ASTRO 2015

Reduced fractionation radiotherapy feasible for localised prostate cancer

Prof Howard Sandler - Cedars-Sinai Medical Center, Los Angeles, USA

The background of the study that was presented at the ASTRO meeting this year was a test to see whether what we call mild hypofractionation, i.e. a shorter course of radiation therapy, is not inferior or essentially the same as standard radiation therapy.

What do you mean by mild fractionation?

What I mean by mild hypofractionation is a shorter course of radiation where each of the treatments is a little bit stronger than a standard radiation. In this study we compared 28 fractions to 41 fractions.

Can you tell us about the study design?

The study was testing hypofractionation in men with localised and low risk prostate cancer and men were eligible if they had low risk disease and were going to get radiation therapy without any hormonal treatment. The study randomised just over a thousand men; half of them received the standard radiation and half received the hypofractionated radiation.

What were the main findings?

The main concerns about the study and the main things that we were interested in looking for were two things. One was whether the shorter treatment was equivalent in terms of cancer control; we didn’t want to sacrifice cancer control whatsoever. The second thing that we were interested in was whether the shorter treatment was safe to deliver i.e. were there more side effects. The cancer control endpoint was totally equivalent, so there was no difference in terms of curing the cancer with the shorter, more convenient treatment. As far as side effects go, we did detect a very slight increase in side effects of 1% in grade 3 toxicity of GI and the GU areas. So overall we believe that the trial is a positive trial and shows that hypofractionation is not inferior to a standard fractionation. I think it’s safe for physicians and patients to discuss this and when I go back to Los Angeles I’ll start offering hypofractionated therapy to my men with early prostate cancer.

1% of patients had side effects, how big a problem is that clinically?

The study carefully assessed for toxicity and so far what has been reported is physician reported toxicity: physicians describing what is going on with the patients. Clearly both groups of patients in this study did very, very well. The difference in grade 3 toxicity where grade 3 toxicities are noticeable but often not very bothersome, the difference in grade 3 toxicity was only 1%, so from 2% to 3%. That’s a very small difference and for many men they would be willing to accept a minimal increase in toxicity for a substantially more convenient treatment. But I think that’s a good discussion for doctors to have with their patients.

Can you comment on Dr Shaikh’s data showing that hypofractionation was associated with higher rates of urinary incontinence?

In studies that have been done besides our study, including studies that were reported by the Fox Chase Group with long term follow-up, you can detect an increase in toxicity perhaps with these hypofractionated regimens. It’s my feeling that the toxicities are extremely low in both arms; both arms are very well tolerated. We’re very carefully assessing for toxicity and so we are able to notice small changes. But in medicine, when you have the data it allows you to have an informed discussion with your patients. You can say, ‘Look, here are the treatment options, here’s the cure rate, here’s the toxicity. Let’s work together and find out,’ using an informed decision-making process, and help the patient identify what they think would be their best treatment option.

What would be your take home message?

There’s enough evidence and enough follow-up to suggest that it’s reasonable to deliver mild hypofractionated regimens as tested in this RTOG-0415 study. I think that’s clear. Future directions for investigation are how far can we take this hypofractionation approach? Can we go as short as five fractions? I think that the studies being done in Europe and studies being done in the US will in the not too distant future give us pretty good evidence on whether we can go all the way down to five fractions. But for now I think it’s a big step to go from over eight weeks to approximately five weeks of therapy. That’s a tremendous amount of convenience for patients.