Blood test may show if prostate cancer treatment is working

“Prostate cancer blood test helps target treatment,” BBC News reports.

A study found a blood test could detect which men with advanced prostate cancer would benefit from new drug treatment.

Researchers analysed blood samples from nearly 50 men taking part in a trial of a new drug (olaparib) for prostate cancer that has spread to other parts of the body.

They wanted to see whether changes to tumour DNA circulating in the men’s blood could indicate whether the treatment was working or not. 

They found that levels of circulating tumour DNA halved after four weeks of treatment in men who had the best progression-free survival (period of time when the cancer doesn’t get worse).

They also found that in men who initially responded to olaparib, the development of new gene mutations could indicate when the tumour was becoming resistant to the drug and the treatment was no longer working.

This suggests that a blood test looking at tumour DNA early in the course of treatment could indicate which men the drug was working for and which men would be better off trying an alternative treatment. 

The findings are a promising step forward in helping men with advanced prostate cancer receive the best treatment for them.

But this research is still in its early stages, with findings in a relatively small sample of men, and needs further follow-up.

Where did the story come from?

The study was carried out by researchers from the UK Institute of Cancer Research, the Royal Marsden NHS Foundation Trust, the University of Michigan, and the Peter MacCallum Cancer Centre.

Funding was provided by several sources, including the Movember Foundation, the Prostate Cancer Foundation, Prostate Cancer UK, and Cancer Research UK.

The study was published in the peer-reviewed journal, Cancer Discovery. It’s available on an open access basis and is free to read online.

The way the media covered the study is generally representative of its findings, reporting the trial details and quoting experts involved in the research.

What kind of research was this?

This was pre-planned laboratory analysis of blood samples collected as part of a trial of a new treatment for prostate cancer that’s spread to other parts of the body (metastatic prostate cancer). 

Metastatic prostate cancer is a major cause of cancer deaths among men worldwide. It can’t be cured – the aim is to try to control it and give men a good quality of life for as long as possible.

Previous research identified that up to a third of men with advanced prostate cancer have certain gene mutations, such as BRCA1 and 2.

The TOPARP-A trial tested the effectiveness of the drug olaparib (brand name Lynparza), which is specifically licensed for people with BRCA gene mutations.

It works by blocking a particular enzyme, poly ADP-ribose polymerase (PARP), and this stops the growth of tumours with BRCA mutations.

The researchers considered that circulating tumour DNA in the blood could give an indication of the person’s likely response or resistance to treatment.

They therefore assessed the DNA of blood samples collected from men in the trial to see whether DNA changes could have prognostic significance.

What did the research involve?

The TOPARP-A trial included 50 men with metastatic prostate cancer that hadn’t responded to previous hormone treatment and chemotherapy, and were subsequently treated with the drug olaparib.

Blood samples were collected from trial participants at the start of the study, then at 1, 4, 8 and 16 weeks of treatment, and at the time when the disease got worse (known as disease progression).

Researchers analysed the circulating DNA in these blood samples and looked at how DNA changes were associated with responses, such as a fall in prostate specific antigen (PSA) levels and circulating tumour cells in the blood. 

What were the basic results?

Of 46 men with DNA data available, 16 (a third) responded to treatment and 30 did not.

The researchers found a greater than 50% decline in circulating DNA concentration was associated with improved progression-free survival by four weeks and overall survival by eight weeks.

Looking at specific gene mutations, six of the men in the trial had mutations linked to advanced prostate cancer (BRCA2, ATM and PALB2).

These were all detected in circulating DNA at the start of the study, but the concentration fell to less than 5% in the five of six men who responded to the treatment.

Ten of the 16 men who responded had blood samples available at the time their disease progressed again.

The researchers observed new mutations developing – for example, in the BRCA2 gene – which suggests possible mechanisms of resistance to the PARP-inhibitor drug.

How did the researchers interpret the results?

The researchers concluded that their data “supports the role of liquid biopsies as a predictive, prognostic, response, and resistance biomarker in metastatic prostate cancer”.

They used the term “liquid biopsy” to refer to accessing tumour DNA in a man’s blood, acquired from plasma by a simple blood test.

Conclusion

This pre-planned analysis of blood samples collected as part of a trial for metastatic prostate cancer suggests that looking at circulating tumour DNA could act as a form of biopsy to inform whether the cancer is responding to treatment.

The findings indicate that a decrease in tumour DNA could suggest treatment is working, while the development of new DNA mutations could suggest the cancer is becoming resistant to treatment.

But there are several points to bear in mind. Though the findings show promise, this study only looked at blood samples taken from a relatively small sample of 46 men. Only six of these men had gene mutations linked to a poor prognosis.

On that basis, the study isn’t able to give definite answers at this stage about particular levels of circulating DNA, or any specific mutation changes, that have prognostic significance.

The findings need to be followed up in further studies of other men receiving olaparib for advanced prostate cancer.

The findings also can’t be applied to men with metastatic prostate cancer being treated with any drug other than olaparib, or men being treated for other stages of prostate cancer.

And even if a blood test could indicate whether or not a man is responding to treatment for metastatic prostate cancer, these findings don’t represent a cure for this advanced stage disease: in the majority of men who initially responded to olaparib, the cancer still eventually progressed. 

Nevertheless, if a test were developed, this may allow treatment to be changed at an early stage if blood results indicate it isn’t working.

This could hopefully help men with this advanced stage disease have the best quality of life by making sure they only receive treatment likely to bring benefits.

Links To The Headlines

Prostate cancer blood tests ‘helps target treatment’. BBC News, June 19 2017

New blood test could see personalised prostate cancer treatment. Guardian online, June 19 2017

Links To Science

Goodall J, Mateo J, Yuan W, et al. Circulating free DNA to guide prostate cancer treatment with PARP inhibition. Cancer Discovery. Published online April 27 2017, fully published June 19 2017