As the CEO of Prostate Cancer Research, Oliver Kemp has spent the past five years supporting new therapies for advanced prostate cancer. There has long been little to offer patients for whom tumours have metastasised, spreading out of the prostate and into the bones and other organs, but 2022 has already seen a number of signs that this may be
about to change.
A recent Phase III clinical trial conducted by an international consortium of scientists from nine countries demonstrated some of the progress that has been made. It found that a potent new hormone therapy called darolutamide, produced by the pharmaceutical company Bayer, could significantly prolong survival in men with advanced forms of prostate cancer as well as reducing pain, when used in combination with standard therapies.
These findings are just the latest breakthrough in the past few months, for patients in the latter stages of the disease. In December, a major clinical trial called Stampede found that using two existing prostate cancer drugs in combination – abiraterone and ADT – could increase the six-year survival rate from 69 per cent to 82 per cent. Kemp is also bullish about a new medicine called olaparib, the first drug that is specifically targeted at a subgroup of advanced prostate cancer patients.
Aimed at those who have a mutation in the genes BRCA1 and BRCA2, olaparib works by interfering with an enzyme that helps cancer cells repair themselves, inhibiting the ability of tumours to grow and spread. Clinical trials have shown that it can double the average survival time for patients with BRCA mutations.
“In the UK, we’re talking about probably 500 patients a year whose lives could be saved by olaparib,” says Kemp. “So it’s really significant.”
Interest is also growing in another new class of treatments called targeted radionuclide therapies. These drugs attach to tumours before releasing very small amounts of radiation which dissipates within a few hours, meaning that there are far fewer side effects than traditional radiotherapy.
“That’s the one where when we look at the results, we think, ‘Wow’,” says Kemp. “You could be sitting here a few weeks away from death, and that will extend your life quite significantly. The pharma company Novartis is currently running a Phase III clinical trial which we’re awaiting.”
There have also been advances for patients who have been recently diagnosed with prostate cancer. A minimally invasive technique called NanoKnife, which uses bursts of quick electrical pulses guided by MRI scans to kill tumours, has been approved for use on the NHS. Experts hope that it can help avoid many of the problems associated with conventional surgery.
“In many cases, patients who have been recommended for surgery are subsequently left with erectile dysfunction and incontinence,” says Kemp. “NanoKnife can have a significant impact on those outcomes, because it spares the nerve endings so it makes a big difference to quality of life. It’s also less invasive, so patients are less scared about it, and it spares the burden on the NHS because it can be done in day surgery.”
But with new treatments comes the issue of finding ways to finance them. While NanoKnife was given the green light by the National Institute for Health and Care Excellence (NICE) – which makes recommendations on which medicines should be funded by NHS England – the health body baulked at the £37,000 per patient annual cost for olaparib.
Aamir Ahmed, who heads the Prostate Cancer Research Centre at Kings College London, believes that more research needs to be directed towards drugs that have already been clinically proven to be safe for use in humans in other diseases and which could be repurposed for prostate cancer.
“Improvements in cancer therapy have slowed over time, while costs have increased exponentially,” he says. “The average cost of cancer drugs increased from $100 per month in 1965, to $10,000 per month in 2018. Repurposed drugs can cut through large swathes of the drug development and clinical trial phases, which could reduce the financial burden on
Another approach is to invest more in therapies such as cancer vaccines that offer the potential to halt the disease in its tracks, preventing it from spreading or metastasising to other organs.
Swedish biotech RhoVac has spent the last few years developing a vaccine that stimulates T-cells to attack and destroy cancer cells that have high levels of a protein called RhoC. This protein gives cancer cells their ability to migrate and infiltrate other tissue, making them metastatic.
“There have been some attempts at developing vaccines for prostate cancer in the past, but they have been aimed at the very late-stage tumours,” says Anders Månsson, CEO of RhoVac. “It’s much better to vaccinate when the immune system has a reasonable chance of overcoming the obstacle, when there are as few metastatic cancer cells as possible.”
So far, the results have been highly promising. RhoVac launched a phase I/II clinical trial of the vaccine in 2018, and more than three years on, Månsson says that almost all the patients involved still have immunity against the disease. A phase IIb trial is currently ongoing, with the findings set to be revealed later in 2022.
If the latest trial proves successful, Månsson believes it could represent a paradigm shift in terms of how we treat patients in the earlier stages of the disease.
“At the moment, typically, you’re diagnosed with localised cancer in the prostate, and treated with surgery or radiation,” he says. “But there’s nothing available in terms of treatment that prevents metastases.”
But for cancer vaccines to be most successful there is a need for better diagnostic and screening programmes that can pick up the disease earlier in its course. According to the charity Prostate Cancer UK, 9,500 men in the UK every year are diagnosed with prostate cancer at a stage where it is already incurable.
Right now the gold standard diagnostic tool is the prostate-specific antigen (PSA) test, which measures the levels of PSA in the bloodstream, a protein secreted by both cancerous and non-cancerous tissue in the prostate. But while high levels of PSA can indicate cancer, this is not always the case, leading to false positives.
“Currently, it’s the best thing we have,” says Kemp. ”It’s cheap, and it should be part of the process for leading to further investigation. But the issue is the false positives, and a lot of people are treated quite aggressively.
“Or you could have a very slow-growing cancer and you opt for surgery just because you’ve had a positive PSA test and you may not need that surgery immediately. You may end up with erectile dysfunction and incontinence for five to 10 years of your life. So we hear a lot of individuals who have treatment regrets.”
However, the combination of increasing advances in imaging technology and artificial intelligence (AI) may yield the way forward. Last month, scientists from the University of California, San Francisco, presented data at a conference which described how AI models can use pathology image data to predict long-term prognosis for prostate cancer patients, and do so with greater accuracy than the PSA test.
In North Wales, the Betsi Cadwaladr University Health Board became, in December, the first clinical centre in the UK to utilise an AI pathologist to assist with diagnosing men for prostate cancer. The tool takes scans from biopsies of suspected prostate cancer patients and feeds them through an app called Galen, which can process slides from multiple patients in a matter of minutes. If abnormalities are detected then a consultant is automatically alerted.
Kemp believes this is the way forward. “AI technology is a lot cheaper,” he says. “And it’s actually more accurate as well.
The human eye has faults, and if somebody is tired at the end of the day, you’ll have a worse outcome than if someone is looking at your scan at the beginning of the day. So we’re excited about this because we can encourage a different way of diagnosing rather than just relying on the traditional PSA test, which has its faults.”
‘I am living proof that research can have a real and lasting impact’
In September 2016, Brian Milne had just arrived in Florida for a family holiday when he began to experience persistent backache and difficulties urinating. He visited a walk-in clinic expecting to be treated for a urinary tract infection, but instead doctors ran a series of tests and diagnosed him with metastatic prostate cancer.
He was told he had between three and five years left to live, a devastating blow for a 64-year-old who had always regarded himself as leading a healthy life.
“I was informed that the cancer had spread to the bones,” says Milne. “This meant I could be treated but never cured. A lot to take in for someone who hadn’t seen his family doctor in 40 years.”
But on his return to the UK, Lee was given the opportunity to take part in Stampede, a groundbreaking clinical trial that has transformed the lives of many advanced prostate cancer patients over the past six years by showing how combination therapies can keep the disease in check and prolong life.
In December 2021, a breakthrough finding showed that using two commonly prescribed hormone treatments in tandem can increase the six-year survival rate from 69 per cent to 82 per cent.
Milne has now been taking a combination of chemotherapy and hormone treatments as part of Stampede for more than five-and-a-half years.
“I thought of chemotherapy for prostate as part of palliative care, but we all loved the sound of the average patient living longer and having a better quality of life,” he says. “Roll forward to February 2022 and the latest scans show that I have no active bone metastases.”
He credits the treatment with greatly prolonging his life. “I am proof that research can have real and lasting impact on the lives of individuals and their families,” he says. “Being involved in the lives of my grandchildren has been particularly rewarding. I continue to take full advantage of the additional time that my family and I have been given.”