Germline variant carriers with prostate cancer: more PI-RADS 5 lesions and more extraprostatic extension

Design

Single-centre retrospective case-control study

Population

62 men with prostate cancer and a germline pathogenic variant, compared with 246 consecutive controls

Primary outcome

Clinical, pathologic and MRI characteristics

Effect

PI-RADS 5 OR 2.7 (95% CI 1.5 to 4.9); grade 3 extraprostatic extension OR 3.0 (1.5 to 5.8); upgrading 37% vs 20%

This single-centre retrospective case-control study compared 62 men with prostate cancer, a germline pathogenic variant and an MRI at diagnosis with 246 consecutive controls. The variants were mostly in CHEK2 (21.0%), BRCA2 (19.4%), ATM (17.7%) and Lynch syndrome genes (17.7%).

The proportion with a positive MRI was almost the same (98% against 96%). Carriers were more likely to have a PI-RADS 5 score (OR 2.7, 95% CI 1.5 to 4.9) and grade 3 extraprostatic extension (OR 3.0, 1.5 to 5.8). At prostatectomy, 37% of carriers were reclassified to a higher grade group against 20% of controls (P = 0.046). Age at diagnosis was similar (65 vs 67 years, P = 0.05).

The design is retrospective with selected carriers, and the upgrading P value is borderline. It supports reading MRI in known carriers with a lower threshold for caution about extent, but not a change in reporting criteria.

• Note a known germline variant in the clinical history on the MRI request.
• Look carefully for extraprostatic extension in carriers, where grade 3 extension was more frequent.
• Mention in the report when a PI-RADS 5 lesion is seen in a known carrier.
• Expect a normal MRI in carriers to be uncommon: 98% were positive here, as in controls.
• Remember the study could not show effects on outcomes.

Why it matters

Hereditary disease may look more aggressive on imaging, which matters when MRI is used to plan surveillance or surgery.

Don't overread it

A single-centre retrospective comparison does not show that carriers need different imaging pathways or that outcomes differ.

The statistics, in plain English

An odds ratio of 2.7 with an interval of 1.5 to 4.9 means carriers had roughly two to five times the odds of a PI-RADS 5 score, but the study was retrospective with 62 carriers. A P value of 0.046 for upgrading is only just below 0.05, so that finding is fragile.

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