Abstract
Objectives
To assess whether prostate‐specific antigen density (PSAD) stratifies long‐term risk of clinically significant prostate cancer (csPCa) after a negative magnetic resonance imaging (MRI; Prostate Imaging‐Reporting and Data System score ≤2) and to evaluate the potential of PSAD to guide follow‐up in a screening setting.
Patients and Methods
This pre‐specified sub‐analysis of the population‐based, randomised Göteborg‐2 screening trial included 1685 men who underwent PSA testing between October 2015 and June 2021 and had a subsequent negative initial MRI. Follow‐up continued until 30 September 2024. The primary endpoint was cumulative incidence of csPCa (Gleason score ≥3 + 4). Men were categorised by baseline PSAD (2
). Cumulative incidence was estimated using Kaplan–Meier methods and compared using the log‐rank test. The clinical implications of PSAD‐based follow‐up strategies were explored.
Results
Over a median follow‐up of 5.5 years, 160 PCas were diagnosed, of which 80 were csPCa, including 22 cases of Gleason score ≥4 + 3. At 7 years, cumulative csPCa incidence was 7.1% overall and 5.5%, 13.8%, and 11.9% in the PSAD 2
groups, respectively (
P
2
vs both higher groups). Overall, 87% of repeat MRIs remained negative. Although men with baseline PSAD 2
had the lowest overall risk, 42 csPCas occurred in this group, including 12 Gleason score ≥4 + 3, emphasising the importance of continued regular PSA‐based follow‐up. A PSAD‐guided strategy with biennial PSA testing and repeat MRI triggered by PSAD ≥0.10 ng/mL
2
could reduce MRI use by 60% and biopsies by 46%, halve detection of clinically insignificant PCa, and delay csPCa diagnosis in 17% of cases including 10 men with Gleason score 3 + 4 and one with Gleason score ≥4 + 3.
Conclusions
The PSAD stratifies long‐term risk of csPCa after a negative MRI and supports risk‐adapted follow‐up in PCa screening.