Citations

Abstract Introduction Discrimination and sexual harassment within the workplace have a negative impact on well-being and productivity and are often underreported due to lack of comfortability in confronting the offender. Objective We aim to assess the prevalence of these abusive behaviors within a urology department and the impact of a dedicated training session on comfortability reporting/confronting discrimination and harassment. Methods Employees within a urology department at a single institution were invited to take a survey regarding discrimination and harassment both before and after a dedicated training session on reporting and confronting these behaviors. Statistical analyses were performed between pre- and post-survey groups, genders, and roles within the department. Results A total of 166 employees completed the pre-training survey, while 79 (47.6%) completed the post-training survey. 116 (69.9%) respondents identified as female. Roles within the department included physician (48/166, 28.9%), advanced practice provider (21/166, 12.7%), nurse (42/166, 25.3%), and nonclinical staff (51/166, 30.7%). The training demonstrated a positive impact in respondent comfort level with addressing gender discrimination, where 19/23 (82.6%) people who answered neutral/ disagree/strongly disagree changed their answer to agree/strongly agree compared to 7/56 (12.5%) who changed their answers in the opposite way (p=0.02). More women reported experiencing sexual harassment at least once a year compared to men (38.6% vs. 16.7%, p<0.0001). Patients were the most commonly reported offenders of abusive behaviors towards staff. Conclusions Specific training on strategies for addressing abusive behaviors can help employees feel empowered to confront gender discrimination by both patients and their peers. Disclosure No

Abstract Introduction Inflatable penile prosthesis reservoir herniation or migration may occur with space of Retzius or submuscular placement. The dangers of high submuscular placement include bowel or bladder perforation (from blind instrument passage) and or bowel herniation (from unintentional peritoneal placement and stretching of small opening with reservoir filling). Even under direct vision submuscular placement, reservoirs can ultimately reside into the scrotum, retroperitoneum, and lateral abdominal wall. The Transfascial Fixation (TFF) technique was recently developed to prevent reservoir migration with placement either submuscularly or in the space of Retzius, but video of this technique has not been previously published. Objective To visually demonstrate the proper surgical technique of TFF during IPP reservoir placement. Methods An IPP surgical candidate at high risk of complications should reservoir migration occur was identified. Video of TFF technique performed during IPP surgery was recorded using an in-light overhead camera and a GoPro aseptically positioned on the lead surgeon. Results Successful demonstration of TFF technique during IPP placement. Conclusions TFF technique is a feasible option to aid prevention of penile implant reservoir herniation. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast, Boston Scientific, Metuchen Pharmaceuticals, Acerus Pharmaceuticals, Endo Pharmaceuticals, AbbVie Inc.

Abstract Introduction Inflatable penile prosthesis reservoir herniation or migration may occur with space of Retzius or submuscular placement. The dangers of high submuscular placement include bowel or bladder perforation (from blind instrument passage) and or bowel herniation (from unintentional peritoneal placement and stretching of small opening with reservoir filling). Even under direct vision submuscular placement, reservoirs can ultimately reside into the scrotum, retroperitoneum, and lateral abdominal wall. The Tubing, Hitch And Lasso, Intussusception Anchor (THALIA) technique was recently developed to prevent reservoir migration with placement either submuscularly or in the space of Retzius, but video of this technique has not been previously published. Objective To visually demonstrate the proper surgical technique of THALIA during IPP reservoir placement. Methods An IPP surgical candidate at high risk of complications should reservoir migration occur was identified. Video of THALIA technique performed during IPP surgery was recorded using an in-light overhead camera and a GoPro aseptically positioned on the lead surgeon. Results Successful demonstration of THALIA technique during IPP placement. Conclusions THALIA technique is a feasible option to aid prevention of penile implant reservoir herniation. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Coloplast

Abstract Introduction There is no agreed-upon definition for acute/chronic phases of Peyronie’s Disease (PD). Collagenase Clostridium histolyticum (CCH) is the only FDA-approved treatment for PD, but original phase-3 trials included patients with symptom duration > 12 months (“chronic phase”). Objective Here, we sought to evaluate the influence of time between symptom onset and starting CCH on treatment outcomes. Methods Men receiving CCH from 2014-2021 were included in an IRB-approved database. Pertinent data were reviewed, including demographics and curvature assessments. The duration between symptom onset and starting treatment with CCH was assessed to determine if the time from symptom onset to treatment impacted objective outcomes. Results One hundred forty-five patients completed the entire series of 8 injections and had complete data for review. Mean baseline curvature 53.2o (SD 18). The mean time between symptom onset and CCH was 14.8 months (SD 18). Mean absolute and percentage improvements were 20.3o (SD 16) and 39.4% (SD 35). Symptom duration did not significantly impact curvature improvement (Figure 1). Similarly, symptom duration did not significantly impact the risk for CCH-related side effects. Conclusions The time between symptom onset and treatment did not significantly impact outcomes with CCH. Our findings support the utility of using CCH early in the course of PD and emphasize the opportunity to delay if necessary without compromising efficacy. Disclosure No

Abstract Introduction Intralesional Collagenase Clostridium histolyticum (CCH) is approved for men with Peyronie’s Disease (PD). Most studies use curve improvement ≥ 20% to define treatment success. Objective Here, we sought to further characterize objective and subjective treatment outcomes with CCH. Methods We reviewed our prospectively maintained database for all patients who underwent CCH at our institution from 2013 through the present. We specifically identified those who completed four series of CCH (or elected to discontinue prior to completing four series due to satisfactory penile straightening or lack of results) and had available curvature assessment data. Treatment outcomes were broken down by level of curve improvement (0%, 10%, 20%, 30%, and > 40% improvement). Treatment success was also evaluated by improvements in the ability to engage in penetrative sexual intercourse and perceived surgery avoidance. Statistical analyses were performed using JMP Pro 14.1.0 (SAS Institute, Cary, NC). Results 127 patients had complete data available. The mean age was 57 years (SD 8.4). The mean PD duration was 27 months (SD 59). The mean baseline curvature was 66.1O, and the mean post-treatment curvature was 45.1O (p<0001). The mean curvature improvement was 32% (SD 33). 68% of patients achieved a 20% or greater improvement in penile curvature, including 38% who achieved ≥ 40% improvement. 72% (n=48/67) felt that CCH prevented the need for surgery, and 68% reported CCH restored the ability to penetrate. Stretched flaccid penile length (SPL) increased by ≥ 1 cm in 50% of patients who used concurrent penile traction (PTT) and CCH, including 28% of patients who experienced ≥ 2 cm of length gain. In contrast, only 16% of patients who did not perform concurrent PTT had a ≥ 1 cm increase in SPL (p<0.0001). Conclusions CCH may restore the ability to penetrate with intercourse, and most patients feel that CCH prevents the need for surgery. Almost 40% of patients experienced a 40% or greater curvature improvement. However, 13% of patients may go through the entire series with minimal improvement. Concurrent PTT allows for simultaneous penile length gain in some patients. These data are helpful when counseling patients on expected outcomes. Disclosure No

Abstract Introduction Collagenase Clostridium Histolyticum (CCH) is an FDA-approved treatment for Peyronie’s Disease (PD). Based on phase-3 trials, the recommended treatment course consists of 8-injections over the course of roughly 18-20 weeks. While its efficacy has been established, less is known about patient-specific reasons for electing to discontinue CCH injection therapy. Objective To evaluate patient-reported factors associated with premature CCH discontinuation. Methods We queried a database of all patients (n=406) who underwent CCH at a single institution from 2014-2021. Patients who did not complete the recommended 8 injections were identified, and a detailed review was undertaken to determine causes of discontinuation. Patients were excluded from our analysis for the following reasons: deceased at the time of chart review, declined to participate, or could not be reached in 3 phone calls. Results Out of 406 patients who underwent Xiaflex treatment at our single institution, 133 did not complete 8 injections (32.8%). The mean number of CCH injections was 4.42 (SD 1.65). The most common reasons for discontinuing Xiaflex were satisfactory curve reduction (27%), unsatisfactory curve reduction (21%), bothersome side effect (15%), and decision to pursue surgery (12%) [Figure 1]. Other less common reasons included other health concerns, pausing treatments due to the Covid-19 pandemic, high treatment cost, transferring care elsewhere, and lack of awareness that more injections were indicated. Conclusions In our single institution study, we find that nearly 1/3 of patients who begin Xiaflex injections will not complete the full recommended treatment course. Understanding the reasons for discontinuation can help providers better stratify patients for Xiaflex treatment versus other modalities. In addition, given previous studies that indicate that 2/3 of men who fail to achieve a 20% curve reduction after their first 4 injections will go on to achieve this curve reduction after their final 4 injections, our data points to the potential impact of improved patient education for the 21% of individuals who discontinue due to unsatisfactory curve reduction (Alom et al 2021). Disclosure No

PURPOSE Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms. PATIENTS AND METHODS MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response. RESULTS One hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P = .02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P < .001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P = .01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P = .03). Serial analysis of JAK2V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P = .001, EFS P = .001, overall survival P = .01) and clearance of JAK2V617F stem/progenitor cells. ASXL1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P = .003). The safety profile of ruxolitinib was as previously reported. CONCLUSION The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.

Abstract Background: Arginine deprivation with ADI-PEG20 (pegargiminase) alone or combined with chemotherapy displayed antitumor activity in early phase clinical trials of argininosuccinate synthase 1 (ASS1)-deficient cancers, including pleural mesothelioma (PM). The non-epithelioid subtype of mesothelioma is particularly aggressive and arginine-auxotrophic due to frequent ASS1 loss. ATOMIC-meso is a pivotal phase 2-3 trial comparing standard of care (SOC) chemotherapy plus pegargiminase or placebo for patients (pts) with non-epithelioid PM. Methods: In this double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned ECOG PS 0-1 pts with chemonaïve non-epithelioid PM in an intention-to-treat 1:1 ratio to receive q3 week SOC chemotherapy with pemetrexed (500mg/m2 i.v.) and cisplatin (75mg/m2 i.v.) with q1 week pegargiminase (36 mg/m2 i.m.) or placebo i.m. up to 6 cycles. Carboplatin (AUC5) was permitted in the phase 3 portion instead of cisplatin. Maintenance therapy with pegargiminase or placebo was continued until progression, toxicity or 24 months. The primary end point was median OS (mOS) and secondary end points included median PFS (mPFS), safety, pharmacodynamics and immunogenicity. ORR was assessed by blinded independent central review (BICR) for the phase 2 portion only using modified RECIST or RECIST v1.1. Results: 249 pts with non-epithelioid PM (median age 71, range 28-86; male 82.7%; 48.2% biphasic and 51.8% sarcomatoid) from 5 countries were randomized between Aug 2017 and Aug 2021: 125 pts were assigned to the pegargiminase-chemotherapy group and 124 pts to the placebo-chemotherapy group. The experimental arm showed a superior mOS respect to SOC: 9.3 months (95% confidence interval [CI], 7.9-11.8) vs. 7.7 months (95% CI, 6.1-9.5) (hazard ratio [HR], 0.71; 95% CI, 0.55-0.93; p=0.023). Also, the mPFS was higher in the experimental vs. control arm: 6.2 months (95% CI, 5.8-7.4) vs. 5.6 months (95% CI, 4.14-5.91) ([HR], 0.65; 95% CI, 0.46-0.90; p=0.019). The ORR by BICR was 13.8% in the pegargiminase-chemotherapy group vs. 13.5% in the placebo-chemotherapy group (p=0.95) with more stable disease in the former (71.3% vs. 62.9%). Plasma arginine declined with a reciprocal increase in citrulline. Anti-ADI-PEG20 antibodies were detected in 97.4% of patients by week 25 on pegargiminase. Grade ≥ 3 treatment-related adverse events to pegargiminase occurred in 28.8% and to placebo in 16.9%; grade ≥ 3 drug hypersensitivity and skin reactions occurred in 3.2% and 1.6% in the experimental arm, respectively, and none on placebo. Post-study drug treatment was comparable in both arms (45.6% post-pegargiminase vs. 46.8% post-placebo). Conclusions: In this first randomized trial of an arginine-depleting chemotherapy in cancer, the pegargiminase-pemetrexed-platinum triplet prolonged survival and had a favorable safety profile in pts with non-epithelioid PM (ClinicalTrials.gov Identifier NCT02709512) Citation Format: Peter W. Szlosarek, Ben Creelan, Thomas Sarkodie, Luke Nolan, Paul Taylor, Olga Olevsky, Federica Grosso, Diego Cortinovis, Meenali Chitnis, Amy Roy, David Gilligan, Hedy Kindler, Dionysis Papadatos-Pastos, Giovanni L. Ceresoli, Aaron Mansfield, Anne Tsao, Ken O’Byrne, Anna K. Nowak, Jeremy Steele, Michael Sheaff, Amanda Johnston, John Bomalaski, Marjorie Zauderer, Dean A. Fennell. Phase 2-3 trial of pegargiminase plus chemotherapy versus placebo plus chemotherapy in patients with non-epithelioid pleural mesothelioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT007.

Abstract Purpose: Treatment options are limited beyond JAK inhibitors for patients with primary myelofibrosis (MF) or secondary MF. Preclinical studies have revealed that PI3Kδ inhibition cooperates with ruxolitinib, a JAK1/2 inhibitor, to reduce proliferation and induce apoptosis of JAK2V617F-mutant cell lines. Patients and Methods: In a phase I dose-escalation and -expansion study, we evaluated the safety and efficacy of a selective PI3Kδ inhibitor, umbralisib, in combination with ruxolitinib in patients with MF who had a suboptimal response or lost response to ruxolitinib. Enrolled subjects were required to be on a stable dose of ruxolitinib for ≥8 weeks and continue that MTD at study enrollment. The recommended dose of umbralisib in combination with ruxolitinib was determined using a modified 3+3 dose-escalation design. Safety, pharmacokinetics, and efficacy outcomes were evaluated, and spleen size was measured with a novel automated digital atlas. Results: Thirty-seven patients with MF (median age, 67 years) with prior exposure to ruxolitinib were enrolled. A total of 2 patients treated with 800 mg umbralisib experienced reversible grade 3 asymptomatic pancreatic enzyme elevation, but no dose-limiting toxicities were seen at lower umbralisib doses. Two patients (5%) achieved a durable complete response, and 12 patients (32%) met the International Working Group-Myeloproliferative Neoplasms Research and Treatment response criteria of clinical improvement. With a median follow-up of 50.3 months for censored patients, overall survival was greater than 70% after 3 years of follow-up. Conclusions: Adding umbralisib to ruxolitinib in patients was well tolerated and may resensitize patients with MF to ruxolitinib without unacceptable rates of adverse events seen with earlier generation PI3Kδ inhibitors. Randomized trials testing umbralisib in the treatment of MF should be pursued.