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A study and related editorial published in the New England Journal of Medicine looks at follow up data from the European Study of Prostate Cancer Screening.
Prof Derek Rosario, Consultant Urological Surgeon, Honorary Professor at the University of Sheffield, and Clinical Advisor (Prostate) to the UK National Screening Committee, said:
“The report is well written and balanced, and provides the best evidence that we have to date that PSA-based population screening results in a reduction in deaths due to prostate cancer by approximately 13%.
“To put this in context, had we started screening 20 years ago (or so) for prostate cancer, instead of having 12000 men a year dying of prostate cancer in this country, we would have around 10400 doing so. In order to achieve this, for every death prevented, we would have had to diagnose (and treat) 12 x 1560 = 18000 men.
“This is clear evidence of benefit, but perhaps not as much as we might have anticipated. It is important to note that alongside this, there was no discernable difference in the overall all cause mortality i.e. approximately 50% of men died in each arm, whether screened or not.
“The authors highlight the need to improve this through a targeted approach, but provide no good prospective data to support this statement and neither does the accompanying editorial. Along the way, many men will have come to harm from treatment of prostate cancer (estimated 12 diagnosed for each life saved) and the degree of harm caused by overdiagnosis with psychological impacts and overtreatment with physical impacts has not been quantified any further.
“The challenge therefore is how to improve on the reduction in deaths whilst at the same time reducing the number of men being unnecessarily treated. Newer technologies such as MRI might well reduce the harms done, but we do not have any outcome data yet to show that they actually can replicate the reduction in mortality, let alone improve on it.
“Finally we need to consider the costs of screening – might the huge sums of money spent on a prostate cancer screening programme be better spent on reducing deaths in men caused by other conditions, or is this the way to go.”
Dr Matthew Hobbs, Director of Research at Prostate Cancer UK, said:
“The ERSPC trial was one of the largest prostate cancer screening studies ever conducted, and 23 years on it is still providing valuable insights.
“As researchers have continued to track men from the trial, the overall balance between the benefits and harms of screening has improved with longer follow up. We can now see that PSA screening prevents more deaths than previously thought, while overdiagnosis – and its associated harms – has fallen.
“The latest results show that PSA screening in this trial prevented 22 prostate cancer deaths per 10,000 men screened, compared to 14 deaths in the previous analysis. It also shows that the harms of screening have continued to fall with longer follow up, as the number of additional men who needed treatment to prevent one death fell from 18 to 12.
“This research highlights both the value of large, long-term studies like this one, and the need for continued research to improve screening approaches, reduce harms, and save more lives. This is exactly the kind of high-quality evidence that the National Screening Committee needs to consider in its upcoming review – especially for groups who might get more benefit than the ‘average man’ screened in the ERSPC trial such as Black men and men with a family history.
“Although the level of harm remains a real concern in these latest results, there have been major advances in the way we diagnose and treat prostate cancer since this trial happened. For example, the ERSPC does not account for modern use of mpMRI scans, developed through research we funded over a decade ago, or greater use of active surveillance – both of which reduce unnecessary biopsies and treatments and could further improve the harm-to-benefit ratio of PSA testing today.
“But we need equally robust evidence of that harm reduction, and we need to go further. We need to save more than 22 lives per 10,000 men, and we need to treat even fewer men who don’t need to be treated. With more than 12,000 men still dying of prostate cancer each year, we can’t keep leaving diagnosis to chance. That’s why Prostate Cancer UK has invested £42 million in the TRANSFORM trial – the crucial next step to test modern screening approaches in today’s diagnostic pathway, reduce unnecessary harms, and save thousands more lives in the future.”
Professor Sam Hare, CEO of the HLH Imaging Group, Past National Specialty Adviser Imaging (NHS England), said:
“We are seeing increasing rates of prostate cancer across Europe, especially the significant proportion of men diagnosed with advanced disease at presentation. This study adds further weight to the evidence in favour of some form of prostate cancer screening. That said, we should be cautious about any proposed prostate screening programme that is either wholly or largely reliant on a single PSA test. It is heartening to see the UK leading the way in terms of the evaluation of AI in MRI prostate scans and the introduction of pre-biopsy MRI prostate scans. Along with the transformation of prostate biopsy practise, moving from transrectal (TRUS) to transperineal (TP) biopsy in recent years, these advances further tip the scales in favour of early and opportunistic PSA blood testing in targeted populations. If we are aiming to avoid over diagnosis and over treatment of clinically insignificant cancer, it is highly likely that good quality MRI, potentially with the addition of AI, will be essential to any screening programme that aims to be both clinically and cost effective in the NHS.
“The findings are timely given the much awaited decision from the UK’s national screening committee and the imminent launch of the TRANSFORM prostate screening trial here in the UK – the biggest prostate cancer screening trial in 20 years.”
Mr Veeru Kasivisvanathan, Associate Professor of Urology, University College London (UCL), said:
“The ERSPC study is a landmark study in Urology originally published in 2009. The authors present the 23-year follow up data from the study. This randomised trial of organised PSA screening in 55-69 year olds, carried out across eight European countries, confirms that an organised PSA screening approach reduces prostate cancer specific mortality by 13% compared to a standard of care arm without organised PSA screening. This corresponds to needing to invite 456 men for screening and needing to diagnose 12 men with prostate cancer to prevent one prostate cancer death. These figures demonstrate an improved risk-benefit balance in favour of screening compared to the prior update of the study at 16 years but overall the results are broadly consistent with their previous reports. The magnitude of benefit in reduction of cancer-specific mortality is now similar to the benefit seen from established colon cancer screening programs and near to the benefit seen from breast cancer screening programs. The authors should be congratulated for carrying out such a large, high-quality study with such long follow up, which is very challenging.
“However, the major drawbacks of their screening approach, as acknowledged by the authors, include the substantial overdiagnosis of many prostate cancers that may not have offered benefit to patients. Many of the cancers found may not have benefitted from treatment, but patients would have been subjected to treatments and treatment-related side effects, which can include life-changing effects such as erectile dysfunction. Further, there are substantial organisational and resource implications for setting up and maintaining an organised screening program to make it feasible, which would need to be considered but are not the subject of this paper.
“The implications for practice are that we should be investigating risk-adapted approaches to organised screening incorporating not just PSA but modern tools such as MRI scans of the prostate, which we at University College London alongside colleagues at Imperial, Queen Mary and the ICR are doing in the UK via the Prostate Cancer UK-funded TRANSFORM study, which will commence in 2026. It would be sensible to investigate this via clinical studies in the first instance to ensure that the risk-benefit balance and infrastructural requirements are well understood before wider population roll outs. Of promise, is that the treatment paradigms from 20 years ago that were used in the trial are quite different to what we have today, where treatments now, such as active surveillance, robotic surgery and radiotherapy are more precise, with fewer side effects and we also have newer minimally invasive treatment options such as focal therapy which have a more favourable side effect profile.”
Mr Ben Lamb, Consultant Urological and Robotic Surgeon, Barts Health and UCLH NHS Trusts, and Clinical Senior Lecturer, Barts Cancer Institute, Queen Mary University of London (QMUL), said:
“This study is an update from a randomised trial of prostate cancer screening using PSA testing among men aged 50-70, now with an average follow-up duration of 23 years. The reduction in absolute risk of death from prostate cancer from screening with PSA has improved since the previous update to 0.22% and the number needed to screen to prevent one death from prostate cancer has also improved to 456. The study team suggest that further benefit may be seen by screening men at higher risk of prostate cancer at a younger age.”
Is this good quality research? Are the conclusions backed up by solid data?
“Yes, this is a robust study with reasonable conclusions regarding the reduction in risk of death from PSA based prostate cancer screening. There are continued concerns about the overdiagnosis insignificant low risk prostate cancers, and the harms from over investigation and over treatment. Further work is needed to assess health economic benefits in different healthcare systems. This study suffers from the paradox affecting many long terms studies: by the time we have long terms data our practice has already changed, and the application of this new data is therefore contentious.”
How does this work fit with the existing evidence? And evidence from other long term clinical trials into prostate cancer screening and treatment?
“The evidence for prostate cancer screening using PSA testing has been mixed, but this study suggests longer-term that they are clear reductions in the risk of death from prostate cancer. Other studies have suffered from contamination between the intervention and control arms and therefore failed to detect a significant difference. This study’s conclusions are consistent with general understanding of prostate cancer screening in that testing of men without symptoms for early prostate cancer does reduce the risk of death from prostate cancer, but significant benefits take many years to realise due to the slowly growing nature of the disease. In addition, there are concerns about the over investigation and diagnosis of men without cancer, or with low-risk cancers that may never cause any problems, which are either over treated, or have to be monitored. However, this study suffers from the paradox affecting many long terms studies: by the time we have long terms data our practice has already changed, and the application of this new data is therefore contentious. Modern NHS practice involves the use of MRI scans after PSA test, which reduces the number of unnecessary biopsies, and makes biopsy more accurate, along with advances in treatment to reduce side effects, and the use of active surveillance to safely monitor men with a favourable risk profile, so that treatment can be safely deferred until it is absolutely necessary. We also know more now about men at greater risk of harm from prostate cancer – those with a family history, black men and younger men – who might benefit more from screening. Taken together, the current study demonstrates reduced risk of death from prostate cancer with PSA screening, which, coupled with current understanding of who might benefit most, and how we can make screening/diagnosis and treatment more effective, we might be in a position to implement effective risk stratified screening for prostate cancer. The optimal way of doing this is yet to be determined, and studies like TRANSFORM will help to answer questions of implementation.”
Have the authors accounted for confounders? Are there important limitations to be aware of?
“Yes, their discussion covers these.”
What are the implications in the real world? Is there any overspeculation?
“The current results don’t account for the cost and harms of screening, which are acknowledged by the authors, and have to be carefully considered prior to any policy change.”
Are there implications of this research for any UK screening decision?
“This study suggests that the potential reduction in the risk of death from prostate cancer increases over time, which was already suspected. This might be weighed in the balance when considering screening in the UK, but is unlikely to drive a significant change on its own.
Prof Rhian Gabe, Professor of Biostatistics and Clinical Trials Director of Barts Clinical Trials Unit, Wolfson Institute of Population Health (WIPH), Queen Mary University London (QMUL), said:
“These results confirm prevention of prostate cancer death with repeat PSA testing, however concerns remain about the unnecessary biopsies and harms of overdiagnosis and overtreatment. Newer technologies provide great hope that these negative aspects can be addressed. Evidence from randomised controlled trials of prostate cancer screening strategies incorporating these new technologies is needed to inform UK screening policies.”
Professor Ros Eeles, Professor of Oncogenetics, The Institute of Cancer Research, London, said:
“This is an impressive study of PSA screening for prostate cancer and has reported a reduction in mortality of 13% over a 23 year follow up. This therefore raises the question – are there still questions to be answered to incorporate into a screening programme? There is clearly a reduction in mortality from regular PSA screening, but we still need further research to identify the optimal screening interval, the use of MRI in the pathway and the identification of higher risk groups from genetic profiling.”
Professor Nick James, Professor of Prostate and Bladder Cancer Research at The Institute of Cancer Research, London, said:
“The latest analysis from the ERSPC further strengthens the evidence base in favour of PSA based prostate cancer screening.
“The overall reduction, with longer follow up, in risk of death is comparable to that seen with breast or bowel cancer screening.
“The numbers needed to screen and treat to prevent a death are also in line with these other diseases. What is more, the trial probably underestimates the benefits that could be achieved due to opportunistic PSA testing occurring in the control arm.
“The well-known harms of screening, of over diagnosis and over treatment, can be substantially mitigated with technologies such as MRI pre-biopsy and for monitoring.
“The side effects of treatment, such as incontinence, are substantially less with modern surgery and radiotherapy than the rates documented in the trial, further strengthening the case for screening.
“In the accompanying editorial, Andrew Vickers emphasises that the current policy of self-referral for testing is resulting in over-testing in older men (who benefit less) and under-testing in younger high-risk men (who benefit more). We are thus wasting money on ineffective testing and missing the opportunity to reduce mortality. These data are very timely with the UK National Screening Committee due to make a decision on screening in the near future.”
Paper: ‘European Study of Prostate Cancer Screening— 23-Year Follow-up’ by Monique J. Roobol et al. was published in The New England Journal of Medicine at 21:00 UK time on Wednesday 29 October 2025.
DOI: 10.1056/NEJMoa2503223
Related editorial article: ‘Early Detection of Prostate Cancer — Time to Fish or Cut Bait’ by Andrew Vickers was published in The New England Journal of Medicine at 21:00 UK time on Wednesday 29 October 2025.
DOI: 10.1056/NEJMe2509793
Declared interests
Prof Derek Rosario: I have acted as clinical advisor on Prostate cancer to the UKNSC
Mr Ben Lamb: Member PCUK Clinical Champion and CAG, Paid to deliver training to NHS Cancer Alliances, Paid consultancy or honoraria from Astellas, Digital Surgery Ltd, MDoutlook LLC, AstraZeneca, Parsek.
Prof Nick James: No COIs
Dr Veeru Kasivisvanathan: I have served as a medical advisor to Telix Pharmaceuticals in the past year.
Prof Rhian Gabe: I am Co-lead for the UK TRANSFORM trial of prostate cancer screening and Professor of Biostatistics and Clinical Trials at QMUL.
Prof Sam Hare: No conflicts of interest directly relevant to this work. I am a past National Speciality Adviser for imaging to NHS England. I am CEO and co-founder of the HLH Imaging Group Limited.
Prof Ros Eeles: I am on the transform trial steering committee
For all other experts, no reply to our request for DOIs was received.