ASTRO 2015

Geonomic testing may help predict metastatic risk after prostatectomy and salvage radiotherapy

Dr Robert Den - Thomas Jefferson University, Philadelphia, USA

This year at ASTRO I’m presenting research that I did collaboratively with investigators at three institutions: Thomas Jefferson University, the Mayo Clinic as well as Duke University. Currently in prostate cancer there’s a lot of controversy amongst the treatment – who should be treated, how intensively should they be treated. So we wanted to address this by looking at a genomic classifier and we used a commercially available genomic classifier and analysed the patients in this cohort to see if we could identify patients that benefit from radiation therapy versus those that wouldn’t.

Can you describe the genomic classifier you used?

The genomic classifier is a 22 set of both coding and non-coding genes. What that means is that not all of the products within the genome actually code for genes that are used in the building of our cells and systems. But that doesn’t mean that they don’t contain important information. Using a cohort from the Mayo Clinic the company, along with investigators from the Mayo Clinic, were able to show that they could use a 22 marker set, so looking specifically at the expression levels of 22 specific markers determined those patients at highest risk for developing metastases. This is very important because this allows us to determine which patients are at the highest risk for having death from prostate cancer.

Is this genomic classifier specific to prostate cancer?

This is actually a prostate cancer specific classifier which makes it very unique and it’s very robust within the field of prostate cancer.

Can you provide the background to the study you did?

The study premise is that there has been a huge shift over the past several years from using adjuvant radiation to salvage radiation. Just to explain what that means is that after patients undergo radical prostatectomy the expectation is that their PSA will become undetectable. For those men that have an undetectable PSA and then receive radiation therapy that’s classified as adjuvant treatment; for those men whose PSA rises to above 0.2 ng/ml that’s classified as salvage radiation. Now, a lot of people feel that if you treat men with adjuvant radiation therapy you’re going to result in overtreatment of men so that more men will receive treatment unnecessarily. So this really looked at the patients that were receiving salvage radiation therapy and determining whether the genomic classifier could help us understand which men were at highest risk for developing metastases. So the unique aspect of our study is that it actually contained 30% of African Americans and this is something that’s unique in our study because if you look at a lot of the clinical trials that are done within prostate cancer and the cancer field at large, a lot of them have under-representation of minorities. What this means is that our studies and our findings are very generalizable to the general populous, both in the US and worldwide.

What did you find?

What we found was that our genomic classifier was the strongest factor in predicting metastasis following salvage radiation therapy. It was better than any individual clinical parameter as well as any combination of clinical parameters. What this says is that the genomic classifier is really reflecting the underlying biology of the prostate cancer. What it also tells us is that this is a critical piece of information that practitioners and patients need to know and is very beneficial for the people to know about because it will impact in terms of what treatments they need, what intensification they need and, vice versa, those that don’t need any further treatment.

Can you tell us about the rates of metastases seen?

We classified men based on the genomic classifier into high risk and low risk groups. What we found is we found that for men at high risk group it could be up to 30-40% of men developing metastasis. We then did an analysis looking at the timing of radiation. So even though all men received salvage radiation, some men received radiation when their PSA was less than 0.5 whereas others received it when the PSA was greater than 0.5. What we found was that in the low risk group by the genomic classifier there was no difference in terms of the outcomes of men whether they received early salvage radiation or late salvage radiation. However, in the men at the high risk by the genomic classifier there was a significant reduction in the development of metastasis from men who received early salvage radiation therapy, really identifying a group of men that should be receiving treatment much earlier in their disease state.

How should the genomic classifier be used then in clinical practice?

It’s currently commercially available; it’s currently covered under Medicare. All the data that we have generated thus far comes from retrospective studies. Now, people have questioned whether retrospective studies are sufficient or if prospective trials are needed. Clearly, using evidence based medicine, the ideal is to have phase III prospective trials, however, given the length of time which it takes for the events to occur, meaning that it will take decades for men to develop metastasis, the best approach currently is to use retrospective studies and to do a comparative effectiveness study, which is what we did in this case, meaning that we’re using real world data to understand this problem and to address it. So I would say it is early but I would definitely recommend the use of the genomic classifier to help both practitioners as well as patients understand the risks and understand what might be necessary for eradication of their disease.

Do you have anything else to add?

I will say one thing, the genomic classifier is based off of prostate tissue. So all these men have already undergone radical prostatectomy so there’s no extra prodding, there’s no extra test that men need to do. Given that this is now being covered under most insurances, there shouldn’t be any cost to the patient and if there is a small cost this can be defrayed by assistance from the company. So I think that it’s an important piece of information to know. This and other genomic approaches are really changing the way we think about prostate cancer and really helping us as a field identify those men that really should be the focus of our future clinical trials and treatment intensification.