PD52-03: Multi-parametric magnetic resonance imaging of multi-focal prostate cancer unmasks intra-prostatic genomic heterogeneity and novel radio-genomic correlates: results of the Smarter Prostate Interventions and Therapeutics (SPIRIT) study

Joseph Chin, Rohann Correa, Erfan Aref-Eshghi, Ryan Alfano, Bekim Sadikovic, Aaron Ward, Paul Boutros, John Bartlett, Zahra Kassam, Stephen Pautler, Mena Gaed, Jose GomezLemus, Madeleine Moussa, Glenn Bauman

Introduction: Multi-focality and heterogeneity in prostate cancer can confound the selection of appropriate clinical management. Our study aimed to explore radio-genomic correlations using multiparametric magnetic resonance imaging (mpMRI) against a histopathologic reference standard.

Methods: Eight men with prostate cancer who underwent mpMRI followed by prostatectomy were selected for this pilot. Whole-mount histopathology was digitized and co-registered to corresponding MRI slices using a validated high-fidelity methodology.(1) Foci, including central/transitional and peripheral zone lesions were identified by a pathologist, and contoured on digitized histopathology specimens and these digitized maps were used to guide macrodissection of the individual foci for genomic copy-number aberration (CNA) analysis. Correlation of radiomics signatures with the histologic findings and genomic analysis was performed.

Results: We found a broad range of CNAs revealing inter-patient and intra-prostatic heterogeneity. Recurrently-altered loci (e.g., 8p21) containing genes of known significance (e.g., NKX3-1) were observed. Only radiomic features derived from apparent diffusion coefficient (ADC) independently correlated with both Gleason grade (Rho = -0.62, p = 0.003) and median CNA burden (Rho = -0.68, p < 0.001). While greater CNA burden expectedly correlated with higher grade, intermediate-grade (Gleason score 3+4 or 4+3) lesions appeared more like either high-grade (Gleason scores =4+4) or low-grade (Gleason score 3+3) disease when clustered based on CNA and ADC metrics.

Conclusions: These findings suggest ADC derived radiomic metrics may be a useful imaging biomarker across both central and peripheral zone lesion and could aid in further characterization of intra-prostatic biologic heterogeneity. These proof-of-principle data reveal novel radio-genomic correlations that could supplement histologic grading and conventional imaging, thus warranting expanded study and validation. Source of

Funding: Canadian Institute for Health Research; Ontario Institute for Cancer Research;

Dr. Boutros was supported by a TFRI New Investigator Award, a Prostate Cancer Canada Movember Rising Star award and by the NIH/NCI under award number P30CA016042.