ASTRO 2015

Conventional vs hypofractionated IMRT for localised prostate cancer

Dr Talha Shaikh - Fox Chase Cancer Center, Philadelphia, USA

There are many different treatment options for patients with prostate cancer – surgery, radiation, different types of radiation. We have long thought that treating patients with larger radiation doses daily can have potential advantages and that’s due to the nature of prostate cancer, it’s a slow growing tumour. We believe that slow growing tumours may be more sensitive to higher doses per fraction; historical studies have shown that a little bit. Currently the standard radiation treatment for prostate cancer is about eight weeks, so it’s every day, Monday through Friday, for eight weeks which is time consuming for the patient, it’s costly for a healthcare system, it requires a lot of resources. That’s where hypofractionation can potentially have that advantage of reducing cost, convenience for patients and it can also potentially have a therapeutic advantage.

Can you outline the study design, methods and patient population?

This was a study that was conducted between 2002 to 2006, it took patients with clinically localised prostate cancer and it randomised to either conventionally fractionated IMRT or hypofractionated IMRT. Conventionally fractionated IMRT consisted of 76Gy in 38 fractions, so that’s 2Gy fractions every day, which is a pretty standard dose, that’s about seven to eight weeks. The hypofractionated, the experimental arm, was a total of 70.2Gy in 26 fractions and that’s at 2.7Gy per fraction. That reduces the treatment time to about five or six weeks.

How were the patient-reported outcomes measured?

We used three validated quality of life self-assessment tools that patients completed prior to initiating radiation; that served as their baseline. They completed at six months and then they completed it at a year every year for five years. So the three self-assessment tools that they used were the Expanded Prostate Cancer Index, or the EPIC tool, that has five different domains including sexual function, hormonal function, bowel function, urinary irritative obstructive symptoms and urinary incontinence. We used the IPSS which focusses more on just urinary function; it has been used for many years and is another validated instrument. That has two different components: one component patients just measure their symptoms and you come up with a composite score, the other part of that IPSS tool is a quality of life component where patients just measure how they feel about their urinary function. Finally the EQ5D was the last component we used which also has two sub-domains. One domain is an overall score which is compiled by measuring the patient rates their mobility and pain and ability to take care of themselves and those types of things. The other component of that is a visual analogue score which the patient just rates on a score from 0 to 100 with 100 being the best health state imaginable.

What were the main study findings?

What’s great about this study is that it’s the first long term study looking at patient reported outcomes. So what we found at three and four years, there appeared to be worse genitourinary incontinence scores in the hypofractionated arm. That’s something that is consistent with some other findings; other studies have shown that maybe there’s more toxicity with hypofractionated radiation but it has always been physician reported, it’s always what the physician thinks. This is the first time we have patients reporting this themselves. So at three and four years we saw maybe the patients had a little bit of worse incontinence scores in the EPIC domain, this was no longer statistically significant at five years but we think that’s probably because not as many patients were completing the survey. So that’s probably the most significant finding of this analysis.

Could patients’ age have affected the outcomes seen?

There was no significant difference in the age between the two groups so the median age was in the 60s for the conventional arm and the hypofractionated arm. In order to make sure that this was basically true we did construct a multivariable analysis and what that does is it controls for every other factor so it controls for baseline score, age, etc. When we did that multivariable analysis the fractionation schedule was no longer significant. So it’s hard to say if maybe there was something else going on that maybe we’re missing because the fractionation schedule did not impact the EPIC, any EPIC domain or IPSS score or EQ5D score.

Could a nursing clinic dedicated to showing patients what to expect improve their experience of hypofractionation?

In general both of our arms received essentially the exact same care during treatment. So patients in both arms were seen every week by a nurse, by their physician, typically by a resident physician as well. Generally we feel like they received a pretty similar explanation of what to expect then and were counselled very similarly throughout their treatment.

What can be concluded? Could the findings change current practice?

We are increasingly looking at hypofractionated radiation for prostate cancer. At this meeting alone there are multiple studies looking at hypofractionated radiation; one of the plenaries was RTOG-0415 which also looked at hypofractionated radiation. There’s increasing evidence demonstrating that maybe this is a potential option for patients with clinically localised prostate cancer. One of the big fears that practitioners have generally had is not whether it’s effective but whether the toxicity will be worse. Our study is one of the first studies that is demonstrating maybe some patients may not be perfect candidates for this, maybe people that have poor baseline genitourinary function may want to stray away from using this type of treatment. But outside of that I think the evidence is mounting that hypofractionated radiation may be an excellent option for a lot of these patients.

What future research plans do you have?

This looked at moderate hypofractionation, so it was 2.7Gy per fraction. There have been trials that we have been involved in where it’s looking at extreme hypofractionation, or SBRT. SBRT has been used in lung cancer and other disease sites but we’ve always been a little bit afraid to use it for prostate cancer because of the potential impact on urinary function or other potential toxicity. So we were involved in a trial with the RTOG which I believe completed last year so our institution was involved with that. There is also a similar trial conducted through the University of Michigan Group which we were also collaborators on so we eagerly await what the results of those show to see if there are potentially candidates who don’t even have to get 26 treatments, they can potentially get five treatments or twelve treatments. So that’s the future where prostate cancer radiation is going.