As a man in my mid-50s, I am starting to think about what might be coming to haunt me in later life. One persistent worry is prostate cancer. I have a family history of it, which puts me at higher risk. I donât have any major symptoms. Still, I should probably have gone for a test by now. But for years I have read that they arenât very accurate and can lead to unnecessary surgeries that carry a risk of incontinence and impotence. And people keep telling me that even if you have prostate cancer, you are unlikely to die of it.
I am not the first person to be confused about prostate cancer and whether to test for it, but today these questions are of increasing importance because we are in the midst of a troubling global trend. According to recent projections, cases of prostate cancer are set to shoot up over the next 15 years, and if nothing is done, deaths will rise substantially too.
However, while the increase in cases is a foregone conclusion â a reflection of our ageing population â the increase in deaths isnât. That is because, in recent years, we have begun to see a transformation in our diagnostic tools. These are helping doctors to identify the most severe prostate cancers earlier and more accurately than ever before, helping people like me make more informed choices about our options and increasing the likelihood that we wonât die of the condition. So, what exactly has happened, and what tests â if any â should I be signing up for?
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To understand why prostate cancer diagnosis has ended up being such a minefield, it helps to understand a bit about the prostate itself. This small, chestnut-shaped gland is situated beneath the bladder. Its role is to produce fluid that, along with secretions from other glands, mixes with sperm cells to form semen.
What is the prostate anyway?
The prostate doubles in size during puberty and enters a second growth phase around the age of 25, which continues indefinitely, eventually leading to an enlarged but non-cancerous gland, a condition called benign prostatic hyperplasia. âAll men get it as they get older,â says prostate specialist at the Institute of Cancer Research in London. About , according to the US National Institute of Diabetes and Digestive and Kidney Diseases. At age 80, the figure is 90 per cent.
Cancer is a different matter. âThe two are separate processes,â says James. Tumours arise in the lining of the glandâs internal cavity and can start at any age, though they become more common as people get older. The trajectory from there is variable, ranging from slow-growing and essentially harmless cancers, which are called âindolentâ, to highly aggressive and lethal ones.
The majority of prostate cancers fall towards the indolent end of the spectrum, which has given rise to the truism that âmore men die with prostate cancer than die of itâ. Around 1 in 8 people with a prostate will be diagnosed with prostate cancer in their lifetime, but vastly more go undiagnosed. Around 80 to 90 per cent of men aged 80 or over who die of something else turn out to have indolent prostate cancer, says James.
But that doesnât detract from the fact that the condition is extremely dangerous. Roughly every year, and a quarter of them will die from it. Those already-scary statistics are set to get much worse. Last year, the editors of The Lancet convened to discover, among other things, what the future holds. In April, they , predicting that between 2020 and 2040, cases will more than double, to around 2.9 million a year, and deaths will rise by 85 per cent to 700,000.
The projections shocked even seasoned prostate cancer experts. âWe didnât know,â says James, who chaired the commission. âI was genuinely quite surprised.â
The lionâs share of cases and deaths will be in low and middle-income countries. But nowhere is immune. Western Europe, for example, is projected to see a roughly 25 per cent increase in cases and 20 per cent increase in deaths. North America will see deaths rise by a third.
The predicted surge is down to an expanding and ageing global population. And, according to The Lancetâs commission, almost nothing can be done to avert the rising number of cases. Unlike many other cancers, the risk of prostate cancer canât be significantly reduced by lifestyle changes or public health interventions. This makes the increase in the condition a different challenge from the inevitable rise in cancer overall as populations age. As the commission concluded, âdealing with this rise in cases will require urgent and radical interventionsâ.
So, what can be done? Prevention may not be an option, but curing it is. Early-stage prostate cancer, where the tumour is confined to the gland itself, is eminently curable using surgery and radiotherapy. âThe treatments, by and large, work very well,â says James. Fifteen years after diagnosis, only who have treatment for early-stage prostate cancer will have died from it in most high-income countries. However, once the cancer has spread, or metastasised, and invaded the bones, liver or lungs, it is nigh- on incurable. âAlmost everybody who presents with metastatic disease dies of it,â says James. The key, therefore, is to catch it early.
How to diagnose prostate cancer
Easier said than done. Prostate cancer symptoms, such as reduced urinary flow, donât usually manifest until late in the game. âSymptoms are a very poor guide,â says James. âCancers tend to be in the peripheral part of the gland, so they have to be really very big before theyâre starting to impact urine output.â
The solution to that is screening, where anyone of a certain age â most commonly 45 to 50 â who has a prostate is routinely tested. But historically this has been extremely hit-and-miss. Prior to the mid-1990s, the best-available detection method was a rectal exam, where a doctor felt the prostate with a gloved finger. There was, however, scant evidence that this led to the or .
Then came the PSA revolution. In 1979, researchers at the Roswell Park Cancer Institute in Buffalo, New York, purified a protein from seminal fluid that they called . PSA was often elevated in those with prostate cancer and the team proposed that it could be exploited for diagnosis. In 1994, the US Food and Drug Administration approved a PSA test to aid the detection of prostate cancer in men over 50.
For a while, PSA testing seemed to have changed the game. According to at Northwestern University in Chicago, Illinois, the widespread uptake of PSA testing in the US led to a much higher rate of early detection, with the number of diagnoses of late-stage cancer falling by 80 per cent.
But screening doesnât detect all cases of prostate cancer. âSometimes the very worst cancers make very little PSA, so that is a problem with the test,â says James. And thatâs not all. âScreening was associated with substantial harms,â says at Vanderbilt University Medical Center in Nashville, Tennessee. The tests produce a lot of false positives, for example, mainly because having an enlarged but benign prostate raises PSA levels, says James. They also detect indolent cancers that would never have caused symptoms, let alone death.
When PSA tests were first rolled out, an elevated score automatically triggered the next step, a biopsy. Under this protocol, says Tosoian, 1 in 5 people who were screened ended up having a biopsy â 75 per cent of these were negative and the majority of the positives were clinically insignificant indolent cancers. That adds up to a lot of needless anxiety. Plus, the biopsies can lead to infections, urinary and faecal incontinence and impotence. This overdiagnosis and overtreatment meant that around a decade ago, , leaving people like me in a state of confusion.
To screen or not to screen
In 2012, an influential expert panel in the US called the Preventive Services Task Force performed a volte-face and advised against PSA testing. The UK, which had been considering implementing a routine prostate cancer-screening programme, canned it. The EU took a similar anti-screening stance.
There is also mixed evidence on whether screening meaningfully decreases the risk of death from prostate cancer. One , for example, which offered men aged 50 to 69 a one-off PSA test, found that 10 years later, there was no reduction in prostate cancer mortality between those who took the test and those who didnât. A further did find a reduction in mortality among those who had been tested, but it was vanishingly small. A similar trial in Stockholm, Sweden, found 20 years after a one-off PSA test.
Since then, however, the diagnostic landscape has begun to change, making the path forwards a lot clearer. First, it was discovered that while one-off PSA testing may not reduce mortality, repeated testing does. In 1994, Maria FrĂ„nlund at the University of Gothenburg in Sweden and her colleagues recruited aged between 50 and 65 who were either given PSA testing every two years or were part of a control group that only received opportunistic PSA tests, which are when a person decides to request the test for themselves. When the researchers analysed the data after 22 years, they found that men who had been repeatedly tested were around half as likely to have died from prostate cancer as those in the control group. âProstate specific antigen-based screening substantially decreases prostate cancer mortality,â they concluded.
Helpfully, PSA testing itself has also improved significantly, minimising the dangers of overdiagnosis and overtreatment. Instead of going straight to a biopsy, a high PSA score now generally triggers an intermediate step: an MRI scan of the prostate gland to look for abnormalities. This reduces the number of biopsies and also allows for targeted biopsies of any suspicious areas, instead of a standard âsystematicâ one that takes samples from all over the gland. Another recent advance is active surveillance, where those who are diagnosed with benign-looking cancers via PSA and MRI are spared the biopsy knife but are retested every year. Last year, a trial comparing this wait-and-see strategy with immediate treatment , says James.
In 2018, off the back of these improvements, the US Preventive Services Task Force changed its mind again, recommending that those aged 55 to 69 should be able to get a test if they want, as long as they discuss it with their doctor before proceeding. In 2022, the European Union also did a U-turn and urged member states to consider setting up routine screening programmes. In the UK, individuals are entitled to a PSA test but have to request one from their doctor and go through a round of counselling before taking it.
New diagnostic tools
Today, we are seeing yet more changes that could transform our ability to catch prostate cancer early and accurately. For a start, the researchers behind the Gothenburg trial are which combination of PSA results and MRI is most effective. Then there is an ongoing clinical trial in Finland, which is between PSA and MRI improves diagnostic accuracy even further. That step is a blood test called a four-kallikrein panel, which looks at PSA in more detail and also detects kallikrein, another protein produced by the prostate gland that is often elevated in prostate cancer. An suggests the trial is having âgreat successâ in its three main objectives, says Tosoian â to reduce the overdiagnosis of indolent cancers, reduce negative biopsies and detect the most dangerous cases.
Meanwhile, the charity Prostate Cancer UK earlier this year, which aims to find the best way to diagnose the condition without the pitfalls of overdiagnosis and overtreatment. It will test various combinations of PSA and MRI and will also include genetic testing to identify people at high risk of prostate cancer. Genetics will increasingly become part of prostate testing, says James, and may help minimise the other big downside of the PSA test: false negatives.
There are a handful of mutations that are known to significantly increase the risk of prostate cancer. A mutation in BRCA2, for example â one of the genes involved in breast and ovarian cancer â . But mutations in about 200 other genes have been linked with the condition, and the more a person carries, the higher their risk.
Saliva screening
In May, a team from the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust in London unveiled the results of an experimental saliva screening test that , from which an individual genetic risk score can be calculated. The researchers gave the test to 6000 men aged between 55 and 69 and invited those at the highest risk to come in for an MRI. Just â and of the 187 cancers detected by this method, 103 were of high or intermediate risk.
Many of them would have received a negative PSA test. âA number of these men had significant prostate cancer, but with a normal PSA,â says James, who was part of the team. âSo it looks like this test may find at least some of those men with the very worst cancers but very little PSA, though this is very much a work in progress.â
One final innovation is the use of artificial intelligence to interpret MRI scans. At present, this is done by human pathologists, but . âInterpreting the pathology is something that AI can already do,â says James. âAnd while pathologists can only look at a few scans, the AI can look at a thousand per patient. I think AI is going to be transformative.â
All things considered, I have decided to get a PSA test regularly and will accept any MRI scans that are subsequently offered. Iâll also happily take a genetic test if and when they become widely available. With the advances in testing, my chances of being overdiagnosed and overtreated are much reduced.
Whatever the outcome, thanks to our new diagnostic tools, hopefully I will grow old and become one of those men who dies with, rather than of, prostate cancer.
