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Updated: Jun 5, 2025

A Cognitive Fusion-guided Prostate Biopsy Using Multiparametric Magnetic Resonance Imaging and Transrectal Ultrasound
Published on: March 21, 2025
Histopathologic Features and Transcriptomic Signatures Do Not Solve the Issue of Magnetic Resonance Imaging-Invisible
Marco Oderda1, Alessandro Marquis1, Luca Bertero2
1Department of Surgical Sciences, Division of Urology, Molinette Hospital, University of Turin, Turin, Italy.
Background:
Multiparametric magnetic resonance imaging (mpMRI) is pivotal in prostate cancer (PCa) diagnosis, but some clinically significant (cs) PCa remain undetected. This study aims to understand the pathological and molecular basis for csPCa visibility at mpMRI.
Methods:
We performed a retrospective matched-pair cohort study, including patients undergoing radical prostatectomy (RP) for csPCa (i.e., ISUP grade group ≥ 2) from 2015 to 2020, in our tertiary-referral center. We screened for inclusion in the "mpMRI-invisible" cohort all consecutive men (N = 45) having a negative preoperative mpMRI. The "mpMRI-visible" cohort was matched based on age, PSA, prostate volume, ISUP grade group. Included patients underwent radiological and pathological open-label revisions and characterization of the tumor mRNA expression profile (analyzing 780 gene transcripts, signaling pathways, and cell-type profiling). We compared the clinical-pathological variables and the gene expression profile between matched pairs. The analysis was stratified according to histological characteristics and lesion diameter.
Results:
We included 34 patients (17 per cohort); mean age at RP and PSA were 70.5 years (standard deviation [SD] = 7.7), 7.1 ng/mL (SD = 3.3), respectively; 65% of men were ISUP 2. Overall, no significant differences in histopathological features, tumor diameter and location, mRNA profile, pathways, and cell-type scores emerged between cohorts. In the stratified analysis, an upregulation of cell adhesion and motility, of extracellular matrix remodeling and of metastatic process pathways was present in specific subgroups of mpMRI-invisible cancers.
Conclusions:
No PCa pathological or gene-expression hallmarks explaining mp-MRI invisibility were identified. Aggressive features can be present both in mpMRI-invisible and -visible tumors.
Insights
Multiparametric MRI (mpMRI) helps diagnose prostate cancer (PCa), but some aggressive PCa are missed. This study found no specific pathological or gene expression differences explaining why some aggressive PCa are invisible on mpMRI scans.
Area of Science:
- Oncology
- Radiology
- Genomics
Background:
- Multiparametric magnetic resonance imaging (mpMRI) is crucial for prostate cancer (PCa) detection.
- However, some clinically significant (cs) PCa are not visible on mpMRI, posing a diagnostic challenge.
Purpose of the Study:
- To investigate the pathological and molecular underpinnings of csPCa invisibility on mpMRI.
- To identify potential biomarkers for detecting otherwise undetectable aggressive PCa.
Main Methods:
- Retrospective matched-pair cohort study of patients with csPCa (ISUP grade group ≥2) undergoing radical prostatectomy.
- Comparison of mpMRI-invisible and mpMRI-visible cohorts based on clinical-pathological variables and comprehensive mRNA expression profiling (780 gene transcripts).
- Stratified analysis based on histological characteristics and lesion diameter.
Main Results:
- No significant differences in histopathological features, tumor characteristics, or overall mRNA profiles were found between mpMRI-invisible and -visible csPCa cohorts.
- Stratified analysis revealed upregulation of cell adhesion, motility, extracellular matrix remodeling, and metastatic process pathways in specific subgroups of mpMRI-invisible cancers.
- No distinct pathological or gene-expression hallmarks definitively explained mpMRI invisibility.
Conclusions:
- The study did not identify specific pathological or gene-expression features that universally explain why some aggressive prostate cancers are invisible on mpMRI.
- Aggressive features can be present in both mpMRI-invisible and mpMRI-visible prostate tumors, highlighting the limitations of current imaging in detecting all significant disease.

