To test the feasibility of a two-step rule integrating apparent diffusion coefficient (ADC), PSA density (PSAD), and gadolinium wash-in/wash-out rate (GWR) in stratifying prostate lesions for biopsy decision-making, and to compare its performance with PI-RADS v2.1 within a retrospective single-center cohort. This retrospective case series included 110 patients (mean age 70 ± 9 years) who underwent 3.0-T mpMRI and prostate surgery. ADC, PSAD, and GWR were measured from index lesions. Optimal cutoffs (ADC 0.747 × 10⁻³ mm²/s, PSAD 0.344 ng/mL², GWR 9.454%) were derived by 5-fold cross-validation. A two-step rule was constructed: step 1 assigned lesions to four ADC-PSAD quadrants (Q1–Q4); step 2 refined risk using GWR. Performance was compared descriptively with PI-RADS. The four-quadrant framework identified Q2 (low ADC/high PSAD) as the malignant-dominant quadrant and Q3 (high ADC/low PSAD) as predominantly benign. GWR refinement defined a subgroup (Q3 with low GWR) that contained no clinically significant prostate cancer (csPCa) among the 20 patients assigned. In the sensitivity analysis (all-grade PCa vs. benign), the same subgroup contained zero cancers. Compared with PI-RADS, the two-step rule avoided 35.1% (13/37) of unnecessary biopsies in PI-RADS ≥ 4 and detected all occult csPCa in PI-RADS ≤ 3 (12/12). Overall csPCa detection was 97.6% (41/42). Sensitivity analysis yielded consistent findings: unnecessary biopsy avoidance of 46.4% (13/28) and all-grade cancer detection of 98.0% (48/49). This feasibility study suggests that the two-step ADC-PSAD-GWR rule may help guide biopsy decisions by identifying a low-risk subgroup where biopsy may be safely deferred. However, due to the retrospective, single-center design and lack of external validation, the findings should be considered hypothesis-generating. No claim of superiority over PI-RADS or reduction in patient-important outcomes (e.g., mortality) is made. Question: Can a two-step rule combining ADC, PSAD, and gadolinium wash-in/wash-out rate assist in stratifying prostate lesions and guide biopsy decisions within a feasibility setting? Findings: In this retrospective case series of 110 patients, the two-step rule identified a low-risk subgroup (Q3-low GWR) with zero clinically significant cancers, and showed the potential to defer biopsy in 35% of PI-RADS ≥ 4 benign lesions while detecting all occult csPCa in PI-RADS ≤ 3 lesions. Clinical relevance: As an exploratory feasibility tool, this objective rule may offer a practical adjunct to mpMRI interpretation by identifying a defined low-risk subgroup for potential biopsy deferral. Prospective external validation is required before clinical implementation.
Chen et al. (Mon,) studied this question.