Abstracts from the New England Section of the AUA 2020: A Virtual Experience

© The Canadian Journal of Urology TM : International Supplement, August 2020 44 Efficacy and Safety of a NewOral Testosterone (TU) Formulation inHypogonadal Men: Results from the ‘inTUne’ Trial Ronald Swerdloff, MD 1 , ChristinaWang, MD 1 , StantonHonig, MD 2 , John K.Amory, MD 3 , James Longstreth, PhD 4 , Marc Gittelman, MD 5 , Jed Kaminetsky, MD 6 , Brooke Harnisch, MD 7 , Robert Dudley, PhD 8 1 Lundquist Institute at Harbor-UCLA, Torrence, CA; 2 Yale University School of Medicine, New Haven, CT; 3 University of Washington, Seattle, WA; 4 Longstreth & Associates, Mundelein, IL; 5 South Florida Medical Research, Aventura, FL; 6 Manhattan Medical Research, New York, NY; 7 UConn Health, Farmington, CT; 8 Clarus Therapeutics, Northbrook, IL Introduction : Oral delivery of testosterone (T) replacement therapy (TRT) has several potential advantages over currently available options. A novel formulation of oral TU was studied in two prior Phase 3 trials that demonstrated safety and efficacy. However, to further improve pharmacokinetic (PK) efficacy, a new dose titration algorithm was evaluated. Materials & Methods : Hypogonadal men (diagnosis consistent with the Endocrine Society guideline of two morning serum T < 300 ng/dL and signs/symptoms with hypogonadism), age 18-65 y/o, were recruited into a 105 day, randomized, open-label, multicenter, dose-titration trial. Patients were randomized 3:1 to oral TU, BID (JATENZO ® ; n = 166) or a topical T product QD (Axiron ® ; n = 56). Dose titration was based on average T levels (C avg ) calculated from serial 24h pharmacokinetic (PK) samples. T was assayed by LC-MS/MS. Patients had two dose adjustment opportunities (on study day 21 and 56), which were based on plasma T levels (C avg ) calculated frommultiple PK samples, prior to final PK visit. Safety was assessed by standard clinical measures, including ambulatory BP. Results : 87% of patients in both groups achieved mean T C avg in the eugonadal range. NaF-EDTAplasma T C avg for oral TU group was 403 ± 128 ng/dL (~14 ± 4 nmol/L; mean ± SD) [serumT equivalent ~ 489 ± 155 ng/dL(17 ± 5 nmol/L)] and for topical T (Axiron®) was 391 ± 140 ng/dL (~14 ± 5 nmol/L). The overall safety profile of TU was similar to topical T. There were no deaths or T-related serious adverse events. Mean changes in HCT and PSAwere similar in both treatment arms with HCT increase of 2-3% (absolute increase) and PSA increase of 0.2-0.3 ng/mLwith no PSAvalues > 4 ng/mL. Final subject mean increase in systolic BP by cuff in the oral TU and topical T groups was 2.8 (± 11.84) and 1.8 (± 10.76), respectively. Conclusion : A new oral TU formulation restored T to mid-eugonadal levels in hypogonadal patients. Both groups showed a modest change in HCT and PSA. 43 Negative Combined Fusion-Systematic Biopsy Despite Presence of PIRADS 3, 4 or 5 Lesions: A Matter of False Positive Imaging or False Negative Biopsy? Jeffrey Twum-Ampofo, MD , Carl Ceraolo, BS, Daniel Frendl, MD, PhD, Andrew Gusev, BS, Keyan Salari, MD, PhD, Mukesh Harisinghani, MD, Mark Anderson, MD, Matthew Wszolek, MD, Adam Feldman, MD, MPH Massachusetts General Hospital, Boston, MA Introduction: MRI/Ultrasound fusion biopsy of the prostate has enhanced the detection of clinically significant prostate cancer (csPCa). However, the finding of a negative fusion and negative systematic biopsy in patients with suspicious lesion on MRI raises the question of either falsely positive imaging or a false negative biopsy. We investigate outcomes in this patient subgroup. Materials &Methods: We retrospectively reviewed our database of patients undergoing MRI/transrectal US-guided fusion biopsy. All images were graded according to Prostate Imaginag Reporting and Data System (PIRADS) version 2.0. Patients underwent targeted biopsy (3-4 cores per target) followed by systematic 12-core double sextant biopsy within the same session. Patients with no prostate cancer (PCa) found on biopsies were followed. csPCa was defined as Grade Group (GG) ≥ 2 PCa and non- csPCa was defined as benign or GG1. MRI studies with PIRADS v2 score ≤ 2 were considered to have no MRI evidence of PCa. Results: Atotal of 400 patients had at least one PIRADS ≥ 3 lesion and underwent fusion/ systematic biopsy. Of these, 113 (28.3%)patients had no evidence of PCa on fusion or systematic biopsy. Mean follow-up was 32 months. 44 (39%) patients underwent repeat MRI and, of these, 24 (54%) had no suspicious lesion on repeat MRI. Initial PSA density (PSAd) was 0.12 for patients whose original PIRADS lesion disappeared, whereas it was 0.20 for patients with persistent lesions ( p = 0.03). PSA, lesion size, and lesion grade did not correlate with disappearance of PIRADS lesion. 95% of patients with persistent PIRADS ≥ 3 lesions and 8.5% of those whose lesions disappeared proceeded to repeat biopsy. Of the 23 patients who underwent repeat biopsy, 16 (69.6%) had PCa and 11 (47.8%) had csPCa. Thus, of the 113 patients with an initial PIRADS ≥ 3 lesion and negative initial fusion/ systematic biopsy, 9.7% (11) were subsequently found to have csPCa. The only predictor of csPCa on repeat biopsy was PSA change after initial negative fusion biopsy: +2.8 vs. -0.33 ng/mL at 1 year ( p = 0.01) for csPCa and non-csPCa , respectively. PSAd at time of initial combined biopsy was nearly identical for patients with csPCa diagnosed on initial biopsy and those with csPCa diagnosed on repeat biopsy (0.252 vs. 0.245; p = 0.88). Conclusions: In the setting of a negative initial fusion/systematic biopsy, at least 10% of patients will have csPCa. Both elevated PSAd and the persistence of a suspicious lesion on repeat MRI suggest a false negative initial biopsy for csPCa. However, lowPSAd correlates with MRI lesion disappearance which likely represents falsely positive initial MRI. Utilization andOutcomes of Serial ProstateMRI for Prostate Cancer Active Surveillance Andrew Gusev, BA , Jeffrey Twum-Ampofo, MD, Alberto Pieretti, MD, Carl Ceraolo, BA, Florian Rumpf, BA, Alice Yu, MD, Keyan Salari, MD PhD, Douglas Dahl, MD, Adam S. Feldman, MD MPH Massachusetts General Hospital, Boston, MA Introduction: Multiparametric Magnetic Resonance Imaging (mpMRI) is increasingly utilized in the diagnosis and risk stratification of men with prostate cancer (PCa). During Active Surveillance (AS) men often receive multiple MRIs, yet it is not well described how results of subsequent MRIs affect their outcomes. We investigated our AS cohort to assess the outcomes of men who underwent at least two prostate mpMRIs during their time on surveillance. Materials & Methods: We retrospectively reviewed our institutional database of 1268 men enrolled in AS for localized PCa from 1996-2016. We identified men who underwent at least two prostate mpMRIs during the course of surveillance. MRIs without a reported Prostate Imaging Reporting and Data System (PIRADS) version 2.0 score were excluded. Radiologic progression was defined as new lesion (PIRADS ≥ 3) on a previously negative MRI or increase in PIRADS score of a previous lesion. Lesions with PIRADS score > 3 were defined as high-risk. Cox proportional hazards regression was used to identify factors associated with freedom from treatment. Survival analyses were conducted using Kaplan-Meier method and log rank test. Results: The study cohort included 201 men. The majority of patients had GG 1 (97%) and clinical stage T1c (93%) disease. Median values were as follows: number of MRIs meeting criteria: 2 (range 2-3); follow up time: 5.1 years (IQR 3.7-7.7); time between MRIs: 2 years (IQR 1.5-2.8). OnMRI 1, 10% of patients had PIRADS 3 lesions, 19%PIRADS 4, 6%PIRADS 5, while 65%were negative. Figure 1 demonstrates the distribution of PIRADS scores from MRI 2, arranged by initial lesion. Overall on repeat MRI, 62% of PIRADS scores did not change, while 27% increased and 11% decreased. Compared to lesions that remained the same, PIRADS increase was predictive of earlier progression to treatment (HR 3.9 [95% CI 2.2-6.9] p< 0.001), while PIRADS decrease did not have a significant effect. In 131 men with a negative initial scan, MRI 2 remained negative 63% of the time. This cohort of 83 men with two negative MRIs experienced prolonged freedom from treatment, 88% and 83% at 5 and 10 years, compared to 70% and 47% for those whom had at least one PIRADS ≥ 3 lesion [Figure 2]. Compared to a second negative MRI, a new development of a high-risk lesion, which occurred in 28% of initial negatives, was significantly predictive of subsequent progression to treatment (HR 5.7 [95% CI 2.8-11.6] p < 0.001). Conclusions: While a majority of men do not experience PIRADS score change on serial prostate mpMRI, those who have radiologic progression progress to treatment sooner. Men with multiple negative MRIs have significantly prolonged freedom from treatment and may be candidates for an increased interval between surveillance MRI and biopsy. 42 20 Scientific Session IV: Oncology II