Christophe K. Mannaerts

Prediction of Prostate Cancer: External Validation of the ERSPC Risk Calculator in a Contemporary Dutch Clinical Cohort

BACKGROUND The validity of prediction models needs external validation to assess their value beyond the original development setting. OBJECTIVE To report the diagnostic accuracy of the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (RC)3 and RC4 in a contemporary Dutch clinical cohort. DESIGN, SETTING, AND PARTICIPANTS We retrospectively identified all men who underwent prostate biopsy (PBx) in the Jeroen Bosch Hospital, The Netherlands, between 2007 and 2016. Patients were included if they met ERSPC RC requirements of age (50-80 yr), prostate-specific antigen (PSA) (0.4-50 ng/ml), and prostate volume (10-150ml). The probability of a positive biopsy for prostate cancer (PCa) and significant PCa (Gleason score ≥7 and/or higher than T2b) were calculated and compared with PBx pathology results. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Evaluation was performed by calibration, discrimination, and clinical usefulness using calibration plots, area under the receiver operating characteristic curves (AUCs), and decision curve analyses (DCAs), respectively. RESULTS AND LIMITATIONS A total of 2270 PBx sessions were eligible for final analysis. Discriminative ability of RC3 (AUC) was 0.78 and 0.90 for any PCa and significant PCa, respectively. For RC4 the calculated AUCs were 0.62 (any PCa) and 0.76 (significant PCa). The calibration plots of RC3 showed good results for both any PCa risk and significant PCa risk. In the repeat PBx group, RC4 tended to underestimate outcomes for PCa and showed moderate calibration for significant PCa. DCA showed an overall net benefit compared with PSA and digital rectal examination (DRE) alone. Limitations of this study are its retrospective single-institution design, retrospectively assessed DRE outcomes, no time restrictions between the first and repeat biopsy sessions, and no anterior sampling in the repeat PBx protocol. CONCLUSIONS The ERSPC RCs performed well in a contemporary clinical setting. Most pronounced in the biopsy-naive group, both RCs should be favoured over a PSA plus DRE-based stratification in the decision whether or not to perform PBx. PATIENT SUMMARY We looked at the ability of the existing European Randomized Study of Screening for Prostate Cancer risk calculator (RC), using different clinical data to predict the presence of prostate cancer in Dutch men. The RC performed well and should be favoured in the decision of whether or not to perform prostate biopsies over the conventional diagnostic pathway.

Contrast-enhanced ultrasound tractography for 3D vascular imaging of the prostate

Diffusion tensor tractography (DTT) enables visualization of fiber trajectories in soft tissue using magnetic resonance imaging. DTT exploits the anisotropic nature of water diffusion in fibrous structures to identify diffusion pathways by generating streamlines based on the principal diffusion vector. Anomalies in these pathways can be linked to neural deficits. In a different field, contrast-enhanced ultrasound is used to assess anomalies in blood flow with the aim of locating cancer-induced angiogenesis. Like water diffusion, blood flow and transport of contrast agents also shows a principal direction; however, this is now determined by the local vasculature. Here we show how the tractographic techniques developed for magnetic resonance imaging DTT can be translated to contrast-enhanced ultrasound, by first estimating contrast flow velocity fields from contrast-enhanced ultrasound acquisitions, and then applying tractography. We performed 4D in-vivo contrast-enhanced ultrasound of three human prostates, proving the feasibility of the proposed approach with clinically acquired datasets. By comparing the results to histopathology after prostate resection, we observed qualitative agreement between the contrast flow tracts and typical markers of cancer angiogenic microvasculature: higher densities and tortuous geometries in tumor areas. The method can be used in-vivo using a standard contrast-enhanced ultrasound protocol, opening up new possibilities in the area of vascular characterization for cancer diagnostics.

Prediction of High-grade Prostate Cancer Following Multiparametric Magnetic Resonance Imaging: Improving the Rotterdam European Randomized Study of Screening for Prostate Cancer Risk Calculators

BACKGROUND The Rotterdam European Randomized Study of Screening for Prostate Cancer risk calculators (ERSPC-RCs) help to avoid unnecessary transrectal ultrasound-guided systematic biopsies (TRUS-Bx). Multivariable risk stratification could also avoid unnecessary biopsies following multiparametric magnetic resonance imaging (mpMRI). OBJECTIVE To construct MRI-ERSPC-RCs for the prediction of any- and high-grade (Gleason score ≥3 + 4) prostate cancer (PCa) in 12-core TRUS-Bx±MRI-targeted biopsy (MRI-TBx) by adding Prostate Imaging Reporting and Data System (PI-RADS) and age as parameters to the ERSPC-RC3 (biopsy-naïve men) and ERSPC-RC4 (previously biopsied men). DESIGN, SETTING, AND PARTICIPANTS A total of 961 men received mpMRI and 12-core TRUS-Bx±MRI-TBx (in case of PI-RADS ≥3) in five institutions. Data of 504 biopsy-naïve and 457 previously biopsied men were used to adjust the ERSPC-RC3 and ERSPC-RC4. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Logistic regression models were constructed. The areas under the curve (AUCs) of the original ERSPC-RCs and MRI-ERSPC-RCs (including PI-RADS and age) for any- and high-grade PCa were compared. Decision curve analysis was performed to assess the clinical utility of the MRI-ERSPC-RCs. RESULTS AND LIMITATIONS MRI-ERSPC-RC3 had a significantly higher AUC for high-grade PCa compared with the ERSPC-RC3: 0.84 (95% confidence interval [CI] 0.81-0.88) versus 0.76 (95% CI 0.71-0.80, p<0.01). Similarly, MRI-ERSPC-RC4 had a higher AUC for high-grade PCa compared with the ERSPC-RC4: 0.85 (95% CI 0.81-0.89) versus 0.74 (95% CI 0.69-0.79, p<0.01). Unlike for the MRI-ERSPC-RC3, decision curve analysis showed clear net benefit of the MRI-ERSPC-RC4 at a high-grade PCa risk threshold of ≥5%. Using a ≥10% high-grade PCa risk threshold to biopsy for the MRI-ERSPC-RC4, 36% biopsies are saved, missing low- and high-grade PCa, respectively, in 15% and 4% of men who are not biopsied. CONCLUSIONS We adjusted the ERSPC-RCs for the prediction of any- and high-grade PCa in 12-core TRUS-Bx±MRI-TBx. Although the ability of the MRI-ERSPC-RC3 for biopsy-naïve men to avoid biopsies remains questionable, application of the MRI-ERSPC-RC4 in previously biopsied men in our cohort would have avoided 36% of biopsies, missing high-grade PCa in 4% of men who would not have received a biopsy. PATIENT SUMMARY We have constructed magnetic resonance imaging-based Rotterdam European Randomized study of Screening for Prostate Cancer (MRI-ERSPC) risk calculators for prostate cancer prediction in transrectal ultrasound-guided biopsy and MRI-targeted biopsy by incorporating age and Prostate Imaging Reporting and Data System score into the original ERSPC risk calculators. The MRI-ERSPC risk calculator for previously biopsied men could be used to avoid one-third of biopsies following MRI.