Pancreatic cancer is often diagnosed at late stage, leading to poor survival rates, but advances in molecular profiling and development of gene-targeted drugs could offer hope for the future

Despite only making up 3% of newly diagnosed cancers, pancreatic cancer is one of the biggest killers, according to Professor John Zalcberg, medical oncologist and clinical scientist at Monash University’s School of Public Health.

Pancreatic cancer moved from the fifth most common cause of death from cancer in 2019 to third most common last year, and incidence appears to be slowly increasing at a bit under 1% per year.

While traditional risk factors such as a history of smoking, alcohol use and chronic pancreatitis are contributing factors, Professor Zalcberg says we are an aging population and our lifestyle may also be involved, with rising rates of obesity and type 2 diabetes playing a role.

While treatments are improving, he says the five-year survival rate is just 10-12%, but early diagnosis and definitive treatment of the tumour can make a difference.

Warning signs

The onset of painless jaundice is a warning sign of a tumour in the head of the pancreas, Professor Zalcberg says. If the tumour causes biliary obstruction early on, people may be picked up at an earlier stage—but this is often not the case.

“But when people present with a vague history of nonspecific symptoms, without the tumour involving their pancreatic biliary duct, and now you find they’ve got a large mass, encroaching on the blood vessels, or it has spread to the liver, then we are dealing with a much more serious problem. So clearly, the prognosis for an individual depends on the stage at which they present.”

Other warning signs include unintended weight loss, particularly with ongoing and persistent GI symptoms, especially if the patient also has recent onset of type 2 diabetes, a history of smoking and obesity. Steatorrhea and diarrhoea may also be reasons to investigate too, Professor Zalcberg says.

Further investigations are also warranted if pancreatic abnormalities are picked up on CT scans that have been ordered for other reasons, but Professor Zalcberg says diagnosis should only be confirmed based on histology or cytology obtained via endoscopy or percutaneous biopsy.

Chemotherapy prior to surgery

Neo-adjuvant or early chemotherapy is often used before surgery.

“Unless it’s a very small, incidental finding of a tumour, potentially in the tail or the body of the pancreas, we will be thinking about whether there is a role for neoadjuvant chemotherapy…in order to both shrink the tumour itself, but also to try and deal with any micro metastatic disease that has already left the primary tumour, before going on to surgery. And our impression is that that’s probably the way in the future.”

Decisions on how to proceed are made by a multi-disciplinary team— Professor Zalcberg says GPs are most welcome to attend, but recognizes that time constraints often rule this out.

Supporting quality of life

Surgery can have a major impact on the patient’s quality of life, and GPs play a crucial role in post-operative health, pain control and monitoring replacement enzymes.

“The GP is an essential partner in trying to help bring that patient back to some semblance of normal life,” he says.

Common issues to manage after surgery can include pain, diarrhoea, drainage issues and further weight loss and nutritional deficiencies.

However, it needs to be emphasized that only 10-15% of newly diagnosed patients will end up on a surgical path.

“The remainder either have locally advanced disease or metastatic disease in which case they’re inoperable and likely having chemotherapy with a view to ‘maybe it’ll get smaller and suitable for surgery,’ but maybe not.”

Pain control

“Debilitating pain is probably the most distressing symptom for many, many patients.”

Three quarters of newly diagnosed patients will develop pain and it can be debilitating.

“When you say to a patient, ‘how do you rank your pain’ and they say it’s 10 out of 10, you’re dealing from my point of view with a medical crisis. So, pain control is really critical.”

Managing opioid side effects, such as fatigue or constipation, is also crucial.

Nutrition and enzyme replacement

General nutrition is also important.

“People have often lost further weight as a result of their treatment. And we need to think about how we can provide supplements as part of our dietary advice,” Professor Zalcberg says.

He recommends referring to a dietitian and considering pancreatic enzyme replacement therapy, which is often appropriate for people with pancreatic malfunction to help alleviate dietary, nutritional and metabolic consequences of major surgery.

He says that although no amount of enzyme replacement deals with the fact that the pancreas has been resected, pancreatic enzymes are critical in normal digestion and it’s important not to give up too early when it comes to finding the right dose.

“It can be a bit of a titration exercise to get the dosage right,” he says, adding that the patient will be the one to decide in the end whether it’s helping.

It’s also important not to assume they’ve been initiated on enzyme replacement therapy at discharge—one recent survey found that about 50% of patients at one hospital had not been, Professor Zalcberg says.

Involving a dietitian can also make a big difference.

“To be perfectly honest, I usually refer people to a dietician and get their input. They do have the expertise and the time required to actually monitor this carefully.”

They also help ensure the patient gets sufficient calories.

Working with a palliative care team and providing good psychological support is another important aspect to consider, he advises.

A silver lining?

Professor Zalcberg says in the US molecular profiling or genomic profiling of the tumour has become standard.

“In about 10% of patients, you find a mutation or a change in the tumour, which lends itself to a different therapy. Some tumours, for example, have abnormalities in a gene that people may have heard of called HER2, amplification of which is much more common in breast cancer for example, but it does occur in pancreatic cancer,” he says.

As for the other 90% of patients, he says most have a mutation in a different gene called RAS. Although right now that doesn’t alter therapy, Professor Zalcberg is hopeful. He points to lung cancer, where effective drugs to inhibit RAS genes are already in use. Five companies are currently working on drugs to inhibit the type of RAS abnormality that occurs in pancreatic cancer, he adds.

“It’s hard to be optimistic, in some ways, with a disease that’s had such a terrible impact on so many people. But having said that, we’ve seen that the genetic revolution is impacting on patients lives.” He says specific genetic abnormalities have dramatically impacted on the prognosis of patients with other tumour types and hopefully this is not far away for the majority of patients with pancreatic cancer.

“Knowing the molecular profile and having appropriate drugs targeting these genetic biomarkers in breast cancer, colon cancer, lung cancer etc. has had an impact. Why shouldn’t it have an impact in pancreas cancer? I think it clearly will.”

Listen to Professor Zalcberg discuss management options for pancreatic cancer on The Clinical Takeaway podcast.