Clinical performance of magnetic resonance imaging and biomarkers for prostate cancer diagnosis in men at high genetic risk

Abstract

Objectives To evaluate different scenarios for the management of early diagnosis of cancer (PCa) in men at high genetic risk, using recently developed blood and urinary molecular biomarkers in combination with clinical information alongside multiparametric magnetic resonance imaging (mpMRI). Patients and Methods A total of 322 patients with a high genetic risk (familial or personal history of cancers or a predisposing germline variant) were included in this study. The primary outcome was the detection rates of PCa (positive biopsy) or clinically significant PCa (biopsy with International Society of Urological Pathology [ISUP] grade >1). Clinical parameters included age, body mass index, ancestry, and germline mutational status, mpMRI, prostate‐specific antigen density (PSAD), Prostate Health Index and urinary markers (Prostate Cancer Associated 3, SelectMdx™ and T2:ERG score) were assessed. Sensitivity (Se) and specificity (Sp) for each marker at their recommended cut‐off for clinical practice were calculated. Comparison between diagnoses accuracy of each procedure and scenario was computed using mutual information based and direct effect contribution using a supervised Bayesian network approach. Results A mpMRI Prostate Imaging‐Reporting and Data System (PI‐RADS) score ≥3 showed higher Se than mpMRI PI‐RADS score ≥4 for detection of PCa (82% vs 61%) and for the detection of ISUP grade >1 lesions (96% vs 80%). mpMRI PI‐RADS score ≥3 performed better than a PSA level of ≥3 ng/mL (Se 96%, Sp 53% vs Se 91%, Sp 8%) for detection of clinically significant PCa. In case of negative mpMRI results, the supervised Bayesian network approach showed that urinary markers (with the same accuracy for all) and PSAD of ≥0.10 ng/mL/mL were the most useful indicators of decision to biopsy. Conclusions We found that screening men at high genetic risk of PCa must be based on mpMRI without pre‐screening based on a PSA level of >3 ng/mL, to avoid missing too many ISUP grade >1 tumours and to significantly reduce the number of unnecessary biopsies. However, urinary markers or a PSAD of ≥0.10 ng/mL/mL when mpMRI was negative increased the detection of ISUP grade >1 cancers. We suggest that a baseline mpMRI be discussed for men at high genetic risk from the age of 40 years.

Eve's and Adam's rib for prostate cancer screening

“…In this issue of BJUI , Cussenot et al. [1] investigate new strategies to optimize early detection of PCa in men with high genetic risk. A combination of multiparametric MRI with biomarkers (total PSA, PSA density, Prostate Health Index [PHI], PCA3, T2:ERG and SelectMdx) might result in appropriate diagnosis of clinically significant tumours in this subset of patients.…”

Advances in multiparametric magnetic resonance imaging combined with biomarkers for the diagnosis of high-grade prostate cancer

“…Although Asians have a lower incidence of PCa than African Americans and Caucasians, approximately 50.0% of Asian patients with PCa have HGPCa as the pathological outcome ( 9 , 10 ). Notedly, approximately 80.0%–90.0% of clinical trials on mpMRI combined with biomarkers are conducted in Caucasians ( 11 – 13 ), while fewer are conducted in Asian populations. Therefore, we also explored the effectiveness of the combined programs in the Asian population.…”