Men with a negative mpMRI can safely avoid prostate biopsy; however up to 50% of men with positive mpMRI (PIRADS/Likert ≥3) have no significant (≤3+3 or benign) findings at biopsy. VERDICT MRI, an advanced diffusion imaging technique that can non-invasively infer microstructure, may assist stratification of positive mpMRI. We report on the INNOVATE study which evaluated VERDICT derived lesion Fractional Intracellular volume (FIC); mpMRI derived lesion-ADC, and PSA density (PSAD) as determinants of clinically significant PCa (csPCa).
303 biopsy-naïve men with suspicion of PCa were recruited. All men underwent mpMRI and VERDICT MRI; 260/303 men had a positive mpMRI, with 165/260 undergoing targeted biopsy based on clinical decision. Biopsied lesion-ADC, lesion FIC and PSAD were compared between men with csPCa and non-significant histology and across Gleason groups ((a) no cancer, (b) 3+3, (c) 3+4 and (d) ≥4+3). Nonparametric tests were used to analyse differences, Kolmogorov-Smirnov for csPCa and Kruskal-Wallis for Gleason groups. Receiver Operating Characteristic curves (ROC) were derived.
10/76 Likert 3, 25/49 Likert 4 and 38/40 Likert 5 men had csPCa. For Likert 3 and Likert 4 scored men, lesion-FIC was significantly different (higher) in men with csPCa compared to non-significant histology (p<0.01) but not for Lesion-ADC (p≥0.06) and PSAD (p>0.15) for each score. Lesion-FIC was significantly higher and Lesion-ADC lower between 3+3 vs. 3+4 disease (p<0.01, p=0.045) but not PSAD (p=0.99). Lesion-FIC was higher for ≥4+3 vs. 3+3 disease (p<0.01) but not lesion-ADC (p=0.11). The area under the ROC curve for all men (Likert 3-5/5) for discriminating csPCa was: lesion-FIC 0.960 (0.925-0.995, 95% CI), PSAD 0.739 (0.663-0.816) and lesion-ADC 0.697 (0.617-0.778). If men with equivocal 3/5 lesions with lesion-FIC of ≤0.41 (Youden’s index) were not biopsied, 62/125 men with non-significant histology would have avoided biopsy and 1/125 men with csPCa would be missed.
Lesion-FIC provided excellent classification of csPCa and demonstrated more marked differences between Gleason grades compared to lesion-ADC and PSAD. VERDICT-MRI derived lesion-FIC offers men with a positive mpMRI (likely to have a non-significant biopsy) the opportunity to safely avoid unnecessary biopsy. Application of lesion-FIC thresholds within a prospective clinical trial remains the next step.