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Eleven grams of trouble

18 March 2014

Screening for cervical cancer saves lives every day, so surely men should be screened for prostate cancer? Unfortunately it’s a bit more complicated than that, writes Frank Bowden


Existing diagnosis tools are inadequate and, in the case of biopsy, increasingly dangerous. Andrei Malov/iStockphoto

Existing diagnosis tools are inadequate and, in the case of biopsy, increasingly dangerous. Andrei Malov/iStockphoto

IN 2010 the Prostate Cancer Foundation of Australia produced a television advertisement called “It Could Happen to You,” a masterly example of beautifully lit, tightly focused, talking-head communication. In just thirty seconds, fifteen famous Australian actors, celebrities, sportsmen and musicians construct a compelling narrative about the threat that prostate cancer poses to Australian men and what they can do about it. In grabs of a few seconds each, the facts of prostate cancer are established in turn: “It kills more Australians every year than breast cancer. Or skin cancer. Or car accidents. Over 3000 men. One every three hours.” (It must be an important topic – one of the speakers is a Wiggle.) Then three young heads: “Just like me.” (That guy from Underbelly.) “Just like me.” (Nathan Bracken) “Just like you.” (Craig Bolton)

If you thought prostate cancer was an old man’s disease, then the appearance of these three thirty-somethings strongly suggests otherwise. Following the rules of good health promotion, the next step is reassurance and a plan of action: “Prostate cancer is treatable. And early detection is the key. So if you’re over fifty. Or over forty with a family history. Talk to your GP.” And what will my GP say? “It could be as easy as a blood test.” And then, to reiterate the central message, “Because if you get to it early… surviving prostate cancer could happen to you.” The closing words are spoken by Bert Newton.

It’s all very simple, and persuasively done. So why, if prostate cancer is common and treatable, and if early detection will save my life, did I want to throw my mouse through the computer screen when I saw this advertisement recently on YouTube?

THE PROSTATE gland is the female God’s revenge for menstruation. The genitourinary tract of women is like a Mexican-built Volkswagen: beautifully designed but just a bit unreliable. Any woman of child-bearing age can suffer conditions with names that men neither pronounce nor comprehend: Mittelschmerz, dyspareunia, cystitis, menorrhagia and dysmenorrhea are just a few of the things that punctuate the life of even the healthiest woman. The male equipment, on the other hand, doesn’t need servicing until well into middle age. Most owners of a prostate have no idea what it does, but just as the curse of hormonal flux is receding from their female partner’s life, the tiny, walnut-shaped organ starts to exert its malign influence. Now it’s the man’s turn to suffer from conditions with Latin and Greek names – nocturia, strangury – and, worst of all, the one with Anglo-Saxon origins, cancer.

A tumour of the prostate begins as a growth of abnormal cells within the gland itself. No one knows why the cancer cells develop but they appear to be an inevitable part of ageing. Postmortem studies have shown that if a man lives to ninety he is almost certain to have evidence of cancer in his prostate gland. The cancer sometimes reveals itself by compressing the urethra as it exits the bladder and impeding the passage of urine. But many cancers cause no symptoms until they have spread into the surrounding organs, or to bones, lungs, liver or brain.

Prostate cancer is Australia’s number one cancer (18,560 diagnosed in 2012) and the third-highest killer (3235 in 2012). No other male cancer has shown the same rise in case numbers over the past thirty years. In 1982, one in twenty-three Australian men were diagnosed by the age of seventy-five; by 2009 this had risen to one in seven. This rise has been associated with a striking fall in the age of diagnosis: in 1982, the annual rate of diagnosis in men aged forty-five to forty-nine years was only three per 100,000; by 2009 this had risen to fifty-six per 100,000. Rates in men in the fifty to fifty-four age group had risen from twelve per 100,000 to 164 per 100,000. Yet the overall death rate for prostate cancer hasn’t changed much: in fact, the age-standardised death rate in 2008 (thirty-one per 100,000) was only slightly better than it was in 1970 (thirty-six per 100,000). Similar trends are seen elsewhere in the developed world.

What explains this late-twentieth-century epidemic? Agent Orange and dioxins in the environment? Trans fats in our food? Tight underwear and decreased sunlight exposure? Undiagnosed Lyme disease? The best answer, in fact, may be sociological rather than biological.

In the 1970s, the emerging women’s health movement urged women to take control of their own bodies and become more demanding of a medical profession still dominated by men. Around the same time, the belief that early detection of cancers would reduce mortality was taking hold. As a result, screening for two female cancers – breast and cervix – became popular in the 1980s, and coordinated screening programs were established across the developed world. The Pap smear and the mammogram became a normal, if annoying, part of most women’s routine, and an international consensus accepted that these screening programs save lives. Women’s cancers have received considerable media attention and generous public and private funding, adding up to about $320 million per year in Australia’s case.

A kind of backlash was brewing among ageing male baby boomers. During the 1990s, advocacy groups emerged with the aim of redirecting some of the coverage and funding to what is now known as “men’s health.” They chose prostate cancer as one of their flagship diseases. If screening works to save lives for one cancer, they argued, then it will work for all of them. And so the idea that cancer screening is a universal good became an article of faith among many doctors and men’s groups – despite being repeatedly dashed on the rocks of experimentation and evidence. In fact, the evidence has been mounting for more than a decade that prostate cancer screening offers little or no overall benefit to the male population at any age. But, believe me, these are seen as fighting words among men’s health organisations.

SURELY screening is screening, regardless of whether we’re talking about breast cancer or prostate cancer? Unfortunately, as simple as it might seem, that’s not the case. To understand why, we need to go back to the underlying principles.

Put simply, screening tries to identify a disease in people who don’t have symptoms of that disease. If symptoms are present, we are diagnosing, not screening. You may, for example, perform a blood glucose test to screen for diabetes in a fit middle-aged man who presents to his GP for a check-up, but then perform the same test to diagnose diabetes in a young person who has lost weight, has an increased thirst and is passing large volumes of urine. The distinction is critical: patients with symptoms of a disease are far more likely to have the disease than those who don’t. This may sound self-evident but it fundamentally changes the way we should act on test results.

No medical diagnostic test is perfect. Sometimes it will show a negative when the person actually has the disease (a false negative) and sometimes it will show a positive when the person doesn’t have the disease (a false positive). The degree to which these two unwanted (but unavoidable) attributes are present determines the test’s utility: the best tests return very few false negatives (these are called “highly sensitive”) and very few false positives (these are called “highly specific”). But no matter how good the test, it will indicate the presence of disease with less confidence when the chance of the person having the disease is low (when the patient comes in for a routine check-up, for instance) than when the chance of the person having the disease is high (in the case of the young patient with symptoms). Let’s examine this in more detail using the specific example of prostate cancer.

In 1970 Richard Ablin, a New York immunologist, discovered an enzyme in the prostate that was subsequently shown to be present at a raised level in the blood of patients with prostate cancer. It became known as prostate specific antigen, or PSA. At a time when the only digital technology at a urologist’s disposal was his index finger, a blood test for cancer must have seemed like a godsend.

It soon became clear that the PSA was neither highly sensitive nor highly specific. PSA levels were also raised in men with other conditions affecting the prostate, including simple age-related prostate enlargement, infections, the effects of aspirin-like drugs, and fun things like ejaculation and riding a bicycle. In fact, it became apparent that as many as two-thirds of the men with elevated PSA results didn’t have cancer and the test was negative for as many as 15 per cent of those who did have cancer. Despite these recognised weaknesses, by the 1990s millions of men across the world were undergoing PSA screening.

Although there is no government-sanctioned prostate cancer screening program in Australia, Medicare data show that an extraordinary 1,688,370 PSA tests were performed in 2012 at a cost of just under $32 million to the taxpayer. (The estimated cost of testing in the United States is $3 billion per year.) While it isn’t possible to calculate the exact proportion of Australian men who are screened each year, the Medicare data suggest that around 66 per cent of men aged between fifty-five and sixty-four had a PSA test in 2012, which is a higher proportion than the 55 per cent of women who have a Pap smear every two years. Such is the power of simply suggesting to men that they should “talk to their GP.”

Because of its poor specificity, PSA testing is just the first step on the cancer-screening pathway. It would be wrong (unscientific, costly and unethical, that is) to treat one hundred men with a raised PSA to reach the thirty-four with cancer. So a more specific test – a test that returns fewer false positive results – must be performed. This is where things start to get a bit medieval.

When I was a medical student in the early 1980s one of my female colleagues argued that if men had to undergo screening for testicular cancer in the same way that mammograms were performed for breast screening, the male engineers responsible for the development of the technology would invent an X-ray machine that didn’t squash the relevant body part between two cold metal plates while the patient remained motionless for several minutes. She also pointed to the indignity of the Pap smear, implying that the speculum examination was part of a male conspiracy to subject women to needless discomfort and indignity. If there was any truth to this polemic, it was demolished in 1987 when a male urologist introduced the trans-rectal ultrasound guided biopsy – innocently referred to as the TRUS biopsy.

The prostate gland sits at the base of the bladder and is adjacent to the rectum, the last part of the large bowel before it opens to the world through the anus. To perform a TRUS biopsy, an ultrasound probe the thickness of a modest-sized Lebanese cucumber is inserted into the rectum of a patient who is wide awake and, after the location of the prostate is identified by ultrasound, a needle is passed down a channel in the probe, through the wall of the rectum and into the prostate. Multiple biopsies are taken and examined by a pathologist for the presence of cancer.

Male readers who haven’t fainted by this point may already have calculated that, on average, only a third of men with raised PSAs will have a cancer diagnosed using the TRUS biopsy. In 2012, just over 29,000 TRUS biopsies were performed in Australia, so approximately 19,000 men had an unnecessary procedure. Not too bad a price to pay if 10,000 men have had their life saved because the cancer was picked up early?

Again, the commonsense view takes a hit from the complex biology of prostate cancer. It has been known for over a hundred years that the majority of men with prostate cancer die with the disease, not of it. Because it is mainly an older man’s disease, most will succumb to cardiovascular disease or another malignancy before the prostate cancer has a chance to kill them. That might sound like cold comfort, but there are two more subtle concepts to consider here, the first of which is known as “lead-time bias.” All prostate cancers start off as small tumours, confined to the gland, which can be detected by PSA and biopsy many years before they cause symptoms. The increase in prostate cancer in men in their forties and fifties over the past twenty years doesn’t mean that more men are developing prostate cancer, it just means that screening has lowered the age that men are diagnosed. This conclusion is supported by the observation that in the same period there has been a mild decline in the rate of diagnosis among men in their seventies and eighties because they have already been diagnosed in middle age.

The second concept is that screening for prostate cancer will identify people with small tumours that are never going to cause any harm regardless of how long they live. This is known as “over-diagnosis,” and most people (including, surprisingly, many doctors) have difficulty believing in it. Between 30 and 50 per cent of all prostate cancers are “what you don’t know about, won’t hurt you” cancers that will never grow outside the prostate or spread to distant organs. But no currently available test can distinguish between the cancers that will progress and those that won’t. If we apply the low estimate of over-diagnosis, 30 per cent, to our 10,000 men with biopsy-diagnosed cancer, we are left with 7000, out of our original 29,000, who have disease that needs to be treated.

Both of the potentially curative options for prostate cancer – radical prostatectomy and radiotherapy – are complicated, expensive and time-consuming. Both are associated with significant side effects, the most common being impotence, urinary incontinence and radiation-associated inflammation of the bowel. Men who receive a diagnosis of prostate cancer in their forties and fifties will usually be prepared to risk a permanent loss of erections or decades of incontinence if it means that they will be cured of cancer. But this “if” is as big as the Ritz: despite a widely held perception to the contrary, by the time most men have had their cancer identified through screening it will be too late to cure it.

PEOPLE like me who are against PSA screening are sometimes accused of being callous and indifferent to the suffering of those who have prostate cancer. In 2003, a very public stoush between Alan Coates, who was president of Cancer Council Australia, and Wayne Swan, who was Labor’s shadow community services minister, played out on national television. Because his father had died of prostate cancer at the age of sixty-seven, Swan underwent screening when he was forty-seven. He was diagnosed with cancer and elected to undergo a radical prostatectomy. During an interview on ABC TV’s 7.30 Report, he said:

I believe that screening did save my life. My father had died an extremely painful death from prostate cancer. I think it is absolutely critical that men who are particularly at risk, if there’s a history in their family, that they should be tested. I guess the point is that early detection is the best protection.

Coates disagreed:

I decided personally that I will not be tested and I’ve held that decision for over ten years… If there was a really good effective screening test, then we mightn’t be having this discussion because it would be like it is for women with breast cancer or for people with bowel cancer. We know those screening modalities work. We know they save lives. We just don’t know that for screening for prostate cancer.

A Sydney urologist, Paul Cozzi, weighed in with his reservations about Coates’s position:

I don’t believe it’s appropriate for Professor Coates to give a personal opinion in this media under the auspices of the Cancer Council of Australia. I believe it’s up to the individual patient to discuss with the GP the pros and cons of PSA testing prior to proceeding with testing… I personally have had several patients that have been very confused by the recent information in the media as to whether they should proceed, even with the prostate biopsy. There is more confusion of course with regard to treatment but certainly these recent events in the media have not helped the general practitioners, the urologists or the patients…

Swan was even stronger in his condemnation:

I’m absolutely appalled by what he has said. This man is the head of the peak cancer organisation in this country. People would regard him as being highly educated and highly knowledgeable. I believe that the statements that he has made run against the weight of medical opinion…

The debate went on. Cozzi mentioned a major European study on prostate cancer screening that was due to release its results later that year. “I think when the data from this latest trial becomes available,” he wrote, “we will hopefully have a lot more scientific evidence as to the benefit of screening…” Coates also appealed to the evidence: “If putting a fair presentation of the pros and cons causes confusion, then I’m sorry, but the evidence isn’t sufficient to remove that confusion, and I don’t think anybody is well-served by pretending that it’s better than it is.”

The personal experiences of the three men obviously coloured their views. Swan had had cancer, was operated on, and was alive. The urologist had operated on many men and they were still alive. Coates had decided not to be screened and he, in his sixties at the time, was still very much alive, too.

While the three men were debating the issue, two large randomised studies were under way – the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, or PLCO, in the United States and the European Randomized Study of Screening for Prostate Cancer, or ERSPC. The PLCO enrolled 77,000 men over an eleven-year period and the ERSPC included nearly 182,000 men; in each case, half the men were allocated to prostate cancer screening and the other half to “usual” care. Both studies published their results in the world’s premier medical weekly, the New England Journal of Medicine, in 2009. The ERSPC trialists concluded that screening saves lives; the PLCO group found no benefit in screening. Because PSA has been used much more widely in the United States than in Europe, those in favour of screening believe that the negative findings of the PLCO were invalid. A further two years of follow-up has not changed the conclusions of either study.

What is the layperson to make of two mega-studies that produce different results? And how different are they anyway?

The men in the screening group of the ERSPC trial were 21 per cent less likely to die of prostate cancer than were the men in the non-screening arm. Sounds like an important result, doesn’t it? I teach my first-year medical students to ask a simple question whenever they see a “relative” risk reported like this: relative to what? To answer, you have to look at the absolute risk of cancer death in both groups. When you frame it this way, the significance of the findings dramatically changes. Why? Because the absolute risk of prostate cancer death in both groups was actually quite small – about 0.4 per cent in the screened group and about 0.5 per cent in the control group. Translated into absolute numbers, rather than ratios, this means that 1055 men have to be screened and thirty-seven cases of prostate cancer have to be treated to prevent one prostate cancer–related death.

If we apply the ERSPC figures to the Australian setting, about 5965 of the 6130 men (or 97 per cent) who underwent a radical prostatectomy in 2012 derived no survival benefit from the operation. And if that is not enough, the ERSPC and the PLCO both found no difference in the all-cause death rate between the men who were screened and those who weren’t. In other words, screening might prevent a small number of cancer-related deaths (not a trivial result for the men concerned, of course) but it doesn’t save lives overall. This is the wide-angle, public health view. While it is usually a good thing for a doctor to look at you closer up, if that focus is applied to broader population-based programs it can cause more harm than good.

The Medicare data suggest that the publication of the results of the PLCO and ERSPC trials may have changed the practice of Australian medical practitioners to a small degree. The number of radical prostatectomies fell by a few hundred, from 6470 in 2009 to 6130 in 2012. (It is very difficult to get accurate numbers of patients treated with radiotherapy, so the fall in surgical procedures may have been replaced by an increase in radiotherapy.) But TRUS biopsies were also down by 15 per cent in the same period, from 34,280 to 29,029. General practitioners are the main drivers of PSA testing so it is plausible that the evidence has altered the practice of some of them. But it is hard to change the minds of those with personal experience of the disease.

THE US Preventive Services Task Force is the peak American independent expert panel dealing with a variety of public health issues. For ten years, it had recommended against prostate cancer screening on the grounds that there was no high-level evidence in support of it. When the negative results of the American PLCO study and the absence of an all-cause mortality benefit in the European ERSPC trial were published, the issue was settled as far as the panel was concerned. The US Centers for Disease Control and other federal agencies followed suit, and now recommend against prostate cancer screening in any form.

The American Cancer Society, the American College of Physicians and the American Urology Association still believe that there is a place for prostate cancer screening, however. In an important, if partial, concession, the American Urology Association changed their guidelines in 2013 to recommend against screening for men under the age of forty in any circumstances, and it doesn’t recommend screening for men forty to fifty-four years of age at average risk (without a family history, that is). But it still recommends “shared decision-making” for men aged fifty-five to sixty-nine years, “based on a man’s values and preferences.” This nuance is missing from the website of the Prostate Cancer Foundation of Australia. The foundation remains passionately pro-screening and “disputes absolutely” that “it would be better for men not to know whether they have the disease and therefore they should not be tested or treated.”

Each of the groups who advocate for some form of prostate cancer screening recommend that men should “talk to their doctor.” This is, in my opinion, an example of medical weasel words. I’ve used the prostate debate as a case study in the course on evidence-based medicine I’ve taught for a decade to medical students at the Australian National University. The complexity of the arguments and the degree of epidemiological understanding required makes it hard for most of my students to form a balanced view, and most remain uncertain about the best course of action even after hours of lectures and tutorials. To say that laypeople, irrespective of their education and intelligence, can make an informed choice based on a short discussion with their GP is disingenuous. I suspect that the proponents of screening are aware that this nod to patient autonomy will result in patients agreeing to be screened, such will be their fear of having cancer.

DESPITE the evidence, though, personal experience will still tend to trump science. So, in the interests of balance, let me share the personal experience of one of my patients, who I’ll call Dan*.

Ever since his fiftieth birthday, Dan’s wife had been pestering him to see their GP, but it was the inflight magazine article about the Qantas CEO’s diagnosis of prostate cancer that finally convinced him to act. He went to the pathology lab during his lunch break to have the tests his GP had ordered. He slept poorly that night and, for the first time ever, shouted at his daughter over breakfast the next morning. Less than a week later, the GP rang him. She explained that his PSA was just a bit over the normal range for a man of his age. She had written a referral to a urologist, and there was nothing to worry about. He rang the urologist’s rooms and made an appointment, then he cancelled the family trip to Noosa.

The urologist might have been taciturn, but he was neat and tidy and his rooms spoke of material success. After a few questions about Dan’s history and the stockmarket, he asked him to take off his trousers and underwear and to “pop up on the couch and face the wall.” Dan’s mouth was dry now. “This will be a bit uncomfortable,” the urologist said, his right hand now gloved and lubricated. Dan couldn’t recall if the urologist told him that his prostate felt enlarged, but he did remember that he was booked in for a prostate biopsy a week later.

He was given an antibiotic on the morning of the procedure, and he sat in the waiting room overcome by a mounting sense of dread. This was not like him. After the biopsy, his wife picked him up and drove him home. They didn’t talk much in the car but he did ask her to slow down over the speed bumps outside the school. His wife made a few laconic (and not terribly funny) comments about his tentative cowboy swagger when he walked down the hall. He noticed that his urine was a little red – more rosé than pinot, but disturbing nevertheless. He went back to work the next morning and, apart from having to find a reason to spend most of the day on his feet, he felt quite normal.

While he was brushing his teeth that night, though, he suddenly felt a chill. Within half an hour he was shaking uncontrollably. He took a couple of paracetamol tablets and assumed he was coming down with the flu. He went to bed but spent a restless night, intermittently feeling hot then cold, and sleeping for only a few hours at a time. The following morning he felt sicker than he had ever experienced before and he began to feel a little panicky. His wife took him to their GP, who sent them straight to the emergency department.

Dan sat in the waiting room. While his wife spoke to the triage nurse he slid off his chair onto the floor. He was taken by wheelchair to a resuscitation cubicle, where his blood pressure was found to be low and his pulse was racing. His temperature was 39.8 degrees. He noticed that he was starting to detach himself from the noise and action around him. He stopped worrying about things for the first time in twenty-four hours.

I first saw him a few hours later. The sequence of events that had led to his admission had been distilled into a single request from the emergency department consultant: “Would you accept the care of a fifty-year-old man with septic shock?” Septic shock is one of the most serious conditions in medicine. It has a mortality rate ranging from 10 to 60 per cent, depending on the type of germ involved. By the time I saw Dan he had been transferred to the intensive care unit and he had a tube down his throat and a machine was helping him to breathe. The emergency doctors suspected that the shock was caused by a bowel germ that had entered his bloodstream at the time of his prostate biopsy. The most likely culprit would be a Gram-negative bacterium known as E. coli.

I went with the ICU doctor in charge of the shift to talk to Dan’s wife. She asked if he was going to be all right. The ICU doctor managed to gently convey the gravity of the situation while leaving her with a sense of hope and qualified reassurance. Of all the germs to have circulating in your blood, E.coli is among the least worst. The mortality rate is around 10 per cent – so the odds were in his favour. He remained critically ill over the next twenty-four hours, but when I saw him the next morning he was sitting up in bed and eating lunch. The tube down his throat had been removed and his blood pressure and pulse were now normal. His wife was by his side. He couldn’t remember much of what happened leading up to his hospital admission and it appeared that he hadn’t connected the ICU admission with the prostate biopsy.

“I’ve had some excellent news this morning, doctor,” he said between mouthfuls of corned beef and mashed potato. I assumed he meant that he would be getting out of ICU later that day. “I asked one of the docs here to look up the result of my prostate biopsy,” he said, smiling. He grabbed his wife’s hand. And then, with tears welling in his eyes, he told me that the biopsy was clear – which meant that he didn’t have cancer. “I’m a very lucky man,” he said.

It was neither the time nor the place to do anything but agree.

INFECTION is one of the most important complications of prostate biopsy. (Others include blood in the urine and semen, rectal bleeding and difficulty passing urine, and these are usually referred to as “frequent” and “minor” in the urological literature.) Since the biopsy needle is passed through the wall of the rectum it is almost inevitable that some of the bacteria that live in the bowel will be carried with it.

The prostate gland is known as a “sterile site.” Under ordinary conditions it doesn’t have any bacteria in it, unlike the mouth, nose, stomach and bowel, where the “good” germs and the “bad” germs live side by side. The plumbing of the male urinary tract is interconnected, so an infection in the prostate can spread to the bladder and the kidneys. Bladder infections are usually relatively benign, but kidney infections are more serious and almost always require hospitalisation. Sometimes, as in Dan’s case, the infection moves directly from the prostate to the bloodstream. We see about 300 bloodstream infections each year in our hospital in Canberra, which serves a population of about 500,000. They are more common than a heart attack, and more lethal by a factor of at least two and as much as twelve. As is the case with a heart attack, mortality rises if you don’t institute the correct treatment as a matter of urgency.

In the early days of TRUS biopsies as many as 70 per cent of men developed a urinary tract infection after the procedure. But it soon became clear that antibiotics taken before the procedure (known as “prophylaxis”) would reduce the risk of infection. The choices of effective prophylaxis are limited, and until recently a drug known as ciprofloxacin has been the most popular in a very narrow field. With prophylaxis, between 1 and 5 per cent of men undergoing TRUS biopsy develop a bladder or kidney infection and between 0.5 and 2 per cent develop a bloodstream infection. Most urologists consider something that occurs at a rate of between 0.5 and 2 per cent to be rare.

Let’s do some more maths, using 0.5 per cent, the low end of the estimated rate of bloodstream infection following TRUS biopsy. There were just over 29,000 prostate biopsies performed in Australia in 2012, giving a conservative calculated bacteraemia rate – the rate of bacterial infection – of 145 cases. Almost all of these patients will need hospital admission and many will end up in ICU. Most TRUS biopsies are performed in otherwise well men, so they would be expected to have a lower death rate from bacteraemia than patients with concomitant illnesses. There is currently no national surveillance of infections related to prostate biopsy so we don’t know what that rate is. Let’s assume it’s a very small number. The deaths would be distributed across Australia and it is unlikely that any single urologist would see more than one or two in a professional career. Similarly, no single ICU will have a concentrated experience of TRUS-related septic shock. A distributed problem usually remains a hidden problem.

But this is all changing very rapidly. A Canadian study has shown a 400 per cent increase in the rate of serious infections following TRUS biopsy in the ten years up to 2005, and it is assumed that most of this rise is due to emerging antibiotic resistance. People who travel to India, China or South East Asia have roughly a 50 per cent chance of picking up a ciprofloxacin-resistant organism in their bowel that will stay there for up to six months after they return home. As we have seen, germs can live happily in your bowel and cause you no harm. Unless, that is, we stick a needle through your rectum into your prostate.

The problem is that there is no other antibiotic that can be taken by mouth that works as well as ciprofloxacin. The alternatives need to be given by an intravenous infusion, adding to the cost and time that prophylaxis takes. And the more we use these previously reserved antibiotics, the faster we drive resistance to them.

It’s important for infectious diseases doctors to give our urology colleagues antibiotic advice, but focusing on the microbiological detail misses the real point: the best way to prevent an infection associated with a TRUS biopsy is to avoid doing the biopsy in the first place. We don’t know it for a fact yet, but it is plausible that the reason that there is no difference in the all-cause mortality between those who are screened for prostate cancer and those who aren’t is that the reduction in cancer deaths is replaced by a corresponding rise in infection-related deaths. The emergence of more resistant bacteria will increase the risk of infection associated with every TRUS biopsy. Inevitably, the current drawn contest will turn into a one-sided bout, with infection winning hands down.

So, where does that leave us? We have seen how the PSA test misses people who do have cancer, incorrectly diagnoses it in those who don’t, identifies it decades earlier than necessary, finds it even when it will never cause a problem and, in the majority of cases where it does identify cancer, does so too late for it to be cured. The TRUS biopsy is associated with pain, bleeding and life-threatening infection and turns the “what you don’t know about, won’t hurt you” cancers into “what you now know can hurt you” cancers. If that isn’t enough, the treatments for prostate cancer cause impotence and incontinence and cure only 2 to 3 per cent of the men who receive them.

I fear that prostate cancer screening is one of the most unfortunate medical examples of the Law of the Instrument: the idea that when all you have is a hammer, everything looks like a nail. Our current tools for diagnosis are inadequate and, in the case of biopsy, increasingly dangerous. (Some urologists are now using MRI scans instead of TRUS biopsies but the sensitivity and specificity of this approach is not known with any certainty. Others recommend passing the biopsy needle into the prostate through the skin of the perineum, the part of the body between the anus and the scrotum, to avoid the rectum.) It is clear that we need a better screening test and more effective therapies before we can safely and ethically recommend coordinated screening for prostate cancer.

I’VE TRIED here to confine my case against screening to scientific argument and to avoid ascribing anything but good intentions to those groups and individuals who promote it. This may be a little naive, so I’ve saved the last word for the person who made contemporary prostate cancer screening possible – the discoverer of PSA, Richard Ablin, now a professor at the University of Arizona. In a piece for the New York Times in 2010 titled “The Great Prostate Mistake” he observed that the PSA test “is hardly more effective than a coin toss.” He went on:

As I’ve been trying to make clear for many years now, PSA testing can’t detect prostate cancer and, more important, it can’t distinguish between the two types of prostate cancer – the one that will kill you and the one that won’t… So why is it still used? Because drug companies continue peddling the tests and advocacy groups push “prostate cancer awareness” by encouraging men to get screened… I never dreamed that my discovery four decades ago would lead to such a profit-driven public health disaster. The medical community must confront reality and stop the inappropriate use of PSA screening. Doing so would save billions of dollars and rescue millions of men from unnecessary, debilitating treatments.

When the father disowns a scion this famous – and he does it at greater length in a book due out in Australia soon – it is probably wise to pay attention. •

Some details in Dan’s story have been changed for privacy reasons.

Show Comments


David Roth

29 April 2014

I have a number of criticisms:

Firstly, I cannot believe that 'treatments for prostate cancer ..... cure only 2 to 3 per cent of the men who receive them.'The current 10 year survival rate for prostate cancer is much, much higher than that, above 90%. Since 1950, there has been a absolute increase of 50% in the survival rate. Bowden's figure of 2 to 3% effectiveness for PC treatments is inconsistent with these data.

Another question that needs to be answered is whether the total costs of unnecessary treatment + risks of TRUS-related infections are greater than the very high costs for men (and their families and the health system) whose fatal cancers were not diagnosed until they were too advanced for treatment.

In 2010 there were ca. 320 urology service providers in Australia. Taking Bowden's 2012 figure of serious TRUS-related infections of 145 p.a., this means that ca. 45% of these practitioners would come across 1 case in a calendar year (assuming a random distribution). Therefore Bowden's claim that ' is unlikely that any single urologist would see more than one or two (cases) in a professional career' seems implausible.

Personal interest: My PSA level is still undetectable 7 years after effective treatment for prostate cancer.

Chris Downy

20 March 2014

Interesting story. I understand where the author is coming from but I am one of those who is thankful for my GP suggesting that I go for a check after my PSA

had risen over a period of two years. I was diagnosed with cancer after having a biopsy, suffered no after effects from the biopsy, had the robotic surgery at St Vincent's in Sydney and have absolutely no regrets about having the operation.

It is the individual's choice but after my experience a number of my mates now have regular check ups and that's can't be a bad thing. I was 57 when I was diagnosed and I am in good health and hopefully will be that way for many years to come.

Frank there are two sides to every story. The picture you paint may be one side of the story but the other side is men should look after themselves and get tested. It's one blood test a year.

By the way I don't buy into your argument about the drug companies etc. That's an old and wearied argument that just does not wash anymore.

Mina Roberts

1 May 2014

To quote the article, "The deaths would be distributed across Australia and it is unlikely that any single urologist would see more than one or two in a professional career". I'm confident that it's referring to deaths.

As for the maths, both your and my calculations are consistent with the statement that 1-2 would be seen in a professional career. If 95% of practitioners don't see a death in a year, then it's unlikely to be viewed as anything more than uncommon, even in discussion with others. On the other hand, infections must be more visible, as you say, and this is supported by the article's statement that prophylactic antibiotics are used and alternative biopsy methods are advocated by some. So perhaps while the problem's not entirely hidden, its scope and impact on a population level is also not that obvious.

It's also worth noting that Professor Bowden, as an infectious disease specialist, is going to see only the most serious infections. For him, these adverse outcomes must seem much more common than to a urologist who sees most patients without major issues (and 145 in 29,000 makes infections pretty uncommon, even if potentially significant at the population level).

Finally, on reflection I think relative survival rates would be a better indication of cure than absolute, and they're pretty good for prostate cancer. I'm not sure where the 2-3% figure comes from, but with cancers, it seems the definition of cure depends on your point of view!

David Roth

5 May 2014

Ms Roberts, because your calculations come up with a number in the ballpark doesn't mean they are mathematically correct. With respect, you cannot use an average to calculate the outcome of a time series of independent probabilities.

I had a long chat to my urologist at a recent consultation. He says he and his colleagues tragically see far too many men who present when the PC is too advanced for cure. There is a difference between testing people in higher risk groups and mass screening, the latter does not take place for PC.

I'm glad you accept my point about survival rates. I won't repeat what my urologist said about the 2-3% figure for cures.

Dave Richards

21 March 2014

Thank you for saying this. Slowly the message is getting across. The biggest barrier is our 21st century inability to live with uncertainty. Fortunately, my doctor advised me several years ago that he did not routinely recommend PSA tests and would only include them in a general health check if the patient asked for it. I wonder how often this happens. (I just turned 60.)

Henry Hatch

23 March 2014

Interesting article but adds to my uncertainty. The impression I get is that there is too much noise from false positives and false negatives plus the inability to differentiate between benign and aggressive cancers to achieve any useful certainty of diagnosis. By the time things are certain then it is too late (a bit like climate change...).

Frank Bowden seems to be arguing for ignoring it, and when it does happen then just accept palliative care. Are there any circumstances where earlier intervention is justified?

I have a direct interest as I have had a bowel cancer removed in 2012 and then prostate cancer last year (lucky I guess...). I had a radical prostatectomy in December and as the cancer had started to spread outside the prostate gland capsule, I am undergoing a course of radiation therapy. Sounds dramatic but it has been mostly an inconvenience so far. I am now 68.

Rowan Stanley

14 April 2014

Professor Bowden gives a good explanation of the prostate story.

I wonder if here is any substance to the belief held by some that the consequence of any biopsy is to remove the safety of an encapsulated tumour and replace it with the possibility of metastasis from allowing cancer sells to spread to other parts of the body?

An otherwise slow process may be speeded up as a result?

What constitutes a "cure" in the eyes of the medical profession?

Mina Roberts

30 April 2014

In all honesty, without knowing where Professor Bowden's getting his information from, I can't really argue his point! My point was only that 10-year cure rates are not good measures of cure for indolent cancers, which the majority of prostate cancers are, apparently.

On the other hand, a little more support for the article - from what I could find on the internet, the survival rates for prostate cancer keep decreasing beyond 10 years. One site claimed a 15-year rate of 77%, compared to a 10-year rate of 93%, which may indicate that almost 20% of those apparently cured at 10 years actually harbour a slowly-growing and eventually fatal cancer, so aren't really cured. Some analysis along those lines could well be where the claimed 2-3% cure rate come from - a common-sense rather than technical definition of "cure".

With regards to serious TRUS-related infections, the article claimed that most urologists would only see 1-2 deaths from infection in their working careers (rather than infections). If there's 145 infections per year and 10% are fatal, that's 15 deaths per year over 320 urology service providers, and, on average, a death every 21 years per provider - only 1 or 2 in a career. I'm thinking that the urology community does recognise that it's an issue if they're using alternate methods to make the diagnosis, but again, without knowing much about prostate cancer, I can't really argue the point.

David Roth

30 April 2014

Ms Roberts, if Dr Bowden's point about serious TRUS-related infections was about fatalities, rather than the rate of infection, your maths are incorrect. If there are 15 deaths p.a. then the chance of an urologist not seeing a death in any one year is roughly 95% and the chance of not seeing a death in 20 years is ca. 40%. So 60% of urologists would have seen at least 1 death in that time. And more than 95% would have seen a serious infection in the same period. It's implausible that urologists don't discuss deaths or infections with their professional colleagues who have not seen them. Not exactly a 'hidden' problem in my view.

As for 10 years survival rates, a 93% survival rate is a common sense 'cure' for most sufferers, given that most PC victims are in their sixties and many have co-morbidities.

Mina Roberts

29 April 2014

Mr Roth, unfortunately survival rates from 1950 do not provide a comparison of treatment effectiveness between then and now.

This is because the tumours being treated are significantly different - in 1950 the vast majority of non-fatal cancers wouldn't have been diagnosed due to a lack both of screening and imaging techniques that could've detected smaller tumours. The cancers diagnosed then were likely those that were symptomatic, and hence much more likely to be aggressive, invasive types. These are much more likely to cause death (through spread to other parts of the body).

Today, even asymptomatic and small tumours are being diagnosed, including those which never would have been fatal (30-50% of all diagnoses according to the article). Inclusion of these cases in the statistics will naturally lead to a longer survival period regardless of the effectiveness of the treatments.

David Roth

30 April 2014

Ms Roberts, I accept your point about survival rates from the 50s. Nevertheless, modern 10-yr survival rates (over 90%) are not consistent with Dr Bowden's claim that: ‘treatments for prostate cancer ….. cure only 2 to 3 per cent of the men who receive them.’ unless you are in effect saying that these 2 to 3 percent are cures of the 'aggressive, invasive' types of PC; the remaining 97% being cures of PCs that would never have been fatal. But was Bowden making such a claim?

I note that you do not contest my point about the incidence of serious TRUS-related infections.

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