MAPS: A Quantitative Radiomics Approach for Prostate Cancer Detection.

126 Background: Up to 20% of patients with negative multiparametric magnetic resonance imaging (MRI) harbor Gleason score ≥7 prostate cancer (PCa). We sought to elucidate the molecular basis of and determine the prognostic significance of PCa visibility on MRI. Methods: We identified a retrospective cohort of patients who underwent MRI prior to prostatectomy with both MRI visible (PIRADS 3 – 5) and invisible PCa. MRI for each patient was re-reviewed and co-registered with whole-mount histopathology. DNA and RNA were co-isolated from all tumor foci pre-identified on FFPE specimens. High depth, targeted DNA and RNA next generation sequencing was performed to characterize the molecular profile of each tumor focus using the Oncomine Comprehensive Panel (DNA) and a custom targeted RNAseq panel assessing PCa relevant alterations. A multigene RNAseq model was developed and validated in two independent cohorts to predict MRI visible PCa and to determine the prognostic significance of MRI visibility. Results: A total of 26 primary tumor foci from 10 patients were analyzed. Of the 14 (54%) invisible lesions on MRI, 5 (36%) were Gleason 3+4 = 7 and the remainder were Gleason 6. We detected high-confidence prioritized PCa relevant mutations in 54% (14/26) of tumor foci, 43% (6/14) of which were in MRI invisible lesions. Notable point mutations were in APC, AR, ARID1B, ATM, ATRX, BRCA2, FAT1, MAP3K1, NF1, SPEN, SPOP, and TP53. A 9-gene RNA signature, the majority of which were under-expressed cellular organization and structure genes, was developed to predict MRI visibility with an AUC of 0.89. Validation of this signature in an independent data set (n = 16) yielded an AUC of 0.88 with a specificity of 100% for predicting MRI visible tumors. Using this signature in a cohort of 375 patients with clinical follow up, we found that predicted MRI visibility status was not an independent predictor of biochemical recurrence, metastasis-free survival, or PCa specific mortality (all p > 0.05). Conclusions: We observed under-expression of cellular organization and structural genes in MRI visible tumors compared to MRI invisible cancer foci. Using our validated signature to predict MRI visibility status, we found that MRI visibility is not a significant predictor of oncological outcomes.

Prostate MRI: Toward Imaging Tumor Histology.

A Single Center Evaluation of the Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging against Transperineal Prostate Mapping Biopsy: An Analysis of Men with Benign Histology and Insignificant Cancer following Transrectal Ultrasound Biopsy

To compare diagnostic accuracy of T2-weighted magnetic resonance (MR) imaging with that of multiparametric (MP) MR imaging combining T2-weighted imaging with diffusion-weighted (DW) MR imaging, dynamic contrast material-enhanced (DCE) MR imaging, or both in the detection of locally recurrent prostate cancer (PCa) after radiation therapy (RT). This retrospective HIPAA-compliant study was approved by the institutional review board; informed consent was waived. Fifty-three men (median age, 70 years) suspected of having post-RT recurrence of PCa underwent MP MR imaging, including DW and DCE sequences, within 6 months after biopsy. Two readers independently evaluated the likelihood of PCa with a five-point scale for T2-weighted imaging alone, T2-weighted imaging with DW imaging, T2-weighted imaging with DCE imaging, and T2-weighted imaging with DW and DCE imaging, with at least a 4-week interval between evaluations. Areas under the receiver operating characteristic curve (AUC) were calculated. Interreader agreement was assessed, and quantitative parameters (apparent diffusion coefficient [ADC], volume transfer constant [K(trans)], and rate constant [k(ep)]) were assessed at sextant- and patient-based levels with generalized estimating equations and the Wilcoxon rank sum test, respectively. At biopsy, recurrence was present in 35 (66%) of 53 patients. In detection of recurrent PCa, T2-weighted imaging with DW imaging yielded higher AUCs (reader 1, 0.79-0.86; reader 2, 0.75-0.81) than T2-weighted imaging alone (reader 1, 0.63-0.67; reader 2, 0.46-0.49 [P ≤ .014 for all]). DCE sequences did not contribute significant incremental value to T2-weighted imaging with DW imaging (reader 1, P > .99; reader 2, P = .35). Interreader agreement was higher for combinations of MP MR imaging than for T2-weighted imaging alone (κ = 0.34-0.63 vs κ = 0.17-0.20). Medians of quantitative parameters differed significantly (P < .0001 to P = .0233) between benign tissue and PCa (ADC, 1.64 × 10(-3) mm(2)/sec vs 1.13 × 10(-3) mm(2)/sec; K(trans), 0.16 min(-1) vs 0.33 min(-1); k(ep), 0.36 min(-1) vs 0.62 min(-1)). MP MR imaging has greater accuracy in the detection of recurrent PCa after RT than T2-weighted imaging alone, with no additional benefit if DCE is added to T2-weighted imaging and DW imaging.

Selecting Patients with Favorable Risk, Grade Group 2 Prostate Cancer for Active Surveillance-Does Magnetic Resonance Imaging Have a Role?

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Up to 35% of men on active surveillance (AS) for clinically localized prostate cancer will experience biopsy reclassification during follow-up. Currently, annual prostate biopsy is recommended in AS programmes. Multiparametric MRI has shown promise in identifying men at risk for immediate reclassification at the time of entry into AS; however, the MRI characteristics of men already enrolled in AS who may be at low risk for disease reclassification have not been fully described. In the present study, we describe the MRI findings of a cohort of men enrolled within AS, with extended follow-up. Among these men, multiparametric MRI demonstrated excellent specificity (0.974) and negative predictive value (0.897) for the detection of pathological index lesions (determined on serial biopsies). These results suggest that men enrolled in AS with a non-suspicious MRI are unlikely to harbour an index cancerous lesion. To assess the performance of multiparametric magnetic resonance imaging (MRI) in identifying pathological-index (path-index) lesions, defined as cancer present in the same prostate sextant in two separate surveillance biopsies, in men followed within an active surveillance (AS) programme for low-risk prostate cancer (CaP) with extended follow-up. A total of 50 men, representing >215 person-years of follow-up in an AS programme, who were referred for prostate MRI were randomly chosen to have their images reviewed by a radiologist with expertise in prostate MRI, who was blinded to biopsy results. Index lesions on MRI were defined as a single suspicious lesion ≥10 mm or >2 lesions in a given prostate sextant. Lesions on MRI were considered suspicious if ≥2 abnormal parameters co-registered anatomically. Path-index lesions were defined as cancer present in a given prostate sextant on two separate biopsy sessions. Sensitivity and specificity were calculated to test the performance of MRI for identifying path-index lesions. Clinical and pathological features were compared between men with and without a MRI-index lesion. A total of 31 path-index and 13 MRI-index lesions were detected in 22 and 10 patients, respectively. Multiparametric MRI demonstrated excellent specificity and negative predictive value (0.974 and 0.897, respectively) for the detection of path-index lesions. Sensitivity (0.19) and positive predictive value (0.46) were considerably lower. Patients with an index lesion on MRI were younger and less likely to have met the 'Epstein' criteria for very low-risk CaP. Compared with men without an MRI lesion, a significant increase in biopsy reclassification was noted for men with a MRI lesion (40 vs 12.5%, P = 0.04). A non-suspicious MRI was highly correlated with a lack of path-index lesions in an AS population. Multiparametric MRI may be useful in both the selection and monitoring of patients undergoing AS.

6554 Background: Evidence of racial disparity in the use of prostate MRI presents new obstacles to closing recognized gaps in treatment and outcome for black men with prostate cancer. To anticipate strategies for improving equity in cancer care, we examined mediators of racial disparity in the use of prostate MRI surrounding the diagnosis of prostate cancer. Methods: We conducted a multiple mediation analysis among patients with localized prostate cancer in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between January 2008 and December 2015. We assessed claims for prostate MRI within the six-month period preceding or following diagnosis. We first identified candidate clinical and sociodemographic meditators based on their association with both race and prostate MRI, including the Index of Concentrations at the Extremes (ICE), a measure of racialized residential segregation calculated at the zip code or census tract level. We used non-linear Multiple Additive Regression Trees (MART) models to estimate the direct and indirect relative effects of mediators. Results: We identified 71,597 eligible patients. Black patients with prostate cancer were less likely (5.3%) to receive a prostate MRI when compared with white patients (7.0%; unadjusted odds ratio 0.75, 95% CI 0.67-0.84, p &lt; 0.001). 33.1% (95% CI 20.6-44.9) of the racial disparity in prostate MRI use was attributable to variation in SEER region, 22.5% (95% CI 13.0-30.2) to residence in a high poverty area, 17.2% to residential segregation (ICE group 17.2%, 95% CI 8.1-27.9%), and 13.2% to dual eligibility for Medicaid (95% CI 8.6-20.2%). Clinical and pathologic factors were not significant mediators. After accounting for the mediators, the direct effects of race accounted for 6.2% of the observed disparity in prostate MRI use. Conclusions: Sociodemographic factors including geographic region, and area-level measures of income and residential segregation explain the majority of the observed racial disparity in the use of prostate MRI among older Americans with prostate cancer. The findings underscore that measurable structural factors can be readily identified that underlie racial disparity in access to emerging diagnostic tools for patients with cancer.

Negative predictive value of multiparametric MRI for prostate cancer detection: Outcome of 5-year follow-up in men with negative findings on initial MRI studies

MP79-10 THE ROLE OF PROSTATE CANCER ANTIGEN 3 TEST AND MULTI-PARAMETRIC PROSTATIC MAGNETIC RESONANCE IMAGING FOR DIAGNOSIS OF PROSTATE CANCER IN PATIENT WITH MULTIPLE PRIOR NEGATIVE BIOPSIES

Standard clinicopathological variables are inadequate for optimal management of prostate cancer patients. While genomic classifiers have improved patient risk classification, the multifocality and heterogeneity of prostate cancer can confound pre-treatment assessment. The objective was to investigate the association of multiparametric (mp)MRI quantitative features with prostate cancer risk gene expression profiles in mpMRI-guided biopsies tissues.Global gene expression profiles were generated from 17 mpMRI-directed diagnostic prostate biopsies using an Affimetrix platform. Spatially distinct imaging areas (‘habitats’) were identified on MRI/3D-Ultrasound fusion. Radiomic features were extracted from biopsy regions and normal appearing tissues. We correlated 49 radiomic features with three clinically available gene signatures associated with adverse outcome. The signatures contain genes that are over-expressed in aggressive prostate cancers and genes that are under-expressed in aggressive prostate cancers. There were significant correlations between these genes and quantitative imaging features, indicating the presence of prostate cancer prognostic signal in the radiomic features. Strong associations were also found between the radiomic features and significantly expressed genes. Gene ontology analysis identified specific radiomic features associated with immune/inflammatory response, metabolism, cell and biological adhesion. To our knowledge, this is the first study to correlate radiogenomic parameters with prostate cancer in men with MRI-guided biopsy.

PurposeTo compare the diagnostic performance between biparametric MRI (bpMRI) and multiparametric MRI (mpMRI) using split dynamic MRI for detecting clinically significant prostate cancer (csPCa) with Prostate Imaging and Reporting Data System (PI-RADS) v2.1, using prostatectomy as the reference standard of pathologic analysis.Materials and MethodsWe retrospectively analyzed 77 PCa cases in 60 patients who underwent radical prostatectomy for biopsy-proven prostate cancer. The MR Images of the prostate were interpreted in consensus by two experienced radiologists (aged 3 and 35 years). We retrospectively reviewed the MRI images according to PI-RADS v2.1 and recorded the scores from T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) imaging, and peak relaxation rate (R2*) for each lesion at three different time points: 1) bpMRI (T2WI, DWI, and ADC), 2) mpMRI1 (T2WI, DWI, ADC, and DCE), and 3) mpMRI2 (T2WI, DWI, ADC, DCE, and peak R2*). The diagnostic performances of bpMRI, mpMRI1, and mpMRI2 in detecting csPCa using PI-RADS V2.1 were evaluated. Additionally, we evaluated the diagnostic performance of DCE-MRI and peak R2* for csPCa detection.ResultsThe area under the curve, sensitivity, specificity, and accuracy for diagnosing csPCa with PI-RADS v2.1 in all lesions and peripheral zone (PZ) lesions were not significantly different between the bpMRI, mpMRI1, and mpMRI2 protocols (p > 0.05). DCE-MRI was better than the peak R2* for diagnosing csPCa in PZ lesions (p < 0.001).ConclusionmpMRI using split dynamic MRI has diagnostic performance similar to that of bpMRI for detecting csPCa using PI-RADS v2.1.

Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging and Fusion Guided Targeted Biopsy Evaluated by Transperineal Template Saturation Prostate Biopsy for the Detection and Characterization of Prostate Cancer

Accuracy of Prostate Multiparametric MRI in Identification of Intraprostatic Tumor Deposits Validated on Transperineal Biopsies

Multiparametric MRI (mpMRI) has shown a substantial impact on prostate cancer (PCa) diagnosis. However, the understanding of the spatial correlation between mpMRI performance and PCa location is still limited. To investigate the association between mpMRI performance and tumor spatial location within the prostate using a prostate sector map, described by Prostate Imaging Reporting and Data System (PI-RADS) v2.1. Retrospective. One thousand one hundred forty-three men who underwent mpMRI before radical prostatectomy between 2010 and 2022. 3.0 T. T2-weighted turbo spin-echo, a single-shot spin-echo EPI sequence for diffusion-weighted imaging, and a gradient echo sequence for dynamic contrast-enhanced MRI sequences. Integrated relative cancer prevalence (rCP), detection rate (DR), and positive predictive value (PPV) maps corresponding to the prostate sector map for PCa lesions were created. The relationship between tumor location and its detection/missing by radiologists on mpMRI compared to WMHP as a reference standard was investigated. A weighted chi-square test was performed to examine the statistical differences for rCP, DR, and PPV of the aggregated sectors within the zone, anterior/posterior, left/right prostate, and different levels of the prostate with a statistically significant level of 0.05. A total of 1665 PCa lesions were identified in 1143 patients, and from those 1060 lesions were clinically significant (cs)PCa tumors (any Gleason score [GS] ≥7). Our sector-based analysis utilizing weighted chi-square tests suggested that the left posterior part of PZ had a high likelihood of missing csPCa lesions at a DR of 67.0%. Aggregated sector analysis indicated that the anterior or apex locations in PZ had the significantly lowest csPCa detection at 67.3% and 71.5%, respectively. Spatial characteristics of the per-lesion-based mpMRI performance for diagnosis of PCa were studied. Our results demonstrated that there is a spatial correlation between mpMRI performance and locations of PCa on the prostate. 4 TECHNICAL EFFICACY: Stage 2.

Background: There is a critical need to develop novel therapeutic strategies and diagnostic tools to precisely deliver treatments to improve survival for men with prostate cancer (PCa). To support this development, improved strategies are needed to better understand heterogenous tumor microenvironments and tumor biology that associate with variable treatment responses. We hypothesized that the tumor immune microenvironment (TIME) plays a critical role in treatment resistance. In this study we aimed to evaluate TIME signatures of treatment response and resistance utilizing a novel, integrated technological tool to identify response patterns and enable precision sampling for comparative cellular and molecular analysis. Methods: 30 patients with newly-diagnosed, locally advanced, high-risk, primary PCa underwent 18F-DCFPyL PSMA PET with multiparametric MRI (mpMRI) imaging on a dedicated PET/MRI scanner followed by 3 cycles of chemohormonal therapy (NCT03358563). Repeat PSMA PET/MRI was performed prior to prostatectomy and scans were interpreted by an experienced radiologist and nuclear medicine physician as complete response (CR), partial response (PR), no response (NR) or normal tissue. MRI scans were used to print a 3D mold of the prostate to allow PET and MRI directed mapping and microdissection of regions of interest from the resected prostate with slice-by-slice and lesion-to-lesion correlation. Cellular infiltrates were analyzed by flow cytometry in 3 to 5 tissue specimens per patient. Results: The frequency of CD8+ T cells in the total CD45+ infiltrate was highest in normal and CR areas and was significantly reduced in PR vs CR (p&amp;lt;0.01). CXCR3+CD8+ and CD103+CD8+ Tcell frequencies were also reduced in PR vs CR foci (p&amp;lt;0.01, p&amp;lt;0.05, respectively). Meanwhile, the frequency of CXCR3+CD8+ T and CXCR3+++CD8+ T cells was highest and significantly elevated in CR vs normal tissue suggesting enrichment of activated, homing, Tc1 CD8T cells. An increase in total CD8+ and CD103+CD8+ T cells was associated with longer progression-free survival. DESeq2 analysis of bulk mRNA sequencing showed enrichment of CD8a and ITGAE (CD103) gene expression differential in CR vs PR lesions (p=0.028, p=0.00029, respectively). CD8a expression was reduced in panCK- AOI of resistant (PR) foci by GeoMx WTA spatial transcriptomic analysis in two model patients with multi-focal tumors. Flow analysis of EpCAM+ cells had a significant increase in B7H3 expression in PR vs CR lesions (p&amp;lt;0.05). We are currently integrating analysis of myeloid cells and expand spatial transcriptomic analysis of matched multi-focal tumors to further dissect patterns of therapeutic response in our study cohort. Conclusions: In conclusion, PSMA /PET and mpMRI based precision sampling of tumor tissue associated with differential therapeutic response patterns captured differences in the TIME infiltrates and these observations may provide hypothesis to test biological mechanisms to expedite discovery of targetable mechanisms to improve tumor stratification and targeting in high-risk prostate cancer. Citation Format: Erika Heninger, Jamie M. Sperger, Kristin Weinstein, Brian P. Johnson, Peter G. Geiger, Shane A. Wells, Steve Y. Cho, Wei Huang, Philippos Tsourkas, Sean McIlwain, Irene M. Ong, David Quigley, David F. Jarrard, Sheena C. Kerr, David J. Beebe, Joshua M. Lang. Differential Patterns of Immune Infiltration in the Tumor Immune Microenvironment Associate with Therapeutic Response in Primary Prostate Cancer Following Chemohormonal Therapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr A023.