Current PSA guidelines aren’t fit for purpose

Plenty has changed since prostate cancer screening guidelines were released nearly a decade ago.

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Men are risking cancer overdiagnosis courtesy of a reliance on shared decision making when screening with prostate-specific antigen, international experts suggest.

This outdated approach has led to significant harms, European and US authors wrote in the BMJ.

“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,” the BMJ researchers wrote.

Meanwhile, Australian researchers await next year’s long overdue guideline update which will reflect some of these concerns and respond to developments in technology and practices.

Prostate cancer incidence jumped around 50% in the UK since PSA testing was introduced almost three decades ago, now reaching 52,000 cases a year, they noted.

“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, suggesting that overdiagnosis occurs in about 10,000 men in the UK every year.”

Other high-income countries such as France, Italy, Germany and Ireland that have made PSA testing available to men who request it after shared decision making with their doctor also have high rates of testing, particularly in the over-70s who benefit less.

It has also led to high rates of testing in wealthier and educated men, underscoring the inequalities in this approach.  

As a result, it was time for countries to take a new approach to prostate cancer detection, the BMJ authors argued.

“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.”

Professor Karen Canfell, chair of Cancer Council’s cancer screening and immunisation committee, said that Australia’s most recent 2015 guidelines were only approved for five years, so were currently “expired”.

“The risk of prostate cancer being overdiagnosed through the use of the PSA test is well established,” said Professor Karen Canfell, director of the Daffodil Centre. The Centre has been commissioned by the Prostate Cancer Foundation of Australia (PCFA) to deliver the technical work for the new guidelines.

While many Australian experts don’t agree PSA testing should be restricted to only urologists, they welcomed new guidelines that explicitly classified men by their risk.

Professor Canfell said new research over the last decade had shown how technology used to identify high-risk men improved prostate cancer outcomes.

MRI testing, biopsy technique improvements and active surveillance have significantly changed the balance of harms and benefits associated with PSA testing, urologist and uro-oncologic surgeon Associate Professor Weranja Ranasinghe, at Monash Health and Austin Health in Victoria, agreed.

“That has all addressed the two big issues of prostate cancer screening which are overdiagnosis and overtreatment,” said Professor Ranasinghe, deputy leader of the Urological Society of Australia and New Zealand genitourinary oncology special advisory group and a member of the new PCFA guidelines committee.

Professor Ranasinghe told TMR those advances meant fewer “clinically insignificant” cancers were being picked up, and there was less overtreatment as a result. Those advances would be reflected in the much-needed new guidelines, he said.

The urological society agrees there is an “urgent need” to update clinical practice and RACGP Red Book guidelines.

“Since the development of the 2015 PSA guidelines, there have been significant advances in prostate cancer diagnosis, staging and management, which must be incorporated in any future update,” said the USANZ interim position statement.

As well as MRI screening, advances in biopsy techniques and active surveillance programs, it also said the Prostate Cancer Outcomes Registry data had reduced the risks associated with PSA testing.

Improved staging and treatment plans, and advances in surgical and radiation techniques had also resulted in lower treatment-related morbidity, it said.

The benefits of PSA testing have been further strengthened by long-term European data showing significant improvements in survival from appropriate testing.

“Several of the previous concerns regarding the harm of PSA testing are now mitigated with ‘risk-stratified’ PSA testing strategies,” said USANZ.  

One key change since the last guidelines is that patients who have two elevated PSA tests can have an MRI, which is now on the Medicare Benefits Schedule.

“MRI picks up the most significant prostate cancers and reduces picking up the less significant prostate cancers,” Professor Ranasinghe said.

“If there’s no lesion on the MRI, we don’t tend to biopsy people as much as we would in the pre-MRI era.”

This has reduced the number of biopsies and overdiagnosis. Professor Ranasinghe said most cancers detected now were low-grade cancers – with a Gleason score of 6 or lower – and more than 90% of those men would be under active surveillance.

“There’s good long-term data since the last guidelines showing that you can watch these men very carefully, and the majority of them may not need treatment at any point.

“Gleason 6 is very contentious these days as to whether it should even be called a cancer because of how indolent it is.”

Professor Ranasinghe said the “safest approach” used to be treating Gleason 6 tumours as though they were cancer.

“But in doing so, there were a lot of side effects associated with it.

“Rather than just offering everyone a PSA test, I think patients have to be told about the benefits and risks of having a PSA test without just adding it onto a panel of bloods like other tests. That conversation has to be had in a patient who’s over the age of 50, or at a higher risk.”

High-risk patients are those with a family history of prostate cancer, high-risk ethnicities or men who carry a BRCA mutation.

“Talk to the patient about the benefits and risks of doing a PSA test and then once they are aware, that’s when you should be doing the PSA test.”

Adjunct Professor Peter Heathcote, co-chair of the national steering committee reviewing the clinical guidelines for PSA testing, called for even more testing for prostate cancer.

Australia’s five-year relative survival increased from 63% in the late 1980s to 95.5% today, he said.

“The fact remains, however, that 3507 Australian men still die from the disease every year, owing to the high prevalence of prostate cancer among Australian men,” Professor Heathcote said.

“Australia has among the highest rates of prostate cancer in the world, which is why we should be making the case even more strongly for testing.

“We need to give clinicians the tools to confidently discuss PSA testing with their patients, while taking what we have learned from large-scale studies in Europe showing the benefit of using the PSA test to screen selected asymptomatic men.”

Professor Heathcote said the guideline review was Australia’s opportunity to become a world leader in this space.

“Most importantly, it is a chance to save men’s lives, and to save thousands of families from the pain of a prostate cancer diagnosis.”

Who to test

Until the new guidelines are published in 2024, the Urological Society of Australia and New Zealand’s interim guidelines recommend that clinicians:

• Give appropriate counselling on the potential risks and benefits of PSA testing
• Offer an individualised risk-adapted strategy for early detection to a well-informed man over 50 with a life expectancy of at least 10 years
• Offer early PSA testing to well-informed men at an elevated risk of having prostate cancer, including men over 45 with a family history of prostate cancer and men of high-risk ethnicities (including Indigenous men) over 45 and men over carrying BRCA2 mutations
• Stop early diagnosis of prostate cancer in men with a life expectancy of less than 10 years
• For men with an initial PSA test of >3ng/ml, use risk stratification including age, family history, digital rectal examination and PSA density to guide the need for further testing, including MRI and biopsy.

BMJ 2023, analysis online 17 May

BMJ 2023, feature online 17 May

BJUI International 2023, online 26 April