Is CyberKnife better than the current standard treatments for localised prostate cancer?

[Wendy_Winnall]

Men diagnosed with localised prostate cancer often look to the newest technology for their treatment. It can be surprising to find that the latest, most technologically advanced treatments are not necessarily recommended by their specialists. This happens because it takes a long time for reliable evidence to be generated, to be sure of the success rates and side effects from the latest technologies. This week’s blog examines the success and side effects of CyberKnife, a new radiation treatment system.

Cyberknife and SBRT/SABR

It seems that every year there are new treatments for prostate cancer available in Australia. Even the names of these new treatments can be confusing. CyberKnife is a relatively new entry into Australia. Men deciding on their initial treatment for localised prostate cancer may be wondering if CyberKnife is the best treatment for them.

CyberKnife is a system that uses radiation as a treatment. CyberKnife delivers stereotactic body radiotherapy (SBRT), which is used to treat prostate and other cancers. SBRT is also known as SABR: Stereotactic Ablative Body Radiotherapy. The CyberKnife system consists of a robotic arm that delivers a beam of radiation, and an imaging system to guide the direction of the beam. CyberKnife was the first type of SBRT/SABR to be introduced. Now SBRT/SABR is also performed using other systems. Despite the CyberKnife name, the treatment does not involve cutting. The radiation beam stops the cells from dividing and can kill them.

Recent clinical trials (such as CHHiP and PROFIT) have shown that prostate radiotherapy has good outcomes if it’s delivered in higher doses over fewer visits. For example, radiation in higher doses over 20 visits instead of 37 visits can be equally successful. This is referred to as hypofractionation. Hypofractionated radiotherapy is becoming a recommended form of radiotherapy for localised prostate cancer. SBRT/SABR is a more extreme form of hypofractionation. During SBRT/SABR, even higher doses are used over (usually) five visits.

SBRT/SABR is used for treatment by men with localised prostate cancer, as well as men with cancer that has spread as only a few small tumours. This is referred to as oligometastatic prostate cancer. SBRT/SABR for oligometastatic prostate cancer has been discussed in a recent research blog. For men with high-risk, localised prostate cancer, hormone therapy (androgen deprivation therapy: ADT) is often given with the radiation treatment.

Update on SBRT/SABR for localised prostate cancer

A new review has been published that assesses the current evidence for the use of SBRT/SABR to treat prostate cancer. The authors are radiation oncologists from the Odette Cancer Centre and University of Toronto in Canada. Their review examined evidence for SBRT/SABR for localised and oligometastatic prostate cancer. This blog focusses on localised prostate cancer.

Although SBRT/SABR is considered the latest advanced technology for radiation treatment of prostate cancer, we don’t yet have high-level evidence to say that it is any better than other treatments. It has not been rigorously compared to the current radiotherapy or other treatments such as surgery in randomised controlled trials. These trials are underway. But long-term outcomes such as rates of prostate cancer returning, or survival rates, take many years to be measured.

Issues with short-term trials for prostate cancer treatments

There have been many different studies around the world examining the benefits of SBRT/SABR and its side effects. SBRT/SABR is considered relatively safe and effective due to the results from these  studies. But these studies can’t directly compare SBRT/SABR to other treatments for a number of reasons:

1. Most studies are case series or cohort studies, not randomised controlled trials. In a case series, doctors keep records of the patients they have treated and see how they go in the future. A cohort study follows up with patients over time. Cohort studies can compare different treatments, but there are potential problems with bias. Cohort studies do not randomise people into different treatment groups. Patients choose their treatment based on their doctor’s advice. This means that there are usually many differences between the people the different treatment groups. This makes it harder to be sure that different outcomes result from the different treatments, or other differences between the groups.

For a new technology, the patients are often carefully selected as those whom the doctors think would most benefit. So the results cannot be used to predict how well the treatment will work for everyone, only people who are similar to those in the case series. This is called lack of generalisability.

2. Most studies do not compare to control groups who had other types of treatment or no treatment (active surveillance). So no conclusions can be made on how safe or effective this treatment is compared to alternatives.

3. As SBRT/SBRT is a relatively new technology for treatment of localised prostate cancer, data on long-term survival are missing. We need a study to go for 10 to 15 years before we can compare survival rates. Measures of PSA levels and time until PSA rise are used in the short-term.

Success of SBRT/SABR for localised prostate cancer

The Canadian review summarised many studies that have measured the success of SBRT/SABR for localised prostate cancer. In short-term trials, success is often measured by determining the average disease-free survival. For prostate cancer, this is usually stated as the average amount of time a man lives without a significant rise in PSA levels or other indication of prostate cancer returning.

The largest study with the longest follow-up was performed at the Flushing New York Centre. In this study, SBRT/SABR was delivered using the CyberKnife system. 515 patients were treated and followed-up for an average of 8 years. The disease-free survival rates after treatment were 94.6% for men with low-risk prostate cancer, 94.3% for men with intermediate risk and 65% for men with high-risk prostate cancer. The authors state that “early outcomes of SBRT/SABR look very promising”.

The review summaries many other studies with similar results. An Australian study has analysed the experiences of men who were treated with the CyberKnife system in Western Australia. A mix of Australian men with low, intermediate or high-risk prostate cancer had the CyberKnife treatment. Seven men received ADT with their radiation treatment. This case series looked at PSA levels over the 18 months after treatment. PSA levels fell to an average of 1.5 ng/ml by 6 months after treatment, then to 0.6 by 18 months. The rates of bowel and urinary side effects were considered to be comparable to results from non-hypofractionated radiotherapy and to international prostate SBRT studies. These results look very promising, but there is no direct comparison to other treatments types or to active surveillance for men with low-risk prostate cancer. From experiments like this, we know that this treatment is safe and effective, but we don’t know whether it is any better than the current treatments.

Side effects after SBRT/SABR

Similar to radiotherapy techniques, SBRT/SABR comes with a risk of side effects. These may include problems with bowels, urination and sex. While some men recover well, others may have ongoing problems.

The Canadian authors state that “SABR appears to be well-tolerated”. This means the results from the short-term studies indicate a reasonable level of side effects compared to what would be expected for radiotherapy. They refer to studies of 835 men who had SBRT/SABR. These men were followed-up over a period of over 5 years. The proportions of men with long-term serious side effects was 2.6% for genital or urinary problems and 1.0% for bowel or intestinal problems. Surveys were used to help understand the side effects from the patients’ points of view. These showed that the less serious side effects were more common. Bowel and bladder problems remained stable over time, but sexual function became worse over time, even with no treatment. It should be noted that sexual function declines, on average, over time for older men. A phase 2 trial also showed that the reduced time of treatment meant that side effects were better for SBRT/SABR immediately after treatment, but similar in the long run.

Some men who have SBRT/SABR need to have ADT as well. In choosing this treatment regime, they also need to consider the side effects of ADT, which are often challenging.

SBRT/SABR is currently being compared to other treatment options for localised prostate cancer in randomised controlled trials. Randomised trials provide the highest levels of evidence, but they are expensive and take a long time to finish. Unfortunately, long-term results from these trials will take many years to become available.

The initial research described herein has been very useful, in showing that SBRT/SABR has acceptable safety and success rates. Whether it is better than other radiation treatments or surgery for localised prostate cancer is still being assessed. Even if the success rates and side effects are no different, the convenience of only 5 visits may be a more attractive option, particularly for men who need to travel or work during the treatment.