25 January 2016

By Dr Wendy Winnall - PCFA Research Team

"First do no harm". You may recognise this; it's an often-quoted principle of medical ethics. If only it were that straightforward, but medical science is rarely so simple. A more realistic aim is to achieve a balance whereby the benefits far outweigh the harms. Unfortunately, with PSA testing the balance of benefits and harms is very uncertain. This is the reasoning behind the decision not to use PSA testing as a screen for all men, in the same way a mammogram is used to screen for breast cancer.

But how can a simple PSA blood test cause any harm? The problem is that while PSA testing leads to earlier detection of prostate cancers thereby saving lives, it also leads to detection of many cancers that would have never caused any symptoms or health problems in the man’s lifetime. A prostate biopsy and Gleason score is not very accurate at distinguishing between cancers that would not cause a problem and those that would go on to cause symptoms and possibly death. Hence a positive PSA test can lead to a cascade of further investigation and treatment that may cause harm to men, some of whom would not otherwise have been diagnosed with prostate cancer and would not benefit from treatment. This is known as over-treatment. Treatments for prostate cancer, such as surgery and radiotherapy, come with a substantial risk of debilitating side-effects such as urinary incontinence, difficulties getting or maintaining an erection, and bowel problems.

If PSA testing was offered to all men aged between 50 and 74, it’s estimated that up to 60% would undergo over-treatment. The decisions of who to recommend testing to, and when to treat, must be carefully considered and based on the best available evidence. A new study that looks at the balance of good and harm from PSA testing and treatment helps us to make these decisions.

A small team from the Netherlands used computer modelling with large data sets to estimate the benefits of immediate treatment versus active surveillance after a positive PSA test. The researchers used real data from previous studies of PSA testing, and from US Medicare records. They took into account factors such as age, prostate cancer stage and other serious illnesses, focussing men between 66 and 72 years old. The computer modelling calculated the chance of over-treatment, where a man is treated for a cancer that would otherwise not have harmed him. For older men diagnosed with low risk prostate cancer, the chance of over-treatment was very high, 61% to 87%, but this dropped to 37% to 46% if they underwent active surveillance, rather than immediate treatment. Switching to active surveillance came with very little increase to the chance of mortality from prostate cancer.

The story was more complex for those diagnosed with intermediate-risk disease after PSA testing. If these men were younger (66 years) with no other severe illness, then the benefits of treatment over active surveillance were significant. However, 72 year olds with intermediate disease and another illness were less likely to benefit from treatment. These men were much more likely to die with prostate cancer than of it. Both the age factor, and having another serious illness strongly influenced the chances of over-treatment. This new information is very useful in our fight against prostate cancer. It helps us to predict who will benefit from PSA testing and who is less likely to. Effective PSA testing is a balancing act, if we can recommend it to the right group of men, then it will do more good than harm.

Active surveillance will often be recommended for older men with a positive PSA test and low-risk cancer. This study, and many others, shows that older men are more likely to die with prostate cancer than from it. Before having a PSA test, older men should consider whether they are willing to live with the knowledge that they have a cancer that remains inside their body. The alternative is to risk treatment that is likely unnecessary, and may have side effects such as incontinence and impotence. Both options may not be too appealing for many men, especially if they have other illnesses to worry about.

The decision to be PSA-tested should be made by each man with full knowledge of the potential benefits and harms. This has not always been done up till now. One of the important recommendations in the new PSA-testing guidelines says that a doctor should always discuss these implications, to ensure that each man has the facts necessary to make the best choice for himself about PSA testing.