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Recommended approach to prostate cancer screening in high-risk men with an inherited predisposition to prostate cancer

For males with a personal history of BRCA1/2 mutation, Lynch syndrome, or pathogenic variants in other prostate cancer-associated risk genes:

Begin screening at 40 years of age (BRCA2); for other high-risk pathogenic variants, shared decision making on risks and benefits of screening beginning at age 40 to 45.*

For most, screening consists of annual PSA and DRE.

Influence of PSA level on frequency of screening:

Males who have a PSA above the median for their age group are at higher risk for prostate cancer and aggressive prostate cancer; the higher above the median, the greater the risk.
If the PSA is below the age-adjusted median and there is no other indication for biopsy, repeat screening in 12 months.
If the PSA is above the age-adjusted median, recheck the PSA in 6 to 12 months; if increased, consider extended pattern biopsy with mpMRI or TRUS guidance.
Any PSA >3 ng/mL or abnormal findings on DRE should prompt a biopsy. A lower cutpoint for biopsy may be considered in males at higher risk, after accounting for age-based normal ranges.

Upper limit of age-adjusted median PSA range:

≤49 years: PSA 1.5 ng/mL
50 to 59 years: PSA 2.0 ng/mL
60 to 69 years: PSA 2.5 ng/mL

BRCA: breast cancer susceptibility gene; PSA: prostate-specific antigen; DRE: digital rectal examination; mpMRI: multiparametric magnetic resonance imaging; TRUS: transrectal ultrasound; HOXB13: homeobox B13; MSH: mutS homolog; TP53: tumor protein p53.

* For most males with high-risk conditions, we recommend participation in a clinical trial of screening, where possible. Germline abnormalities in BRCA2 have the most evidence for elevated risk and poorer prognosis, and all affected males are recommended to start screening at age 40. Other germline prostate cancer risk variants that could be considered for this approach include HOXB13, MSH6, MSH2, and TP53. The presence of a strong family history (even without a known germline pathogenic or likely pathogenic variant) should also prompt shared decision making around modified screening.

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