ASCO 2012, Chicago, USA

BRCA carrier status as a prognostic factor for prostate cancer

 Dr Elena Castro – The Institute of Cancer Research, Sutton, UK

Dr Elena Castro, you’re talking at the meeting, you’re presenting on BRCA carrier status. Now this is not in women and their breast cancer risk but in men with prostate cancer risk which is associated with BRCA1 and 2. What’s the information on this and what are you doing that’s new?

We know that the BRCA2 mutation increases the risk of prostate cancer by 8.6 times the risk in the general population. For BRCA1 it’s a bit more controversial and the risk seems to be lower, around 3.5. So it is known that the BRCA mutations are usually associated with more aggressive disease, the tumours usually have a higher Gleason score and we have previous studies where we demonstrated that these patients also have worse outcomes. They have worse survival and they metastasise earlier and what we wanted to know now is the response to different types of treatments.

And as a predictor of those worse outcomes you’ve been looking at biochemical progression free survival?

Yes, absolutely. To know the response to a treatment, the cause of specific survival is still the gold standard to assess how good a treatment is but in prostate cancer we can use PSA relapse. So, if after radiotherapy or surgery the PSA starts to rise again, we can talk about biochemical failure.

What exactly then did you do in the study?

What we did is to look at the time to this biochemical relapse in a cohort of men with BRCA1 and BRCA2 mutations and compared to a cohort of men without any BRCA mutation. What we did is in the study we included three non-carriers per carrier and we matched the carriers and non-carriers by age of diagnosis, tumour size, PSA levels, type of treatment and year of the treatment.

So an elegantly statistically balanced experiment or study; what was the outcome?

The median follow-up was 75 months and what we have observed is that there’s no difference in the time to PSA relapse when patients are treated with surgery but there is a difference when patients are treated with radiotherapy and that’s the BRCA carriers relapse earlier.

That seems as if you’re encouraging surgery then, because radical prostatectomy did rather well? Although that’s swimming against the tide – there’s an interest in doing less radical prostatectomy, isn’t there?

Yes. The thing is, probably yes but more studies need to be done to be able to affirm that. The reason for that is that patients with more advanced disease are usually treated with radiotherapy rather than prostatectomy, even when the tumour is a local disease. So in our studies also the patients with radiotherapy, no matter whether they were BRCA carriers or not, had more advanced disease than those treated with prostatectomy so we cannot make a direct comparison.

So you haven’t got a conclusion to make about the efficacy of surgery at this point?

To compare, yes, but what we know is that when patients have the same stage, the same characteristics, those treated with radiotherapy do worse than the non-carriers but there’s no difference for those treated with prostatectomy.

What then are the basic conclusions of your study?

The basic conclusion is that there’s no difference for the patients who are treated with surgery. Always then, if possible, probably we will suggest that if the patients are to decide whether they can be treated with surgery or prostatectomy, it’s a very early conclusion but we would recommend them to have surgery if that is eligible but we cannot present data directly comparing surgery and radiotherapy.

That’s a provisional hint only then.

Yes.

And what is coming out of this is a reassuring message that if you have the mutation you aren’t necessarily going to do any worse with any particular treatment. The treatments are all doing rather well.

With surgery definitely, with radiotherapy BRCA carriers seem to do worse than the non-carriers. We still don’t have data on chemotherapy and what we are planning is to do a bigger study collecting data from other hospitals around the world so we can have a bigger study and actually we think we will be able to answer all these questions. Important enough knowing what happens with BRCA carriers and prostate cancer is not only what happens with these patients because the number of patients who carry BRCA mutations and develop prostate cancer is small, it’s just around 12% of those patients, but actually if we are able to identify the characteristics of those tumours, we may be able to identify those characteristics in patients without BRCA mutations that are going to have a very bad prognosis, something, we could call it BRCAness, in prostate cancer.

How important then is it to know the BRCA status of your patient and what should busy doctors be doing about that?

At the moment the frequency of the incidence of BRCA2 mutations in patients with prostate cancer is less than 2% and for BRCA1 it’s around 0.44% so there’s no indication to do screening for BRCA mutation in all prostate cancer men. So at the moment it’s only if there’s a family with breast and ovarian cancer and prostate cancer, then that family should be screened for BRCA mutations. We are working on trying to identify all the factors that will help us to identify which are the patients with prostate cancer, even without a family history of other types of cancer, that should be screened for BRCA mutations but at the moment we just know that these patients just tend to have more aggressive disease and tend to progress earlier. But, up front, when patients are diagnosed, trying to know which are the ones that should be screened, at the moment we don’t know.

So the bottom line message for cancer doctors to take from this would be what?

Definitely these patients will benefit from prostate cancer screening, even when for the general population it’s very controversial. For BRCA2 carriers an early diagnosis may make a difference. So, if possible, if there is a possibility of treating the patients with either radiotherapy or surgery, probably surgery will be…

You’d be leaning towards surgery?

Yes, it would be better for them.

Thank you very much.