Stool-based screening shows promise in early detection of pancreatic cancer
Fecal microbiota-based screening may help with early detection of pancreatic ductal adenocarcinoma, according to a study published in Gut.
“The study identified a fecal microbiome signature that robustly detects pancreatic cancer at high disease specificity,” Nuria Malats, MD, PhD, study author and head of the genetic and molecular epidemiology group at the Spanish National Cancer Research Center in Madrid, told Healio. “The fact that this uses noninvasive obtained samples (stool) makes this panel a potential test towards cost-effective [pancreatic ductal adenocarcinoma (PDAC)] screening and monitoring.”
Malats and colleagues analyzed stool and saliva samples from a Spanish case-control study that included 57 newly diagnosed cases, 50 controls and 29 patients with chronic pancreatitis in the discovery phase, as well as 76 cases from a German case-control study in the validation phase.
According to study results, fecal metagenomic classifiers performed significantly better compared with saliva-based classifiers, with investigators noting that fecal classifiers identified patients with PDAC with an accuracy of 0.84 area under the receiver operating characteristic curve (AUROC) in the Spanish cohort, based on a set of 27 microbial species. This value improved to 0.94 AUROC after investigators combined their microbiome-based predictions with serum levels of carbohydrate antigen (CA) 19–9, an FDA-approved, low-specificity PDAC diagnostic biomarker.
Investigators further validated the classifiers in the German PDAC cohort with an accuracy of 0.83 AUROC and confirmed PDAC disease specificity against 25 publicly available gut metagenomes from global study populations.
“The described fecal microbiome signatures enabled robust metagenomic classifiers for PDAC detection at high disease specificity, complementary to existing markers and with potential towards cost-effective PDAC screening and monitoring,” Malats and colleagues concluded.
Perspective
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Currently, there is a lack of an accurate and noninvasive screening method for pancreatic cancer. The increased utilization of genetic testing has identified a growing number of patients at elevated risk for pancreatic cancer. These “high-risk individuals” are offered the opportunity to undergo yearly imaging tests, such as MRI and endoscopic ultrasound, to screen for pancreatic cancer. Yearly imaging is a costly endeavor, and the yield for finding clinically significant lesions is somewhat low. Also, this method cannot be offered to the general population due to its cost and invasiveness. Less costly and noninvasive tests are needed to screen asymptomatic patients for this deadly disease.
Low counts of bacteria exist in the pancreatic duct, and it is postulated that certain microbes may promote carcinogenesis. Direct or indirect assessment of the microbiome signature of the pancreas may allow early detection of pancreatic cancer or identify patients at risk. Using a state-of-the-art metagenomic approach, Kartal and colleagues assessed the microbiome in the feces and saliva of patients with different stages of pancreatic cancer and chronic pancreatitis, as well as in healthy controls. They found that a fecal panel consisting of 27 organisms combined with serum CA19-9 showed excellent recognition of pancreatic cancer from controls (0.94 AUROC). The stool analysis alone also (without CA19-9) produced very good detection (0.84 AUROC). In addition, they found certain bacteria increased in the stool of pancreatic cancer patients also was found in pancreatic mass resection or biopsy specimens.
These findings hold great promise for stool microbiota testing as a diagnostic test for pancreatic cancer. However, further validation is required before it can be implemented in clinical practice. Fecal testing is unlikely to replace imaging tests for patients who present with symptoms of pain, jaundice or weight loss. Instead, the hope is that it may someday be used to screen asymptomatic individuals for early cancer detection. Large longitudinal studies are needed in which stool testing is obtained yearly in a high-risk population to determine if changes in the microbiome correlate with the development of cancer. Such a study would require collaboration of many centers with expertise in familial pancreatic cancer-screening. If the test performs well in the high-risk cohort, it may even be applied in the general population or in those with other risk factors, like smoking or diabetes.
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