Men at higher risk of prostate cancer due to genetic changes may benefit from regular screening, according to preliminary results from the first multinational study of patients with known prostate cancer predisposition genes.
Scientists have already found a number of genetic factors that increase prostate cancer risk, including heritable mutations in the genes BRCA1 and BRCA2. These mutations are not common but can have major impact, as a BRCA2 mutation increases risk by up to seven-fold while a BRCA1 mutation is thought to double risk in men under 65.
Scientists from The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust are leading a study, called IMPACT, to determine whether screening men with a known BRCA1 or BRCA2 mutation would lead to earlier diagnosis of prostate cancers. The study will ultimately screen 1,700 men for at least five years, and preliminary results from the first 300 men enrolled in the study are published today in the British Journal of Urology International.
The men – 205 with confirmed BRCA1 or BRCA2 mutations and 95 who had tested negative for the mutations - were all offered annual prostate specific antigen (PSA) blood testing. The 24 men who had an elevated PSA were given a follow-up biopsy.
The biopsies revealed that a higher proportion of mutation carriers had prostate cancer than non-carriers: nine, representing a 3.9 per cent diagnosis rate, compared with two, a 2.1 per cent diagnosis rate.
The predictive value of the test – the number of cancers detected relative to the number of biopsies conducted – was 48 per cent, whereas such tests in the general population have a lower value of 24 per cent.
PSA testing is controversial because it does not differentiate between men with aggressive prostate cancer and those who would never experience symptoms and require treatment, and it can also return elevated results in men who do not have prostate cancer. There are therefore concerns that widespread PSA testing may lead to overdiagnosis, unnecessary therapy and side-effects for some men. In this study, the majority (78 per cent) of mutation carriers had intermediate or high-risk disease which needs treatment, compared with 35 per cent of men diagnosed in a major population-wide screening study that reported last year*.
“This adds to the increasing evidence that BRCA mutation carriers develop more aggressive disease,” Chief Investigator Professor Ros Eeles from the ICR and The Royal Marsden says. “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.”
This research was funded in the UK by grants from The Ronald and Rita McAulay Foundation, Cancer Research UK and support from the National Institute for Health Research for the Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research.
IMPACT stands for Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted Screening in BRCA1/2 mutation carriers and controls.
* The European Randomized Study of Screening for Prostate Cancer (ERSPC), which began in the early 1990s and included more than 162,000 men, last year reported a 20 per cent reduction in prostate cancer mortality through population-wide screening. This was equivalent to a benefit for one in 1,400 men screened, while around one in 30 had treatment for prostate cancer that would never otherwise have caused problems.
The ERSPC study found 64 per cent of prostate cancers diagnosed were low grade, 27 per cent were intermediate grade and eight per cent were high grade. The present study targeted screening only at mutation carriers and found 22 per cent of those diagnosed had low risk disease, 67 per cent had intermediate risk and 11 per cent high risk.
More than 36,000 men are diagnosed with prostate cancer each year in the UK and one Briton dies every hour from the disease.
Institute of Cancer Research
