Abstract 2636: Combined MRI and molecular signatures of prostate cancer: Association with biochemical recurrence
Authors: Stephanie A. Harmon, William Gesztes, Denise Young, Sherif Mehralivand, Brad J. Wood, Peter A. Pinto, Gyorgy Petrovics, Albert Dobi, Inger L. Rosner, Baris Turkbey, Shiv Srivastava, Peter L. Choyke, Isabelle A. Sesterhenn
Journal: Cancer Research (2018)

Abstract Purpose: To assess the correlation of histologic and prostate cancer associated gene oncoprotein expression and imaging features in MRI-detected lesions of prostate cancer patients with biochemical recurrence (BCR) after definitive treatment. Methods: Patients underwent multiparametric MRI (mpMRI) at 3T at a single institution prior to TRUS/MRI fusion-guided biopsy of MRI-defined index lesions and prior to definitive therapy (radical prostatectomy), for which clinical follow-up was available. All mpMRI lesions were prospectively scored low, moderate, moderate-high, or high for suspicion of harboring clinically significant cancer, as determined by positivity on individual MRI sequences and indication of extraprostatic extension (EPE) on imaging. The expression of prostate cancer drivers (ERG, PTEN, AR and p53) and PSA were examined on targeted-biopsy specimens by immunohistochemistry (IHC). All histological assessments were completed blinded to imaging findings and treatment outcomes. Cox proportional hazard regression was used to evaluate associations between imaging, molecular, and surgical characteristics with interval to BCR. Results: In a preliminary cohort of 56 patients, 29 patients met clinical criteria for BCR (median interval 12.46 months, range 1-55 months) and 27 patients remain recurrence-free (median follow-up 30.75 months, range 1-72+ months). Median interval between mpMRI and targeted biopsy was 29 days (range 12-167 days) and radical prostatectomy was 4.13 months (range 1.3-8.0 months). Pre-operative serum PSA was the strongest correlate with time to BCR (HR: 1.63, 95%-CI: 12.-2.1, p&amp;lt;0.0001). The p53 staining intensity 3+ in &amp;gt;1% of cells or 2+ in &amp;gt;10% of cells was associated with poor BCR interval (HR: 3.35, 95%-CI: 1.5-7.2, p=0.002), remaining so in multivariate model with pre-operative MRI, PSA, and post-surgical findings on pathology. p53 positivity was observed more frequently in Gleason≥4+3, for both biopsy (fisher's exact p=0.006) and final pathology grading (fisher's exact p=0.01). Moderate/high to high index MRI suspicion was found to correlate with EPE at surgery (fisher's exact p=0.03) and showed modest correlation to time-to-BCR in univariate analysis (HR: 2.11, 95%-CI: 0.99-4.5, p= 0.052) and remained so in multivariate analysis. PTEN loss was observed in 8 patients (14%). PSA+ expression by IHC was observed in 49/56 patients, with remaining 7 patients showing variable/heterogeneous (PSA+/-) expression. Conclusions: MRI impression and p53 status from MRI index lesion were independent predictors of time to biochemical recurrence, along with pre-operative PSA levels. These results are part of an ongoing study to identify histo-radiological features of aggressive prostate cancers. Citation Format: Stephanie A. Harmon, William Gesztes, Denise Young, Sherif Mehralivand, Brad J. Wood, Peter A. Pinto, Gyorgy Petrovics, Albert Dobi, Inger L. Rosner, Baris Turkbey, Shiv Srivastava, Peter L. Choyke, Isabelle A. Sesterhenn. Combined MRI and molecular signatures of prostate cancer: Association with biochemical recurrence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2636.