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Updated: Dec 9, 2025

A Cognitive Fusion-guided Prostate Biopsy Using Multiparametric Magnetic Resonance Imaging and Transrectal Ultrasound
Published on: March 21, 2025
Biologic Significance of Magnetic Resonance Imaging Invisibility in Localized Prostate Cancer
Simpa S Salami1,2, Jeremy B Kaplan1, Srinivas Nallandhighal1
1Michigan Medicine, Ann Arbor, MI.
Purpose:
Multiparametric magnetic resonance imaging (mpMRI) is used widely for prostate cancer (PCa) evaluation. Approximately 35% of aggressive tumors, however, are not visible on mpMRI. We sought to identify the molecular alterations associated with mpMRI-invisible tumors and determine whether mpMRI visibility is associated with PCa prognosis.
Methods:
Discovery and validation cohorts included patients who underwent mpMRI before radical prostatectomy and were found to harbor both mpMRI-visible (Prostate Imaging and Reporting Data System 3 to 5) and -invisible (Prostate Imaging and Reporting Data System 1 or 2) foci on surgical pathology. Next-generation sequencing was performed to determine differential gene expression between mpMRI-visible and -invisible foci. A genetic signature for tumor mpMRI visibility was derived in the discovery cohort and assessed in an independent validation cohort. Its association with long-term oncologic outcomes was evaluated in a separate testing cohort.
Results:
The discovery cohort included 10 patients with 26 distinct PCa foci on surgical pathology, of which 12 (46%) were visible and 14 (54%) were invisible on preoperative mpMRI. Next-generation sequencing detected prioritized genetic mutations in 14 (54%) tumor foci (n = 8 mpMRI visible, n = 6 mpMRI invisible). A nine-gene signature (composed largely of cell organization/structure genes) associated with mpMRI visibility was derived (area under the curve = 0.89), and the signature predicted MRI visibility with 75% sensitivity and 100% specificity (area under the curve = 0.88) in the validation cohort. In the testing cohort (n = 375, median follow-up 8 years) there was no significant difference in biochemical recurrence, distant metastasis, or cancer-specific mortality in patients with predicted mpMRI-visible versus -invisible tumors (all P > .05).
Conclusion:
Compared with mpMRI-invisible disease, mpMRI-visible tumors are associated with underexpression of cellular organization genes. mpMRI visibility does not seem to be predictive of long-term cancer outcomes, highlighting the need for biopsy strategies that detect mpMRI-invisible tumors.
Insights
Multiparametric MRI (mpMRI) can miss aggressive prostate cancer (PCa). Molecular analysis revealed mpMRI-visible tumors show fewer cell organization genes but mpMRI visibility does not predict long-term PCa outcomes.
Area of Science:
- Oncology
- Radiology
- Genomics
Background:
- Multiparametric magnetic resonance imaging (mpMRI) is a key tool for prostate cancer (PCa) detection and evaluation.
- A significant proportion of aggressive PCa, approximately 35%, remains undetected by mpMRI.
- Understanding the molecular basis of mpMRI-invisible tumors is crucial for improving diagnostic accuracy.
Purpose of the Study:
- To identify molecular alterations in mpMRI-invisible prostate tumors.
- To determine if mpMRI visibility correlates with prostate cancer prognosis.
- To develop a genetic signature for predicting tumor visibility on mpMRI.
Main Methods:
- Patients with both mpMRI-visible and -invisible prostate cancer foci underwent radical prostatectomy.
- Next-generation sequencing was used to analyze gene expression differences between visible and invisible tumor foci.
- A nine-gene signature for mpMRI visibility was developed and validated, and its association with oncologic outcomes was assessed.
Main Results:
- Next-generation sequencing identified genetic mutations in 54% of tumor foci, with differences between mpMRI-visible and -invisible lesions.
- A nine-gene signature accurately predicted mpMRI visibility in validation cohorts (AUC = 0.88).
- In a large testing cohort, mpMRI visibility did not significantly predict long-term outcomes like recurrence, metastasis, or cancer-specific mortality.
Conclusions:
- mpMRI-visible prostate tumors exhibit underexpression of cellular organization genes compared to invisible tumors.
- mpMRI visibility alone is not a reliable predictor of long-term prostate cancer outcomes.
- Improved biopsy strategies are needed to detect mpMRI-invisible prostate cancers.
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