Men with localised prostate cancer often choose radiotherapy to treat their disease. Recent advances in radiotherapy technology are helping to improve treatments and reduce side effects. Australian men have access to cutting-edge radiotherapy technologies for their treatment. But there is one therapy that has not yet been possible in Australia - proton therapy. A new proton therapy treatment centre is now being built in Adelaide. Will proton therapy revolutionise prostate cancer treatments in Australia?
Radiotherapy for prostate cancer
Radiotherapy to treat localised prostate cancer is a common option for Australian men. External beam radiation therapy (EBRT) uses high energy X-ray beams directed at the prostate from outside the body. This radiation kills the cancer cells, or damages them to stop them from dividing. Normal cells close to the radiation beam can also be affected by it. Radiotherapy can also be given by a process called brachytherapy. This involves radioactive “seeds” that are inserted directly into the prostate. These seeds give off concentrated amounts of radiotherapy to the prostate, killing cancer cells.
Radiotherapy, like any type of medical treatment, has a chance of causing side effects. Some of the possible side effects are bowel and urinary problems, sexual difficulties, and fatigue. Radiotherapy usually causes infertility. Often radiotherapy side effects are temporary, gradually resolving after treatment. Some men do not experience any side effects, while others have more severe or ongoing problems.
Over the past 20 years, improvements to radiotherapy technologies have resulted in better treatments with fewer side effects. One example is intensity-modulated radiotherapy (IMRT). This treatment focusses the radiation beam closely to the shape of the tumour. IMRT helps to increase the amount of radiation hitting the tumour, and reduce the amount that affects nearby parts of the body. IMRT is now a very common option for treating prostate cancer in Asutralia.
Newer techniques are being developed to try to improve on the success of IMRT. Stereotactic body radiotherapy (SBRT) can be given over less treatments days, making treatments more convenient and less expensive. Proton therapy, on the other hand, aims to decrease radiation exposure to neighbouring areas even more, protecting nearby organs. This should improve radiotherapy by both reducing side effects and reducing the risks of secondary cancers.
Proton therapy
Proton therapy differs from conventional radiotherapy. It uses a beam of protons rather than x-rays. A proton is a sub-atomic particle; a part of an atom. Protons are found in the nucleus of atoms. They have a positive electrical charge, unlike electrons that have a negative charge. A proton beam needs to be made in a particle accelerator. This large facility uses an electromagnetic field to form a focussed beam of protons, moving at close to light speed. A proton therapy facility is therefore a very expensive and specialised treatment centre.
Proton therapy is used to treat a number of different types of cancer. Like x-rays, proton beams either kill cells, or damage them, which stops them from dividing. The proton beam has some advantages over x-rays. The protons behave differently to x-rays; they don’t scatter as much. So they are less likely to affect the cells and organs close to the tumour. Protons penetrate the body at a very narrow range, with very few going further through the body than the specified distance. Therefore they are less are likely to pass through the tumour, damaging cells on the other side of it.
Proton therapy aims to deliver almost all the radiation dose to the tumour, with little spreading to normal tissues. This approach is particularly useful for difficult-to-reach tumours, and tumours close to vital organs. Proton therapy is used to treat tumours such as those in the skull, the retroperitoneum (area behind the lining of the abdominal space, that covers the abdominal organs), the prostate and the eyes.
There are many proton therapy centres that offer treatment to prostate cancer patients around the world. Unfortunately, these treatments are usually extremely expensive. Australian men with prostate cancer who choose proton therapy must travel overseas to receive it.
Australian Bragg Centre
Australia’s first proton therapy unit is currently being built in Adelaide. Once built, it will be the most advanced proton therapy centre in the Southern Hemisphere, according to its website. The Australian Bragg Centre for Proton Therapy and Research is to be housed within the new SAHMRI 2 building in Adelaide’s centre. This 14-story building will also be home to research laboratories and biomedical companies.
According to its website, the Australian Bragg Centre aims to provide proton therapy for 800 patients per year. They hope to be open and treating the first patients by 2022. The proton therapy centre will treat Australian patients, but an estimated 25% of patients will be full fee-paying people from overseas countries in the southern hemisphere. Presumably prostate cancer patients will be included in those treated by this new facility. The cost of proton therapy at the Australian Bragg Centre is difficult to predict.
Proton therapy for prostate cancer
The big question for Australian men with localised prostate cancer is – is it worth having proton therapy instead of conventional radiotherapy? A number of large studies have addressed this question. However, none of these were conducted in Australia.
There have been many “case series” studies that have followed-up on proton therapy patients to track their progress. An example is this Japanese study of 218 men receiving proton therapy for localised prostate cancer. These studies have indicated a relatively low rate of side effects and relatively good outcomes. However, most studies have not directly compared proton therapy to other forms of radiotherapy. So from these case series, we cannot predict whether this expensive new treatment is more effective, or has a better safety profile, than conventional methods.
Three large studies have compared proton therapy to IMRT, a popular x-ray-based technique. A US study from 2012 compared proton therapy in 1,368 men to IMRT in 12,976 men for non-metastatic prostate cancer. This study showed that the outcomes were very similar, but proton therapy patients had a higher rate of gut problems. Another study from the US compared 553 men who received proton therapy to 27,094 who received IMRT. 6 months after treatment, the proton therapy patients had slightly less gut side effects than the IMRT patients. However, by 12 months, these differences were no longer apparent; both groups had about 18% of men with continuing gut problems by 12 months after treatment.
A recent publication in the Journal of Clinical Oncology compared proton therapy to IMRT. Their goal was to compare the side effects and costs of the two treatments. The researchers were a group based at the University of Texas, led by A/Prof Benjamin Smith. As most previous studies had recruited older men, these researchers focused on men under 65 years of age. In Australia, this would be almost half of newly-diagnosed men with prostate cancer.
The researchers used existing medical records to track the outcomes for men having proton therapy or IMRT. The study compared 693 men having proton therapy to 3,465 men having IMRT for localised prostate cancer. In this study:
- Proton therapy had a lower rate of urinary problems for these men. 33% of the proton therapy patients had urinary problems, compared to 42% of the IMRT patients, measured 2 years after the treatment.
- Proton therapy also had a lower rate of erection problems. 21% of these men had erection problems 2 years after proton therapy, compared to 28% of men having IMRT.
- Men having proton therapy had a higher rate of bowel problems by 2 years after treatment. 20% of these men had bowel problems compared to 15% of men who had IMRT.
The study also calculated the total cost of the two different treatments. The average total cost of the conventional radiotherapy was $59,012, compared to $115,501 for proton therapy (adjusted to 2015 US dollars). However, these were American patients, and our health costs are vastly different. But these figures do show that the cost to Australia’s health system for proton therapy will likely be much higher than those for conventional radiotherapy for prostate cancer.
The results of the above study are very interesting, but we need to be careful with interpreting them. This was not a randomised trial, so there were other differences between the two groups of patients. For instance, the IMRT patients were more likely to live in areas with a lower average household income. Proton therapy patients were more likely to be younger and have health insurance. It is possible that the different outcomes between the groups have come about due to other differences between the groups, rather than the treatment types.
What does this mean for Australian men with localised prostate cancer?
The benefits of proton therapy for localised prostate cancer remain unclear. Three large cohort studies have compared proton therapy to conventional IMRT. These studies have differing results. A randomised trial is necessary to be really sure of the differences between the two methods. The only thing we can be sure of is that proton therapy is really expensive.
PCFA asked A/Prof Andrew Kneebone, prominent Australian Radiation Oncologist specialising in prostate cancer, for his opinion of the relative benefits of proton therapy. His answer was:
Protons can be a very nice way of delivering radiation as they release their dose of radiation (called the BRAGG peak) deep down in the body with relatively little dose to the surrounding tissues. This will become invaluable for paediatric tumours especially as minimising the dose of radiation to young growing tissue can make a large difference.
With older style of radiation (e.g. 3D conformal radiotherapy), proton therapy had distinct advantages by reducing dose to surrounding tissues such as the rectum and bladder but many of the older proton machines struggled in their ability to be accurate localising the prostate during each treatment creating the potential for a geographic miss. With modern techniques (e.g. IMRT/VMAT), it can be possible to minimise the dose to surrounding tissues and it is possible to displace the rectum out of harms’ way with the use of hydrogel. Also, many modern machines can now use techniques to ensure 1-3mm accuracy when delivering treatment again reducing dose to the adjacent rectum and bladder.
I therefore feel the new proton facility is unlikely to have a significant impact on the Australian prostate radiotherapy landscape but will be a useful facility for paediatric cancer and certain tumours (such as base of skull tumours).
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