Whenever you use radiation to treat cancer patients one of the first questions you have to ask is what are you going to radiate? In some circumstances we only radiate the primary tumour site. So, for example, if you’re treating somebody with head and neck cancer, if they have a tongue cancer do you just radiate the tongue or do you radiate the neck nodes? In prostate cancer one of the questions that has been out there for many years is what do we radiate? Based on pre-treatment features such as PSA, Gleason score and stage, we can estimate which patients are at risk for having recurrences in their lymphatics and with modern imaging, with PSMA-PET scans, we’re able to see that a common pattern of recurrence is in the lymph nodes. So the question is can we identify which patients are likely to benefit from having their pelvic lymph nodes irradiated and if we can and we do, that is we radiate the lymph nodes, will that treatment of the lymph nodes result in survival, increased survival, from prostate cancer?

So this study really is designed to take the patients that are at risk but are relatively low risk or modest risk, around 15% which means 85% don’t have it, all the way up to patients that have a higher risk of lymph node involvement to try and figure out whether there’s a specific category of patients that might benefit. So we randomised patients who were receiving hormone therapy and radiation who were categorised as having unfavourable intermediate risk or favourable high risk. We didn’t want to take the very highest risk patients who had obvious lymph node involvement or were extremely high risk, because we were concerned that it may not be ethical.  All of our old studies we treated, we routinely treated the pelvic lymph nodes in the old studies going back 20 years, 30 years, like that. So we wanted to see if we moved it earlier into categories of patients that were at risk but not so high risk that we felt uncomfortable that they could benefit from having their lymph nodes treated.

So, as the title of the abstract suggests, these are the early results. I would say that, just to be brief, I think we need a longer follow-up to answer the questions. But you haven’t read the abstract but it does suggest that there’s a difference in the risk of having biochemical failure but biochemical failure is not a surrogate for death from prostate cancer. So the bottom line is that we still don’t know because the follow-up is relatively short. The median follow-up is 7.3 years and most of the people that die of prostate cancer die after ten years. So we are encouraged by the fact that with longer follow-up we should be able to answer the question but at this point we don’t have an answer.

What was the study design?

It’s just randomise patients to either have only their prostate irradiated or to have their prostate and their lymph nodes irradiated. Then, again, the primary endpoint was survival, overall survival. The importance – most trials that are done involve drugs and drug companies pay for them, so one of the great challenges to doing a study like this is that this is simply a radiation question, it’s not a drug question. Most drug question studies are paid for by drug companies so this had to be paid for by the National Institute of Health or the National Cancer Institute in the US because this is simply a radiation question – do we radiate only the prostate?

We will have biomarkers and maybe that if somebody put a gun to my head and said, ‘You’ve got to tell me what’s going to happen downstream,’ I would say that probably using biomarkers we will be able to identify subsets of patients who might benefit, using biomarkers, but that our clinical estimates of which patients are at risk for lymph node involvement are too crude and insensitive to be able to select out patients well. That’s why it’s a pretty large study, it’s the largest study ever done in localised prostate cancer with the primary endpoint being survival. We felt like we needed this many people because there’s a lot of drop-off. You have 500 patients have died in the first ten years, most of the vast majority of which had nothing to do with prostate cancer. So you can see that if you’re going to need enough patients between 10-20 years to be able to answer the question statistically, you have to start off with a high number of patients in order to get the question answered. A small study cannot do it because there are other competing causes of death other than prostate cancer.

What were the results of this study?

At ten years there’s no survival difference.

Is there anything else you would like to add?

Part of the reason I decided to do this, you haven’t seen the abstract, the presentation is not until Sunday, is that there are a lot of people that are going to walk away from the results and conclude that the results are negative, that it proved that you don’t need to do it. I would argue that, no, the results are not negative, that longer follow-up is needed. So the bottom line is stay tuned – in the next 3-5 years I suspect that we will have sufficient statistical power to tell us whether or not radiating the lymph nodes prophylactically will actually result in a survival difference.