Prostate cancer trial results should mean fewer hospital trips to have radiotherapy

Radiotherapy has long been a cornerstone of cancer treatment. And it’s particularly important in treating prostate cancer – a disease that affects a huge number of men (more than 40,000 new cases are diagnosed each year in the UK).

The treatment men have depends on what stage their disease is diagnosed. For those diagnosed early, when their cancer is contained inside the prostate and hasn’t spread (so-called ‘localised’ cancer), doctors have three options: daily radiotherapy; surgery to remove their prostate; or monitoring the patient for signs of their cancer becoming more aggressive.

In practice, around 16,000 men each year receive radiotherapy, which is extremely effective. But this can sometimes cause side effects too – and they can be serious.

“Prostate cancer and its treatment are the leading cause of disability in cancer survivors,” says Professor David Dearnaley, from The Institute of Cancer Research, London and consultant at the Royal Marsden. “These side effects can include incontinence – both bladder and bowel – and sexual problems like impotence.”

At the moment, for men given radiotherapy, the gold standard is treatment five days a week, over a period of just over seven weeks. But over the years, evidence has emerged that fewer, stronger doses of radiation could be just as effective in treating the disease. If true, this would mean fewer trips to the hospital for men, potentially fewer side effects, as well as savings for the NHS.

So more than a decade ago, with funding from Cancer Research UK, Dearnaley’s team set out to test this approach in what turned out to be the largest clinical trial of its type in history – the CHHiP trial.

The results, published in full today, should change clinical practice. But there’s a catch: to allow all men who need it to benefit, the NHS needs to invest substantially in new radiotherapy machines – something we’re pressing the Government to do.

CHHiPping away at better radiotherapy

In 2002 CHHiP began recruiting men with localised prostate cancer, aiming to test how the size and number of radiotherapy doses might affect survival and side effects.

Over a period of nearly a decade, more than 3,000 men joined the trial and were treated with a type of radiotherapy called intensity modulated radiotherapy (IMRT).

Men were randomly split into three groups:

• Group one had the standard treatment: a total dose of 74 Gray (a ‘Gray’ is a measurement of radiation dose) in 37 daily treatments, Monday-Friday, over a course of 7.4 weeks. Each daily dose was 2 Gray.
• Group two had a total dose of 60 Gray in 20 daily treatments over 4 weeks. Each daily dose was 3 Gray: While the overall amount was smaller, each individual dose was stronger (called ‘hyperfractionation’).
• Group three had the same strength dose (3 Gray) as group two but over a slightly shorter time (hence, a lower overall dose – 57 Gray in 19 treatments over 3.8 weeks).

The men had regular check-ups after treatment, both for any sign of their prostate cancer growing again, and for side effects.

Dearnaley unveiled the top-line results of the study last year at a large European conference. And today, the full data have been published in The Lancet Oncology, and is the result of five years of follow-up.

What did the results show?

Reducing the number of treatments men need to get the best outcome is a positive step – Professor David Dearnaley. © John Angerson 2016. All rights reserved.

As expected, the standard radiotherapy course was very effective at controlling prostate cancer: after five years almost nine in 10 men (88%) were still free from any signs of their cancer growing.

And if radiotherapy was given in fewer, stronger doses, the 60 Gray overall dose (group two) was just as effective at keeping prostate cancer at bay. And the lower dose of 57 Gray (group three) was only marginally less effective, with 86% of patients seeing their disease under control after 5 years.

But what about side effects? As a result of using IMRT, very few men experienced serious bowel or bladder problems – and this was the same in both groups one and two. This was important, as it showed that stronger daily doses didn’t cause an increase in serious side effects. Similarly, sexual problems, while much more common, occurred at much the same rate in both groups.

But men in the third group, who got the lowest overall dose of radiotherapy (who fared slightly worse in terms of disease control), were slightly less likely to have side effects from their treatment. And, as Dearnaley points out, this means a new option for certain men.

“While the lowest dose wasn’t quite as effective at controlling prostate cancer, the reduced side effects might make it a better option, particularly more elderly or frail men,” Dearnaley tells us.

A win-win situation

Giving a bigger dose of radiotherapy with each session requires state of the art radiotherapy machines and precise planning – Professor Malcolm Mason

“This was an important trial to carry out,” says Dearnaley, “because reducing the number of treatments men need to get the best outcome is a positive step.”

“For patients, it means fewer visits to hospital. Their treatment is more convenient and finished sooner, allowing them to go back to their normal lives.”

It also has big advantages for the NHS too. Fewer treatments would cost less – 10s of millions of pounds in savings – and free up radiotherapy resources, potentially reducing waiting times and allowing more time for research.

But using these higher doses of radiotherapy also has implications for how hospitals plan treatment, according to Professor Malcolm Mason, Cancer Research UK’s prostate cancer expert.

“Giving a bigger dose of radiotherapy with each session requires state of the art radiotherapy machines and precise planning,” he says.

“And ensuring treatment is accurate, using the most modern techniques, is paramount.”

So while these findings point to great news for patients, there is still more work to be done to ensure that all hospitals can safely offer this approach to their patients.

Will this change standard treatment?

The short answer is ‘yes’. In fact, most of the hospitals taking part in the study have already changed to the shorter schedule.

It’s crystal clear from this, the largest trial ever for localised prostate cancer, that men should be treated with fewer, stronger doses

– Professor David Dearnaley

And following the publication of these results, the NHS is looking to change the standard of care for all men. NHS England is in the process making this official, which we understand will happen over summer.

And the health services in Scotland, Wales and Northern Ireland should be doing the same.

“It’s crystal clear from this, the largest trial ever for localised prostate cancer, that men should be treated with fewer, stronger doses,” Dearnaley explains.

“There’s no arguing with the results. And crucially, this was the first study to set limits on the amount of radiation to healthy tissue like the bladder and bowel.”

This is important, he says, because it sets the standard for how men across the country should be treated.

It’s now up to the government and the health service to ensure this can happen. And that’s something we’ll be pressing governments and health authorities to do.

“It’s vital that, once proven in clinical trials, patients across the UK get swift access to the latest innovative radiotherapy treatments,” says Emlyn Samuel, Cancer Research UK’s senior policy manager.

“Last year’s cancer strategy for England called for national funding to urgently update and replace outdated radiotherapy equipment, but we are yet to see any commitment from NHS England or the Government on this,”

“They need to rectify this, so that patients can have the best, evidence-based treatments they need.”

What happens next?

The men on the CHHiP trial are still only five years post-treatment, so Dearnaley and the rest of the team will need to keep monitoring the men for another five to 10 years, to find out if the new radiotherapy dosing has any effect on long term survival.

“Another interesting side story from the trial is we’ve been keeping samples of the tumours,” says Dearnaley. “We’ll be looking at the molecular and genetic characteristics of the tumours to find out if there are ways to predict the best course of radiotherapy for each patient.”

And it’s not the end of the story for research into hypofractionation. As radiotherapy becomes ever more precise, doctors will be able to limit damage to nearby organs more, allowing each treatment to deliver a higher dose. “We could one day see men needing just five or six rounds of radiotherapy,” he says.

And Dearnaley predicts that an important next step will be the development of a new technique called Magnetic Resonance Imaging (MRI)-guided radiotherapy.

“This will be so precise, it will allow us to focus treatment on specific areas within the prostate itself. I think in around five years we’ll be well on the way to using this technology.”

It might seem like a small step, and not as headline-grabbing as a new drug, but this trial will improve the lives of a thousands of patients and lead to financial savings for the NHS.

We’re proud to be supporting the vital clinical trials that are setting the standard of care for cancer patients in the UK.

Emma