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PSA screening and prostate cancer over-diagnosis

OVER-DIAGNOSIS EPIDEMIC – We finish our first week of this series with Robert Burton, Christopher Stevenson and Mark Frydenberg examining prostate cancer screening. Scientific oncology started with the…

To prevent one death from prostate cancer, 1,055 men would need to be screened and 37 cancers detected. Isaac Leedom

OVER-DIAGNOSIS EPIDEMIC – We finish our first week of this series with Robert Burton, Christopher Stevenson and Mark Frydenberg examining prostate cancer screening.

Scientific oncology started with the creation of the modern microscope, which provided the basis for the modern pathologic study of cancer in the late 19th century, and established the “fatal cancer” myth. As one researcher arguing against breast cancer screening put it, “since then, without pause for thought, the microscopic identification of cancer according to the classic criteria has been associated with the assumed prognosis of a fatal disease if left untreated.”

Earlier this week, an article in this series looked at the adverse effects of breast cancer screening. Today, we will examine the role of screening in the over-diagnosis of prostate cancer.

The fatal cancer myth began to unravel a century later. A 1993 study for instance, noted that prostate cancer was unique because “the frequency of histologically (pathologically) confirmed invasive cancer at autopsy greatly exceeds the prevalence of clinically significant carcinoma during life.”

The authors then affirmed that in no other malignancy was there such a vast reservoir of undetected cases that may never be clinically significant or cause death. They also noted that up to 40% of all men might be treated for prostate cancer but only 8% would ever have a cancer large enough to be diagnosed and only 3% would die of it.

Over-diagnosis of cancer is the detection of asymptomatic cancers that will not become clinically significant and cause disease or death in the patient’s lifetime. How many men have prostate cancer that might never come to light without screening and are therefore at risk of over-diagnosis?

High prevalence

A 2010 review of a 1996 study found that microscopic asymptomatic prostate cancers had been detected in 525 men of various ages killed in motor vehicle accidents in the United States (U.S). The findings indicated that this type of cancer could affect approximately a third of American men aged 30 to 39 years, increasing to about 70% at age 70 to 79 years.

Looking at these figures, together with similar autopsy studies, the authors of the review concluded prostate cancer was likely detectable in between 30 to 70% of men over 60 years old.

And a 2009 Australian study of prostate tissue, sampled from 133 cadavers referred for coronial autopsy, found invasive prostate cancer in about a quarter of the 70 men aged 50 or more years.

It seems over-diagnosis of prostate cancer was already inevitable by the time the Prostate Specific Antigen (PSA) blood test was introduced for prostate cancer screening in Australia in the late 1980s, because it could detect cancers that had previously gone undiagnosed.

Since PSA testing began in the late 1980s, over 75,000 Australian men may have been turned into prostate cancer patients, possibly for only a small benefit. Alex E Proimos

Winds of change

In July 2012, the U.S. Preventive Services Task Force (USPSTF) found that “The mortality benefits of PSA-based prostate cancer screening through 11 years are, at best, small and potentially none, and the harms are moderate to substantial”. The task force recommended against PSA-based screening for prostate cancer, stating that the recommendation applied to men in the general U.S. population, regardless of age.

The recommendation was based on an analysis of the evidence from trials of PSA screening in the U.S. and Europe, but mainly on the 2009 report of the European randomised controlled trial (RCT), where 182,000 men aged 50 to 74 years from seven European countries were randomised to either PSA testing every two to seven years or to usual care.

This report was updated in 2012 with an average follow-up of 11 years. It found a statistically significant reduction (21%) in prostate cancer mortality in the population of men invited to screen and a 29% reduction in those who were actually screened.

But this reduction in mortality came at a cost. The authors reported that to prevent one death from prostate cancer at 11 years follow-up, 1,055 men would need to be invited for screening and 37 cancers would need to be detected. The USPSTF also noted that there was convincing evidence PSA-based screening led to substantial over-diagnosis of prostate tumours.

Unknown quantity

The amount of over-diagnosis of prostate cancer is an important concern because men with cancers that would remain asymptomatic for the remainder of their lives cannot benefit from screening or treatment.

Based on our analysis of trends in prostate cancer incidence (new cases per year) since PSA testing began in the late 1980s, over 75,000 Australian men who might never have known they had prostate cancer may have been turned into prostate cancer patients, possibly for only a small benefit.

At the same time, the men were exposed to the potential harms (incontinence, impotence) of unnecessary treatment. These harms can be avoided if the prostate biopsy shows that they have low-risk disease and are then managed by active surveillance, rather than immediate treatment of their cancer.

Deaths from prostate cancer have fallen by approximately 13,000 during that same time. Some men can be saved by early detection and treatment but others clearly do not benefit.

Performing PSA tests on everyone leads to substantial over-diagnosis. But not performing PSA tests at all would inevitably lead to under-diagnosis of some men who may have been cured by early detection and treatment. Before consenting to undergo PSA screening, men should understand that while there are possible, if modest, benefits to getting tested, they may be exposed to substantial harms from over-diagnosis and over-treatment.

Have you or someone you know been over-diagnosed? To share your story, email the series editor.

This is part five of our series on over-diagnosis, click on the links below to read other articles:

Part one: Preventing over-diagnosis: how to stop harming the healthy

Part two: Over-diagnosis and breast cancer screening: a case study

Part three: The perils of pre-diseases: forgetfulness, mild cognitive impairment and pre-dementia

Part four: How genetic testing is swelling the ranks of the ‘worried well’

Part six: Over-diagnosis: the view from inside primary care

Part seven: Moving the diagnostic goalposts: medicalising ADHD

Part eight: The ethics of over-diagnosis: risk and responsibility in medicine

Part nine: Ending over-diagnosis: how to help without harming