Becky McCall

October 04, 2016

MUNICH — A combination of biomarkers could be used in noninvasive screening for pancreatic cancer in patients with new-onset diabetes, suggests new research presented at this year's European Association for the Study of Diabetes (EASD) 2016 Annual Meeting.

"This approach would both reduce the delay in diagnosis of pancreatic cancer and improve the prognosis of diabetic patients with this malignant disease," said lead author of the study, Pavel Škrha, MD, from Charles University, Prague, Czech Republic.

Pancreatic cancer has an extremely poor prognosis because the cancer-specific symptoms are evident only at an advanced stage, noted Dr Škrha, who reported his results in a poster.

But up to 80% of patients with pancreatic cancer are either prediabetic or diabetic in the presymptomatic phase, suggesting a potential opportunity to identify the cancer early in this high-risk population, with new-onset diabetes (duration of less than 2 years) being most commonly associated with pancreatic cancer.

Dr Škrha and his colleagues found that concentrations of a currently employed biochemical marker, CA 19-9, and two promising new ones, microRNA-196 and microRNA -200, were significantly raised in any patients with pancreatic cancer, but levels were not elevated in patients with diabetes but no pancreatic cancer or in controls with neither disease.

"Ultimately, we want to find a marker that could enable us to diagnose pancreatic cancer as early as possible," said Dr Škrha, adding that "currently, people only get diagnosed when they present with symptoms connected with the cancer such as excessive weight loss."

Asked to comment, William Phelps, PhD, program director at the American Cancer Society, said that methods to diagnose pancreatic cancer early are desperately needed, because these cancers are typically discovered too late for treatment impact.

"The concept of combining biomarkers is good, and increasingly we are likely to see more [of this]. Whether these three markers will track out in the future is unknown, because it is still early," he noted.

But "as a preliminary investigation, the combination looks okay, but the error bars overlap, so larger numbers of patients are needed to explore this further. The approach, however, is good. I like the incorporation of microRNAs too, and there is potential here."

New-Onset Diabetes and Pancreatic Cancer Occur Together

The aims of the study led by Dr Škrha were twofold: to examine the prognostic ability of the biomarkers, and second, to determine the specific prevalence of both new-onset and long-term diabetes in pancreatic-cancer patients.

Of 77 patients with pancreatic cancer — diagnosed either by needle biopsy or by surgical resection of the tumor — 44 patients (57%) also had new-onset diabetes, 16 (21%) had long-term diabetes, and 17 (22%) had no diabetes.

Also tested were 34 patients with type 2 diabetes but without pancreatic cancer, and 30 controls, with neither diabetes nor pancreatic cancer.

Serum from each patient group was tested for CA 19-9, microRNA-196, and microRNA-200 biomarkers.

While sensitivity and specificity (to detect pancreatic cancer) of CA 19-9 alone were 85% and 73% respectively, a combination of CA 19-9, microRNA-196, and microRNA-200 improved both tests to 95% and 77%.

"It seems that using the combined test improved the sensitivity and specificity, so the microRNA provided some additional information to CA 19-9," Dr Škrha observed.

There were almost three times as many patients with pancreatic cancer who had new-onset diabetes than long-term type 2 diabetes.

"We found that glucose metabolism disorder is quite prevalent (80%) in patients with pancreatic cancer, reflecting the literature, and nearly 75% of patients with both diabetes and pancreatic cancer had new-onset diabetes," remarked Dr Škrha, in an interview with Medscape Medical News.

Combined Test Also Identified More Early-Stage Cancer

The combined biomarker test also identified more early — stage I and II — pancreatic cancers.

"When the 77 pancreatic-cancer patients were evaluated according to cancer stage, [only] six had early-stage cancer. All six were identified with the combined test, but only two by the CA 19-9 test alone," Dr Škrha observed.

"This suggests that the combined test is better at identifying early pancreatic cancer than CA 19-9 alone," he pointed out.

Targeted Screening for Pancreatic Cancer?

Dr Škrha stressed that new-onset diabetes can often "be the first symptom of pancreatic cancer," which is why ways of pinpointing these individuals is needed.

But wide-scale screening is not a feasible option due to large numbers of new diabetes cases but a relatively low incidence of pancreatic cancer in the general population.

"Around 10% of the general population in the Czech Republic has diabetes compared with only a very small number of patients with pancreatic cancer."

"It's an increasingly concerning problem, not least because pancreatic cancer is difficult to treat but because in the US, for example, pancreatic cancer is estimated to become the second-leading cause of cancer-related death in 2030."

He suggested that it might be more justifiable to screen a subgroup of patients with new-onset diabetes or prediabetes who show certain risk factors for pancreatic cancer.

For example, "If the patient is lean but has diabetes, or has experienced rapid weight loss, or requires rapid escalation of diabetes medication, for example, it would be good to focus on these patients for [pancreatic-cancer] screening."

With further validation, the use of a combination of biomarkers might emerge as less expensive than other diagnostic methods — for example, computed tomography (CT) — as well as being a speedier way of identifying patients with pancreatic cancer, according to Dr Škrha.

Moving forward, he said he plans to enroll patients with new-onset diabetes into a larger, prospective study and use the combination of tests to explore further whether there is any elevation in these biomarkers in patients with pancreatic cancer.

Dr Phelps noted that any potential screening program would need careful consideration.

At the general population level, "this would be challenging for lots of reasons, including the financial standpoint, but targeting people with early-onset diabetes is interesting, and certainly there is a connection between obesity and diabetes and a connection between obesity and pancreatic cancer."

And Ellena Badrick, PhD student from the Farr Institute of Health Informatics, University of Manchester, United Kingdom, who has published on this topic previously, said that biomarkers were key to this field of work, where early identification of disease is essential.

But she added, "I would be cautious about overinterpretation of their results at this stage.

"To determine whether the biomarkers make better predictions about pancreatic-cancer risk in people with newly diagnosed type 2 diabetes, the control group needed is people newly diagnosed with type 2 diabetes who don't have pancreatic cancer.

"The poster shows results comparing biomarkers among pancreatic-cancer cases with controls (without type 2 diabetes) and long-term type 2 diabetes, which is not ideal. I would like to know if the research group is able to do the comparison I've suggested," she commented to Medscape Medical News.

Dr Škrha, Dr Phelps. and Ms Badrick have declared no relevant financial relationships.

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European Association for the Study of Diabetes 2016 Annual Meeting; September 15, 2016; Munich, Germany. Abstract 572.


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