Expert commentary on emerging research in genitourinary cancer

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Published: 28 Feb 2015
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Dr Chris Parker - The Royal Marsden Hospital, London, UK

Dr Parker talks to ecancertv at ASCO GU 2015 about some of the most interesting and provocative research in genitourinary cancers emerging from the symposium.

He addresses the ASCENDE-RT trial, comparing external beam therapy vs. brachyotherapy, discusses the update of the GETUG-15 trial, and touches on the controversial and exciting results of the MCR-PR07 trial on statins. 

This programme has been supported by an unrestricted educational grant from Janssen Pharmaceutica (A Johnson & Johnson Company). 

Now you’ve been one of the important people here at the meeting, I’m delighted to get hold of you. But I’ve asked you to pick out a few interesting papers and one of them is on brachytherapy. I heard about this too, whether to use external beam radiation, or brachytherapy. What is this study, what did this study, first of all, tell us? What did we find out?

Yes, this is the ASCENDE-RT trial, it comes from Canada, and for me this is the highlight of the meeting. It’s a randomised controlled trial in men with high risk localised prostate cancer and they all received treatment with twelve months of androgen deprivation, they all received pelvic radiotherapy and then they were randomised to receive either a brachytherapy boost to the prostate or an external beam radiotherapy boost to the prostate. 400 patients randomised. Now I didn’t know what the results would be and I rather imagined it would be a close-run thing. It turns out it wasn’t a close-run thing at all; in terms of biochemical control there was a big advantage for the brachytherapy boost, it actually halved the risk of biochemical failure.

And this was in high risk, localised disease. So was the brachytherapy doing a better job of targeting do you think?

I think one can conclude that the effective dose to the prostate was significantly higher for the brachytherapy than for the external beam. Now there are some buts, so the brachytherapy treatment was significantly more toxic and in fact there was quite a worrying rate of grade 3/4 GU toxicity at five years, so an 8% risk. This is things like urethral strictures requiring surgery or catheters and subsequently leading to incontinence. So whilst I think the trial is very positive and demonstrates there’s a big gain to be had from more intensive treatment, I do think we need to find less toxic ways of giving more intensive treatment.

This may have raised eyebrows here at the conference but would it change practice, do you think, yet?

I think it challenges current practice because the control arm of the trial was 78Gy in 39 fractions to the prostate and 46Gy to the pelvis. Now that’s a very standard treatment that’s widely used and it looks like it’s not as good as we thought it was. I always thought that local control would be pretty good with that treatment, it turns out that there’s the potential for much better local control with more intensive treatment. Now it would be a big leap to all shift to brachy on the basis of one relatively small trial. However, I think it will come as an encouragement to surgeons because surgery to the prostate is, if you like, the ultimate boost of local treatment. It makes me think that potentially there might be something to be gained by hormones, surgery and radiotherapy rather than the current standard of hormones and radiotherapy.

There has been a lot of interest and a surprising result on the early use of docetaxel, this is in hormone naïve metastatic prostate cancer. Could you tell me about these findings from the GETUG-15 study?

Yes. We had an update of the GETUG-15 trial presented here and they’ve now got about eight years of follow-up. In actual fact it isn’t a huge update compared with what we knew already because that’s only 210 events compared with about 180 before. So what was new was they looked at risk groups. They divided patients into high risk and low risk and they did this because of the CHAARTED trial. So last year the CHAARTED trial showed a big, huge, survival benefit for early docetaxel and that was reported as particularly in the high risk subgroup. So GETUG-15 have now looked at the subgroups and no difference. So both the high risk and the low risk subgroup in GETUG, no survival advantage from early docetaxel. That came as a surprise to many people because I think most US oncologists at this meeting have completely bought in to the CHAARTED approach. They advocate, strongly advocate, early docetaxel for men with hormone naïve metastatic disease.

What do you think is going on here?

We’ve got two trials, CHAARTED and GETUG-15, saying very different things, they can’t both be right. The truth perhaps lies somewhere in between. I think the most important point in trying to reconcile these trials is that the difference between them is all what happens after men become castrate refractory. So both trials agree that docetaxel delays the onset of castrate refractory disease but it’s what happens next where they’re different. So in the GETUG-15 trial patients do about the same, whether they have early docetaxel or not, whereas in the CHAARTED trial they do much better after they become castrate refractory if they’ve had prior docetaxel.

Do you think there are any simple guidelines coming out of this for future therapy with early docetaxel?

I think it’s very hard to be dogmatic right now because just around the corner we’re going to get the results from the STAMPEDE trial which is far bigger than both of these trials put together. However, if I had to go out on a limb and guess what STAMPEDE might show I think it will not be as positive as CHAARTED. I think the benefit of CHAARTED is, to a large extent, from additional treatment – things like abiraterone, enzalutamide and cabazitaxel that happened long after their early docetaxel.

I want to ask you about another interesting area, again that raised eyebrows here, about statin use. It seems to have a protective role in prostate cancer doesn’t it?

It’s an interesting, provocative idea. We saw results from the MRC/PRO7 trial which was a large randomised trial of continuous versus intermittent androgen deprivation. What was new is they looked at the outcomes in relation to baseline statin use and they compared statin users versus non-users. Now obviously not a randomised comparison, however, it turns out that the statin users did much better, not just in terms of overall survival but also in terms of prostate cancer specific survival and, perhaps most interestingly of all, in those patients that were on the intermittent ADT arm they spent longer off hormones if they were on a statin compared with those who were not on a statin. So that’s interesting, provocative, intriguing.

Could there be some practice changes there? People are going to want to prescribe statins maybe?

I suppose that’s possible. Of course, many middle aged men in the UK are on a statin already so there’s no change in practice for them. It’s an interesting thought that perhaps people not yet on a statin, maybe they should be. But on the other hand perhaps all men of our age should be on a statin.