Prostate cancer screening program based on patient risk yields greatest benefit
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Screening men for prostate cancer based on their risk for the disease can potentially reduce overdiagnosis and improve a program’s cost-effectiveness, according to data from a modeling study published in PLoS One.
Tom Callender, MSc, MB, public health registrar and academic clinical fellow at University College London, and colleagues created a hypothetical cohort of 4.48 million older men in England. The men were followed until they reached 90 years of age. Researchers then compared the benefits and harms of three screening models:
- no screening;
- age-based screening with PSA testing every 4 years; and
- risk-tailored screening based on age and polygenic risk profile.
In the model, men were screened between the ages of 55 to 69 years, Callender and colleagues wrote.
The researchers found that, compared with no screening, age-based screening prevented the most deaths from prostate cancer over a 35-year period — 39,272 (95% uncertainty interval [UI], 16,792-59,685) — but it did so at the expense of 94,831 (95% UI, 84,827-105,630) overdiagnoses. Age-based screening also was the least cost-effective approach, researchers said.
Callender and colleagues wrote that risk-based screening “improved the benefit/harm tradeoff and cost-effectiveness of a screening program for prostate cancer.” Specifically, offering screening to men at a 10-year absolute risk threshold of 4% led to 64,384 (95% UI, 57,382-72,050) fewer overdiagnoses but averted 9,695 (95% UI, 2,853-15,851) fewer deaths from prostate cancer compared with age-based screening. At that same threshold, risk-based screening was cost-effective 57.4% of the time when it was assumed society would cover 30,000 euros ($39,386) of the costs for each quality-adjusted life-year (QALY). The cost-effectiveness of the model rose as the amount society was willing to cover rose.
Ultimately, the best screening strategy “will depend on both a society’s willingness to pay for each QALY gained as well as the tradeoff between benefits and harms considered acceptable both at an individual and population level,” the researchers wrote.
Callender and colleagues noted that their findings compare favorably with a microsimulation model that was previously conducted in United States. – by Janel Miller
Disclosures: The authors report no relevant financial disclosures.
Perspective
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Robert A. Smith, PhD
There always has been interest in risk-based screening. For most cancer screening tests, there has been limited progress in tailoring screening so that all adults at all risk levels would still have a similar chance of having cancer detected early, but undergo screening differently, perhaps more efficiently, based on risk. More commonly, hypothetical risk-based screening models result in less screening for the same current population-based benefit. This may be appealing to national programs that seek to reduce the investment in screening and divert resources elsewhere if the same benefit can be maintained (say, a 30% reduction in cancer deaths), but thus far, it comes at the cost of the lower risk population having less protection against the diagnosis of an advanced cancer. This alternative approach commonly is promoted based on cost-savings and a reduced rate of harms (false positives, biopsies, overdiagnosis, anxiety) in the lower risk groups.
Over time, various combinations of risk factors have been applied to risk-based screening models. These range from age and first-generation risk factors (family history, etc.) in the early years of cancer screening to using some of these same risk factors and adding molecular markers, high penetration genetic mutations, polygenic risk scores, etc. in more recent years. Polygenic risk scores are based on the combined influence of small genetic variations, each of which alone contributes to a small increase in an individual’s risk for disease but in combination may be useful to distinguish lower and higher risk groups.
In well-understood ways, prostate cancer screening is different vs. other screening tests, because a considerable fraction of detected prostate cancers will not pose a risk of death in a man’s natural life, and therapy carries a risk of significant, quality of life diminishing post-treatment side effects. Thus, rather than directly recommending screening, all organizations recommend that men undergo a process of shared decision making about prostate cancer screening. Thus, a decision about screening (for example, men with family history) and treatment (men with an elevated PSA) may be enhanced by risk factor scores that are predictive of the risk of being diagnosed with a lethal cancer, or specifically, the lethal potential of the recently diagnosed patient’s cancer. Ideally, we would have a risk-estimation model that would identify men who needed to be screened, and those who did not, or at least, those that should be treated and those who should not. Cost considerations are important, of course, but compared with screening all men, such a model would be more cost-effective.
Callender and colleagues’ model demonstrates that using a polygenic risk-tailored screening program might reduce overdiagnosis, maintain the mortality benefits of age-based screening, and improve the cost-effectiveness of a screening program for prostate cancer.
They demonstrated a range of strategies for applying polygenic risk scores to prostate cancer screening, and while some of the hypothetical strategies are more cost-effective and are associated with a lower rate of overdiagnosis, none are associated with a lower rate of death from prostate cancer. In fact, each is associated with a significantly lower rate of preventing prostate cancer deaths because fewer men are screened for prostate cancer.
Over the past decade, we have seen considerable progress in men being counseled to not rush into curative therapy in order to avoid the treatment side effects if they have a prostate cancer that is not particularly aggressive. Aggressive monitoring with PSA and regular imaging can rapidly identify prostate cancers that are progressing or have become aggressive, and at this point necessary treatment can take place. Risk-based screening has great promise, but a consideration of paramount importance must be the degree to which a proposed strategy will leave one group in the target population with less opportunity to have their cancer detected early so that another group will have more. The more desirable approach is to develop risk-based screening strategies increase the benefits and reduce the risk of harms of screening for all individuals in a target population.
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