Defining a Safe Biopsy Deferral Strategy in Patients With Low-Risk or Equivocal MRI Findings Using Prostate-Specific Antigen-Based Metrics.

Background

Management of men with equivocal MRI findings remains uncertain, while low-risk MRI may still harbor clinically significant prostate cancer (csPCa). We examined whether prostate-specific antigen (PSA)-based measures could identify a low-risk subgroup suitable for biopsy deferral in patients with Prostate Imaging-Reporting and Data System (PI-RADS) 1-3 lesions, and which clinical & imaging factors further refined risk stratification.

Methods

This prospective single-center study included 473 consecutive patients with index PI-RADS 1-3 findings on prostate MRI who underwent systematic and/or MRI/US fusion-guided biopsy between May 2019 and December 2025. Patient-level csPCa (grade group ≥ 2) detection rates (CDR) were calculated across PI-RADS groups. csPCa detection, biopsy avoidance, and missed csPCa were assessed using biopsy-deferral thresholds based on PSA (< 3 ng/mL), age-adjusted PSA, and PSA density (PSAD) (< 0.10 and < 0.15 ng/mL2). Logistic regression analyses identified independent predictors of PCa and csPCa.

Results

The cohort comprised 172 patients with PI-RADS 1, 126 with PI-RADS 2, and 175 with PI-RADS 3 index lesions. In PI-RADS 1-2, csPCa was detected in 2.2% (1/46) of patients with PSA < 3, whereas for PSAD < 0.10, the CDR was 5.3% (10/190). Avoided biopsy rates were 15.4% (46/298) and 63.8% (190/298), and missed csPCa rates were 3.3% (1/30) for PSA < 3% and 33.3% (10/30) for PSAD < 0.10, respectively. In PI-RADS 1-3, csPCa was detected in 5.6% (4/76) of patients with PSA < 3 ng/mL, while for PSAD < 0.10, CDR was 8.8% (26/295). Biopsy avoidance was 16.1% (76/473) for PSA < 3 ng/mL and 62.4% (295/473) for PSAD < 0.10, with missed csPCa rates of 5.6% (4/71) and 36.6% (26/71), respectively. On multivariable analysis, higher log2(PSAD) was independently associated with csPCa in both PI-RADS 1-2 (OR, 2.171; 95% CI, 1.255-3.757; p = 0.006) and PI-RADS 1-3 (OR, 2.727; 95% CI, 1.844-4.033; p < 0.001) cohorts. In patients with index PI-RADS 1-3 findings, prior negative biopsy was independently associated with lower odds of csPCa (OR = 0.425; 95% CI, 0.182-0.991; p = 0.048). Non-diagnostic MRI quality was independently associated with PCa detection in the PI-RADS 1-2 cohort (OR, 2.367; 95% CI, 1.276-4.388; p = 0.006).

Conclusions

In men with index PI-RADS 1-3 lesions, PSA < 3 ng/mL identified a very low-risk subgroup with low csPCa detection, and few missed csPCa. Conventional PSAD cutoffs performed worse for biopsy deferral, with a higher rate of missed csPCa. Biopsy decisions for PI-RADS 1-3 lesions are best guided by a composite assessment that incorporates PSA, PSAD, PI-RADS category, prior biopsy status, MRI quality, and lesion burden.