In a five-part series, the Herald investigates controversies in cancer testing and treatment and reports on the moving stories of people afflicted with cancer. In the fifth and final part of the series, Herald health reporter Martin Johnston turns his attention to prostate cancer.

Hundreds more men will be encouraged to go about their lives with cancer slowly growing inside them.

This may seem odd as we in New Zealand and other Western countries, fed a diet of medical science, have come to abhor cancer. When it is found we typically want cancer out. Zapped. Surgically removed. Gone.

Urologists, however, have been urging men with low-risk prostate cancers to consider living with their tumour long-term.

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This has been now given official approval in a Ministry of Health guideline on using so-called "Active Surveillance".

Prostate cancer is New Zealand's most commonly registered cancer, with more than 3000 cases in 2012, and the fourth most common cause of cancer death, killing 607 in 2012.

The ministry guideline is part of a $4.3 million Government plan to provide better prostate cancer information and care to men. This plan arose from a health select committee inquiry into prostate cancer that investigated the idea of an organised screening programme, like those for cervical and breast cancer. But in its report in 2011, the committee couldn't recommend creating one because of lack of evidence that the benefit would outweigh the harm.

Little has changed on that score. Some say testing healthy, asymptomatic men from middle age with prostate specific antigen (PSA) blood tests saves lives. Others object over the PSA's high false-positive rate and say that because the test doesn't reliably differentiate aggressive, lethal tumours from slow-growing cancers that would not cause clinical symptoms, screening does more harm than good.

The compromise fashioned by the committee, and now perpetuated by the ministry's updated guidelines and information for men, is that PSA testing should be a man's choice. This is different from how the ministry approaches bowel cancer testing, in which it actively discourages the use of the screening test outside the one area, Waitemata, where organised bowel screening is being done.

The case against screening

Epidemiologists Associate Professor Brian Cox, of Otago University, and Professor Ann Richardson, of Canterbury University, are among those against PSA screening of men who have no prostate cancer symptoms.

Professor Richardson notes that no country has a national prostate screening programme and that a number of medical and public health organisations around the world do not recommend organised screening for prostate cancer because the benefits do not outweigh the harms.

"It's not as simple as saying each individual man can decide. [That would be like saying] each individual person could decide whether to take a drug before it has been assessed and approved for use."

She and colleague John Potter have calculated in the New Zealand Medical Journal that screening 1000 men for 10 years would result in no more than one man gaining extra years of life from having prostate cancer detected and treated. There would also be prostate cancer diagnosed in 110 men, false positive results in 100 to 120 men, biopsy (diagnostic tissue sampling) complications in 20-30, complications of treatment in 20-30 and the death of less than one man.

Treatment complications include chronic impotence, urinary incontinence, blood clots following surgery, and, following radiotherapy, faecal incontinence for about 5 per cent.

"Up to half the cancers detected in a prostate-cancer screening programme would not have caused problems during a man's lifetime but if treated, carry risks of these complications."

Dr Cox says around a third of men over 50 have a prostate tumour, but only 5 per cent of men develop prostate cancer symptoms.

"A lot depends on what individual doctors think regarding PSA screening, rather than any authority. To some extent that's unfair. There's a lot for men to take in in terms of the pluses and minuses of having a PSA test. We are coming to a debate around what information should be provided and in what format, which isn't all that helpful either. It just shows you there's a lack of evidence in favour of ... screening."

The case for screening

"We are not arguing with the epidemiologists," says Professor John Nacey, a urologist and head of the ministry's Prostate Cancer Working Group. "I'm looking at a man across the desk from me. It's an individual decision, not a population.

"We don't want to do population screening," Professor Nacey says, acknowledging the potential harms of treatment, but noting men are likely to take their chances in order to live.

"I think maybe men would rather be impotent and have some incontinence of urine rather than die of their cancer."

He tells all men who ask about prostate cancer that the great benefit of testing is that if cancer is detected and it is at an early stage, then the chances of a good outcome are excellent. But the downsides are that a positive test result may not be cancer or, if it is cancer, it may turn out to be a low-grade tumour.

"You may [face] a dilemma: whether to go into active surveillance or undergo curative treatment and the risks associated with that."

Most want cancer gone

United States and European studies cited in the Richardson-Potter paper found 90 per cent and 70 per cent respectively of men with low-risk prostate cancer opted for immediate surgical or radiation treatment.

Active surveillance entails ongoing PSA tests, repeat biopsies using fine needles to extract multiple tiny tissue samples from the prostate tumour, and possibly extra scans.

A US study of men with cancer that had not spread beyond the prostate found that the death rate was the same in men who had surgery to remove the gland as it was in those who only received observation. The surgery group, however, had a lower rate of cancer spread to the bones after eight years.

Professor Nacey says that of the roughly 3500 newly diagnosed prostate cancer cases a year in New Zealand, around 3000 would have disease that had not spread, of whom at least 2000 would qualify for active surveillance. But he estimates only about 400 a year go on to active surveillance and says a "good target for us" is to lift that to 600-800 a year.

Men have to ask first

For all the effort the ministry has put into improving prostate cancer information, the new guidelines hinge on men raising "prostate-related concerns" because, with the unresolved conflicts over PSA testing of men without symptoms, the ministry couldn't ethically promote it, in the way that it actively encourages women to have breast and cervical screening.

The guidelines navigate this conflict by telling GPs of both sides of the issue: "Some men may benefit from early diagnosis and treatment"; and routine PSA testing may detect a non-progressing tumour and the diagnosis "may increase men's exposure to unnecessary treatment-related harms".

Prostate Cancer Foundation chief executive Graeme Woodside says that although the guideline puts the onus on men to ask, it "does [encourage GPs] to have a conversation".

The foundation endorsed the guidelines, "but when they come up for review I think we will be looking for a more 50/50 [onus on] both the GP and the patient".

Every day, people ring the foundation's helpline with stories of cancer being treated because of early detection and others in which it was found only after having spread.
"Some are pretty distressing, for instance the wife of a 59-year-old who has serious metastatic cancer which will be seriously life limiting. He's been going to the same doctor for a number of years and was never checked. When they asked the doctor - after the diagnosis - the doctor said, 'I don't do PSA testing'. Had he had a routine test it would have been picked up earlier for sure. The doctor was ignoring prostate cancer, to the peril of this particular gentleman.

"The way it is worded now, the GP can technically say 'the patient never raised that concern with me' - that would be in a legal sense. Many are proactive but there [are some GPs] who don't use PSA and don't actively test for prostate cancer."

New tests and treatments

The hunt goes on for a better test than PSA, although in men already diagnosed it remains a good marker of the effect of treatment and recurrence.

"The most promising tests coming through are PCA3 and TMPRSS2:
ERG," says Professor Helen Nicholson of Otago University.

"The benefits of these are that they can be measured in urine but like PSA there is not a clear switch in expression, so it is difficult to know where the cut off level between normal and cancer is. Also I'm not sure that they can identify aggressive tumours."

The PCA3 test is available commercially in the US, where it can reduce the need for repeat biopsies in active surveillance. However, Professor Nacey says the PSA test is preferable.

Otago University scientist Dr Karen Reader's research group is investigating growth factor proteins in the hunt for a test to replace the PSA.

"It's looking at prostate cancer tissue samples, a retrospective study looking at the levels of protein in those samples and seeing if there's any correlation between particular ones and the grade or outcome of the cancer, whether it can be used as a marker for a test to determine which are aggressive and which aren't."

An Auckland biotech company is also working on a new prostate test.

"Caldera Health has ... confirmed a panel of gene biomarkers for use in an affordable diagnostic test which ... gives significantly better accuracy in terms of sensitivity and specificity than the PSA test," the company says.

Mr Woodside says major improvements are occurring in the management of advanced prostate cancer.

Some New Zealand men are receiving enzalutamide in clinical trials. This drug can block the action of the male hormones that help prostate tumour cells to divide and grow.

In May, Government agency Pharmac began funding Zytiga for men to take before or after chemotherapy for advanced prostate cancer that continues to grow despite surgical or drug-induced castration, which are both hormone-deprivation therapies. Trials have found Zytiga extends the lives of men with advanced prostate cancer by around five months.

Mr Woodside says another major improvement is Mercy Radiology's introduction of a new type of PET scanning.

It targets a certain prostate enzyme and, compared with the main scanning methods, can identify much smaller collections of tumour cells that have spread outside the prostate.

This greater accuracy can help confirm tumour cells haven't spread. Or if found in a single lymph node, localised radiation or surgery may be possible, allowing deferral of hormone therapy and chemotherapy.

Says Mr Woodside: "Some say it is a game-changer in tracking the development of metastatic disease."

The Series


Bowel Cancer



Today: Prostate Cancer