Pancreatic Cancer: An Invisible Killer (1/3)

Written by Federico Citterich
Conceived and reviewed by Alessandro Rossetta

Pancreatic cancer is one of the deadliest malignancies, often remaining undetected until its late stages. With high mortality rates, aggressive progression, and vague, often delayed symptoms, developing an effective early detection method is crucial.

Pancreatic cancer, the uncontrollable mutation and growth of pancreas cells, is among the deadliest forms of cancer. Of every hundred people diagnosed with this cancer, only a small handful – just over ten – will still be alive five years later. But timing makes a difference. When the tumor is caught early, when it’s still localized and before it has had the chance to spread, survival improves significantly: in that case, nearly half of those diagnosed will still be alive after five years. However, if the cancer begins to invade nearby tissues, the odds drop sharply, leaving only a small fraction of patients with a chance at long-term survival. And when the disease reaches its most advanced stage, spreading to distant organs, survival becomes tragically rare – just a few out of every hundred will make it past those five years. In these numbers lies a stark truth: early detection can mean the difference between life and death.

Despite this, pancreatic cancer is relatively rare. With around 63,000 new cases diagnosed annually in the U.S. and a lifetime risk of developing it of 1 in 64, pancreatic cancer only accounts for about 3% of all cancers. How does one get pancreatic cancer, then? The exact causes aren’t always clear, but several risk factors can increase the likelihood, the major one being age. Most patients receive a diagnosis after the age of 50, with incidence peaking in their 60s and 70s. Among preventable risk factors, tobacco smoking is the most significant and well-studied. Smokers face a two- to threefold higher risk of developing pancreatic cancer compared to non-smokers, with evidence of a dose-dependent relationship and a beneficial effect of smoking cessation. Estimates suggest that between 15 and 30 out of 100 cases of pancreatic cancer are due to tobacco smoking. Additionally, the use of smokeless tobacco products may also elevate the risk.

Obesity and low physical activity have also been linked to pancreatic cancer. Certain dietary factors, including high consumption of saturated fats, low intake of fruits and vegetables, and frequent consumption of red and processed meats, are associated with an increased risk. However, the impact of other dietary factors – such as coffee – remains unclear. On the other hand, heavy alcohol consumption has been linked to an increased risk, whereas moderate drinking does not appear to have the same effect. Chronic pancreatitis¹, which may result from excessive alcohol intake, raises the risk of pancreatic cancer more than tenfold, with similar attributable risk between alcoholic and non-alcoholic forms of the condition.

In the context of diseases, diabetes is both a risk factor for and a potential consequence of early-stage pancreatic cancer. Long-term diabetes roughly doubles the risk of developing the disease. Additionally, pancreatic cancer can cause type 3c diabetes², and new-onset diabetes in elderly patients may serve as an early indicator of pancreatic cancer. Finally, gastrointestinal ulcers³ and prior gastrectomy⁴ have been associated with a slight increase in pancreatic cancer risk, though their overall impact on disease burden is minimal in modern medicine.

Genetic factors may also affect the likelihood of developing pancreatic cancer, with approximately 1 in 10 patients having a family history of the tumor. Certain hereditary conditions, such as Peutz–Jeghers syndrome⁵, are also known to increase the risk of developing the disease.

Despite being relatively rare, pancreatic cancer remains highly lethal. Globally, it holds the 12th position among the most frequently diagnosed cancers but stands as the 7th leading cause of cancer mortality. Part of what makes pancreatic cancer so lethal is its aggressive nature. Pancreatic cancer grows and spreads rapidly to nearby organs, even when it is small in size and in its early stages. The reason is related to the environment in which pancreatic cancer cells grow. Studies have shown that areas within pancreatic tumors have very low oxygen levels, a condition known as hypoxia. The lack of oxygen inside the tumor creates a hostile environment, where the tumor cells are struggling to survive. At first glance this may appear to be a favourable situation. However, in reality, it exerts a selective pressure that promotes the proliferation of the more malignant cells. In other words, in this oxygen-deprived environment, only the most adaptable and aggressive tumor cells survive, ultimately leading to a tumor composed entirely of highly aggressive cells. These cells become more and more invasive, meaning they can spread into surrounding tissues and organs even at the early stage of the tumor’s development. And when doing so, cancer cells often spread along the nerves, which helps them invade deeper tissues. This, along with the fact that the tumor stimulates the formation of a surrounding, dense tissue (stroma) that increases protection, makes pancreatic cancer extensively resistant and less responsive to most forms of treatment and therapies.  

Additionally, there are limited treatment options for this form of cancer. Surgical options for pancreatic cancer resection are not always possible to perform, since surgery is only an option when the cancer is detected early and remains confined to the pancreas. When it is impossible to remove the tumor surgically, chemotherapy can be used instead. Yet, due to the aggressiveness of the cancer, it is often ineffective.

 Consistent with the fact that only a minority of patients diagnosed with pancreatic cancer present with surgically-resectable disease, the disease frequently causes few, if any, symptoms before it develops to the advanced stage. Unfortunately, when symptoms do arise, they are often nonspecific – such as back pain, nausea, bloating, abdominal fullness, or changes in stool consistency. These vague symptoms are frequently attributed to benign conditions, which can lead to delays in diagnosis. Additionally, unlike breast, colon, or cervical cancer, there is no routine screening test for pancreatic cancer in asymptomatic adults. Accordingly, the development of early detection methods seems necessary.