The next 20 years will see an estimated 600,000 men be treated for prostate cancer. The current review of national guidelines aims make their outcomes more favourable and the journey less confusing.
Eric Martin reports
A diagnosis of prostate cancer was a life-altering discovery for more than 24,000 men last year, one which set off a chain of events involving rounds of testing, treatment, and what could have been significant side effects for the patient and their family.
Potentially, just as concerning for the diagnosing clinician, was the question of whether to launch the patient on that journey, especially if they were an older person, as well as wondering if they might have found the lump earlier with a digital rectal examination (DRE), which was dropped from the Australian screening guidelines at the end of 2015, causing uncertainty for GPs and patients in the process.
The other issue raised by specialists was that the reliance on PSA testing was resulting in overdiagnosis and overtreatment, which according to the Australian Institute of Health and Welfare (AIHW) peaked during the mid to late 2000s – after the 2002 decision to reduce the PSA threshold for a prostate biopsy referral.
In addition, false-positive test results were common with PSA screening and US research suggested that only 25% of people who had a prostate biopsy due to an elevated PSA level were found to have prostate cancer.
While the 2016 guidelines helped address these concerns, reducing the potential risk of misdiagnosis or over-treating prostate cancers that posed minimal risk, further confusion was added that year with the emergence of a large, Australian-led, international study that called the whole screening process into question.
Screening for prostate cancer, an international, a systemic review of best practice, led by Monash University’s Department of Epidemiology & Preventive Medicine, examined the entire data set generated by the UK’s randomised controlled trials (RCTs) and found that prostate cancer screening did not significantly decrease prostate cancer-specific mortality.
“Only one study reported a 21% significant reduction of prostate cancer-specific mortality in a pre-specified subgroup of men aged 55 to 69 years, and pooled data currently demonstrates no significant reduction in prostate cancer-specific and overall mortality,” the authors reported.
“Any reduction in prostate cancer-specific mortality may take up to 10 years to accrue; therefore, men who have a life expectancy less than 10 to 15 years should be informed that screening for prostate cancer is unlikely to be beneficial.
“Men should be informed of this and the demonstrated adverse effects when they are deciding whether to undertake screening for prostate cancer,” – a recommendation echoed in the Australian guidelines.
However, the risk of missing or delaying the diagnosis could be worse.
According to one recent UK study, prostate cancer was found to have a missed or delayed diagnosis (despite red-flag symptoms) in 2.4% to 13.8% of cases, with a severity-weighted serious harm rate per diagnostic error of 52.2%.
With these things in mind, the Federal Government commissioned the Prostate Cancer Foundation of Australia (PCFA) to review the national guidelines at the end of 2022, a process being co-Chaired by Professor Jeff Dunn – PCFA’s Chief of Mission Head of Research and President of the Union for International Cancer Control – and Adjunct Professor Peter Heathcote, a past president of the Urological Society of Australia and New Zealand.
Medical Forum spoke with both men as well as the PCFA’s CEO, Ms Anne Savage, to discuss the progression of the two-year review, some of the issues revealed by the process, and examine the advances in research and treatment that will inform the new guidelines.
“Chief among our aims is to harmonise testing protocols, ensuring full alignment between GP practice and relevant areas of implementation, such as MBS item numbers and a uniform model for measuring and reporting pathology thresholds for PSA levels,” she said.
“Currently, the guidelines recommend PSA testing every two years for men over the ages of 40/45 with a strong family history of the disease and/or symptoms, and asymptomatic men between the ages of 50 and 69, with no PSA testing for men over the age of 70 on the basis that the ‘harms may outweigh the benefits.’
“However, the risks of over-diagnosis have almost entirely been mitigated and the 2016 guidelines are now out of step with current evidence and practice and require review: data supporting PSA testing has matured, reinforcing long-term significant survival advantages with appropriately utilised PSA testing.
“In addition, there have been substantial changes in practice with a paradigm shift in prostate cancer diagnosis and treatment pathways which have reduced the risks associated with PSA testing, as well as significant advances in prostate cancer diagnosis, staging and management, which must be incorporated in a revised set of guidelines.”
Several of the previous concerns regarding the harm of PSA testing are now mitigated with “risk stratified” PSA testing strategies, whereby the shortcomings of ineffectively performed PSA testing programs have been identified.
For example, the Chinese Prostate Cancer Consortium published research in 2021 which showed that by adjusting the prostate-specific antigen density (PSAD) they were able to detect nearly 89% of prostate cancers, avoiding the need for biopsies in 20.2% of patients.
Likewise, the introduction of multi-parametric Prostate Magnetic Resonance Imaging (mpMRI) has reduced unnecessary prostate biopsies and the detection of clinically insignificant prostate cancers, and advances in biopsy techniques (including transperineal biopsies and MRI fusion) have increased clinically significant prostate cancer detection.
These techniques have also reduced the morbidity associated with biopsy.
“Australia has among the highest rates of prostate cancer in the world yet the prospects for survivorship are excellent, with five-year relative survival increasing from 63% in the late 1980s to 95.5% today – which is why we should be making the case even more strongly for testing,” Professor Heathcote said.
“The guideline review is Australia’s opportunity to become a world leader. 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.”
There are just over 89,000 men currently living in Australia who were diagnosed with prostate cancer in the past five years, and while detailed national data on the impact of treatment is unavailable, the Life After Prostate Cancer Diagnosis (LAPCD) study, part of the UK’s Prostate Cancer Outcomes program, investigated the quality of survival of more than 35,000 men from the UK dealing with the same situation – living 18-42 months after diagnosis of prostate cancer – between October 2015 and January 2018.
Men were asked to rate their overall health on a scale of 0-100 and while the average self-assessed health score was 76.6, participants commonly reported problems with pain and discomfort (42%), usual activities (37.7%), mobility (36.1%), anxiety/depression (33.6%), and self-care (14.3%), with 62% of men reporting at least one of these issues.
While high functional outcome scores indicated positive results for bowel function (89%), urinary irritation (86%) and urinary incontinence (82.7%), sexual function scores averaged just 25.2% and nearly half of respondents (45.3%) experienced moderate to severe problems.
Most prostate cancer treatments carry the risk of infertility, but erection problems are a common side effect of surgery, radiation and hormone therapy and many men “may not be able to have or maintain an erection firm enough for sexual penetration.
“In those men experiencing psychological distress following diagnosis and treatment, contributing factors centred around a theme of loss: loss of self (identity, masculinity, self-confidence); loss of function (sexual, urinary, bowel); loss of connection (partner, family and friends) and loss of control (over lives and future),” the study noted.
“Follow up interviews found that little changed for most men over 12 months with regards to the problems they faced, and while some became increasingly resigned to them, or found co-morbidities became more important, for others the physical and psychological impact of unresolved problems remained undiminished.”
The UK study also found that men’s experiences of decision-making about possible treatment pathways with their doctor differed greatly.
“Where clinicians promoted a shared approach to decision-making, men generally reported feeling comfortable with their treatment decisions,” the authors said.
“However, respondents often undertook greater responsibility for deciding their treatment pathway than they desired, often reporting that no clinical recommendations were offered or that they received conflicting recommendations.”
Professor Heathcote (right) urged better tools for clinicians so they could confidently discuss PSA testing with their patients.
“Managing how we communicate with patients about screening and the discovery of low-risk cancers where active surveillance may be the best option,” he said.
He explained that the benefits of testing have been further strengthened by a recently published long-term data follow-up from the European Randomised study of Screening for Prostate Cancer (ERSPC) trial, which revealed a significant population survival advantage from appropriately performed PSA testing programs.
Similarly, the LAPCD study found that while most men (58.0%) still received a diagnosis of prostate cancer after attending their GP with symptoms, a third of men (33.9%) were now diagnosed without symptoms after receiving a PSA test.
“Taking what we have learned from large-scale studies in Europe showing the benefit of using the PSA test to screen selected asymptomatic men, we can reduce the burden of prostate cancer on Australian men, their families and the healthcare system,” Professor Heathcote said.
Cancer Australia found that only 36% of prostate cancers are detected at Stage I in Australia, most (46%) are detected at Stage II, 11% are detected at Stage III, and 4% are detected at Stage IV.
“Yet research has found that 98% of Australians support the introduction of reminders for eligible men to get tested,” Professor Dunn said.
“In terms of the potential harms of treatment itself, improved staging (such as with PSMA Positron Emission Tomographic scans) has ensured optimised treatment plans and improvements in surgical and radiation techniques have resulted in lower treatment-related side-effects and morbidity.
“Estimates suggest that over 600,000 Australian men will be diagnosed with prostate cancer between 2020 and 2044, and 116,385 men will die from the disease. We can save many lives if we simply detect the disease earlier and new guidelines will help us do that.”
“Consumers will be involved at all stages of the review and their voices will be reflected in a refreshed set of recommendations for clinicians and consumers,” Ms Savage said.
“Following publication of our findings, our highest priority will be awareness and education, to ensure the guidelines are observed, and in the interim, PCFA has endorsed the USANZ Position Statement on PSA Testing.”
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