The Best Australian Science Writing 2014 (29 page)

Again, the commonsense view takes a hit from the complex biology of prostate cancer. It has been known for over 100 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 40s and 50s over the past 20 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 70s and 80s 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 to 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 a 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 40s and 50s 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 67, Swan underwent screening when he was 47. 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 60s 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 11-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 37 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 40 in any circumstances, and it doesn't recommend screening for men 40–54 years of age at average risk (without a family history, that is). But it still recommends ‘shared decision-making' for men aged 55–69 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 50th 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 stock market, 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.