Avoiding Unnecessary Biopsy after Multiparametric Prostate MRI with VERDICT Analysis: The INNOVATE Study

Abstract

GENITOURINARY IMAGINGM ultiparametric MRI (mpMRI) is now established as the first-line investigation for suspected prostate cancer (PCa) (1), but overall specificity for clinically significant cancer (csPCa) (Gleason score 314) is reported at a modest 37% (2,3). This results in one in two men with positive mpMRI findings undergoing biopsy, the results of which were negative for significant cancer, with associated morbidity and a health economic cost (4-6).Adjunct markers have been proposed to complement mpMRI to assist in the decision to biopsy. Several prostate-specific antigen (PSA) density (PSAD) thresholds (ranging from 0.08-0.15 ng/mL 2 ) are commonly used for men with indeterminate mpMRI findings, but no consensus exists on the optimal threshold (7,8). The apparent diffusion coefficient (ADC) is the most often investigated quantitative marker derived from mpMRI results and has shown value in differentiating significant PCa, but it can cause false-positive findings (9-11).Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumor (VERDICT) MRI is a Background: In men suspected of having prostate cancer (PCa), up to 50% of men with positive multiparametric MRI (mpMRI) findings (Prostate Imaging Reporting and Data System [PI-RADS] or Likert score of 3 or higher) have no clinically significant (Gleason score 313, benign) biopsy findings. Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumor (VERDICT) MRI analysis could improve the stratification of positive mpMRI findings.Purpose: To evaluate VERDICT MRI, mpMRI-derived apparent diffusion coefficient (ADC), and prostate-specific antigen density (PSAD) as determinants of clinically significant PCa (csPCa). Materials and Methods:Between April 2016 and December 2019, men suspected of having PCa were prospectively recruited from two centers and underwent VERDICT MRI and mpMRI at one center before undergoing targeted biopsy. Biopsied lesion ADC, lesion-derived fractional intracellular volume (FIC), and PSAD were compared between men with csPCa and those without csPCa, using nonparametric tests subdivided by Likert scores. Area under the receiver operating characteristic curve (AUC) was calculated to test diagnostic performance.Results: Among 303 biopsy-naive men, 165 study participants (mean age, 65 years 6 7 [SD]) underwent targeted biopsy; of these, 73 had csPCa. Median lesion FIC was higher in men with csPCa (FIC, 0.53) than in those without csPCa (FIC, 0.18) for Likert 3 (P = .002) and Likert 4 (0.60 vs 0.28, P , .001) lesions. Median lesion ADC was lower for Likert 4 lesions with csPCa (0.86 3 10 23 mm 2 /sec) compared with lesions without csPCa (1.12 3 10 23 mm 2 /sec, P = .03), but there was no evidence of a difference for Likert 3 lesions (0.97 3 10 23 mm 2 /sec vs 1.20 3 10 23 mm 2 /sec, P = .09). PSAD also showed no difference for Likert 3 (0.17 ng/mL 2 vs 0.12 ng/mL 2 , P = .07) or Likert 4 (0.14 ng/mL 2 vs 0.12 ng/mL 2 , P = .47) lesions. The diagnostic performance of FIC (AUC, 0.96; 95% CI: 0.93, 1.00) was higher (P = ....

Background prostate tissue is quantitatively abnormal on MRI in patients with clinically significant prostate cancer

“…Furthermore, T2-weighted signal in the BP indicated the presence of csPCa with surprising accuracy. Indeed, the csPCa discrimination performance achieved using T2-weighted signal in the BP alone was comparable to the performance reported for methods that examine signal properties within radiographically identified lesions (20)(21)(22).…”

Joint estimation of relaxation and diffusion tissue parameters for prostate cancer with relaxation-VERDICT MRI

“…The improved performance of rVERDICT over VERDICT is probably due to the compensated relaxationinduced biases on the signal fractions and the extra information on the relaxation times. Additional numerical simulations we performed showed that rVERDICT reduces the error of classic VERDICT on (f ic , f ees , f vasc ) by respectively (65, 93, 12) percentage points for the ex vivo and (64,83,20) percentage points for the in vivo case (see Supplementary Material and Supplementary Fig. S4).…”

“…Results from the recent clinical trial INNOVATE 19 reveal that VERDICT f ic can discriminate between Gleason 3 + 3 and 3 + 4 lesions (AUC = 0.93, p = 0.002) 16 and that its diagnostic performance in identifying lesions with clinically significant PCa (AUC = 0.96) is higher than that of ADC from mp-MRI (AUC = 0.85, p < 0.001) and prostate-specific antigen density (AUC = 0.74, p < 0.001) 20 .…”

Comparison of synthesized and acquired highb-value diffusion-weighted MRI for detection of prostate cancer

“…For example, RSIrs outperformed both sDWI and aDWI in the present study. Other promising multi-compartment models have proved to be superior to conventional multiparametric MRI, like a biomarker derived from VERDICT that outperformed ADC in the detection of csPCa 14 . Hybrid multidimensional MRI acquisitions also showed promising results for classifying csPCa with a reported AUC of 0.94 34 .…”

“…More advanced DWI models have been developed to better account for tissue microstructure, including intravoxel incoherent motion imaging 8,9 , diffusion kurtosis imaging 10,11 , Vascular, Extracellular, and Restricted Diffusion for Cytometry in Tumor (VERDICT) [12][13][14] , hybrid multidimensional MRI (HM-MRI) [15][16][17][18] , and Restriction Spectrum imaging (RSI) 12,19 . In RSI, the diffusion signal is modeled as a weighted sum of different compartments representing different tissue types 19,20 .…”