Updated 24 February 2025
Are you a male over 50? Has your GP advised you to have a PSA (prostate specific antigen) test, ‘Just as a routine check’? Many of my older male clients report to me that every time their GP orders ‘routine blood tests’, a PSA test is included – even if the patient specifically asks that it not be. And there are very good reasons why men might decline to be screened for prostate cancer using a PSA test.
Before I dig into those reasons, let’s start with the basics.
What is PSA anyway?
Prostate specific antigen (PSA) is a protein produced by the cells of the prostate gland – both healthy cells, and cells that have turned cancerous. Levels tend to rise when the prostate gland enlarges. The majority of men with an elevated PSA – up to 91 per cent of them – do not have prostate cancer; instead, they have benign prostatic hyperplasia, urinary tract infections, prostatitis or other non-cancerous conditions. Elevated levels of parathyroid hormone (which were found in 10 per cent of white and 19 percent of black American men), can raise PSA levels in men who do not have prostate cancer. And having a digital rectal examination, passing a hard bowel movement, and recent ejaculation can all temporarily increase PSA levels.
Unfortunately, the PSA blood test does not differentiate between benign prostate conditions and cancer; or between slow-growing, non-metastasising cancers which would never cause harm, and aggressive, potentially lethal cancers. And in addition, some men who do have prostate cancer have a low PSA level; this is called a ‘false negative’. Even worse, men with the deadliest cancers may have a low PSA because the most wildly undifferentiated prostate cancer cells may not be able to produce it.
No wonder the scientist who developed the PSA test, Dr Richard Ablin, decries its use as a prostate cancer screening tool, labelling it “a public health disaster” because of the enormous sums of money wasted on “a test that can’t do what it’s purported to do”, and the almost incalculable harm done to men (and their families) through overdiagnosis and overtreatment.
More refined versions of the PSA test – including the free to total PSA test and the Prostate Health Index (PHI) test which takes into account free and total PSA as well as proPSA – can help doctors to more accurately estimate the risk that a raised PSA level is due to cancer rather than benign causes, but these tests still generate both false negative and false positive results.
The PSA-to-cancer-treatment pipeline
Because no form of PSA testing can distinguish between prostate cancer and benign conditions with complete accuracy, many men with a persistently elevated or rising PSA will be referred for a prostate biopsy. This procedure involves inserting a long, spring-loaded needle into the prostate gland, via either the rectum or the perineum, and removing up to 15 tissue samples which are then visually inspected by a pathologist, and assigned a Gleason score; more on that, shortly. Unfortunately, prostate biopsy carries significant risks (including rectal bleeding, blood in the semen and/or urine, difficulty with passing urine, fever, infection and erectile dysfunction), and incurs financial cost and anxiety for the man involved, and his family.
And after all that, both patient and doctor are still likely to face a dilemma: the biopsy probably will detect prostate cancer, because it’s an age-related condition, but whether it was worth detecting is far from certain. If a man lives to 80, there’s a roughly 80 per cent chance that he will have cancer cells in his prostate gland. Yet while one in nine men will be diagnosed with prostate cancer in their lifetime, only around one in 39 will die of it.
The discrepancies between the extremely high prevalence rate, the high diagnosis rate and the low death rate are explained by the fact that most prostate cancers are indolent – that is, they grow slowly, and don’t invade surrounding tissue or metastasise to distant organs. And the older a man is at the point of being diagnosed with prostate cancer, the more likely he is to have an indolent form of the disease.
These indolent cancers are, in H. Gilbert Welch’s ‘barnyard pen of cancers’ analogy (outlined in last week’s post, On the futility of breast cancer screening), turtles. They’re not going anywhere, so there’s no point chasing them or attempting to contain them. A man with an indolent prostate cancer will die with his cancer, not from it. Yet the mere fact of being told that he ‘has cancer’ is immensely psychologically stressful. His own health anxiety, or pressure from his concerned spouse or family members, or the urging of his doctor, may lead him to undertake treatment for it even when the risks of treatment outweigh the benefits.
One of the major factors influencing a doctor’s likelihood of recommending treatment for prostate cancer is the Gleason score. This is determined by a pathologist, who examines the biopsy samples under a microscope to see whether they look like normal, healthy prostate gland cells, or whether they’ve completely lost their distinct appearance (‘poorly differentiated’), or are somewhere in between. The pathologist assigns a grade from 1 to 5, where grade 1 represents the most well-differentiated, normal-looking cells, and grade 5 represents the most cancerous-looking, poorly differentiated cells. The Gleason score is calculated by summing together the two most prevalent pattern grades, resulting in a score from 2 to 10.
A Gleason score of 6 is considered a low-grade cancer, although many researchers in the field argue that it “is so common in aging males as to be perhaps a normal aspect of aging”, and should be reclassified as an indolent lesion of epithelial origin, or IDLE, in order to reduce the anxiety and fear that drives overtreatment of tumours that have no potential to metastasise and cause death. A Gleason score of 7 is ranked as a medium-grade cancer; and a score of 8, 9, or 10 is a high-grade cancer. A score of 4+3=7 or more is considered clinically significant.
Do you see the problem with this method of diagnosing prostate cancer? It relies on the subjective assessment of the pathologist examining the biopsy samples. The entire trajectory of a man’s life might depend on whether the pathologist rated his tissue samples mildly undifferentiated – in which case his doctor would tell him he’s a candidate for ‘watchful waiting’ or active surveillance (periodic repeat PSA tests and biopsies but no active treatment) or moderately undifferentiated – in which case he might be urged to commence treatment. And pathologists are human beings, subject to both random error and systematic bias:
“There is evidence that, over time, pathologists have tended to award higher Gleason scores to the same histological patterns, a phenomenon sometimes termed grade inflation.[23,24] This phenomenon complicates comparisons of outcomes in current versus historical patient series. For example, prostate biopsies from a population-based cohort of 1,858 men diagnosed with prostate cancer from 1990 through 1992 were re-read in 2002 to 2004.[23,24] The contemporary Gleason score readings were an average of 0.85 points higher (95% confidence interval, 0.79–0.91; P < .001) than the same slides read a decade earlier. As a result, Gleason-score standardized prostate cancer mortality rates for these men were artifactually improved from 2.08 to 1.50 deaths per 100-person years—a 28% decrease even though overall outcomes were unchanged.”
Prostate Cancer Treatment (PDQ®)–Health Professional Version; Gleason score
Furthermore, as of 2021, roughly 40 per cent of US men diagnosed with low-risk prostate cancer were still opting for some form of treatment, even though they were ideal candidates for active surveillance. And prostate cancer treatment is no walk in the park.
Prostate cancer treatment: cut, burn, poison and neuter
The standard treatments for prostate cancer are surgery to remove the prostate gland (prostatectomy), radiation therapy, hormone therapy (essentially, blocking the activity of androgens [masculinising hormones]), chemotherapy and immunotherapy. All have the potential to cause side-effects that significantly diminish quality of life. For example, more than 80 per cent of men treated for prostate cancer develop erectile dysfunction; 46 per cent of men suffer from urinary incontinence after radical prostatectomy and up to 20 per cent of men develop persistent diarrhoea after radiation therapy, with bowel function deteriorating rather than improving over time as the damage wrought by the radiation accumulates.
Is all that suffering worth it? Not according to Dr Otis Brawley, former Chief Medical and Scientific Officer and Executive Vice President of the American Cancer Society. In an editorial published in the Journal of the National Cancer Institute in 2009, Brawley blunted stated that
“More than 90% of men getting [treatment for prostate cancer] do not need it.”
Prostate Cancer Screening; Is This a Teachable Moment?
What Dr Brawley meant is that these men have been overdiagnosed – told that they ‘have cancer’ when what they have is an indolent tumour that they would almost certainly have died with, not from; and overtreated – given surgery, radiation and drugs that they could not possibly benefit from, and which may impair their quality of life and perhaps even shorten their lifespans.
But isn’t it worth overdiagnosing and overtreating some men whose prostate tumours would never have threatened their lives, in order to save other men’s lives by detecting cancer at an earlier, more treatable stage? If only that were so. A 2013 Cochrane review concluded that prostate cancer screening yielded “no statistically significant reduction in prostate cancer‐specific mortality” – that is, men who were screened were no less likely to die of prostate cancer than men who were not. This is despite the fact that PSA testing does reduce the risk of having metastases present at the time of diagnosis of prostate cancer, although only slightly: 1000 men would have to be PSA tested in order for two of them to avoid metastatic prostate cancer diagnosed before the age of 85. Remember, it’s metastatic disease that kills men, not the primary tumour in the prostate gland, and up to 14 per cent of patients with prostate cancer have metastatic disease at the time of diagnosis.
So why doesn’t ‘catching prostate cancer early’ result in less men dying of it? Partly because the treatment itself causes harms (including a serious cardiovascular event, such as a heart attack, in one out of every 2000 men who enters the PSA-to-treatment pipeline), and partly because most men who develop prostate cancer have other comorbidities (such as coronary artery disease, diabetes or colorectal cancer) that probably would have knocked them off their perch at roughly the same time that they would otherwise have died of prostate cancer. No one gets out of here alive, after all.
But fundamentally, the reason why ‘catching prostate cancer early’ doesn’t save lives, is that neither of the principal treatments offered to men with localised prostate cancer – radical prostatectomy and radiation therapy – have any effect on either prostate cancer-specific or all-cause mortality. The distinguished urologist Willet Whitmore pithily summarised this therapeutic futility as
“The quandary in prostate cancer: Is cure necessary in those for whom it is possible, and is cure possible in those for whom it is necessary?”
Prostate Cancer Screening; Is This a Teachable Moment?
The changing landscape of PSA screening recommendations… and what we can learn from it
I published the original version of this article in the late noughties. Back then, the Prostate Cancer Foundation of Australia (PCFA) aggressively promoted annual screening, via PSA testing and digital rectal examination (DRE) to all men over 50 and men over 40 with a family history:
The PCFA’s strident advocacy for universal annual screening was predicated on the claim that ‘catching prostate cancer early’ led to better outcomes for men:
They even went so far as to assert that men were dying because they had not had a PSA test, and to not-so-subtly threaten that patients might, or maybe should, sue their doctors for not recommending it:
Meanwhile, the Cancer Council of Australia was issuing very different recommendations on prostate cancer screening. Their 2008 position statement did not mince words:
The PCFA derided this cautious, evidence-based approach, even implying that it was some kind of nanny-state interference with men’s ‘right to choose’:
But what was the PCFA’s pro-screening position based on? In a nutshell, anecdote and ‘expert opinion’:
Right-o then.
Some time after 2009, the PCFA’s ‘experts’ began walking back their strident advocacy for annual PSA testing. The recommendations cited above disappeared from their website; luckily, the internet is forever (at least for now), and I managed to find the deleted pages using the Wayback Machine. The PCFA’s current recommendation is for men to follow the current Australian guidelines, which are far more circumspect than their previous, rather rabidly pro-screening position:
(Side note: a recent JAMA Network Open article reported that most men receiving health care through the US Veterans Health Administration continue to undergo PSA screening after the age of 70, despite their low absolute risk of dying of prostate cancer in the next 10 years, and the absence of evidence that screening offers them any benefit.)
What can we learn from the PCFA’s shift in attitude toward screening? Three major things:
1. ‘Experts’ can be wrong.
Those “foremost experts from the medical and scientific community” who helped the PCFA formulate their 2009 screening guidelines were plainly drinking a little too much PSA Kool-Aid. There was simply no evidence then, or now, for their contention that “many men are dying because they did not seek a PSA test.” Their claim that “caught in its early stages prostate cancer can be cured especially when the cancer is still confined within the prostate gland”, is similarly baseless. If it’s still confined within the prostate gland, it probably doesn’t need to be ‘cured’.
2. Conflicts of interest matter.
D’ya reckon any of those ‘experts’ advising PCFA might have been provided by their major financial backers, Novartis Oncology and AstraZeneca Oncology? I mean, it’s not like a pharma company producing drugs for prostate cancer would stand to benefit from increasing the number of men entering the PSA-to-cancer-treatment pipeline, is it?
3. You have to take charge of your own health decisions.
The oft-repeated advice to ‘talk to your doctor’ will not be of much help to you if your doctor has not kept up with the research on the risks and benefits of PSA testing. Imagine if, back in 2009, you had sought opinions on whether you should get a PSA screening test from two different doctors, one of whom was influenced by the PCFA’s position, and the other by the Cancer Council’s? You would be utterly confused.
At the end of the day, it’s your values that matter. If you would refuse the recommended treatments even if your PSA test led to a diagnosis of prostate cancer, then why get the test in the first place? If you have a family history of prostate cancer that’s making you anxious about your own prospects of developing it, a clear PSA test may relieve your anxiety… but don’t forget, false negatives do occur, especially with highly aggressive cancers.
For what it’s worth, here’s my take: You’re far better off learning about the modifiable risk factors that influence your risk of developing prostate cancer, and optimising your diet and lifestyle habits accordingly, than going for a screening test that has not been shown to reduce your risk of dying of prostate cancer, or to help you live any longer.
I’ll close with Dr Otis Brawley’s wise words on prostate cancer screening, penned over 15 years ago but just as relevant today:
“The most important lesson of the prostate cancer screening saga is that we should appreciate the truth and clearly explain it as best as possible. Many men who thought their lives were saved by being screened, diagnosed, and treated for localized prostate cancer are perplexed to learn that so few benefit. They may be even more amazed that this is not a new finding. What is new is the fact that many health professionals are finally accepting it as true. They are accepting that there is overdiagnosis, unnecessary treatment and overtreatment, and questions regarding screening for this disease… Some of the confusion of prostate cancer screening can be avoided if we all clearly label what we know, as what we know; what we do not know, as what we do not know; and what we believe, as what we believe.”
Prostate Cancer Screening; Is This a Teachable Moment?
Amen to that.
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