Where is the Reliable Test for Prostate Cancer?

Image: Cancer Research UK

Every 45 minutes, a man in the UK dies from prostate cancer and the latest official report leaves a troubling question hanging in the air: are we really fighting prostate cancer with the ambition, purpose and coordination it demands?

Prostate cancer is the most commonly diagnosed cancer among men; it claims more lives than breast cancer, and it is the third biggest individual cancer killer among the population as a whole after lung and bowel cancer. And yet it remains the only major cancer without a national population screening programme. Nor, with one very small exception, is there any targeted screening even for people with a higher than average risk profile.

The absence of any significant prostate cancer screening programme was unchanged by the report delivered in May by the UK National Screening Committee (NSC), chaired by Professor Sir Mike Richards, the former National Cancer Director for England. Is prostate cancer public health policy being propelled both by the sense of urgency which it demands, and also by the growing public attention which it receives? Perhaps. But the latest weighty official review leaves a lingering suspicion that the campaign might benefit from more purposeful leadership, a more ambitious timetable, more cohesive research, and certainly more integrated data collection.

The distinguished NSC members pored over the evidence for months before concluding that “screening is more likely to cause more harm than good in the whole population”. They also highlighted the problem of overdiagnosis based on PSA tests alone, indicating that “around 75% of men with a raised PSA do not actually have cancer”.

The major diagnostic problem here is that there is currently no “test that can successfully differentiate between a faster-growing, more aggressive cancer and the slower-growing, more common form of prostate cancer.” This is crucial because, as the NSC notes, around 40-50% of prostate cancer cases detected by PSA screening are slow-growing cancers that might never cause harm.

The NSC warns that, “for every 1,000 men offered screening, 2 lives may be extended, up to 20 are likely to have been over-diagnosed and 12 of those to have undergone unnecessary treatment.”  And so, the NSC reports, “the harms of screening have been assessed to quickly outweigh any potential benefits.”

While acknowledging that early detection can save lives, the NSC concludes that, if general screening were introduced, it would produce too many cases of “...overdiagnosis and overtreatment, causing unnecessary anxiety and lifelong side-effects such as incontinence, erectile dysfunction and bladder problems”. With admirable understatement, the NSC notes that, “A more accurate test than PSA is needed.”

The NSC’s draft recommendations comprised no population screening, and no targeted screening for men with a family history. They recommended targeted biennial screening only for men aged 45–61 with the BRCA1 gene variant (a less well-established genetic risk marker for prostate cancer) and the BRCA2 variant (a significant genetic risk marker for prostate cancer). To put this group in context, the prevalence of both the BRCA1 and the BRCA2 gene variants among both men and women is approximately 0.25%.

When the NSC submitted its draft recommendations for public consultation last November, the public verdict was a resounding “No!” Out of the 974 responses reported by the NSC, 85% disagreed with the NSC’s draft recommendations as a whole, while only about 4% agreed with them.

The only significant change the NSC made following the public consultation was to modify the eligibility criterion for targeted BRCA screening: carriers of BRCA1 variant were excluded, and a relevant family history of breast, ovarian, pancreatic or prostate cancer was added as a requirement for BRCA2 carriers.

Black men are twice as likely as white men to develop prostate cancer and they face a higher mortality rate, but the NSC did not extend screening to them because it concluded that there is insufficient evidence that screening this group would do more good than harm. One major unknown here is whether black men have more aggressive prostate cancer, or simply more prostate cancer.

This is just one area in which the NSC report highlights an enormous data void. One study designed to remedy this is TRANSFORM, a randomised UK trial aimed at identifying improved prostate cancer screening methods. In June, the government increased TRANSFORM’s funding by £18 million specifically to generate evidence on higher risk black men.

Unfortunately, the NSC report did not include data from TRANSFORM because it had only just started work when the report was published. Moreover, TRANSFORM will only “be able to share data in the next three years”.

It is certainly useful that the NSC’s model accounts for MRI scanning ahead of biopsy, rather than basing its analysis on the old “raised PSA to biopsy” pathway. But the mortality numbers central to their calculations are based on older trials (the European ERSPC and the UK CAP studies) which both predate multi-parametric MRI, targeted biopsy, and modern active surveillance.

In the absence of definitive modern trial data, the statistical basis for the NSC report was probably the best it could do, given that the UK only started recommending an MRI-first diagnostic pathway in 2019.

The screening debate therefore exposes a wider problem: the evidence required to design public health policies depends on research but, astonishingly, the UK has no transparent, up-to-date national account of prostate cancer research spending. The last comprehensive analysis of UK prostate cancer funding was conducted by the National Cancer Research Institute (NCRI) and covered 2018/19. Based on NCRI’s 2018/19 figures, it appears that approximately £44 million was spent on breast-cancer research, compared with only about £22 million on prostate cancer research.

The NCRI closed in 2023, since when there has been no single national body tracking funding for different cancers, and no single authoritative database providing specific prostate cancer funding information.

Cancer research is funded by many sources, including government bodies (NIHR, UKRI), and charities (Cancer Research UK, Breast Cancer Now, Prostate Cancer UK). Mountains of cancer-related data are collected by organisations such as the UKCRC Health Research Analysis Forum (UKHRA), the International Cancer Research Partnership (ICRP), and the National Cancer Registration and Analysis Service (NCRAS). But there is still no comprehensive picture combining data from all of them.

The UKHRA 2022 report provides the latest comprehensive information about total health research spending across the UK. Under the UK's official health research classification system, it found that cancer received approximately £469 million in direct funding in 2022, making it the UK’s highest-funded disease category.

But UKHRA’s methodology makes it virtually impossible to answer one simple question – what percentage of total cancer research funds are spent on prostate cancer?  This is presumably intentional, given that the UKHRA instruction, “Do not code to the site of the cancer”, means that prostate cancer, together with other cancers, is simply lumped into one general “Cancer and neoplasms” basket.

There is, possibly, a reason for this apparent statistical nonchalance in governmental circles and, perhaps, even in the medical research sector. But it would be a matter of concern to most corporate boards for whom the old adage that “What can’t be measured can’t be managed” will instantly spring to mind.

Another striking feature of the report is that men at the highest risk - black men, and men with a family history but no known genetic variant - are precisely the men left out of any formal screening programme. This was done because evidence for those groups was judged to be insufficient. Yet another data collection problem?

Following the NSC report, Imperial College surveyed over 200 UK urologists, the clinicians on the front lines of diagnosing and treating prostate cancer. Roughly 67% of them disagreed with the decision not to screen all black men, and 64% also believed that men with a family history should also be offered testing.

The urologists are clearly not thrilled by the NSC report. Does the urologists’ negative reaction perhaps reflect a wider perception that the NSC approach treats insufficient evidence as equivalent to evidence of no benefit?

The BRCA2 variant group is the only one singled out for targeted screening. But how many of these men actually know that they have the BRCA2 variant, unless they have had some form of genetic testing? Basing a meaningful targeted screening programme only on men who already know their BRCA2 status will presumably be a challenge, given the UK’s limited genetic testing services. Even more challenging is the fact that NHS genetic testing criteria effectively block asymptomatic men from getting tested in the first place. This approach has been described as “launching a search party with instructions not to look for the missing”.

A paradox here is that while the committee has recommended screening for the BRCA2 group, a genetic minority which is difficult to identify, it has rejected screening for another group - black men whose higher risk is already well documented.

Appropriately, the NSC report takes the risk of harms seriously, and mentions them frequently. Based on the existing statistics, the NSC appears to have a strong case when it says that the harms from a broad prostate cancer screening programme would outweigh the benefits. One problem here is that the screening and treatment of different cancers vary so much that it is not possible to establish a universal harm-to-benefit ratio for all screening programmes. Nevertheless, it would be interesting to know if the NSC prostate cancer recommendations incorporate an acceptable ratio of unnecessary treatments to lives saved and, if so, what it is.

Fortunately, not all is doom and gloom. Congratulations are in order for all the professionals who are improving methods for detecting and treating prostate cancer, as well as for those achieving dramatic successes against cancer in all its forms.

UK prostate cancer mortality rates have been falling recently, and overall survival following diagnosis has improved, partly helped by new techniques such as pre-biopsy MRI and active surveillance. Nevertheless, over 12,000 men still die from prostate cancer in the UK each year, and survival and mortality rates are worse than in some comparable European countries.

Since 2000, the UK has conducted numerous major prostate cancer research programmes, not to mention hundreds of clinical, epidemiological, genetic and laboratory studies. These programmes have undoubtedly improved MRI-based diagnosis, active surveillance, radiotherapy and treatment of advanced disease, and yet...still no effective screening programme.

As Prostate Cancer UK said in 2019, huge improvements are needed in the speed and accuracy of diagnosing prostate cancer.  Sadly, seven years later, the same is still true.

The question is therefore not simply whether screening should begin, but whether we are moving quickly enough to discover what an effective and safe screening programme would look like.

Notwithstanding the urologists’ collective thumbs down, the NSC’s statistically-based recommendations are hard to refute. But the recommendations still leave a frustratingly wide gap between the problem (over 12,000 deaths a year), and one possible remedy (an accurate prostate cancer test).

This frustration is highlighted by the many compelling celebrity stories which have helped to raise awareness. Sir Chris Hoy and Dermot Murnaghan are both examples of how prostate cancer can lurk silently until it emerges as an incurable stage 4 killer.

Joe Biden’s prostate cancer illustrates the risk of discouraging proactive screening of the elderly. Even in this group, an aggressive, incurable cancer can go entirely unnoticed until it metastasizes.

Some public figures reportedly diagnosed early enough to receive successful treatment include David Cameron, Stephen Fry, Jeremy Clarkson, Sir Elton John, Andrew Lloyd Webber, Sir Rod Stewart, Sir Ian McKellen, Colin McFarlane, Michael Parkinson, Nelson Mandela, Robert De Niro, Harry Belafonte, Benjamin Netanyahu.

This random, anecdotal list does nothing to undermine the NSC’s recommendations. But their collective voice is a powerful reminder that it is time to convert the recommendations into results.

Unlikely as it seems, and unlike their predecessors, will the NSC recommendations finally provide the long-awaited breakthrough?

It’s a fair bet that most people with prostates are certainly hoping so.