My offer for a public debate was accepted after I co-published opposing viewpoints about the high rates of over-diagnosis and over-treatment of early stage prostate cancer with leading urologist Professor Tony Costello in a Melbourne newspaper last year.
The debate took place at a Melbourne conference on prostate cancer last week. It received wide coverage in newspapers – here, here and here, television radio, and online. All of this is useful and important because it helps stimulate the very important debate about widespread PSA screening.
Prostate specific antigen (PSA) is an enzyme secreted in large amounts by normal as well as cancerous prostate cells. Only small amounts of PSA leak into circulation from a normal prostate, but this increases with any prostatic disease, benign or malignant.
PSA concentration is expressed as a number and its discovery in 1983 led to it being used as a screening blood test for early prostate cancer. A level below four is considered normal and men with abnormal results are usually sent for biopsies. It has been widely performed in Australian men for over ten years as part of a general health check but its ability to save lives is now being assessed and tested.
For years now, family physicians, the Urological Society of Australia and New Zealand and spokespeople for treatment advocacy groups, such as the Prostate Cancer Foundation of Australia have been telling men to have blood tests with a PSA as part of their regular health check up because early diagnosis may save their life.
The constant message is that men need to look closely for any signs of early prostate cancer by having a PSA and a digital rectal examination. This is because, up until recently, our belief and practice was that if the PSA was high, the patient should be referred to a urologist for a transrectal biopsy (a large and very unpleasant needle, inserted under local anaesthetic through the wall of the rectum up to 24 times, just above the anus). And if this biopsy showed prostate cancer, the man would usually be offered immediate radical treatment with surgery or radiation to cure the cancer.
But we’ve long known that prostate cancer is a disease that men can harbour for most of their lives without knowing. It is very commonly found during postmortem (even in very young men). We also now know that PSA is highly unreliable as a predictor of cancer.
False results and consequences
A major prospective prostate cancer trial actually found cancer in 15% of men with normal direct rectal examination results and PSA of less than the “normal” concentration of four (considered as the cut-off between “normal” and “abnormal”). It also found cancer in 25% of the participants with levels between three and four. This is similar to the rate of 25% of biopsies showing prostate cancers in men with so-called abnormal PSA. So you have an almost equal chance of having cancer found irrespective if your PSA is normal or abnormal!
Indeed, the false-positive and false-negative rates of PSA alone make it a useless screening test. Our current rate of PSA testing uptake threatens to diagnose up to 60,000 men a year in Australia, 25 times the number destined to die from it.
Prostate cancer appears to be two diseases, an uncommon one that can kill you (at an average age of 81 years) and a very common one that poses no risks. Even though prostate cancer is a leading cause of male mortality in Australia (with over 2000 deaths a year), it’s never been known whether radical treatment of early stage disease can alter the natural history of those cancers biologically destined to kill the patient or whether it only “cures" those cancers destined to remain indolent for many decades and not affect lifespan.
Some believe that the term “early stage prostate cancer” is misleading and a misnomer for most men, similar to the condition called chronic lymphocytic leukaemia, which sounds frightening but is usually a very indolent disease that lies dormant for decades and rarely ever needs treatment.
All harm, no help?
Recent evidence from several high-quality prospectively randomised clinical trials have shown two stunning results. The first two (here and here) showed that regular screening with PSA and treatment of detected cancers produces no overall survival benefit for the treated group, and only a tiny reduction in deaths due to prostate cancer. The third showed that radical treatment with surgery or radiation therapy provides no benefit for the vast majority of men who have been treated this way and causes very serious and long-lasting side-effects.
PSA screening of the male Australian population probably doesn’t save any lives at all, but leads to a lot of over-diagnosis of a condition called early prostate cancer that will not shorten the lives of the overwhelming majority of men. This creates serious harms, including toxicities from unnecessary and radical treatments and imposes vast financial and manpower costs on our health system.
The harms come from the transrectal biopsies (pain, infection and haemorrhage), and initial radical treatments. Then, there are penile implants and drugs to treat sexual impotence resulting from treatment and the cost of urethral sphincters (around $20,000 for every initial insertion and then replacement). Add to this the time of physiotherapists and nurses for urinary incontinence and the psychologists for the depression and associated relationship stresses.
Time to change
Following an extensive and detailed review of all the literature, an expert team from the US Preventative Services Taskforce has very recently issued the lowest possible recommendation for PSA screening because it’s highly likely that its harms significantly outweigh its benefits. And the test has been called a public health disaster by Dr Richard Ablin, who invented it. I clearly concur with him.
It’s time for family physicians to stop doing routine screening PSA tests of Australian men unless patients decide to proceed after being told about the latest research and indicate they understand the potential benefits and harms. Indeed, they should be asked to provide informed consent.
For those diagnosed with early prostate cancer, immediate and radical treatment is unnecessary for the vast majority and active surveillance or watchful waiting should be recommended. It’s now reasonable and preferable that all men be offered a second opinion before proceeding to radical treatment for early stage prostate cancer.
As with all advances in medical treatment over the last 350 years, we depend on constant clinical research comparing what we currently do with what we hope may be better by some measurable parameter. When the evidence changes, we must all revise our beliefs and practices.
Read the case for PSA testing