Prostate cancer has moved on. The focus used to be on diagnosing this cancer at an early stage. Now that testing is common and so many early cancers are being found, the focus has shifted to trying to prevent these early cancers from developing into advanced disease.
This is a significant shift because most men in their 60s will have a microscopic form of prostate cancer and there aren’t accurate tools to predict whose cancer will stay indolent and whose will become active.
“We know the majority will not be lethal,” says Professor Graham Giles, a leading Australian prostate cancer researcher. “But we don’t know which will remain pussy cats and which will become tigers and kill us.
“This remains the essential research question: How can we tell the tigers from the pussycats?
“Until we have that question answered, many men will undergo unnecessary treatment and we’ll have a lot of older men made miserable by the side effects.”
Professor Giles, Head of Research at the Cancer Epidemiology & Intelligence Division of the Cancer Council in Victoria, is leading a huge project to try to identify what flips the switch causing an indolent cancer to wake up and become active.
This unique project, which began five years ago, involving more than 2200 men from private urology practices in Victoria. It aims to determine if any of the factors that cause the flip are amenable to change.
Lifestyle factors and genetics
The project has begun publishing preliminary results, which hint at risk factors that may influence the conversion. So far, three papers have been published, a fourth is about to appear and many more are set to follow.
Early results cover the role of alcohol, ejaculatory frequency, balding, height, obesity and medication – but these findings differ by genetic profiles obtained from analysing a large genome-wide scan.
“Given the weak associations with lifestyle factors, we are holding most hope for the genetics and we hope to produce risk prediction models that incorporate genetic profiles next year,” says Giles.
Funded by the National Health and Medical Research Council, the project is based at Cancer Council of Victoria and includes well-known urologists Professor Damien Bolton and Associate Professor Nathan Lawrentschuk.
So far, there are only four known risk factors for initially developing prostate cancer. These are: growing older, having a family history of the disease, race (African men are at high risk) and having an intact supply of testosterone.
The prostate is under the control of androgens (male hormones), which explains why eunuchs never get prostate cancer, says Giles.
To investigate this control, the team looked for signs of androgen activity, such as sexual function and male pattern balding.
There is little reliable research on factors that wake up an indolent cancer, but it is speculated that factors for aggressive and non aggressive disease may differ.
So what have they found so far?
The researchers found only those men who begin going bald by the age of 20 are at an increased risk of an indolent cancer becoming aggressive and of this happening at an earlier age.
This was not observed in men who developed male pattern balding at 40.
Although men can’t prevent early balding, the finding is useful because it suggests they should be more vigilant about prostate cancer as they get older.
Published in the journal Cancer Causes & Control, the study suggests this small group of men should have closer follow-up with blood tests and urological investigations throughout their lives.
Forthcoming genetic studies will help to define further those at high risk of lethal cancer.
Professor Bolton, clinical professor of surgery at Melbourne University, says about 2 per cent of men start to develop frontal pattern baldness before 20.
Although early balding reflects a man’s hormonal milieu and his genetic background, it is also possible he may have been exposed to relatively high levels of testosterone in utero.
Sexual activity remains a grey area.
The important factor here is not how many sexual partners a man has or whether they are male or female, but how often he ejaculates alone or in company.
The prostate is a secretory organ and its function is to provide a large part of seminal fluid, just as the function of the female breast is to provide milk. So it is thought it might matter how much a man makes this organ work.
Past research by the same group on all prostate cancers reported that the more men ejaculate, the greater the demand they place on the prostate and the lower their risk of cancer.
The biology is not understood, but one popular theory speculates that frequency flushes the gland clean of secretions or residues that might eventually cause disease.
In this study, however, the researchers were interested in the relationship between ejaculatory frequency from the ages 20 and 50, and the subsequent development of aggressive prostate cancer.
The study, published in the journal Urologic Oncology, found that ejaculating twice a week between the ages of 30 and 39 appeared to lower the chance of prostate cancer becoming aggressive.
Although the finding was statistically significant, the researchers say it may yet be spurious, and further studies need to be done.
One problem with studying the effects of alcohol is that people don’t reliably report their consumption. It’s known, however, that those with cancer often reveal more than healthy controls in case it is helpful. This is called an “information bias”.
Among the participants in this study, about 1300 men had aggressive prostate cancer. The rest, who constituted the control group, had been suspected of having prostate cancer but were found to be negative on biopsy.
That they had all been through similar anxiety and the full testing process was anticipated to reduce the information bias between the two groups.
Previous research found heavy alcohol consumption confers a modest increase in the risk of aggressive prostate cancer and suggested a high intake of beer raised the risk, while red wine modestly reduced it.
This new study, published in the journal Prostate Cancer and Prostatic Diseases, added to the existing evidence that increasing the volume and frequency of beer increased risk, although it stressed other health risks associated with alcohol had not been assessed.
The study also suggested drinkers of all types of wine (red and white), regardless of quantity consumed, had a decreased risk of cancer compared with those who did not drink wine.
Abstainers appeared to be at increased risk compared with wine drinkers, but at decreased risk compared with beer and spirit drinkers.
The biological mechanism underlying these finding are unknown, although it has been suggested beer’s association with obesity and wine’s association with the natural compound resveratrol, found in the skin of red wine, may be factors.
Professor Giles is not too confident these findings on alcohol will stand the test of time.
Height, obesity, body shape
This study, which is yet to be published, looked at early life, at how men grew, when they had a growth spurt, their body shape and fat distribution.
The findings were complicated.
Professor Bolton says it shows men with a shorter pre-pubertal height – relative to friends at age 11 – were at increased risk of prostate cancer.
If this early shortness translated to obesity in mid-life, at the time of an initial biopsy, the men would be at a significantly higher risk of aggressive prostate cancer.
But if these men grew tall and didn’t become obese towards mid-life, they would overcome the risk of early shortness.
He said men who are slim and tall in their youth and become obese towards mid-life have an increased risk of aggressive cancer.
Some of the findings, yet to be published, relate to smoking and medication.
While there has been some evidence that smoking is protective against developing prostate cancer, once a man has the cancer, the data appears to suggest that by continuing smoking, he increases his risk of it turning aggressive.
Previous studies have also suggested that medicines such as aspirin and anti-cholesterol drugs called statins reduce prostate cancer cells.
Obesity is known to be a risk factor for cancer. One way it is thought to do this is through creating chronic low-grade inflammation. This is the reason anti-inflammatories such as aspirin are thought to help reduce risk.
Statins are thought to help in other ways, but this new research has found both classes of drug have no impact either way.
Professor Giles said the theory that obesity encourages a dormant cancer to grow and become nasty remained speculative.
He remains hopeful that the fairly weak associations observed so far with lifestyle factors will become sharper when combined with the genetic data.
Other papers on factors including vitamins, sun exposure, shift work and exposure to toxins such N-nitroso compounds found in processed meat, are yet to be produced.
Dr Nathan Papa, a research Fellow at Melbourne University, crunched the data for the first four papers as part of his PhD thesis and is their lead author.
Professor Lawrentschuk says the studies are based on solid research and reiterate that genetics and lifestyle are important factors.
“I get asked the same question every day. Men want to know what they can do for their prostate health.”
He’s hoping that this study will ultimately provide some guidance on preventing progression and on when to seek counselling and/or treatment.
Jill Margo is The Australian Financial Review’s health editor and an associate adjunct professor at the University of NSW.