Research model supports strategies that increase PSA screening interval and age-specific thresholds for biopsy

Using higher thresholds for biopsy referral for older men and screening men with initially low prostate-specific antigen (PSA) levels less frequently seem to reduce harms of screening while preserving lives, a study found.

To evaluate comparative effectiveness of alternative PSA screening strategies, researchers created a model of prostate cancer incidence and mortality, quantifying harms and lives saved for 35 PSA screening strategies. The model was based on national and trial data on PSA growth, screening and biopsy patterns, incidence, treatment distributions, treatment efficacy and mortality.

Results and a summary for patients appeared in the Feb. 5 Annals of Internal Medicine.

Researchers assessed the screening strategies because of current controversy over age to start (40 or 50 years) and stop (69 or 74 years) screening; screening intervals (annual or biennial); and thresholds for biopsy referral (PSA level of 4.0 µg/L; PSA level of 2.5 µg/L; PSA level of 4.0 µg/L or PSA velocity of 0.35 µg/L per year; or PSA level >95th percentile for age [2.5, 3.5, 4.5, and 6.5 µg/L for ages 40 to 49, 50 to 59, 60 to 69, and 70 to 74 years, respectively]).

Without screening, the risk for prostate cancer death is 2.86%. The strategies studied included the following:

• A strategy that screens men age 50 to 74 years annually with a PSA threshold for biopsy referral of 4 µg/L reduces the risk for prostate cancer death to 2.15%, with risk for overdiagnosis of 3.3%.
• A strategy that uses higher PSA thresholds for biopsy referral in older men achieves a similar risk for prostate cancer death (2.23%) but reduces the risk for overdiagnosis to 2.3%.
• A strategy that screens biennially with longer screening intervals for men with low PSA levels achieves similar risks for prostate cancer death (2.27%) and overdiagnosis (2.4%), but reduces total tests by 59% and false-positive results by 50%.

Researchers noted that aggressive screening strategies, particularly those that lower the PSA threshold for biopsy, do reduce prostate cancer mortality relative to the reference strategy while possibly raising the harms of unnecessary biopsies, diagnoses and treatments.

Also, they wrote, there are substantial improvements in the harm-benefit tradeoff of PSA screening with less frequent testing and more conservative criteria for biopsy referral in older men.

Using age-specific PSA thresholds for biopsy referral reduces false-positive results by a relative 25% and overdiagnoses by 30% while preserving 87% of the lives saved under the reference strategy. Alternatively, using longer screening intervals for men with low PSA levels reduces false-positive results by a relative 50% and overdiagnoses by 27% while preserving 83% of the lives saved under the reference strategy, the study found.

These adaptive, personalized strategies represent prototypes for a smarter approach to screening, researchers concluded.

Researchers wrote, “As shown in the PLCO [Prostate, Lung, Colorectal and Ovarian Cancer Screening] trial and supported by our model results across a broad range of alternative strategies, there are diminishing returns to intensive screening. If we recognize that realistic screening strategies must achieve an acceptable balance of benefits and harms as opposed to unconditionally maximizing benefits, we can improve on the effectiveness of existing PSA-based screening for prostate cancer.”