Targeted Genetic Risk-Based Prostate Cancer Screening Would Save the Most Lives at the Best Costs: UK Study

Targeted screening of men at high genetic risk of the disease could prevent nearly one in six prostate cancer deaths. That is the tantalizing finding of a new computer modeling study led by the University College London (UCL).

The Prostate Cancer Diagnostic Challenge

Prostate cancer is the most common form of cancer in men, claiming more than 10,000 lives per year. But screening for prostate cancer is more problematic than screening for its sister diseases, breast and cervical cancer. The effectiveness of current prostate-specific antigen blood testing is marred by the PSA protein’s lack of reliability as a biomarker. Thus, while high PSA levels denote prostate cancer, the cancer is often low grade and poses no threat to the patient. High PSA may also indicate infection, inflammation or other disease. But because of the risks involved, physicians commonly order biopsies to rule out prostate cancer for patients whose screening tests show high PSA levels. Ultimately, a large percentage of these biopsies prove unnecessary.

The Study

These diagnostic problems explain why the UK has a national screening program for cervical and breast cancer but not for prostate cancer. With this in mind, UCL researchers performed a study computer modeling the harms and benefits of introducing four-yearly PSA screening for two groups:

• All men ages 55 to 69; versus
• A more targeted checks for those at higher genetic risk of the disease, nearly half of the men in the above age group.

The study, published in PLOS Medicine, created a hypothetical cohort of performing different kinds of screening on 4.5 million men, the number of men aged 55 to 69 in England. Outcomes including prostate cancer deaths averted, unnecessary diagnoses and screening costs were compared against:

• No screening;
• Universal age-based screening; and
• More targeted screening using a range of genetic risk thresholds.

The simulated scenarios posited that men ages 55 to 69 would have four-yearly checks once they reached the risk threshold. This would mean a widening proportion of men having checks the older they got, as older men are at greater risk of the disease.

The Study Results

The researchers found that testing the population at higher risk of prostate cancer yielded the biggest health benefit in terms of both preventing prostate cancer deaths and minimizing unnecessary treatments for harmless tumors.

The optimal scenario, the study found, would be to screen men with a 4% to 7% risk of getting prostate cancer over the next 10 years, i.e., between roughly half and a quarter of all men ages 55 to 69.

Screening all men in that age group would result in the most deaths averted (20%); but it would also lead to extra cost and a large number of unnecessary diagnoses, with nearly one in three cancers detected by screening proving harmless.

Screening at a threshold of 4%, by contrast, would prevent 15% of (nearly one in six) deaths from prostate cancer while delivering the greatest gains in terms of quality adjusted life years, meaning more years of good health across the population. As compared with screening all men ages 55 to 69, screening at the 4% threshold would also reduce the number of unnecessary diagnoses of harmless cancers by about one third.

Screening men with a 4% to 7% risk would also be much more cost effective than screening all men ages 55 to 69, saving between one fifth (for the 4% risk threshold) to nearly half of the cost (7% risk threshold), while maintaining the benefits of screening.

Takeaway

“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,” noted senior study author Professor Nora Pashayan (UCL Applied Health Research).

“Our study shows that targeted screening can reduce unnecessary diagnoses while helping to prevent people dying from the disease by enabling earlier detection.”

It should also be noted that prostate cancer screening in the UK has historically been utilized less frequently than in the US.