Study suggests screening in men with genetic predisposition to prostate cancer is more effective

In collaboration with Adfero

A new multinational study suggests that regular blood testing to measure levels of prostate specific antigen (PSA) is more effective at detecting prostate cancer in men with a genetic predisposition to the disease.

Use of the PSA test as a screening tool for prostate cancer is controversial because many men with high levels do not have prostate cancer.

It also cannot tell the difference between men whose prostate cancer is aggressive and men who will never develop symptoms and do not need treatment.

There are therefore concerns that population-wide screening with the PSA test could lead to over-diagnosis and unnecessary treatment in some men, including invasive surgery with serious side effects.

However, preliminary results from the latest study indicate that the degree of unnecessary treatment could be reduced by targeting PSA testing at men who have an increased risk of prostate cancer as a result of inheriting faulty BRCA1 or BRCA2 genes.

BRCA2 faults increase a man's risk of prostate cancer by up to seven-fold, while BRCA1 faults are thought to double risk in under-65s.

The IMPACT study is part-funded by Cancer Research UK and led by scientists at the Institute of Cancer Research (ICR) and the Royal Marsden NHS Foundation Trust.

Results for the first 300 men enrolled in the study, 205 of whom tested positive for faulty BRCA1 or BRCA2 genes, have now been published in the British Journal of Urology International and suggest that screening men with these gene faults may lead to earlier diagnosis of aggressive prostate cancers.

Participants were all offered annual PSA testing and those with elevated levels were given a biopsy to look for cancer cells.

The biopsies revealed that prostate cancer was more common in men with faulty BRCA genes than in those with normal versions of the genes.

Nine of the mutation carriers were found to have prostate cancer, compared to just two of the non-carriers.

Nearly half of biopsy samples (48 per cent) tested positive for prostate cancer, whereas the proportion of biopsies carried out in the general population that test positive for prostate cancer tends to be just 24 per cent.

The study also found that 78 per cent of faulty BRCA carriers who had developed prostate cancer had intermediate or high-risk disease that needed treatment.

In contrast, a previous population-wide screening study - the ERSPC, which was published in the New England Journal of Medicine last year - found that just 35 per cent of men diagnosed as a result of PSA testing had aggressive prostate cancer that needed treatment.

Chief investigator professor Ros Eeles, from the ICR and the Royal Marsden, commented: "This adds to the increasing evidence that BRCA mutation carriers develop more aggressive disease.

"Although these are early results, it appears that PSA screening is reasonably accurate at predicting potentially aggressive prostate cancer among men at higher risk of the disease due to a genetic predisposition. This study provides support for continued screening in men with genetic mutations."

Ed Yong, Cancer Research UK's head of health evidence and information, said: "Measuring PSA levels could potentially cut a man's chance of fatal prostate cancer. But we know that for every life saved, a lot of men will go through unnecessary tests and treatments, including invasive surgery with serious side-effects.

"This new study suggests that we could limit the number of men who undergo unnecessary treatment by targeting PSA testing at very specific groups of people, who have particularly high risk of prostate cancer. It's a promising result and we'll need to see if it bears out in future research.

"Cancer Research UK advises men to discuss with their doctor whether or not to have a PSA test. Some cancers are slow-growing and unlikely to cause problems in a man's lifetime, especially as prostate cancer is more common in older men. But in others it will grow aggressively and require treatments such as surgery or radiotherapy.

"It's still not known what the best treatment approach might be, so it's important we find answers to this as soon as possible through research currently funded by Cancer Research UK and others."

The IMPACT study is still going and will ultimately screen 1,700 men for at least five years.

References

Mitra AV et al, Targeted prostate cancer screening in men with mutations in BRCA1 and BRCA2 detects aggressive prostate cancer: preliminary analysis of the results of the IMPACT study (2010) BJU INTERNATIONAL doi:10.1111/j.1464-410X.2010.09648.x