Prioritising investment and research into pancreatic cancer treatment

Prioritising investment and research into pancreatic cancer treatment
© iStock/Chinnapong

Chris Macdonald, Head of Research at Pancreatic Cancer UK explains why increased investment and research in pancreatic cancer treatment and symptoms are urgently needed.

Early diagnosis is one of oncology’s greatest tools in giving cancer patients the best chance of survival. In recent years, evolving research across many common cancer types has facilitated better diagnostic procedures and preventative strategies to alleviate the burden of the disease, but disparities remain in the way research for different cancers is funded and incentivised. Pancreatic cancer is one of the deadliest cancer types with the number of people dying each year akin to those seen for breast cancer, yet compared to breast cancer, research in this field receives 93% less funding.

A lack of awareness around the symptoms of pancreatic cancer and its etiology often mean patients are diagnosed too late, with few, if any, treatment options available. According to Pancreatic Cancer UK, pancreatic cancer will likely become the fourth biggest cancer killer by 2026, yet only receives a mere 3% of the UK cancer research budget.

HEQ spoke to Chris Macdonald, Head of Research at Pancreatic Cancer UK about why increased funding and awareness around pancreatic cancer treatment and symptoms are urgently needed.

How significant is early diagnosis for people with pancreatic cancer?

Early diagnosis is hugely important. The vast majority of people with pancreatic cancer are diagnosed too late, mainly due to the vagueness of symptoms, and 50% die within three months of receiving a diagnosis. Many symptoms are non-specific such as back pain, indigestion, bowel problems, fatigue, and weight loss – all of which can be attributed to lots of other conditions. It would be quite a leap of faith for a GP to suspect someone has pancreatic cancer when presented with these symptoms, this is why we need more diagnostic tools to enable GPs to refer patients to the correct diagnostic pathway.

There is a huge difference in the type of pancreatic cancer treatment offered to patients depending on what stage of the disease they have. For those in the later stages of the disease, the vast majority will not receive the only curative treatment for pancreatic cancer, which is surgery. Only around 10% of people who are diagnosed with pancreatic cancer will be offered surgery because they are just too ill to undergo this. There is a strange scenario with many cancers whereby you can be symptomless, and the disease is not heavily impacting your life. However, with pancreatic cancer it is the opposite, people are often experiencing severe symptoms before they are diagnosed.

Additionally, the treatments currently available for pancreatic cancer can be very toxic and when a person is very ill, it can be extremely difficult for them to withstand this. 70% of people do not receive any active treatment to extend their life so early diagnosis is paramount.

How has the COVID-19 pandemic impacted patients’ access to pancreatic cancer treatment and support?

The pandemic massively impacted access to vital surgery for those patients capable of receiving it, and so few with pancreatic cancer are eligible for surgical intervention. Many of the surgical units needed to be re-purposed as COVID wards which was an acute problem.

Gastroenterologists, who are the gatekeepers of detection, struggled to perform endoscopies which is a procedure used to identify and diagnose pancreatic cancer and now there is a huge waiting list. We are also noticing that people with symptoms are frightened of coming forward to see their GP. This delay in seeing and referring people, especially those with more severe symptoms, will have a big impact on healthcare services.

In terms of research, all research across the UK has struggled. Clinical research is beginning to recruit to levels similar to those we saw pre-pandemic, but it is not there yet, and it took a huge nosedive with the onset of COVID. In the context of a patient group, it is very hard to recruit people with pancreatic cancer onto trials because, inherently, they are very ill. That is a problem for us generally in the community, and we need to do something about it.

The vast majority of people with pancreatic cancer are diagnosed too late, mainly due to the vagueness of symptoms which can include back pain, indigestion, bowel problems, fatigue, and weight loss

How could the treatments be improved?

Fundamentally, we do not have sufficient treatments available for pancreatic cancer and that is because we do not yet have sufficient knowledge about the biology of the disease.

We have not had a concerted and focused investment in pancreatic cancer to understand the basic underpinnings of why it occurs. Like so many other cancer types, we really need to understand why and how it develops as well as how it progresses to other parts of the body and ways in which it can be targeted with treatments.

It is very difficult to obtain a sample from the pancreas and to model pancreas cells in the laboratory. This could be partly why there has been a very low success rate in clinical trials for pancreatic cancer and why we do not know enough about its biology. Because we do not have specific targets, our limited treatment options, which include cytotoxic chemotherapy, are very toxic and were developed long ago for other cancer types. Unfortunately, this type of treatment is the only option for many people, but it is not very effective.

We need to energise the research community so that they see the development of new pancreatic cancer treatments as an opportunity, and a way to support people with the disease. We have developed effective treatments for other cancer types and though you have to work incredibly hard to make gains, there are huge gains to be had and so many questions about pancreatic cancer. Of course, funding follows funding and research tends to navigate towards those areas that have already shown progression and have a lot of research and good treatments available. This is a bit of a paradox. We should be funding those areas where there is currently little progress, where treatments are not really effective. As an organisation, we want to establish progress because more progress will follow, and we can build a research community from there.

How was the Early Diagnosis Research Alliance formed and what is its main purpose?

The Early Diagnosis Research Alliance was a recognition that we needed a programme of work that brought together a community that was well intended, but maybe did not collaborate and were not as cohesive as they needed to be. It has brought together a community of early diagnosis researchers in pancreatic cancer to allow them to have better partnerships, collaboration, and coordination around the way in which pancreatic cancer is detected and the diagnostic tools that support this.

The Alliance is made up of four work packages which are complimentary to one another and delivered by different researchers in different centres throughout the UK. One is focused on decision-making tools to support GPs in being able to flag frequency severity combinations of symptoms and ensure patients are put on a fast-track pathway for further testing if needed.

Another strand of the Alliance is dedicated to research on biomarker validation. At present, there are few key indicators for pancreatic cancer. This team is therefore focused on trying to understand, define and refine combinations of biomarkers taken from the body, which are captured through urine, blood, and other means and mechanisms, to see if they can get a combination that, when you combine them, you get a really accurate and sensitive test. In the laboratory, they have some of the most accurate biomarker tests ever developed. The challenge is how you bring this testing into real life situations and understand the best sample to take and method of testing.

More often than not, biomarkers are tested on samples from people either with or without pancreatic cancer, and that is all well and good when you know what one is. The gold standard test or biomarker, even in the laboratory, should be able to define pancreatic cancer from the noise of vague symptoms. The aim is that for people who present themselves with vague, nonspecific symptoms in GP settings, we can detect those pancreatic cancer cases, out of the noise of people who generally have very similar, vague symptoms. The team has therefore set up a study to collect thousands of samples, be it from blood, urine or DNA from people presenting at what we call rapid diagnostic centres, and through GP clinics. It is a unique and rare resource which recognises that although biomarkers are getting better, improvements can always be made. We can always find a new biomarker and that resource will be a utility for everyone for many years to come.

Another work package is about identifying where the greatest benefit would be when implementing these tests and tools within the NHS. We want to fully understand where patients would get the most benefit and where it is most viable for the practitioners of detection and treatment. So, that work package is essentially about understanding the health economics. It is a real synergy of activity to be able to bring the community together but also to have a focus on how we truly make a step forward in the early detection of pancreatic cancer.

Indeed, early detection is a big space, in cancer generally. The earlier you can diagnose a condition, the more treatable it is. There are lots of other kinds of investments in the UK and internationally around diagnosis: 50% of people have diabetes at the time of diagnosis in pancreatic cancer and researchers are trying to understand how that can be used as a screening tool to better inform detection. There is also a lot of work around understanding how you can correlate lots of complex multimodal information – sample collections, patient history, genetics – to be able to compare them and combine them into risk scores.

What are some of the key risk factors associated with pancreatic cancer and are there certain societal groups that are more susceptible to developing the disease?

Cancer is a condition of ageing, and this is certainly true for pancreatic cancer. The disease is also related to obesity and smoking, like many other cancer types are. Comorbidities are a challenge, particularly for older people and for those who become seriously ill from pancreatic cancer. Comorbidities are really difficult to treat alongside a really destructive cancer that wears away your ability to derive nutrients from the food that you eat. We know that diet plays a huge role in our health and if you are unable to derive essential nutrients, this can impact your immune system and your body’s ability to repair itself.

A lot of people are very interested in the genetic causes of pancreatic cancer and there are some, but, predominantly, the disease comes from a completely sporadic mutation in your pancreas. You can decrease the likelihood of sparking that sporadic mutation by maintaining a healthy lifestyle, exercising, not smoking, and reducing alcohol intake.

There is an opportunity to screen and identify people based on genetics, and we should have better risk monitoring. We fund a study in Liverpool called Europac Study which looks at people at risk from family histories of pancreatic cancer, but also pancreatitis. It is something that patients or their families can rightly feel very strongly about but when you look at the wider patient population, it is probably not as influential as it is in some other cancer types.

How would you like to see diagnostic procedures and awareness around pancreatic cancer improve?

Awareness is so important in getting people to understand symptoms and get checked out. We have data that demonstrates that if your GP refers you on the basis that there is a suspected cancer, your diagnosis and treatment times for pancreatic cancer are actually really quick compared to other cancer types. The problem is that people may be presenting various symptoms to their GP across multiple appointments, even over a number of years, and nothing gets done about it. This is not a criticism of GPs because they may only see a patient with pancreatic cancer every four or five years in their surgery and they should not suspect everyone with back pain and GI symptoms to have pancreatic cancer. Rather, what we need to do is raise awareness about the collection of vague symptoms and recognise that these should not be ignored. We need to give GPs the tools to support people with vague symptoms and to put them on the correct diagnostic or treatment pathway. If GPs can create symptom profiles, this would enable them to put the patient on a pathway that performs a suite of diagnostic tests, including scans and blood tests, so they can ascertain what these vague symptoms indicate. Rapid diagnostic centres that were brought in by the NHS do exactly this and the second most commonly identified cancer in these pathways is pancreatic cancer.

At the same time, we recognise that pancreatic cancer is a relatively rare cancer type and, unfortunately, you cannot advocate for big screening processes as it is just not economically viable. Furthermore, you could misdiagnose and underdiagnose hugely, we do not have the tools to be able to accurately screen people on a large scale. It is important that even with diagnostic pathways, we need better testing tools, to be able to refine and enrich patients, what you cannot do is put too many people on these pathways because then, you are essentially creating de facto screening.

For patients, it is important that they are monitoring their symptoms, maybe over a few months, so they can present this information to their GP which will, in turn, help their GP to put them on the best pathway. Patients’ ability to be able to articulate themselves in anxious, unfamiliar surroundings is a big deal generally within the healthcare system. Sometimes patients can normalise their symptoms or they may have had a certain symptom for a number of weeks but had not really thought about it. Patient empowerment is really important, especially in pancreatic cancer, so that people feel confident when presenting those vague symptoms to their GP and feel they can be honest about their health.

Chris Macdonald
Head of Research
Pancreatic Cancer UK

This article is from issue 20 of Health Europa Quarterly. Click here to get your free subscription today.

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