Blood test may lead to targeted therapy for prostate cancer

“A blood test has been developed that could help target treatment for men with advanced prostate cancer,” BBC News reports. The test could help identify men unlikely to respond to drugs such as enzalutamide.

Enzalutamide and abiraterone are additional treatments for men for whom standard hormonal treatment has not worked, or has stopped working.

Treatment success varies; some men get little benefit, while others have responses that last many years. The new test – if confirmed – could help doctors know in advance who is likely to benefit.

The blood test looks for extra copies of androgen (male hormone) receptor genes. The drugs block signalling from this gene. Researchers found that men with multiple copies of the gene did worse after treatment with either drug. They did not live as long and were more likely to see their disease return and worsen. The researchers say that if these men can be identified in advance, they could be spared these drugs and offered more suitable treatment.

Making sure a treatment actually has a benefit is important as, aside from wasting NHS money, advanced prostate cancer is almost always fatal. So it would be a much bigger waste if the last few years of a man’s live was spent trying out a treatment option unlikely to work, while others such as radiotherapy, could help.

We now need further research to tell us whether selecting patients by this gene test improves treatment results.

Where did the story come from?

The study was carried out by researchers from 24 hospitals or universities in Spain, Italy, the UK and the US, and was funded by Prostate Cancer UK and Cancer Research UK. The study was published in the peer-reviewed journal Annals of Oncology on an open-access basis so it is free to read online.

The study was covered by The Times, ITV News and BBC News. All presented balanced, accurate reports of the results, but didn’t mention that further work is needed to find out whether selecting patients based on the test works.

What kind of research was this?

This was an observational study, involving analysis of blood samples from three clinical studies of enzalutamide and abiratone, intended to look for biomarkers such as gene signatures. The research was designed to investigate the importance of certain mutations and numbers of copies of the androgen receptor genes to better understand which treatments will work in men with prostate cancer that hasn’t responded to commonly used hormone treatments, such as leuprorelin (Prostap).

This type of study is useful to identify potential tests, but it isn’t proof that the test will work to guide treatment and improve patient outcomes. We need clinical trials of the tests to show they work.

What did the research involve?

Researchers looked at the genetic status of men in three trials – two trials of enzalutamide and abiratone in the UK and Italy, with 171 men in total, and one trial of enzalutamide in Spain, with 94 men.

Blood samples taken before treatment and soon after were compared, using two different methods. Researchers classified the men into groups – androgen receptor (AR) gain for those with multiple copies of the AR gene over a certain level, and no AR gain for those under the cut-off point. They then looked to see how the men did after treatment, and compared results for men with AR gain with results for men without AF gain.

All men in the study had previously been treated to reduce their testosterone levels as far as possible (either by hormone drugs or surgery), which is the usual first treatment for prostate cancer. Some had also been treated with chemotherapy. To monitor disease progression and give some idea about men’s response to treatment, the men also underwent regular prostate specific antigen (PSA) tests (which tests for a hormone associated with prostate enlargement), computed tomography (CT) scans and bone scans.

The blood samples were analysed by the standard method of DNA sequencing, and by a much simpler, cheaper droplet digital PCR (ddPCR) test, and the results of the two tests compared. The researchers hoped the ddPCR would work as well as sequencing to identify men’s AR status, as this test can then be widely used.

What were the basic results?

The ddPCR test performed well against DNA sequencing, meaning it should be a reliable way of finding out men’s AR gain status.

In the first two studies:

• 14% of men who hadn’t had chemotherapy and 34% who’d had chemotherapy (with docetaxel) were found to have multiple copies of the AR gene (AR gain).
• These men were about four times less likely to survive until the end of the trial (hazard ratio [HR] 3.98, 95% confidence interval [CI] 1.74 to 9.10] for pre-chemotherapy patients; HR 3.81, 95% CI 2.28 to 6.37 for post-chemotherapy).
• Men who had AR gain lived on average nine and a half months after starting treatment, if they’d previously had chemotherapy, compared to 21.8 months for men without AR gain. The researchers were not able to give the equivalent figures for men who’d not had chemotherapy, as the trial was not long enough to establish this. 

In the third study:

• 12% of men had AR gain (none in this study had previously had chemotherapy).
• Men with AR gain were 11 times less likely to survive until the end of the trial (HR 11.08, 95% CI 2.16 to 56.95).
• On average, men with AR gain saw their cancer progress (measured by PSA test) after just 3.6 months, compared to 15.5 months for those without AR.

How did the researchers interpret the results?

The researchers say they have designed a “robust assay [test]” which “is affordable and can be widely implemented in clinical laboratories”. However, they say further research is needed before the test can be put into widespread use.

Before changing clinical practice to select patients using the test, they say, “our findings require confirmation in prospective trials where plasma AR CN [copy number] defines treatment selection.”

Conclusion

Genetic testing is becoming more common in cancer treatment as a way of tailoring treatment to the individual cancer. It’s already used in breast cancer, for example. This test could help identify which men that have not responded to hormone treatment are most likely to benefit from two of the newer prostate cancer drugs.

It is good news, because men could then be spared treatment that is unlikely to help them, and directed towards more suitable treatment options. Also, both of these newer drugs are very expensive, so a suitable test could save the NHS a great deal of money.

Meanwhile, those men who are likely to benefit will take the drug knowing it’s likely to help.

However, we’re some way off being able to use the test in practice. This research shows that, among a group of 265 men, those with multiple copies of the androgen receptor gene did worse after treatment than those without. That doesn’t prove that selecting patients for treatment based on AR gene status will improve outcomes.

We need to see studies that select patients for treatment based on their test results, and follow them up to see how they do, to be sure the test is truly helpful.

Links To The Headlines

Prostate cancer: Blood test could help target treatment. BBC News, May 4 2017

Blood test could help prostate cancer treatment. ITV News, May 4 2017

£50 blood test boosts chances of surviving prostate cancer. The Times, May 4 2017 (subscription required)

Links To Science

Conteducia V, Wetterskog D, Sharabiani MTA, et al. Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study. Annals of Oncology. Published online May 3 2017