18 Sep 2014
In - Research

Today (18 September 2014) several newspapers have reported on research which suggests there may be a new way to identify when some treatments have stopped being effective for men with advanced prostate cancer.

This research suggests that so called liquid biopsies (testing tumour DNA circulating in the blood) could be used to give doctors an accurate picture of a man’s cancer development.

Some newspapers have focussed on the exciting finding that it may be possible to follow the progression of the disease and match treatment to how an individual man’s cancer is developing. This would allow doctors to ensure men get the right treatment for them at the right time to get the most benefit. Eventually, that should improve survival.

The researchers used the new technique in 16 men with advanced prostate cancer who were receiving abiraterone as part of their treatment. In three of those 16 men the test showed that some of the sites of their cancers had developed (two different) mutations in the androgen receptor, a protein that drives prostate cancer growth when it is ‘turned on’ by binding to the hormone testosterone.

Many treatments for prostate cancer work by preventing or reducing the binding of testosterone to the androgen receptor.  They do this by either stopping the body from producing testosterone, or by blocking its interaction with the receptor. The idea is to keep the androgen receptor in the ‘off’ position, and to stop the cancer from growing.

This does work for a while but eventually the androgen receptor changes to find new ways to turn on. Previous work has show that some of these mutations of the androgen receptor mean that certain steroid treatments (glucocorticoids) can actually turn on the receptor instead of preventing testosterone from binding to it.

This might allow cancer to begin to spread again or may reduce the effectiveness of other drugs given at the same time. Some newspapers have chosen to focus their stories on this aspect of the research.

Dr Gerhart Attard, leader of this research, thinks it could be the beginning of a new treatment model for men with advanced prostate cancer.

“Our results introduce a new paradigm for the management of patients with advanced prostate cancer. In the future, we hope to routinely monitor genetic mutations in patients with advanced disease using just a blood test – enabling us to stop treatments when they become disease drivers and select the next best treatment option. Using these types of blood tests can allow true personalisation of treatment for prostate cancer patients, based on the cancer mutations we detect.”

Our view

We think this work is really exciting as it shows that there might be a way for doctors to change from one treatment to another, at the best time, in response to the way an individual man’s cancer is changing. This could be a game changer for men with advanced prostate cancer and we’re proud that, with funding from the Movember Foundation, we’ve been able to fund Dr Attard to do this research, and to extend these results by looking at a larger number of men with prostate cancer.

However, it’s really important to understand that this is early stage research. A much larger trial will be needed to understand how widely this new technique works. We are even further from being able to say confidently that we could use it to make clinical decisions about specific mutations and specific treatments.

Some of the newspaper reports may have run away with this aspect without providing the context that this was found only in a small number of men. They also failed to mention that men who are taking glucocorticoids at the moment should continue to do so. Here’s Dr Attard again on that point:

“Glucocorticoids are initially effective. They are great treatments which we have been using for more than a decade now. They make people feel better and their tumours shrink. But in time – it could be a couple of years or less, depending on the patient – the cancer manages to adapt and start growing again. In one in five people the treatment might start driving the disease, activating harmful mutations.”

Here’s a breakdown of the important conclusions from this research

  1. This is early stage work and men should not stop taking any treatments as a result of these findings. In particular, glucocorticoids are widely used with much success in a large number of men.Men with advanced prostate cancer that is progressing who are taking steroids and are worried about these results should speak to their oncologist.
  2. The most exciting aspect of this work is that it suggests that analysing circulating DNA from tumours could be used to personalise treatment based on how each man’s cancer develops.
  3. This paper also demonstrates just how complex advanced prostate cancer is. The research shows that different tumour sites mutate in different ways at different times. This suggests that combination therapies are likely to be key to treating advanced prostate cancer. Many clinical trials studying combinations of therapies are currently underway. If you are interested in participating in those trials you should ask your medical team to refer you.
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