How to explain the galloping incidence of pancreatic cancer?

In constant growth, in terms of incidence and mortality, pancreatic cancer could become in the 2030s, in Europe and the United States, the most widespread cancer after lung cancer. In any case, this is the alert launched by French doctors who recently confided in our colleagues from the newspaper The world. “In France, the incidence is galloping, a doubling has already taken place between 2000 and 2006, then between 2006 and 2012. And while mortality from all other cancers has decreased, this one has not benefited from progress current”alerted Vinciane Rebours, head of the pancreatology department at Beaujon hospital in Clichy, in the Hauts-de-Seine.

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Although it is still relatively rare compared to cancers of the lung, breast, prostate or even the colon, this cancer has seen the number of new cases increase by 3% each year in France. And with it, the number of deaths. Belgium is no exception to this upward trend. In 15 years, the number of new cases has doubled, from 1,068 in 2004 to 2,043 in 2020, including 1,015 women and 1,028 men. In more than 90% of cases, these were pancreatic adenocarcinomas.

Diagnoses at a metastasized stage

In our country, pancreatic cancer is today in 9th place in terms of incidence among all cancers and in 4th position in terms of mortality. For this reason, the concern displayed by our French neighbors seems to be less acute here. But Dr Véronique Le Ray, medical director and spokesperson for the Foundation against Cancer (FCC) specifies that “in addition to the increase in cases, the thing that seems most worryingc’is that more than 50% of these cancers are diagnosed at a metastasized stage”.

This is because, unlike breast or colon cancer, among others, this one does not benefit from organized screening. “To date, there is no method for systematic early detection of this cancer.confirms the medical director of the FCC. It also lacks diagnostic and predictive biological markers and it is difficult to obtain a histological sample because the tumor is often difficult to access with a small target volume.. A track for the future would be the metabolic signature of cancer, by identifying, for example, the expression of amino acids, linked to a risk of pancreatic cancer multiplied by two. This would allow the disease to be detected two to five years before a classic diagnosis”. Being able to identify circulating biomarkers, infinitesimal traces of tumor DNA circulating in the blood, is moreover a widely explored and promising avenue.

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As for the hereditary factor, with regard to chronic family pancreatitis with risk of cancerization, “genetic mutations BRCA1 and BRCA2 (BReast CAncer mutation or deletion) are known to lead to an increased risk of developing pancreatic cancer, further specifies Dr. Le Ray. The breast-ovary syndrome, associated with a mutation of the BRCA 1 and 2 genes, in fact exposes you to a risk of pancreatic cancer 3.5 to 10 times higher than normal. In this case, screening is possible but it is expensive and cumbersome, insofar as it is done by endoscopy under general anesthesia.”.

Nevertheless, for the moment, one of the few possible ways to stop the progression of this dreadful cancer would be better screening for people at risk, in this case those who have cases of this cancer in their family. or those with genetic chronic pancreatitis, although no specific gene predisposing to familial pancreatic cancer has yet been identified.

Causes still ill-defined

And if the diagnosis is late, it is also because pancreatic cancer can remain “silent” or asymptomatic for years. In the vast majority of cases (80%), when symptoms appear (abdominal pain, jaundice, rapid weight loss, recent diabetes, etc.), the disease is most often already at a very advanced stage, with the presence of metastases . This is indeed what is observed in more than half of the cases, while the tumor already measures about 3 cm when it is discovered.

Another peculiarity of pancreatic cancer is that the precise causes do not yet seem clearly and fully defined. “We know that smoking (Editor’s note: involved in 20% to 30% of deaths linked to pancreatic cancer)diabetes, obesity and alcohol, among others, increase the riskcontinues Dr. Le Ray. But these risk factors alone do not explain everything”. If we must also take into account the aging of the population, knowing that the median age at the time of diagnosis is 70 years, some studies evoke the role of ultra-processed food or exposure to pollution .

Rarely operable cancers

Diagnosed at a “locally advanced” (30% of cases) or metastatic (50%) stage, pancreatic cancers are rarely operable. And when there may be surgery (which is the case for two out of ten patients), it is particularly heavy, with high operating risks, the tumor having invaded the blood vessels of the abdomen, which are vital. For the 20% of operable cases, the intervention is done either straight away or after chemotherapy (also planned postoperatively) and/or radiotherapy for borderline cases, with prognoses which unfortunately remain unfavourable.

As for immunotherapy, which consists of stimulating the patient’s immune system to kill cancer cells, although it has so far shown some effectiveness in lung cancer and melanoma, it still does not give convincing results in pancreatic cancer. “The tumor is protected by a micro-environment that hinders efficiency drugs that cannot penetrate, explains Dr. Le Ray. Immunotherapy is therefore not effective. Also, the biology is unfavorable. There tumor is self-sufficient: it grows despite the few vessels present to feed it. The division of these cells is unlimited and resists apoptosis (programmed cell death) and chemotherapy agents.

So many realities that explain the complexity and difficulty of overcoming this cancer. In this context, hope will perhaps come from the integration of artificial intelligence data on the various imaging examinations carried out so as to be able to intervene earlier. Be that as it may, in terms of prevention, the twelve recommendations of the International Association for Research on Cancer remain applicable, even if they are not specific to pancreatic cancer. Namely, among other things: do not smoke and avoid passive smoking, maintain a healthy weight, limit alcohol consumption, have sufficient physical activity, limit the consumption of red meat and in particular processed products (charcuterie),…

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