Hypofractionated high dose intensity modulated radiotherapy non-inferior for prostate cancer

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Published: 17 Feb 2023
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Prof Joe M O'Sullivan - Queen's University Belfast, Belfast, UK

Prof Joe M O'Sullivan speaks to ecancer at ASCO GU 2023 about his talk on the 10-year efficacy and co-morbidity outcomes of the CHHiP trial.

The trial was one of the largest ever clinical trials in localised prostate cancer. It compared standard radiotherapy 74Gy/37f to hypofractionated high dose intensity modulated radiotherapy 60Gy/20f for prostate cancer treatment.

Prof O'Sullivan concludes that with a median follow-up of 12 years, oncological outcomes following 60Gy/20f continue to be non-inferior to those with 74Gy/37f. The data support the long-term safety of moderate hypofractionation.

I was presenting data from the CHHiP trial. This is one of the largest ever clinical trials in localised prostate cancer. The trial was comparing standard radiotherapy, that’s giving 74Gy over 37 fractions in 7½ weeks, that’s the standard way we used to do radiotherapy for localised prostate cancer, and comparing it to doing that in a shorter fashion, what we call hypofractionated radiotherapy where we squeeze the radiotherapy into four weeks rather than the standard seven weeks. The idea being, first of all, it’s a benefit for patients to get the treatment done quicker, they like that, but also scientifically and biologically there’s a good rationale that giving the radiation in a shorter period of time will have an advantage in terms of efficacy in curing more prostate cancer.

It was a very large trial, well over 3,000 patients randomised to three arms. One was the standard arm, 74Gy in 37 fractions, then there were two experimental arms – 60Gy in 20 fractions and 57Gy in 19 fractions. 

The primary endpoint of this study was biochemical failure and it was designed as what’s called a non-inferiority trial. So what you’re trying to find out is, you’ve got your standard arm which you know works well, 74Gy in 37 fractions, and you have to compare these two experimental arms and by statistical analysis you can determine is it as good as or the same as or worse than. The measure that we used was called biochemical recurrence, so essentially patients where their PSA, which is a biomarker in prostate cancer, where that was raised significantly after the treatment we determined that was a recurrence of prostate cancer. 

The new data we are presenting today, we already had presented the five year follow-up data some years back and now this is ten year data. So this is really long-term follow-up of a lot of men who have had this treatment. What we found, first of all, is that we confirmed that 60Gy is probably the best of those three doses and that it’s at least as good as the standard arm, whereas 57Gy seems to be a little bit less effective in terms of biochemical control. 

The other very important piece of data in this group of patients was the toxicity because for many of these patients it’s pretty easy to cure these patients, they have a very, very high cure rate, probably well over 80%. But what’s different between surgery and radiotherapy might be the toxicity rates, particularly with regards to bladder and bowel and sexual function. What we showed in this ten-year data is with regards to bladder and bowel side effects they really are quite low overall – less than 2% of patients experiencing problems ten years later. This is very reassuring for patients just about to start radiotherapy for this type of prostate cancer, that, first of all, the cure rates are very, very high, the chance of dying from this prostate cancer are very low. In fact, the chance of developing a metastasis is less than 5% at ten years, which is really amazing. But, very importantly as well, the risk of a serious long-term complication that would be life-altering is very, very low indeed, which is reassuring at this stage.

It really shows the strength of UK clinical trials. There are very few countries that could do a trial of this huge scale and have well over 3,000 patients recruited within a few years. So it’s really testament to the really excellent NHS clinical trial ethos.

How do you think this will impact future treatment of localised prostate cancer?

What’s interesting is that, first of all, this has really proven the point that giving radiotherapy in a hypofractionated way, so giving a bigger dose per day over a shorter period of time, that that principle works. Really, the next phase is the PACE trial, which data was also presented here today, and that’s really shortening the radiotherapy much more, down to five treatments. So that’s really the direction of travel for radiation – highly precise, very accurately delivered radiation using high tech machines like CyberKnife and very complicated linear accelerators. This type of stereotactic radiotherapy is really the way forward because this allows us to really spare tissue, try to protect the bladder and the rectum and the other organs that might be damaged and to give this in a very, very efficient way. So that’s the next step.

Also for patients with slightly higher risk localised prostate cancer, adding drugs to the mix can help as well and there’s a lot of work going into which type of drugs might be added to radiation in prostate cancer in due course.

What is your overall message for medical professionals?

Overall coming from the CHHiP trial is that ten years later we see excellent efficacy data. So this maintains the very high level of prostate cancer cure from this type of radiotherapy, showing that 60Gy in 20 fractions is just as good as 74Gy and also showing that the late toxicities at ten years are really quite low and very reassuring for patients.