Current policies on early detection of prostate cancer create overdiagnosis and inequity with minimal benefit
BMJ 2023; 381 doi: https://doi.org/10.1136/bmj-2022-071082 (Published 17 May 2023) Cite this as: BMJ 2023;381:e071082Linked Feature
Is the UK really ready to roll out prostate cancer screening?
- Andrew Vickers, attending research methodologist1,
- Frank O’Brien, consultant urologist2,
- Francesco Montorsi, professor of urology3,
- David Galvin, consultant urologist4,
- Ola Bratt, professor5,
- Sigrid Carlsson, assistant attending epidemiologist156,
- James WF Catto, NIHR research professor7,
- Agne Krilaviciute, researcher8,
- Michael Philbin, patient advocate9,
- Peter Albers, professor of urology810
- 1Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA
- 2Department of Urology, Cork University Hospital, Ireland
- 3University Vita-Salute San Raffaele, Italy
- 4Department of Surgery, University College Dublin, Ireland
- 5Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden
- 6Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
- 7Academic Urology Unit, Department of Oncology and Metabolism, University of Sheffield, UK
- 8Division of Personalized Early Detection of Prostate Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany
- 9Patient and patient advocate, New York, USA
- 10Department of Urology, University Hospital, Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany
- Correspondence to: A J Vickers vickersa{at}mskcc.org
Screening for prostate cancer with prostate specific antigen (PSA) remains highly controversial because it is unclear whether the benefits of reduced prostate cancer mortality offset the harms of overdiagnosis and overtreatment. Given this uncertainty, most high income countries have chosen not to implement a national programme of prostate cancer screening, but allow men to obtain a PSA test after a conversation with their physician.
Countries that have adopted screening policies based on shared decision making have seen high rates of PSA testing, particularly among men 70 years or older, who are particularly prone to overdiagnosis1 but do not benefit from screening.2 This is one of the reasons why opportunistic screening results in only a small reduction in cancer specific mortality.3 Moreover, relying on shared decision making to guide PSA testing has led to an uneven distribution, with higher rates of PSA testing among those who are wealthier and more educated.
In 2022 the European Union recommended that organised screening programmes should be extended to prostate cancer.4 We argue that high income countries should either implement a comprehensive risk based approach to PSA testing, one that is designed to reduce overdiagnosis and overtreatment, or discourage PSA testing through a clear recommendation against screening, along with policies that make it hard to obtain a test without defined urological indications.
Informed choice approach drives high rates of testing
High income countries that have made PSA testing available to men who request it after shared decision making with their physician now have a high prevalence of PSA testing with an inappropriate age distribution (table 1). In the UK, men aged 80-89 are twice as likely to get a PSA test as men in their 50s.3031 In France, 30% of men aged over 40 get an annual PSA,12 with the highest incidence of PSA testing in men over 70.11 Italy and Germany also have high rates of PSA testing with around half of men aged over 70 having annual PSA.14151920 Ireland has particularly high rates of PSA testing, with 500 000 PSA tests performed each year17 in a population of 600 000 men of screening age.
National recommendations on prostate specific antigen (PSA) screening compared with empirical data on PSA testing in the population*
High rates of PSA testing from “informed choice” policies in high income countries have led to harm from overdiagnosis and overtreatment. In the UK, prostate cancer incidence has increased by about 50% since PSA testing became available in the early 1990sto a current total of 52 000 cases a year.36 Around 25-50% of men who have prostate cancer detected after PSA testing would have lived out their natural lives without a prostate cancer diagnosis,37 suggesting that overdiagnosis occurs in about 10 000 men in the UK every year.
A key problem is that, in current routine care—and despite guidelines to the contrary—most men with an abnormal PSA result have prostate biopsy, even though only a minority will have aggressive prostate cancer. Furthermore, most men with biopsy detected cancers have either surgery or radiotherapy (with or without androgen deprivation therapy) even if they have low risk tumours that are unlikely to cause cancer related morbidity or mortality.3839 Prostate surgery and radiotherapy are both associated with a high risk of long term urinary, erectile, and bowel dysfunction,40 while androgen deprivation causes numerous side effects such as fatigue and loss of libido during treatment and increases the long term risk of cardiovascular events.41 Men who are overdiagnosed thus often experience treatment harms without receiving any benefit.
Approaches to PSA testing that rely on people making an informed choice are likely to reflect and reproduce health inequities in preventive healthcare. Data from Canada, the US, and Switzerland suggest PSA testing is inversely associated with income and education102533; in Canada and the US, PSA testing is less common in people from ethnic minorities.1035 In the UK and Switzerland, rates of PSA testing are lower in economically deprived areas.2529 Although the effects of disparate rates of PSA testing on health outcomes are still unclear, countries should decide who gets offered screening based on a risk assessment rather than leaving it to individuals.
Advantages of a comprehensive, risk based, prostate cancer detection programme
Policy making bodies that advocate for an informed choice or shared decision making model of PSA testing, typically frame their recommendations as contrasting with population based screening. This is generally defined as PSA testing being structured in a similar way to national mammography or colonoscopy programmes: the screening test is provided by a government run body at standardised intervals with follow-up of abnormal results handled within the national health system. A 2012 statistical modelling study based on evidence from randomised trials suggests that this sort of universal PSA testing programme for men aged 55-69 would reduce prostate cancer mortality by 9 per 1000 men but at the cost of 16 quality-of-life adjusted years per 1000 as a result of harm from overdiagnosis and overtreatment.42
A comprehensive, risk based prostate cancer detection programme based on best evidence on how to use PSA testing and manage subsequent diagnostic follow-up and treatment could reduce overdiagnosis and overtreatment.434445 Such a programme would restrict testing to men (and those not identifying as male but who have a prostate) aged 50-70, define testing intervals by PSA levels, stop testing early for those with lower PSA, offer biopsy only to those identified as at high risk of aggressive disease after a secondary test (such as magnetic resonance imaging (MRI) or blood markers), and limit treatment to those with high Gleason grade tumours.434445 The programme would also have a clear algorithm specifying how these approaches would vary for those at high risk (eg, having a BRCA gene mutation or strong family history).
Such a programme would start by defining, identifying, and inviting eligible people for PSA testing. Management of abnormal results and any subsequent treatment would need to be monitored to ensure protocols were followed (eg, confirmatory or secondary testing with MRI in men with raised PSA levels), rather than passively expecting guidelines to be followed; indeed, our current problems stem largely from practices that go against guideline recommended care.3839 Although in the UK most men have a biopsy only after MRI, this is not always the case in other countries, and other elements of the clinical pathway, such as treatment, also need standardisation. As in current informed choice programmes, shared decision making would still take place before testing.46
Swedish regional health authorities are piloting a screening programme using this approach.47 Prevention of overtreatment is not formally part of the programme because Sweden already has extremely high rates of active surveillance, whereby patients with low risk prostate cancer are monitored and start active treatment only on evidence of more aggressive disease.48 An early randomised evaluation of the Swedish pilot found use of MRI testing before biopsy led to a >50% reduction in overdiagnosisof low grade prostate cancer without a significant difference in the detection of high grade disease.49
A comprehensive prostate cancer early detection programme that carefully manages not just testing, but also biopsy and subsequent treatment, could substantially reduce the harms of overdiagnosis and overtreatment that have accompanied PSA screening. About 40% of overdiagnoses currently occur in men aged over 70.1 The use of MRI5051 or secondary markers52 to determine biopsy in men with raised PSA levels has been shown to reduce both biopsy rates and the overdiagnosis of low grade cancer. In one study, patients with raised PSA levels randomised to biopsy only if they had positive MRI findings had a 30% reduction in the rate of biopsy and a 50% reduction in the overdiagnosis of low grade cancer compared with those randomised to routine biopsy, without reducing the number of aggressive cancers detected.50 Use of active surveillance reduces treatment rates by 50% or more in men diagnosed with low grade disease.53
Most of the benefit of PSA testing on prostate cancer mortality would be retained in a comprehensive, risk adapted early detection programme because best evidence suggests screening older men is ineffective,2 men who have negative findings in secondary tests such as MRI or blood markers have extremely low mortality from prostate cancer,54 and conservative management of men with low risk disease does not increase the risk of death from prostate cancer.5556
Moreover, in what might be the central paradox of a PSA based prostate cancer screening policy, implementing a national risk based programme would typically reduce the number of tests compared with the current model. In one risk adapted screening approach,44 men with initially low PSA levels, constituting about half of the population, would have their PSA tested only three times during their lives, with most others getting tested only every 2-4 years. If implemented in Ireland, for instance, such a programme could reduce the number of PSA tests by at least half compared with contemporary practice. One of the few countries that has implemented a national PSA based programme for early detection of prostate cancer is Lithuania. This has led to a near 80% drop in PSA testing in men aged over 70,57 the age group for whom PSA screening is most likely to lead to harm and least likely to lead to benefit. An organized early detection programme may also reduce ethnic, socioeconomic, and regional inequalities. For example, in the Swedish randomised trial of PSA testing, reductions in prostate cancer mortality were greater for those with lower educational levels than for those with higher educational levels.58 Indeed, one of the key benefits of a risk based approach is that it allows better targeting to those at highest risk compared with current informed choice approaches, which are sensitive to affluence and education, as well as undue influence from media coverage, such as celebrities telling their prostate cancer stories.59
Restricting access to PSA testing
A reasonable alternative to a comprehensive, risk based prostate cancer early detection programme, is a clear recommendation against PSA screening along with a policy that the PSA test could only be offered by a urologist to patients presenting with urological symptoms, albeit with a possible exception for men at high risk, such as BRCA mutation carriers. This would mean asymptomatic men would not be able to have PSA testing. Such an approach may require governments or public health insurers to do more than refuse reimbursement for the PSA test. For instance, in Germany, PSA tests offered in primary care are not reimbursed by the public health insurance system, yet 75% of German men of screening age have had a PSA test,14 probably because the test is inexpensive. Specific policies or other mechanisms whereby a national health system could restrict PSA testing are largely untested and would require further research.
Maximising benefit, reducing harm
Although we believe that early detection of prostate cancer should involve shared decision making, the current approach of determining testing by shared decision making has resulted in the worst possible practical outcome of high levels of PSA testing and medical harm, with minimal benefit and inequity. To make better use of PSA testing, policy makers should choose between a comprehensive, risk adapted approach that is specifically designed to reduce overdiagnosis and overtreatment, or restricting PSA testing to people referred to urologists with symptoms. That choice will need to take into account wider patient and public perspective, as well as health economic concerns.
Key messages
Most high income countries have chosen not to implement a population based prostate cancer screening programme but instead allow men to obtain a PSA test if they wish
These policies have led to paradoxically high rates of PSA testing, clear medical harm, scant benefit, and inequities
A national comprehensive, risk based, prostate cancer detection programme that is carefully designed to reduce overdiagnosis and overtreatment would reduce harm, increase benefit and be more equitable
An alternative approach to reducing harm is to restrict PSA testing to those referred to urologists for symptoms
Acknowledgments
This work was supported in part by the National Institutes of Health/National Cancer Institute (NIH/NCI) with a Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center (P30 CA008748). SVC was further supported by a career development award grant from the NIH/NCI (K22-CA234400). JWFC is funded by an NIHR research professorship.
Footnotes
Contributors and sources: AV is a biostatistician with a special interest in prostate cancer screening and decision theory. FO’B, FM, DG, OB, JC and PA are urologists with expertise in prostate cancer. SC and AK are epidemiologists with expertise in prostate cancer screening. MP has been treated for prostate cancer and is a patient advocate. All authors contributed to the content and writing. AV is the guarantor.
Patient involvement: MP provided patient perspective from the earliest stages of article planning.
Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following: AV is a co-inventor of the 4kscore, a commercial test for predicting prostate biopsy outcome. He receives royalties from sales of the test. He owns stock options in Opko, which offers the test. JC has received reimbursement for consultancy from Astra Zeneca, Ferring, Roche, and Janssen; speaker fees from BMS, MSD, Janssen, Astellas, Nucleix and Roche; honoraria for membership of advisory boards for Ferring, Roche, Gilead, Photocure, BMS, QED therapeutics and Janssen; and research funding from Roche.
Provenance and peer review: Not commissioned; externally peer reviewed.