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Once cancer spreads, it becomes far more difficult to treat. And doctors’ attention is pulled towards trying to contain the disease.

This is true of advanced prostate cancer, where standard hormone therapies block the action of male sex hormones and can hold advanced disease at bay. But they can’t kill it completely.

“With the outlook for these men being so poor, we desperately need alternatives to tackle this cancer,” says Dr Chris Parker, lead researcher on one part of the Cancer Research UK-funded STAMPEDE trial.

In the team’s latest efforts, they tested if aiming radiotherapy directly at the prostate could help men whose prostate cancer has already spread beyond the small gland. But it’s an approach that most doctors had, according to Parker, once believed to be futile.

“Until now, our understanding was that if the cancer had spread, then treating the prostate itself would be like shutting the stable door after the horse has bolted. It was thought that there was no point in treating the prostate itself,” he says.

Now, the results from this study, published in The Lancet, look set to change not just opinions, but potentially the way some men with advanced prostate cancer are treated.

It’s all in the detail

Parker and his team studied around 2,000 men whose prostate cancer had spread to other parts of the body. Half were given standard treatment of hormone therapy either with or without the chemotherapy drug docetaxel, while the other half received standard treatment alongside radiotherapy aimed at the prostate. Adding radiotherapy to standard treatment didn’t improve survival when data from all the men on the trial was combined. But digging deeper, the researchers found that, for a specific group of men, radiotherapy did improve survival.

Around 8 in 10 men whose cancer had not spread beyond the lymph nodes and/or nearby bones were still alive 3 years after their prostate was treated directly with radiotherapy. For men who didn’t have additional radiotherapy, around 7 in 10 were still alive at the same time point.

“We thought this might be the case,” says Parker. “We suspected that the radiotherapy might be more effective for men whose cancer hadn’t spread to other organs or distant bones  – called lower metastatic disease burden – and that’s exactly what we found.”

But although this survival advantage is clear, the biology behind the finding isn’t.

Uncovering the biology

Dr Chris Parker

“We don’t know exactly why radiotherapy works for men with less cancer spread,” says Parker. “It might be that there is signalling going on between the primary cancer in the prostate and the metastatic cancer elsewhere in the body.

“It’s possible that by targeting the primary tumour with radiotherapy, this could be stopping these signals so the tumours that have spread progress more slowly – but to be honest we just don’t know the biology yet.”

Understanding why radiotherapy worked for these men is a crucial question for future research.

But for the STAMPEDE team, the next steps are to follow the men from this study to find out more about their long-term survival.

But while the answers to these questions start to emerge, these findings could have a more immediate effect.

Watch: What is cancer radiotherapy and how does it work?

Results with impact

“Radiotherapy, compared to many new drugs for cancer, is relatively cheap, readily available in many countries around the world, and is already used to treat the disease,” says Parker. “As a result, we believe the powerful effect we’ve shown for certain men with advanced prostate cancer should change clinical practice in the UK, and have global impact.”

And as 4 in 10 men with newly diagnosed advanced prostate cancer in the study fall in to the group with lower disease spread, this suggests these findings could benefit more than 3,000 men every year in England, and many thousands more worldwide.

These results are yet another feather in the cap for STAMPEDE, a trial which has already improved the outlook for many men with prostate cancer.

In 2015, results from the trial changed the standard of care for some men with prostate cancer, leading to docetaxel chemotherapy becoming part of the treatment many men receive. Then, in 2017, the Cancer Research UK funded-study found that offering abiraterone (Zytiga) and the steroid prednisolone in combination with standard treatment to men with prostate cancer earlier, before the disease becomes resistant to standard hormone therapy, can help boost survival.

“Thanks to the scale and flexibility of STAMPEDE, the trial is helping to change the face of prostate cancer research at an impressive rate,” says Parker.

“Now we think these new radiotherapy results are compelling enough to change treatment for certain men in the future, improving the outlook for men both in the UK and around the world.”

Catherine

Reference

Parker et al. (2018) Radiotherapy to the primary tumour for newly-diagnosed, metastatic prostate cancer: A randomised controlled phase III trial (STAMPEDE). The Lancet. DOI 10.1016/S0140-6736(18)32486-3

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David Ward October 25, 2018

As a survivor of early stage prostate cancer after brachytherapy eight years ago, when there were not so many treatment options, and knowing when I had it, that there would not be much of a solution if the cancer returned, I am heartened to see the incredible rate of research and treatment options now available, thankfully none of which I need to take at the moment.