How do you tell the lethal cancers from the non-lethal ones?

Cancer Research UK recently set out to find the current major challenges that need combatting in order to beat cancer. They presented seven challenges that would need to be overcome, and in this blog, originally posted on their website, they focus on the fourth: identifying lethal from non-lethal cancers.

The word ‘cancer’ tends to conjure up the idea of an aggressive disease, which grows rapidly, spreading around the body and that ultimately kills if not treated.

But this isn’t always the case. Some things that are diagnosed as ‘cancer’ can grow so slowly that they may not even cause harm in a person’s lifetime, and so don’t need any treatment.

The problem is that at the moment we can’t tell the difference between these slow growing cancers and the aggressive ones.

This ‘overdiagnosis’ is a big problem. We’ve written about it in the context of breast cancer screening before, but it’s also a big issue in prostate cancer, where we often hear about ‘tigers’ (aggressive cancers that can spread and kill) and ‘pussycats’ (slow-growing tumors that wouldn’t cause an issue in a man’s entire lifetime). And overdiagnosis is increasingly being linked to other types of cancers too.

But we also have issues detecting some of the most aggressive types of cancer early enough, meaning we only find them when it’s often too late to tackle them.

We still want to detect cancers early when they’re most curable, but not subject patients to unnecessary treatment if they don’t need it. We want things that are extremely accurate.

Professor Brian Druker

So our fourth Grand Challenge is all about delving deeper into cancer’s biology to solve two of the most important mysteries in medicine – how to tell the difference between the cancers that can kill and the slow-growing forms of the disease that don’t, and how to track down the cancers that stay hidden until it’s too late.

“This grand challenge is critically important,” says Professor Brian Druker, member of the Grand Challenge Advisory Panel and director of the Oregon Health and Science University Knight Cancer Institute in the US.

“We know that cancers are easier to cure if they’re found early – that’s clear for every type of cancer. But the next issue is whether our early detection tests are really what we want them to be right now.”


Harm versus benefit

The impact of ‘overdiagnosed’ cancers can be life-changing and unnecessary – causing people the stress and anxiety of a cancer diagnosis, and all the downsides of treatment, including potentially serious side effects.

“As we get better at detecting cancer, we’re also finding early cancers that don’t need treatment. And then comes the question of whether we’re doing more harm than good by treating these cancers,” says Cancer Research UK’s Professor Peter Sasieni, an expert in cancer screening and epidemiology.

“At the moment there’s a bit of a balance, because despite there being clear benefits, there are also definite harms. But if we were able to identify cancers that don’t need treatment, it would mean the benefits of better detection would out-weigh the harms.”

Another crucial breakthrough would be the ability to find aggressive cancers (like pancreatic, lung, brain and ovarian cancers) sooner which are often deadly because they’re hardest to treat when found late. These cancers, too, can also be difficult to tell apart from more harmless lumps on scans and other tests.

Professor Brian Druker
Professor Brian Druker

According to Druker, technology has a big part to play.

“We’re trying to meet in the middle of these two issues, so that we have much more accurate technologies to help us treat patients appropriately,” he says.

“We still want to detect cancers early when they’re most curable, but not subject patients to unnecessary treatment if they don’t need it. We want things that are extremely accurate.”

Researchers haven’t been able to do this before, because of a lack of knowledge of the biological differences within a certain type of cancer, and how these differ from earlier, pre-cancerous changes they can arise from.

Thankfully, over the last decade or so, there’s been an explosion in new technologies that can analyze our genes in great detail, extract tumor cells and DNA from our blood, and study the proteins in our body and what they do in unprecedented detail.

And alongside our deeper understanding of cancer biology, these technologies now stand us in good stead of overcoming this grand challenge.

“We want a team of biologists who understand what distinguishes a lethal from a non-lethal cancer, combined with a group of technology experts who can find the right technology to apply this,” says Druker.

“When you look at many scientific advances, it’s often when you get different areas of research or technology coming together that you see dramatic breakthroughs.”

An advance of this kind could not only save lives from aggressive cancers by finding them earlier, but also reduce the harm caused by treating people with cancers that will never cause them any problems.

This, in turn, could lead to great improvements in how we screen for cancer, by helping us understand what to do with overdiagnosed cancers.


Re-branding cancers

But there’s also a second challenge waiting for us if we get this right. ‘Cancer’ is a hugely emotive word. The idea that some cancers don’t need treating is a hard one to get your head round. How would people respond to being told that their cancer was safe to live with and won’t need treating?

Professor Druker sees this as an important issue when discussing such tumours: “We have to stop calling things that are non-lethal ‘cancer’, because if a doctor says you’ve got cancer you’re going to want to get rid of it. As soon as you say ‘cancer’ people get worried, so we’ve got to come up with a different name.”

While many cancers will still need prompt treatment, we will get to a place where we will be able to confidently say that others won’t ever cause harm, so don’t need treatment.

Professor Peter Sasieni

Some scientists have already looked at ways to tackle this problem. Dr Laura Esserman and colleagues propose the term ‘IDLE’ (which stands for ‘Indolent Lesion of Epithelial origin’) to describe non-lethal tumours.

She argues that doctors must lead the way in changing how people think about cancer, increasing awareness of IDLE tumors and how they should be dealt with. And that our one-size-fits-all approach to naming cancer isn’t suitable now we know there are lethal and non-lethal versions of the disease.

“Science has taught us quite a bit about the disease in the last few decades, so a one-size-fits-all definition is no longer the right fit because there isn’t just one type of cancer – there are many,” she told CNN back in 2015.

“It’s like allergies; we can easily understand that there is more than just one type of allergy. Allergies vary hugely in type and severity, and not everyone will lead to anaphylactic shock or a fatality.

“Some allergies cause no more than itchy eyes or a runny nose. The same principle is true of cancer. And because the term cancer is surrounded by connotations of panic and death, in the case of extremely low-risk lesions, we should reclassify them accordingly.”

The patient perspective

I think the encouragement and freedom that research teams will be given by the Grand Challenge is really exciting. From my experiences of cancer I’ve seen people diagnosed early but still die of their cancer, while others have been diagnosed late and survived. Early diagnosis is vital to improve survival, but it’s not enough to just detect cancer early – we also need to be able to recognize the lethal ones that need treatment. This encompasses complex science along with changing people’s perceptions of cancer too, which makes it fascinating. In other words, there’s the technical challenge to find ways of distinguishing lethal from non-lethal cancers – which is challenging enough in its own right – but then that has to be put into practice. I hope that research teams can draw inspiration from that to do something incredible.

–  Jim, member of the Grand Challenge patient panel

A change of this kind would have a huge impact in both how society views cancer and how doctors treat it – in all of its guises.

As Professor Sasieni contemplates: “Eventually I suspect that – while many cancers will still need prompt treatment – we will get to a place where we will be able to confidently say that others won’t ever cause harm, so don’t need treatment.

“But they wouldn’t be what many people think of now when they hear the word ‘cancer’ – and certainly not the death sentence that people thought of 40 years ago.”

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