New Jersey Urology

339 Background: PSMA-PET imaging is widely accepted as preferred to conventional imaging (CT, MRI, SPECT) for the management of patients with prostate cancer (PCa). PSMA-PET imaging has demonstrated the ability to more accurately stage patients with PCa. Such information is critical to physicians when determining an appropriate disease management plan for their patients. The long-term impact of PSMA-PET imaging on PCa management in real-world clinical settings has yet to be fully established. In this real-world observational registry study preliminary data on change in management following PSMA-PET imaging were evaluated. Methods: The PYLARIFY Registry (NCT 05712473), conducted under SoNaR, a Cardinal Health Specialty Networks Registry, is a 5-year prospective, multicenter, United States based observational study that follows patients receiving PSMA-PET with piflufolastat F18 imaging as part of their routine PCa management. The registry includes newly diagnosed treatment-naïve patients (Cohort 1) and patients with biochemical recurrence (BCR) (Cohort 2). To evaluate the impact of PSMA-PET with piflufolastat F18 on clinical decision-making, physician-reported treatment plans before and after imaging were assessed. Disease management for the first 325 enrolled patients was characterized and the overall impact of piflufolastat F18 imaging results on changes in management was quantified by calculating the Jaccard Index for both patient cohorts. Treating physicians also rated the confidence in their management plan following piflufolastat F18 imaging. Results: Among the 161 patients in the newly diagnosed cohort, the Jaccard Index was 0.437, indicating a 56.3% variation between pre-imaging and post-imaging treatment plans. Similarly for the 164 patients in the BCR cohort, the Jaccard Index was 0.430 reflecting a 57.0% variation in disease management strategies before and after imaging. These findings are comparable to the 63% change in planned management observed within a BCR cohort in the CONDOR clinical study. Overall, physicians reported increased confidence in their disease management plans for 97.8% of patients following piflufolastat F18 imaging. Conclusions: Present findings support the clinical utility of piflufolastat F18 in guiding real-world clinical decision-making in both newly diagnosed and BCR prostate cancer patients. The observed changes in treatment plans demonstrate a substantial shift in management strategies following PSMA-PET imaging. Our findings are consistent with those of a clinical trial and further underscore the clinical value that piflufolastat F18 provides to physicians and patients in a real-world setting.

5000 Background: Standard of care (SoC) for intermediate to high-risk localized prostate cancer (PrCa) includes surgery or external beam radiation (EBRT) +/- androgen deprivation therapy (ADT). Nearly 30% of men undergoing EBRT will experience recurrence requiring ADT and salvage therapies that negatively impact quality of life. CAN-2409 is a replication-defective adenovirus encoding the HSV-tk gene that, when combined with valacyclovir (prodrug), results in immunogenic cell death. This results in immunization against tumor antigens and long-term tumor control. Methods: We conducted a phase 3, multicenter, double-blinded, randomized, placebo (PBO)-controlled clinical trial in PrCa patients (pts) planning to receive EBRT+/- short course ADT (<6 mos); NCT01436968. 745 pts were randomized 2:1 (496 in CAN-2409+prodrug and 249 in PBO+prodrug) and stratified by NCCN risk group and ADT use. Three intraprostatic injections of CAN-2409 (5x10 11 v/2mL) or PBO were administered, each followed by 14 days of prodrug. Follow-up included a prostate biopsy 2 years after EBRT. Primary endpoint was disease-free survival (DFS), defined as time from randomization to PrCa recurrence (local/regional failure or distant metastasis) or death in the intent-to-treat population. Median follow up time was 50.3 mos. The study was conducted under a special protocol assessment (SPA) granted by the FDA. Results: Treatment with CAN-2409 reduced the risk of PrCa recurrence or death by 30% (median DFS not reached vs 86.1 mos, p=0.0155, HR 0.7, 95% CI 0.52 to 0.94). PrCa-specific DFS (exclusion of non PrCa- related deaths) demonstrated an even greater effect with a 38% decreased risk in the CAN-2409 arm vs. PBO (p=0.0046; HR 0.62, 95% CI 0.44 to 0.87). Statistically significant secondary endpoints included increased percentage of patients achieving prostate-specific antigen nadir (67.1% vs 58.6%, p=0.0164) and an increase in pathological complete responses in the 2-year biopsies in the CAN-2409 arm vs. PBO (80.4% vs. 63.6%, p=0.0015). Most common treatment-related adverse events included chills (33.4% vs. 8.6%), flu-like symptoms (30.5% vs. 13.8%), and fever (25.1% vs. 3.9%), mostly Gr 1-2 and self-limited. Serious adverse events (SAEs, 5.8% vs. 7.3%) and treatment-related SAEs (1.7% vs. 2.2%) were uncommon across treatment groups. Conclusions: In this randomized, double-blind, Phase 3 trial, CAN-2409 significantly reduced the risk of PrCa recurrence or death when added to SoC EBRT+/- ADT. The addition of CAN-2409 was not associated with significant added toxicity. These data represent the first potentially new therapy for patients with intermediate and high risk PrCa in over 20 years. Clinical trial information: NCT01436968 .

PURPOSEGermline genetic testing (GT) is important for prostate cancer (PCA) management, clinical trial eligibility, and hereditary cancer risk. However, GT is underutilized and there is a shortage of genetic counselors. To address these gaps, a patient-driven, pretest genetic education webtool was designed and studied compared with traditional genetic counseling (GC) to inform strategies for expanding access to genetic services.METHODSTechnology-enhanced acceleration of germline evaluation for therapy (TARGET) was a multicenter, noninferiority, randomized trial (ClinicalTrials.gov identifier: NCT04447703) comparing a nine-module patient-driven genetic education webtool versus pretest GC. Participants completed surveys measuring decisional conflict, satisfaction, and attitudes toward GT at baseline, after pretest education/counseling, and after GT result disclosure. The primary end point was noninferiority in reducing decisional conflict between webtool and GC using the validated Decisional Conflict Scale. Mixed-effects regression modeling was used to compare decisional conflict between groups. Participants opting for GT received a 51-gene panel, with results delivered to participants and their providers.RESULTSThe analytic data set includes primary outcome data from 315 participants (GC [n = 162] and webtool [n = 153]). Mean difference in decisional conflict score changes between groups was –0.04 (one-sided 95% CI, –∞ to 2.54; P = .01), suggesting the patient-driven webtool was noninferior to GC. Overall, 145 (89.5%) GC and 120 (78.4%) in the webtool arm underwent GT, with pathogenic variants in 15.8% (8.7% in PCA genes). Satisfaction did not differ significantly between arms; knowledge of cancer genetics was higher but attitudes toward GT were less favorable in the webtool arm.CONCLUSIONThe results of the TARGET study support the use of patient-driven digital webtools for expanding access to pretest genetic education for PCA GT. Further studies to optimize patient experience and evaluate them in diverse patient populations are warranted.

To examine one academic institution's experiences with SpaceOAR placement, its associated complications, and periprocedural characteristics that affect outcomes for the purpose of quality improvement. We conducted a retrospective review of 233 patients who received SpaceOAR from four surgeons and one radiation oncologist between 2018 and 2021. Variables such as demographics, oncologic parameters, radiation plan, and radiographic assessment of hydrogel placement were recorded. The Charlson Comorbidity Index (CCI) was used to assess comorbidity risk. Mann-Whitney and Fisher's exact tests were performed to compare patients with and without complications. Of the 233 patients who received SpaceOAR, 24 (10.3%) experienced toxicity. All complications were Clavien I or II, such as pelvic pain postplacement, pelvic fullness, bleeding, and lower urinary tract symptoms. 16 patients (6.9%) had some portion of the hydrogel injected into the rectal wall, but it was never clinically significant. The average CCI was 3.2 ± 0.95 for patients who experienced complications; the average CCI was 3.6 ± 1.6 (p=0.48) in the group without complications. Of the physicians with higher procedure volumes, Physician #1 had the highest rate of patient-reported complications at 11 out of 68 (16.2%) and Physician #2 had the lowest rate of complications at 4 out of 96 placements (4.2%). Multivariate analysis found that patients who had received hormone therapy previously had less odds of reporting complications after SpaceOAR placement. The listed attending on the procedure had a significant correlation to complications with SpaceOAR placement on univariate analysis, and hormone therapy had some benefits to the tolerance for the procedure on multivariate analysis. Overall, the hydrogel placement was well tolerated with low incidence of mild and transient procedure-related toxicity.

BackgroundUp to 50% of men over 50 and 80% over 80 are affected by BPH. Shared decision-making regarding BPH treatment options can benefit from an improved understanding of relative risks and benefits for various treatments.MethodsData for this longitudinal retrospective population-based cohort study were obtained from a random sample of US Medicare and commercial claims (IBM Watson MarketScan) and restricted to men undergoing BPH surgery (TURP, PVP, PUL, WVTT) from 2015 to 2021 across all sites of service. Retreatments included Holmium laser enucleation and index procedures. Main outcomes were rates of retreatment and procedural complications over 1 year, identified via CPT and ICD-9/10CM codes. Procedural complications that occurred at least 1 day post-index treatment were assessed, as were surgical retreatments with patients who had at least 1 and 5 year’s-worth of data. Baseline phenotype characterization did not control for symptomatology and was limited to age, comorbidities, and BMI. Univariate cumulative incidence estimates, cumulative proportion and log-rank tests justified inclusion for covariate (e.g., age, comorbidities) adjustment in Cox proportional hazard models.Results43,147 men diagnosed with BPH underwent 22,629 TURP, 11,392 PVP, 7,529 PUL, and 1,597 WVTT. At 1-year post-index: PUL was associated with the lowest rate of complication (PUL 15%, TURP 17%; PVP 19%, ; WVTT 26%); retreatment rates were not different (TURP 5.3%, PVP 5.3%, PUL 5.9%, WVTT 6.2%). At 5 years post-index: retreatment was lowest for TURP (7.0%) and was not significantly different between PVP and PUL (8.9% and 11.6%, respectively).ConclusionsReal-world patients diagnosed with BPH may be selected to undergo one of the various available therapies based on patient preference or baseline phenotype. These therapies, however, are associated with different risks for complications. The results of this study suggest that within one year of BPH surgery, one-in-twenty patients may require retreatment regardless of treatment choice, and for some technologies as many as one-in-four may require treatment for a complication.

Abstract Introduction The Optilume Urethral Drug Coated Balloon (DCB) is a novel endoscopic treatment for recurrent male anterior urethral strictures. An important topic of discussion with patients during counseling on treatment options includes the potential affect of treatment on sexual function and fertility. The ROBUST III study was a prospective, randomized study comparing standard of care endoscopic therapy against treatment with the Optilume DCB. Assessments included evaluation of sexual function and andrology parameters. Objective The objective was to study the potential affect of treatment with the Optilume DCB on sexual function and, for younger patients, fertility. Methods A total of 79 men were randomized to receive treatment with the Optilume DCB. Sexual function was assessed via the 15 item International Index of Erectile Function (IIEF) questionnaire. Erectile function, orgasmic function, and overall satisfaction sub-domains were assessed at 3, 6, and 12 months after treatment in patients that were sexually active at baseline. Fifteen additional subjects were enrolled in a non-randomized pharmacokinetic sub-study that included assessments of paclitaxel concentration in semen and sperm quality parameters through 6 months post-treatment. Results Average erectile function and overall satisfaction scores improved from baseline to 12 months post-treatment, while orgasmic function was not changed (Figure). The improvement in satisfaction was statistically significant at 12 months (p=0.003). No adverse events of de novo erectile or ejaculatory dysfunction were reported. Average ejaculate sperm concentration did not change from baseline to 6 months (49 million/mL vs 46.6 million/mL, p=0.88), nor did total spermatozoa per ejaculate (107.2 million vs 104.0 million, p=0.94). Paclitaxel concentration in semen after treatment was maximal at 30 days (2.99 ng/mL) and was reduced near the limit of quantitation of the analytical method by 6 months (0.12 ng/mL). Conclusions Treatment of male anterior urethral strictures with the Optilume DCB did not appear to have an impact on sexual function as measured by the IIEF and adverse event assessments. Average sperm quality parameters did not differ from baseline to 6 months post-treatment. Low levels of paclitaxel were detected in semen after treatment but were nearly undetectable by 6 months. Disclosure Yes, this is sponsored by industry/sponsor: Urotronic Inc. Clarification Industry funding only - investigator initiated and executed study. Any of the authors act as a consultant, employee or shareholder of an industry for: Boston Sci, Coloplast, Medtronic USA Inc., PROCEPT BioRobotic Corporation, NeoTract Inc., Janssen Biotech Inc., Endo Pharmaceuticals Inc., Tolmar Pharmaceuticals, Inc., 180 Medical Inc., AbbVie Inc., Pfizer Inc., Bluewind Medical, Astellas Pharma US Inc., Antares Pharma Inc., Axonic Modulation Technologies Inc., Allergan Inc., Terumo Medical Corporation, Dendreon Pharmaceuticals llc, Blue Earth Diagnostics Limited, Ferring Pharmaceuticals Inc., Olympus America Inc., Karl Storz Endoscopy-America, Clovis Oncology Inc., Dornier MedTech America Inc., Travere Therapeutics Inc., Valeant Pharmaceuticals North America LLC

TPS580 Background: Radical surgery is the mainstay of treatment for muscle-invasive upper tract urothelial cancer (UTUC) and urothelial bladder cancer (UBC). However, even when surgery is combined with cisplatin‐based (neo)adjuvant chemotherapy, recurrence rates are high. Many patients (pts) are ineligible for, do not respond to, or refuse cisplatin-based chemotherapy because of toxicity concerns. Fibroblast growth factor receptor 3 ( FGFR3) genetic alterations occur in 21–38% of muscle-invasive UTUC, and in approx. 20% of invasive UBC. Infigratinib (BGJ398) is an ATP-competitive FGFR1–3 selective oral tyrosine kinase inhibitor that has clinical activity and tolerability in pts with advanced/metastatic urothelial carcinoma (UC) harboring susceptible FGFR3 alterations. PROOF 302 was designed to investigate the efficacy and safety of adjuvant infigratinib in pts with high-risk, muscle-invasive UC (85% UTUC) and susceptible FGFR3 alterations. Methods: PROOF 302 is a global, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial (NCT04197986). Eligible pts have high-risk, muscle-invasive UTUC (85%) or UBC (15%) with susceptible FGFR3 alterations (mutations, gene fusions or rearrangements) confirmed by FoundationOne CDx test, and are ≤120 days following nephroureterectomy, distal ureterectomy, or cystectomy. The study protocol was amended to include pts with carcinoma in situ at surgical margins and those who refuse cisplatin-based chemotherapy (in addition to pts allowed to enroll if ineligible for perioperative cisplatin-based chemotherapy). Eligible pts are M0 and have either disease stage ≥ypT2 and/or yN+ after cisplatin-based neoadjuvant chemotherapy or ≥pT2 pN0–2 or pN+ (UTUC); and ≥pT3 or pN+ (UBC) if not treated with cisplatin-based neoadjuvant chemotherapy. Pts are randomized 1:1 to receive oral infigratinib 125 mg or placebo QD on days 1–21 of a 28-day cycle for up to 52 weeks (13 cycles) or until recurrence, unacceptable toxicity, or death. Primary endpoint: centrally reviewed disease-free survival (DFS) analyzed via stratified log-rank test and Cox model (hazard ratio). Secondary endpoints: investigator-reviewed DFS, metastasis-free survival, overall survival, safety/tolerability. Exploratory endpoints: quality of life, pharmacokinetics, determination of the prevalence of genomic alterations and correlation with features of UC, genomic and proteomic assessment of tumor tissue and cell-free DNA samples from baseline and at recurrence to identify the predictive/prognostic value of biomarkers. PROOF 302 is actively enrolling as of Sep 2021. A second Data Monitoring Committee meeting is planned for Dec 2021. The last pt is expected to complete treatment in 2024. Clinical trial information: NCT04197986.