The role of radiotherapy in the treatment of locally advanced prostate cancer

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Published: 20 Jul 2010
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Prof Malcolm Mason - Cardiff University, Wales
Prof Mason speaks about the results of an inter-group trial conducted by the UK Medical Research Council in collaboration with the National Cancer Institute of Canada. This trial looked at men with locally advanced or localised non-metastatic prostate cancer and challenging the results of a previous study that treatment should be a combination of radiotherapy and hormone therapy. Interim analysis of the results has shown an increase in prostate cancer specific mortality and overall survival when both hormone therapy and radiotherapy were used. Prof Mason discusses two other trials that he is running: one is a study comparing the long term use of hormone therapy with either androgen therapy alone or with an androgen therapy combination; the second study is looking at the role and timing of salvage radiotherapy.

ASCO 2010 Annual Meeting, 4—8 June 2010, Chicago

Interview with Professor Malcolm Mason (Cardiff University, Wales)

The role of radiotherapy in the treatment of locally advanced prostate cancer

Tomorrow we’re presenting the results of an inter-group trial which was done between the National Cancer Institute of Canada and the UK Medical Research Council. And this was looking at men with locally advanced or with high risk, localised, non-metastatic prostate cancer. And to understand the origins of this study you have to go back to the EORTC study that was done by Bowler, the classic study which compared the use of radiotherapy alone versus radiotherapy plus hormone therapy in a similar group of patients. And this was a really influential study because it showed quite clearly that the combination of radiotherapy and hormone therapy was superior in terms of survival. And it became, therefore, standard practice to add hormone therapy to radiotherapy. 

What the study didn’t address was actually, within that combined modality arm, was it really the combination of the two or was it just the hormone therapy? Would we have got equally good results with just hormone therapy? And that was a valid question because in that group of patients there are very many worldwide who are still treated with hormone therapy alone. Many, many urologists regard this as an incurable disease, disease where the appropriate treatment is just hormones. So in that context what’s the role of adding radiotherapy to the hormones? And that was the basic design of the study.

What were the findings of this study?

What we found, and I must stress this is an interim analysis so we were authorised by the Data Monitoring Committee to present the results here at ASCO, but on the interim analysis we have found a significant improvement, not only in prostate cancer specific mortality but also in overall survival, in favour of the use of radiotherapy with hormone therapy. So this is in keeping with the results of the study that was published by Widmark a couple of years ago, but unlike that study our group of patients is a high risk group of patients, they did not have surgical staging of their lymph nodes and so they are, we think, more typical of the sorts of patients who are seen in urology clinics worldwide.

How will these results affect clinical practice?

I think that when you put these results together with the results of Widmark’s study, there’s another study that’s being presented by the French group which is a smaller study, when you look at all of this they’re all telling the same story and I have to say, I think with the state of the knowledge as we have it, the standard treatment for these patients should be hormone therapy plus radiotherapy. I think the important message for urologists is that they need to get these patients to see the oncologist, it’s not appropriate for them just to be put on hormone therapy and not to have that oncological consultation as well.

What is the key message patients should take from these results?

I would no longer be saying to the patient the standard treatment for them in this setting is just hormone therapy, assuming that other things are equal and assuming the patient is fit enough to have radiotherapy, which they usually are, that they don’t have undue co-morbidities that might change the picture. Other things being equal, the standard treatment for these patients should be combined modality therapy and patients should be told that that is, as far as we know, to the best of our knowledge based on the interim findings of this trial and others, that is the standard treatment.

What other trials are you conducting at the moment?

In the UK we have two very large studies which are on-going. One is the Stampede study which is a very innovative design, it’s a multi-arm, multi-stage study that is looking at men who are starting long-term hormone therapy. It’s a six arm study: the control arm is hormone therapy alone and in the various test arms hormone therapy is combined with some other treatment. So that would either be Docetaxel chemotherapy, this is in hormone-sensitive patients so that’s the innovation. So Docetaxel, Zoledronic acid, Selecoxib or a combination of Docetaxel and Zoledronic acid or Selecoxib and Zoledronic acid. Now that sounds immensely complicated but actually it boils down to a study where we are looking at hormone therapy alone, androgen suppression alone, versus androgen suppression plus something else and that’s certainly the way I start explaining it to my patients. A very ambitious study; we’re going to be aiming for 3,000 patients in total. It goes through several stages of interim analysis and at the moment we are proceeding with all of the arms open, and that’s recruiting very, very well indeed.

The other study I would mention is a study called Radicals which is a study looking at the role and the timing of salvage radiotherapy, which we now know to be beneficial in patients who are at high risk of recurrence following a radical prostatectomy. But what we don’t know for certain is what the role of hormones is added to the radiotherapy in that group of patients, or really what the optimum timing of the radiotherapy should be. So that if you have a patient who has a radical prostatectomy, he has adverse findings on the pathology but his PSA is undetectable, should he have immediate radiotherapy or is it OK to delay the radiotherapy until there’s a very small rise in a supersensitive PSA test? So that essentially is the question.