A new study published in the journal PLOS Medicine shows that the number of prostate cancer deaths could be reduced by a sixth by simply introducing targeted screening, which is directed at detecting cases among men whose genes put them at higher risk of the disease. The study employs computer modelling to evaluate the potential risk-benefit ratio of routinely screening all adult males aged 55-69 years for prostate cancer by a simple blood test every four years, vs only those who have a higher risk.
Prostate cancer danger medical concept illustration. Nearly one in six deaths from prostate cancer could be prevented if targeted screening was introduced for men at a higher genetic risk of the disease, according to a new UCL-led computer modelling study. Image Credit: Lightspring
PSA and prostate cancer
Prostate cancer is the most frequently diagnosed male cancer. In the UK, about 130 men are found to have the disease every day, and it claims over 10,000 lives a year. Screening for this disease is not yet part of any national program, though there are such programs for breast and cervical cancer.
A potential screening test for prostate cancer is the blood prostate-specific antigen (PSA) level, which is high in cases of prostate cancer. The issue here is the low specificity of the test – rapidly enlarging or spreading tumors are not properly differentiated from indolent slow-growing tumors. This can result in both unnecessarily aggressive follow-up and overtreatment, while on the other hand some tumors which ought to be treated can be missed.
The reason for this observed benefit is that males who have a higher risk are unlikely to be harmed by screening for this condition and are in a greater position to benefit. Using this approach could reduce up to 1 in 6 deaths from prostate cancer in the UK, according to the study.
The study aimed to provide evidence that could help choose one or the other approach to PSA screening to reduce preventable prostate cancer deaths. The researchers used a virtual group of 4.5 million men as representative of all men aged 55 to 69 years in the UK. They then modelled the effects of screening this group, using outcomes like the number of prostate cancer deaths avoided, the number of wrong diagnoses of prostate cancer, and the cost of screening, in three situations: no screening applied; universal screening on the basis of age; and targeted screening for people at various levels of genetic risk.
The study found that the most cost-effective method to reduce deaths due to prostate cancer would be screening men who had a slightly increased risk (4% to 7%) of this condition in a 10-year period because of their genes. This subgroup accounts for about half the men between 55 and 69 years. If screening is restricted to only the 4% risk subgroup, it would have the greatest benefit in terms of optimizing the rate of diagnosis of tumors that require treatment while avoiding unnecessary treatments for indolent cancers, in most cases.
In numerical terms, universal screening could avoid the greatest number - about a fifth – of the deaths, but would cost more, while also making a larger number of men with harmless tumors liable to unnecessary investigation. About a third of detected cancers could have been left untreated and even undetected, in fact.
If the risk threshold is about 4%, the number of deaths avoided goes down to 15%, but overall, the number of years of good health gained for the whole population is greatest with this intervention. One third more of harmless cancers would be left undiagnosed with this approach.
Whichever of these two thresholds are selected, risk-based screening shows greater cost-effectiveness while also saving lives. If the 7% level is chosen, costs can be cut to half, while with the 4% threshold, a fifth of the costs can be saved. With both thresholds, screening shows significant health benefits.
The researchers modelled situations in which four-yearly PSA screening was instituted for men who passed the risk threshold already defined. With increasing age, therefore, more men would be getting screened, since their disease risk would go up as they grow older.
This study from UCL is only one of several that have already brought about beneficial changes in the diagnosis of prostate cancer. For instance, after two clinical trials showed that using MRI scanning could reduce the requirement for biopsy to diagnose prostate cancer, MRI is now the test of choice in potential prostate cancer patients.
Researcher Nora Pashayan says, “Prostate cancer is a leading cause of death from cancer in men in the UK, but screening is not performed because the harm of overdiagnosis is thought to outweigh the benefits. Our study shows that targeted screening can reduce unnecessary diagnoses while helping to prevent people dying from the disease by enabling earlier detection.” Such screening may require a change in the way things are done and more study into the impact of selective screening based on genetic risk.
Says UCL’s Mark Emberton, “"I feel we now have the tools that help us identify men with clinically important disease - applying these tools to the right patient has to be the future. That is why this work is so important.”
Polygenic risk-tailored screening for prostate cancer: A benefit–harm and cost-effectiveness modelling study Callender T, Emberton M, Morris S, Eeles R, Kote-Jarai Z, et al. (2019) Polygenic risk-tailored screening for prostate cancer: A benefit–harm and cost-effectiveness modelling study. PLOS Medicine 16(12): e1002998. https://doi.org/10.1371/journal.pmed.1002998