Cancer treatment revolution of 2011 is now turning ‘death sentences’ into cures – but UK still lags behind

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Breakthroughs in immunotherapy and improvements in surgery mean cancer is more treatable than ever.

Analysis

Cancer treatment revolution of 2011 is now turning ‘death sentences’ into cures – but uk still lags behind

Caption: Advances in radiotherapy means radiation can be aimed precisely into into the tumour and administered doses can also be many times higher. Pictured is the Rinecker Proton Therapy Center in Munich, Germany (Source: Universal Images Group Editorial, Copyright: AMELIE-BENOIST / BSIP)

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By Tom Chivers

“When I started as a melanoma oncologist,” says Christian Ottensmeier, a professor of immuno-oncology at the University of Liverpool, “nothing ever worked. I did trial after trial after trial. Then, in 2011, we started curing people.”

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Cancer will be the great disease of the next few decades. It’s a disease of ageing, and more of us now live to be old. A few years ago, research by Cancer Research UK suggested that about half of people now alive will develop cancer at some point. That’s not, mainly, because cancer is getting more likely: it’s because we’re not dying of other things.

But that doesn’t make it any less scary to be diagnosed with a malignant tumour. In that situation, the question you would want answered is: have my chances of survival got better?

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i reported at the weekend on a promising development in treatment for pancreatic cancers, one of the most deadly and intractable forms of the disease. The research found a protein involved in delivering oxygen and energy to cancer cells: drugs to block that protein might, scientists hope, effectively starve the tumour.

It’s far from the only development in cancer treatments in recent years. “We can now cure a significant fraction of patients,” says Ottensmeier. It varies from cancer to cancer, and some are far more treatable than others, but for a huge number of people, diagnoses that were all but death sentences only a few years ago are manageable or even curable.

There’s still a long way to go – the new treatments are only effective in a subset of patients and for a subset of cancers (melanoma, Ottensmeier’s specialty, being a notable example). But they are dramatic, and they open up avenues for improving the outcomes for other cancers, and other patients.

Surviving longer or spotting earlier?

Working out whether cancer patients are surviving longer is always tricky. There are a lot of confounding factors, most notably that we spot it earlier.

“In some diseases, but not others, there’s been a strong trend towards early diagnosis,” says Nick James, a professor of oncology at the Institute for Cancer Research. “In breast cancer, for instance, you’re unlikely to be diagnosed with advanced cancer now.” That’s partly because of screening, and partly because everyone is much more aware of the risk: women pay more attention to changes in their breasts than they would have done a generation or two ago.

Early diagnosis genuinely improves survival rates. “It matters how many cancer cells are in the body,” says Ottensmeier. “A lump that’s one centimetre on a CT scan probably has between one and ten million cells. It’s a complete anthill. And each cancer cell might lead to new metastatic disease.

“If you catch it early, before the spread has happened, you remove the problem altogether, and that’s one of the aims of early diagnosis.”

But it also leads to a complication. We measure our success in defeating cancer by looking at survival rates – how many people are alive a given time after diagnosis. But imagine, say, a cancer that always kills patients six years after it arises, and for which you have no cure. Your normal detection system always picks it up after two years, but you develop a new method that picks it up after six months. Under the old method, patients’ five-year survival rate was 0 per cent. Under the new one, it’s 100 per cent. But no one is actually living any longer.

This problem is called “lead-time bias”, and it makes it difficult to establish how much more successful cancer treatments are nowadays: diagnostic methods are improving as well, meaning more cancers are detected earlier. It’s also hard to make comparisons when we are living longer and smoking less.

But there does seem to be a real, and in some cases dramatic, improvement, in some patients and in some cancers. The Oxford University-affiliated site Our World in Data notes that cancer survival times have been going up for decades, even when you take into account the size of the cancer – which should avoid the lead-time bias problem above.

The unfinished revolution

Melanoma was, until relatively recently, a stone-cold killer. If you were diagnosed with metastatic melanoma – that is, a cancer which had spread from its original site to elsewhere in the body – your prognosis was very bad. One 2014 paper estimated the median survival time for a metastatic melanoma at less than six months.

But in 2011, as Ottensmeier said, everything changed. The big development was in immunotherapy. “Our immune system should be able to see cancers,” says James. “They have mutated proteins which should be spotted and eliminated.” But cancers are clever. They hide.

Your immune system is a complex arrangement of checks and balances: it’s incredibly powerful, and if it starts targeting the wrong thing, it can cause huge damage, as in autoimmune conditions like allergies, asthma, and arthritis. Cancers make use of those checks and balances, and give off signals which tell the immune system to leave them alone. “They’re selectively switching off the immune system in their own micro-environment,” says James.

Immunotherapy drugs tell the immune system to ignore the switch-off signals when it sees certain specific molecules. “That targets the cancer’s ‘invisibility cloak’,” says James. “It makes it more visible to the immune system.”

Cancer survival rates have improved in the UK over the last 20 years but the UK still lags behind other developed nations

For some patients, this has been absolutely transformative. “We fundamentally alter their health,” says Ottensmeier. “But only a limited fraction, about 25 per cent.” In that 25 per cent, though, it is extraordinary – an effective cure. “After three or four years, relapses are very uncommon,” he says. “So we say ‘go and enjoy your life, we’d be unhappy to see you again.’”

Immunotherapy works on several other cancers – lung, kidney, head and neck, bladder, among others. And in each case, it seems to work in about a quarter to a third of cases. “Even in really advanced, intractable cases,” says James, “you get amazing responses. The stuff melts away like spring snow. But roughly two thirds will not get a good response. So it’s been a breakthrough, but a bit disappointing as well.”

Ottensmeier thinks that can change, though. Immunotherapy works best on cancers that have lots of mutations – the more different they are to healthy tissue, the easier it is to make the immune system see them. A cancer with 1,000 mutations might only have four or five that are useful targets for immunotherapy.

But, he says, there is work now into looking for other ways to target cancers. One is to look at the novel proteins they make, which aren’t caused directly by mutations but by the abnormal working of the tumour. By widening the immunotherapy net like that, he says, it might be possible to push that 25 per cent higher.

The steady progress

“The biggest change has been immunotherapy,” says Ottensmeier, “but it’s still true that the majority of patients who are cured are cured by radiotherapy or surgery.” And those methods have been getting steadily better: radiotherapy in particular.

“A decade ago, a patient with prostate cancer would have had 37 radiation treatments over seven and a half weeks,” says James. “Now it’s dropped to 20 treatments, and we’re looking at five over a week and a half. It’s gone from seven and a half weeks to a week and a half to cure your prostate cancer.”

The change has been an increase in precision. Radiotherapy used to involve first scanning someone, seeing where a tumour was, and then moving them to a different room with a different machine in it and blasting the general area with high-energy radiation. But it was very imprecise, and much of the radiation would hit healthy cells, meaning it was dangerous to give very large doses all at once.

Modern radiotherapy, though, is image-guided: it has a scanner attached. It means the radiation can be aimed precisely into the tumour, even as the tumour moves with the patient’s breathing. And that means that the doses that can be administered can be many times higher. “It reduces the side effects, rather than improving the cure rate,” says James. “But because it’s less toxic, it allows you to treat people you couldn’t have in the past, and without causing long-term damage.”

Surgery has improved too. “There have been incremental improvements,” says James. “Robot-assisted surgery means you can send people home in a couple of days – prostate cancer operations, you can be in for one night, instead of weeks like a generation ago. It widens the pool of people you can treat, and it lets you stay out of hospitals, which are dangerous places.”

The future

Things have improved for cancer patients. But according to Eva Morris, a professor of epidemiology at Oxford University, progress has not been evenly shared. “There have been improvements,” she says. “But while there have been improvements in the UK, the improvements in the rest of the world have been far bigger.”

She worked on an international study comparing different nations: Canada, Australia, Denmark, Ireland, Norway, New Zealand and the UK. The UK consistently comes bottom or near-bottom in five-year survival rates for various cancers, and while things have improved, they have not closed the gap, and in some cases the gap has widened. Some of the difference might be down to data collection, but, she says, that isn’t the whole story.

Exactly what is clear we don’t know. It could be something to do with how patients interact with their doctors, she says: “A lot of the difference is caused by people in the UK dying very close to diagnosis, especially the elderly,” she says. If you survive two years after your diagnosis, “you’ve probably got the same risk of death as someone in Norway or Denmark, so perhaps it’s to do with how they present.”

It could be a reticence to come forward, or GPs not directing the right people to the right places: she notes that a large percentage of colorectal cancer patients in this country are only diagnosed when they turn up at A&E with a blocked bowel, and at that point the outlook is not good.

Whatever it is, though, it means that there is still progress to be made, and as good as new immunotherapy drugs are, the biggest improvements are likely to be unflashy. “What goes into the newspapers is new drugs,” she says. “But they don’t work for the majority of people.

“Improving the quality of surgery, so the worst-performing surgeons have outcomes as good as the best-performing ones, would give you far more improvement than most new drugs.”

She points out that in Denmark, it was noted that they were lagging behind in colorectal cancer outcomes. “In typical Danish style, what they did was look at their data to work out why,” she says. “They spotted that there were lots of general surgeons doing small numbers of cancer surgeries, with high death rates.” So they centralised the system, with all operations done in a few specialist centres, and outcomes got better. Similar relatively low-tech changes like that could be effective at improving British cancer care, too.

But the new drugs, says Ottensmeier, have had a bigger effect than simply saving the lives of a large fraction of patients. He thinks they’ve also changed how clinicians see cancer. “I spent 20 years on lung cancer oncology, and we used to get very excited if we found something that made people live six weeks longer,” he says. “Many drugs were licensed on that sort of difference, carboplatin for instance. It makes a bigger difference for some patients, but on average, it might give you a couple of months.”

Now, though, he can literally cure people – not all, but many. “It’s conceptually very different,” he says. “And it opens up a challenge: can we make that 25 per cent into 60 per cent, 70 per cent? We want more of it. It’s no longer acceptable that our patients die.”

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