Drug trials are rarely halted halfway through because the drug being tested is so effective — but that’s exactly what happened a few months ago at the Royal Marsden Hospital in London, one of the foremost cancer centres in the world, where doctors were testing a powerful radiation drug for men with advanced prostate cancer.
Patients being given Radium-233 Chloride, known as Alpharadin TM, lived longer and experienced less pain and fewer side-effects compared with those on a placebo.
It was decided that the difference in outcomes between the ‘haves’ and ‘have-nots’ was so marked that it was unfair to withhold the drug from half of the men on the trial.
This is just one of several recent breakthroughs in prostate cancer treatment.
In September, Australian researchers announced they had found that certain types of oestrogen appear to block the growth of tumour cells in laboratory studies.
These tantalising developments are all the more important because there remains a daunting fight against prostate cancer — the most common and the second deadliest among men after lung cancer, killing around 10,000 men in the UK each year, or an average of more than one an hour.
While new treatments are being found to treat every stage of the disease, and older treatments are being refined and developed, mortality rates remain stubbornly high.
Only 51.1 per cent of men in the UK with prostate cancer, which affects the doughnut-shaped gland that surrounds the urethra near the bladder, are still alive five years after diagnosis.
That compares badly with the 91.9 per cent of Americans who manage to make the five-year mark, according to the CONCORD study conducted from 1990 to 1999 — the first worldwide analysis of cancer survival rates. This may be because Americans have traditionally taken a more aggressive approach to prostate cancer.
A recent U.S. study found that 75 per cent of men with low-risk prostate cancer had aggressive therapy including radiation treatment and radical prostatectomy.
‘In the UK, the default option is to tell the patient they have choices — and many opt to wait to see if the disease gets any worse before having treatment,’ says Chris Eden, a consultant urologist who regularly travels to the U.S. to research the latest techniques.
‘About 40 per cent of all patients diagnosed each year in the UK choose to have active surveillance, when nothing is done except for repeated monitoring with blood tests and prostate biopsy.’
This is despite the fact that surgery still seems the most effective way of improving outcomes for patients. A recent U.S. study of 404,604 patients has found that ‘with the exception of men over 80 years, surgery provides the most favourable survival rates in most patients’.
Mr Eden, who performs around 200 nerve-sparing keyhole prostate removals each year — carefully avoiding the nerves which are key to erectile function — feels there are ‘some lessons’ to be learned from the U.S. approach.
‘American men will research their options and take themselves to specialists who have published excellent results, rather than accept what is available locally,’ he says.
‘And when it comes to the other end of the treatment spectrum — men who can no longer be cured of their prostate cancer but can still be effectively treated — the UK also lags behind, not least because NICE (the National Institute for health and Clinical Excellence) takes a long time to make decisions about whether a drug should be available through the NHS, sometimes rejecting drugs that show promise because they are too expensive.’
He says Americans also have far more regular tests for prostate specific antigen (PSA) — raised levels of which can be an early sign of the disease.
However, other experts are not convinced the U.S. approach is the right one.
Emma Malcolm, chief executive of the charity Prostate Action, says the comparisons between UK and U.S. mortality rates do not paint an accurate picture.
‘I suspect there is a lot of over-treating in America — where men who could have lived normal lives for decades undergo procedures, which often leave them with life-altering side-effects.’
Potential problems from surgery include incontinence and impotence.
Depending on the study, between 30 and 70 per cent of men in the UK who undergo prostate removal become impotent, and between two to 15 per cent suffer mild to severe incontinence.
However, as the recent trial at the Royal Marsden shows, these are exciting times in prostate cancer research, with UK academics leading the world in promising new drug therapies.
Here, we look at some of the latest developments…
Surgery plays a very important role when it comes to treating early-stage prostate cancer — and by far the most common procedure is the radical prostatectomy, when the entire prostate is removed.
A growing number of radical prostatectomies are now carried out with the help of sophisticated robots which aid the surgeon as he or she carries out the procedure.
In the U.S., more than 60 per cent of radical prostatectomies are carried out with robotic assistance.
‘This new system helps to achieve the best possible outcome in terms of cancer control, continence and potency,’ says Mr Challacombe.
Clinical trials show this method has improved results over non-robotic procedures, particularly regarding less post-operative pain and shorter stays in hospital.
BEST FOR: Men diagnosed with early stage prostate cancer.
Despite the name, the Cyberknife involves no cutting. It is, in fact, a precise form of radiation therapy where around 150 cross-beams of radiation are fired at the target from multiple directions.
Side-effects are similar to standard radiation therapy: 1-2 per cent of men will suffer incontinence and 30-50 per cent of men become impotent as a result of the treatment, although more surrounding healthy tissue is left unharmed.
Dr Katharine Pigott, a consultant clinical oncologist at the Royal Free Hospital in London and The Prostate Centre, says: ‘The attraction of the procedure is that it is an outpatient-based, one-week treatment, compared with between four and seven weeks of radiotherapy treatment as an outpatient.
‘It is less invasive than surgery, and with a faster recovery period.’
Consultant urologist Chris Eden says: ‘Cyberknife is only available in one (private) UK centre, which is unfortunate for patients who opt for radiotherapy, or who are unsuitable for surgery, as this does show significant promise.’
The CyberKnife treatment for prostate cancer is currently only available at two private centres, but three major NHS hospitals already have CyberKnife centres and may soon start offering the service to patients with prostate cancer. A trial will begin soon to determine its effectiveness.
BEST FOR: Men diagnosed with early-stage prostate cancer.
High Intensity Focused Ultrasound (HIFU) is still considered to be an experimental treatment in the UK because there is no long-term data, but it is gaining ground because it is non-invasive and doesn’t interfere with the nerve supply, meaning a man’s sexual potency and continence are rarely affected.
HIFU uses high-frequency sound waves to superheat prostate cancer cells, destroying them.
A balloon is inserted via the rectum and is filled with cooling water to help protect the tissue of the rectum from burning.
HIFU is only available in a few NHS centres but is offered at a number of private clinics.
‘HIFU is available on the NHS but only in a trial setting after deliberations by NICE,’ explains Mr Eden.
‘This is because of concerns regarding a lack of effectiveness and a significant complication rate from published intermediate-term (up to five years) follow-up.’
BEST FOR: Men diagnosed with early-stage prostate cancer who do not wish to have surgery.
Men who have more advanced forms of prostate cancer, which cannot be treated with surgery alone, can have a range of hormone therapies which work by reducing the amount of testosterone circulating in the blood, which ‘feeds’ the cancer.
In the past, these drugs often ceased to work after several years because patients eventually became resistant to them.
However, new developments hold out real hope to men who’ve reached this stage.
Abiraterone, which was launched at the end of September and can now be prescribed by doctors, is a new hormone-blocking drug which seems to extend life significantly and shrink tumours in men with advanced cancer.
Most hormone treatments focus on cutting testosterone production in the testes — the main site of production — but abiraterone is able to reduce the hormone throughout the body by inhibiting an enzyme essential to its production.
Dr Heather Payne, a consultant clinical oncologist at University College London Hospitals and The Prostate Centre, was involved in clinical trials for the drug, which is manufactured by Janssen, part of pharmaceutical giant Johnson & Johnson.
She says: ‘Historically, there have been few treatment options for advanced prostate cancer when it relapses after hormonal therapy and chemotherapy, so this new treatment has the potential to meet a significant and previously unmet need.’
NICE and the Scottish Medicines Consortium (SMC) are currently assessing whether to approve the medication for use on the NHS. A decision from NICE is expected in May 2012.
Another exciting hormone reducing drug on the horizon is MDV1300, developed by Medivation, which is still undergoing clinical trials in Germany.
Lead researcher Professor Axel Heidenreich says it looks ‘very promising’ and could even prove more effective than abiraterone, as it gets to work blocking the creation of testosterone in the testes, the prostate and in the cancer itself.
‘I am hoping it will be available to patients within the next 12 months in the UK and elsewhere,’ he says.
BEST FOR: Men with prostate cancer that has spread.
Just as for many other types of cancer, chemotherapy has been proven to be effective for men with advanced prostate cancer by slowing the progression of the disease.
Standard treatments, including docetaxel, which is taken with steroids, have now been supplanted by the next generation of chemotherapy drugs, specifically cabazitaxel, developed by Sanofi-Aventis, which has far fewer side-effects such as hair loss, nausea and diarrhoea.
Patients can take the drugs in tablet form, by injections or via a drip. But NICE reported last week that it will not recommended them, as it is too expensive.
‘I think it’s a pity if we don’t continue with it, as it is part of the stepping stones to further improvements,’ says Dr Tom Stuttaford, medical writer and a Trustee of the Urology Foundation. It will still be available to private patients.
BEST FOR: Men with advanced prostate cancer which no longer responds to hormone treatment.
This therapy involves freezing the tissue of the prostate gland, which destroys all the cells within and leaves just the shell.
Doctors insert very fine needles into the prostate via the perineum (the skin between the scrotum and the rectum) and pass freezing gases through the needles until the temperature within the prostate drops to around minus 40c.
The prostate usually undergoes several freeze-thaw cycles until all the cells — including the cancer cells — are dead.
This relatively new therapy is not yet widely available, although there are six NHS cryotherapy clinics in London. There are also no long-term studies to show its effectiveness.
However, it is still chosen by some patients who don’t want to undergo surgery to remove the prostate.
‘Cryosurgery can be used for men who have a recurrence of prostate cancer post-radiotherapy,’ says Mr Eden.
‘It can also be used on men who are unsuitable for major surgery or radiotherapy.’
BEST FOR: Men whose cancer has come back after treatment with radiotherapy.
AT LAST, A TEST YOU CAN TRUST
Checking for prostate cancer initially involves a PSA test. This checks for raised levels of prostatespecific antigen, a protein linked to the cancer.
There has been much debate about whether there should be a national screening programme using the PSA test, with critics pointing out that most men with elevated PSA levels won’t have cancer at all, but a benign disease called enlarged prostate.
However, this debate could soon become outdated: scientists are developing more accurate tests, including PCA-3, which is a urine test that shows levels of a specific enzyme secreted by prostate cancer cells.
Another new test uses a cancer biomarker known as EN2 and can detect cancers with up to 88 per cent accuracy.
(Source: The Daily Mail)