looking to develop a method that would allow
them to evaluate hundreds of samples at once. Eventually, they hope this would
lead to a test in which patients submit blood samples through their local
doctors' offices, which are then sent to centralized laboratories for
processing.
University of Vermont
Study, 2011
A screening modality that combines serum carbohydrate
antigen (CA) 19-9 and endoscopic ultrasound (EUS), applied to persons at high
risk for pancreatic cancer appears to be effective, based on the results of a
feasibility study conducted by researchers from the University of Vermont.
“Our hypothesis was that a high-risk population identified
by age and at least one first-degree relative with pancreatic cancer can be
successfully screened,” said lead author Richard Zubarik, MD. “Our objective
was to determine whether early pancreatic neoplasia can be detected in a
high-risk population by using tumor marker CA 19-9 followed by targeted EUS. We
also sought to determine whether this protocol was more likely to detect early-stage
pancreatic cancer than standard means of detection,” he said.
“As a sole screening test, it would not be appropriate, but
it is a way of enriching the population of patients,” Dr. Zubarik added.
Elevated levels of CA 19-9 indicate screening with EUS with fine-needle
aspiration (FNA) biopsy, “which improves the specificity dramatically.”
Traditionally, CA 19-9 has performed poorly as a screening
modality for pancreatic cancer in studies of the general population, but those
studies have included patients younger than age 50 years or have employed
insensitive imaging modalities. More recent screening protocols have focused on
populations at high risk for pancreatic cancer, as this study did.
Regarding the decision to use CA 19-9, Dr. Zubarik noted
that it is inexpensive and is relatively sensitive (85%) and specific
(90%-95%). The study suggests that potentially curative pancreatic cancer can
be identified with CA 19-9 testing combined with targeted EUS, and that stage I
pancreatic cancer is more likely to be found using this screening protocol than
with standard means of detection, Dr. Zubarik concluded. The potential
advantages of this strategy include acceptable rates of disease diagnosis and
exclusion, as well as acceptable costs, he added. The cost of detecting one
pancreatic neoplasia as part of the protocol was $8,430.75, while detecting one
adenocarcinoma cost $41,133.
In spite of the noticeable positive development, However,
Dr. Ma, involved in the study, suggested that this screening protocol is still
cannot be recommended for clinical applications due to the several obstacles. Only
70% to 80% of pancreatic cancer patients express CA 19-9, so this approach
will not pick up the other 30% who have pancreatic cancer but do not express
this biomarker, he pointed out. "We need a better, more specific serum
biomarker for pancreatic cancer screening than CA 19-9." In addition,
EUS fine-needle aspiration (FNA) is highly complex, operator-dependent, and
requires specialized expertise. "The centers that can do good, safe EUS
FNA of the pancreas are often confined to tertiary centers, posing a limitation
to large-scale screening," he said.
Sources and Additional
Information:
