Blood test could help improve prostate cancer outcomes

"A blood test can determine whether prostate cancer patients are likely to respond to drugs," BBC News reports.

The test assesses whether men with prostate cancer have a good chance, or not, of responding well to a drug called abiraterone – a hormonal treatment designed to block the effects of testosterone, which can stimulate the growth of a tumour.

Many cancers develop resistance to abiraterone, so the drug can be ineffective, but still trigger a range of unpleasant side-effects.

This new test was designed to assess whether it was likely that a cancer was resistant to abiraterone.

The study looked for abnormal genes in DNA from prostate cancer tumours. which were found in the blood serum. The test made use of new technology, meaning that an invasive biopsy wasn't necessary.

In the study, men who carried an abnormal gene relating to the body's androgen receptors were much less likely to respond to abiraterone, compared to men without these abnormal genes. They didn't live as long, and their cancer got worse faster.

The researchers say their test could be used to help decide whether men would benefit from abiraterone, or whether they should take other treatments such as chemotherapy. However, as this was a small study (of just 97 men) more research is needed to be sure the test is reliable.  

Recommendations from the National Institute for Health and Care Excellence (NICE) state that abiraterone should only be made available on the NHS in cases of advanced prostate cancer that have failed to respond to other treatments.

 

It is not currently available for early-stage prostate cancer, as NICE is concerned about whether it is cost-effective.

 

Campaigners hope the results of this latest study, if replicated elsewhere, could lead to a reappraisal of this decision. Having a better idea of who would or wouldn't benefit from the drug could make it more cost-effective.

The study was carried out by researchers from the University of Trento in Italy, the Institute of Cancer Research in London, the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Italy, the Royal Marsden Hospital in London and Weill Cornell Medicine in the US.

It was funded by grants from Cancer Research UK, Prostate Cancer UK, the University of Trento, the National Cancer Institute, the Movember Global Action Plan, and the Institute for Cancer Research. 

The study was published in the peer-reviewed journal Science Translational Medicine.

The Institute for Cancer Research, which employs some of the researchers and provided funding, makes the drug abiraterone. This is not unusual with pharmaceutical research.

The trial was covered well by the BBC and The Independent, both of which made clear that further research will be needed before the test can be widely used.

 

This was a cohort study that looked for links between specific gene mutations in tumour DNA and the effects of the hormonal treatment abiraterone. This treatment aims to block the production of testosterone, as testosterone is needed for prostate cancer cells to grow.

Abiraterone is only effective for some men, so the researchers wanted to see if they could develop a test to predict which men it would be unlikely to work for, so that other treatments could be used instead.

 

Researchers collected blood samples from men with advanced prostate cancer, who had stopped responding to their first therapy, but had not yet started on abiraterone. They were able to analyse samples from 97 patients.

The researchers looked for different types of gene mutations in blood from the start of the study, and as the study progressed. They measured how the men responded to treatment, looking for links between gene mutations and how well the drug worked.

The researchers concentrated on looking for gene mutations which affect the cancer's androgen receptors. Abiraterone works by blocking these receptors, but genetic mutations affecting the receptors may stop the drug from working. The researchers captured DNA from the most common tumours seen with prostate cancer, while ignoring DNA from the body's cells.

They measured the response to the drug by looking at what happened to men's prostate-specific antigen (PSA) levels. PSA, which is also measured by a blood test, is a chemical produced by the prostate. It is normally present at low levels in the blood, but increases with age and if a person has prostate cancer.

The men were thought to have responded to the drug if their PSA levels had dropped by 50% (partial response) or 90%. Because PSA levels don't always translate into what happens to the cancer, the researchers also looked at how long before the men's tumours started growing again, and how long they lived.

 

The men who had mutations to the androgen receptor gene were much less likely to respond to abiraterone. They were five times less likely to have a partial response and eight times less likely to have a full response. They were also less likely to live to the end of the study (hazard ratio (HR) 7.33, 95% confidence interval (CI) 3.51 to 15.34) or to reach the end of the study without their cancer beginning to grow again (HR 3.73, 95% CI 2.17 to 6.41).

 

The researchers say they have shown that genomic aberrations in tumour DNA are closely linked to results of treatment, and that the tumour DNA found in plasma in the blood may be a good indicator of mutations in the tumour that have become resistant to treatment.

They say this, "could suggest that patients with aberrant plasma androgen receptor should be selected for treatments such as chemotherapy or radiopharmaceuticals".

They add that this hypothesis needs to be tested in randomised controlled trials, to be sure this strategy would improve outcomes.

 

Abiraterone is an expensive drug, which can work well in some men, but not in others. NICE is yet to make a decision on whether it can be widely used on the NHS because of cost concerns. 

The cost would be far more palatable if it was possible to tell in advance which men would benefit from using the drug.

This is an early-stage study that establishes an apparent relationship between certain gene mutations detectable on blood tests and the chances of a man benefiting from abiraterone after his cancer has progressed and is no longer responding to first treatments.

The results need to be confirmed in larger studies. The researchers suggest prospective clinical trials, in which men are selected for treatment on the basis of their test results, to see if this strategy helps men get the treatment most suitable for their tumour. This would be a big step towards "personalised medicine" for prostate cancer, in which treatments can be targeted at those most likely to benefit.

However, we do need to be cautious. Only 17 of the men had a complete response to abiraterone, and many who had no gene mutations related to androgen receptors either had a small response, or no response to treatment.

The study seems to identify a group who are less likely to benefit from treatment, but it does not follow that everyone who isn't in that group will benefit. We also don't know the effect of treating men who do have gene mutations with other types of treatment. It may be that they do no better.

This study gives hope that prostate cancer treatments may be better targeted in future, but there is some way to go before the test is used like this in practice.

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