Urology Associates

To provide expert recommendations for side effect management in patients with bladder cancer receiving intravesical-drug releasing system (iDRS) treatment and for optimizing iDRS insertion procedure success. Indwelling iDRS are designed to provide sustained local exposure to therapy. In clinical trials, frequent side effects of iDRS treatment were lower urinary tract symptoms (LUTS) (e.g., dysuria, pollakiuria, micturition urgency), urinary tract infections (UTIs), and hematuria. These side effects are generally low grade, but if not properly managed, may lead to treatment interruptions or discontinuations. As data are limited, practical recommendations based on expert opinion for the management of common side effects and best practices for iDRS insertion procedures may improve treatment adherence and optimize outcomes in patients with bladder cancer receiving iDRS. Two separate expert panels were convened to develop recommendations for side effect management with iDRS and optimizing iDRS insertion procedure success. Stepwise treatment-specific management strategies for LUTS, UTIs, and hematuria in patients receiving iDRS treatment that are familiar to practicing urologists are presented, including considerations for continuation or discontinuation of iDRS treatment. Several advanced techniques can be considered to improve iDRS insertions based on variations in patient anatomy.

Abstract Introduction Catheter-associated urinary tract infection (CAUTI) is a major health problem across the world. Several of the isolates causing CAUTI have become more and more resistant to antibiotics. When prepping a patient for penile implant surgery, there are several different methods, but the bacteria in the fossa navicularis/distal urethra is not treated in most of these methods. Our group has recently shown that different antiseptic solutions have significant differences in the ability to reduce pathogenic organisms on hydrophilic implant disc in hopes of lowering penile prosthesis infection (PPI) rates. The study is designed to evaluate the ability of antiseptics to kill bacteria after inoculation of various common UTI pathogenic species on sterile catheter disks in hopes of reducing catheter associated urinary tract infections (CAUTI). Objective To evaluate different catheters and activating solutions in killing common UTI organisms. Methods An in-vitro Good Laboratory Practices (GLP) microbiological study done at Nelson Labs Bozeman (FDA and EPA registered, ISO 17025 certified)] to compare outcomes of catheter activation with sterile water, 0.05% CHG solution (Irrisept□, Irrimax Corp., Lawrenceville, GA, USA) and CHG lube (Cathejel C .5/ 1gram at 5 grams). Three (3) bacteria were inoculated onto 2 different catheter discs. Bacteria tested were Bacteroides fragilis (ATCC #25285), Enterococcus faecalis (ATCC #29212) and Escherichia coli (ATCC #25922) strains. The two different catheter discs utilized are Hydrophilic Cure Catheter□(HCC) and the GentleCath□(GC) intermittent urinary catheter. The data was derived from three replicates for each activating solution (water, 0.05% CHG solution, and CHG lube), 2 catheter surfaces and for each of the 3 challenge microbial species to be tested. Neutralization was done with Butterfield’s Phosphate Buffer [BPB++] solution with product neutralizers. Following incubation, the colonies were plated and counted. Results Sterile water had the least effect on the three bacteria as compared to 0.05% CHG solution and CHG Lube (see Table 1 and 2). The GC glide catheter demonstrated reduced bacterial load better than the hydrophilic coated catheter when using CHG solutions. E. Coli was the bacteria most affected by the combination of CHG lube and GC glide catheter. Conclusions There is a bacterial load reduction when using CHG activating solutions compared to sterile water and when using the GC glide compared to HCC. E. Coli is the bacteria that demonstrated the greatest response with the combination of CHG activating solutions and GC glide catheter usage. Disclosure Yes, this is sponsored by industry/sponsor: ConvaTec Clarification: Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: ConvaTec, Coloplast, Boston Scientific, Irrisept, Signati, Microgen DX, FocalOne, Pfizer, Blue Wind

Despite treatment advances, most patients with metastatic hormone-sensitive prostate cancer (mHSPC) experience disease progression to castration-resistant disease within 5 years. The placebo-controlled, double-blind, phase III KEYNOTE-991 study evaluated the efficacy and safety of adding pembrolizumab to enzalutamide and androgen deprivation therapy (ADT) in participants with mHSPC. Eligible participants were aged ≥18 years with next-generation hormonal agent-naive mHSPC. Participants were randomly assigned (1 : 1) to receive intravenous pembrolizumab 200 mg or placebo every 3 weeks for ≤35 cycles, with oral enzalutamide 160 mg and continuous ADT. Primary endpoints were radiographic progression-free survival (rPFS) and overall survival (OS). Safety was a secondary endpoint. Between 2 March 2020 and 9 August 2021, 626 participants were randomly assigned to receive pembrolizumab plus enzalutamide and ADT and 625 participants to receive placebo plus enzalutamide and ADT. At the first interim analysis, the median follow-up was 21.1 months (range 14.8-32.0 months). rPFS was not superior with pembrolizumab versus placebo [median not reached in both arms; hazard ratio (HR) 1.20, 95% confidence interval (CI) 0.96-1.49, P = 0.9467]. Median OS was not reached in either arm (HR 1.16, 95% CI 0.88-1.53; not formally statistically tested as per the multiplicity strategy). Grade ≥3 adverse events (AEs) and serious AEs (SAEs) were reported in 61.9% versus 38.1% and 40.3% versus 23.2% of participants in the pembrolizumab versus the placebo arm, respectively. Any-grade rash occurred at a higher frequency with pembrolizumab (25.1%) versus placebo (9.3%). KEYNOTE-991 did not meet its primary endpoint and was stopped for futility. The addition of pembrolizumab to enzalutamide and ADT was associated with higher frequencies of grade ≥3 AEs and SAEs than with placebo. Rash was identified as an additional safety signal with pembrolizumab plus enzalutamide and ADT.

4597 Background: In the ENVISION pivotal phase 3 study (NCT05243550) patients with low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) were treated with UGN-102, a reverse thermal hydrogel containing mitomycin. Primary efficacy and safety results were previously reported. Complete response rate (CRR) at 3 months was 79.6%, with an 82.3% probability of remaining in response at 12 months by Kaplan–Meier estimate. Here, we present a post-hoc analysis evaluating if multifocality and tumor size influenced response rate and durability. Methods: In the single-arm ENVISION study, 240 patients with LG-IR-NMIBC received 6 weekly intravesical instillations of UGN-102; 3 months after the first dose, patients were examined for the presence of bladder cancer using cystoscopy, urine cytology testing, and for-cause biopsy. Patients achieving complete response (CR; no detectable disease) underwent follow-up with surveillance cystoscopy. In pre-specified subgroups, comparisons of patients with tumor burden (calculated as total length of all tumors) ≤3cm vs > 3 cm and single vs multiple tumors were performed for CRR at 3 months and hazard ratios (HRs) of duration of response (DoR) at 12 months after achieving CR. For the comparison of CRR, p values were calculated using Fisher’s Exact Test. HRs of DoR were calculated using a Cox proportional hazards model, and p values calculated using a log-rank test. Comparisons were not powered to identify a difference and p values were unadjusted for multiple comparisons. Results: CRR at 3 months was 82.8% vs 73.2% for patients with tumor burden ≤3 cm and > 3 cm, respectively. Of patients with CR at 3 months with tumor burden ≤3 cm and > 3 cm, 15.4% vs 20%, respectively, experienced either recurrence of LG disease, progression (either stage or grade), or death by 15 months. In patients with multiple vs single tumors, 3-month CR was 79.3% vs 82.9%; recurrence rates were 18.5% vs 11.8%. DoR HRs were not statistically significant for any comparison made (Table). Conclusions: The CRR and DoR were favorable in all subgroups and no significant differences were observed. Study limitations were the small sample size of comparator groups, single arm design, and post-hoc nature of the analysis. UGN-102 may represent a valuable treatment option for many patients with LG-IR-NMIBC. Clinical trial information: NCT05243550 . CR at 3 months CRR ratio(95% CI)/p value Recurrence within 15 months a DoR HR (95% CI)/p value Tumor burden≤3 cm>3 cm 149/180 (82.8%)30/41 (73.2%) 1.13 (0.93, 1.38)p=0.1854 b 23/149 (15.4%)6/30 (20.0%) 0.777 (0.317, 1.909)p=0.5816 b Tumor countMultipleSingle 157/198 (79.3%)34/41 (82.9%) 0.96 (0.82, 1.12)p=0.6740 b 29/157 (18.5%)4/34 (11.8%) 1.644 (0.578, 4.677)p=0.3459 b a 3-month CR patients only. b Nominal. CI, confidence interval.

Advanced prostate cancer is a cancer that began in the prostate (a part of the male body) and has spread to other parts of the body. This is a review of two clinical research studies of patients with advanced prostate cancer who were treated with relugolix combination therapy. Relugolix is a medicine taken by mouth that lowers a male sex hormone, called testosterone. Relugolix is sometimes combined with other medicines such as novel hormonal therapies (NHTs) or chemotherapy to treat advanced prostate cancer. In one study, patients were treated with relugolix combined with an NHT (abiraterone or apalutamide). In a second study, patients were treated with relugolix combined with an NHT (enzalutamide) or chemotherapy (docetaxel). Researchers wanted to understand what possible side effects may happen due to taking these medicines together as prescribed. They also wanted to see if relugolix combination therapy worked to lower testosterone in the same way as relugolix taken alone. Researchers found that most of the side effects of relugolix combined with an NHT or chemotherapy were mild or moderate. Side effects of relugolix combination therapy were similar to the side effects of the medicines when taken alone. However, patients who received relugolix with enzalutamide or docetaxel were more likely to have a serious side effect compared with patients who received relugolix taken alone. Testosterone stayed below 50 nanograms per deciliter (known as castration levels) for patients who received relugolix with NHT or chemotherapy. Patients who receive relugolix combination therapy generally experience mild or moderate side effects, rather than serious side effects. No new safety issues were found during these studies. Patients maintained low testosterone levels. Patients and their doctors should discuss the benefits and possible harms of relugolix combination therapy to treat advanced prostate cancer.

Introduction: Tapinarof cream 1% (VTAMA®, Dermavant Sciences, Inc.) is a non-steroidal, topical aryl hydrocarbon receptor agonist approved for the treatment of plaque psoriasis in adults with no restrictions on location, extent, or duration of use. In the phase 3 PSOARING trial program, tapinarof cream 1% once daily (QD) for the treatment of plaque psoriasis was efficacious and well tolerated. Plaque psoriasis affecting the head and neck region occurs commonly, with a high impact on patients’ health-related quality of life, through pruritus and psychological distress. Patients may consider topicals unacceptable for scalp/facial use due to poor cosmetic properties (e.g., greasiness), leading to low medication adherence. There is a need for efficacious, cosmetically elegant, non-steroidal topicals that can be used without restrictions.Objective: To assess patient-reported outcomes (PROs) with tapinarof cream for adults with mild to severe plaque psoriasis in the head and neck region, including the scalp, in a phase 4, open-label trial.Methods: Adults with head and neck region target lesion Physician Global Assessment (tPGA) score of 2 (mild), 3 (moderate), or 4 (severe) received tapinarof for 12 weeks. PROs included Peak Pruritus Numerical Rating Scale (PP-NRS) score for the head and neck region; achievement of ≥4-point reduction in PP-NRS score; Dermatology Life Quality Index (DLQI) score by visit; and responses to a Patient Satisfaction Questionnaire© (PSQ) at Week 12.Results: 31 patients received tapinarof; 58.1% (18/31) had the target lesion on the scalp. Baseline mean PP-NRS (head and neck region) and total DLQI scores were 5.8 and 9.7, respectively, demonstrating significant pruritus and disease impact. Improvement in mean PP-NRS score was demonstrated at Week 1 (–1.6), the earliest assessment, surpassing the minimal clinically important ≥4-point improvement by Week 12 (−4.2). At Week 12, 70.0% (n=14/20) achieved ≥4-point reduction in PP-NRS score. Mean DLQI minimal clinically important difference of −4.0 was demonstrated as early as Week 1 (−4.0), improving to −7.2 at Week 12. Most patients strongly agreed or agreed with PSQ questions assessing satisfaction with cosmetic elegance (93.3%), quick absorption (96.7%), application ease (86.7%), efficacy (83.3%), and confidence in tapinarof (83.3%). Compared with topicals used previously for plaque psoriasis, most strongly agreed or agreed that tapinarof was more effective (76.9%) and easier to use (76.9%).Conclusions: In patients with plaque psoriasis affecting the head and neck region, tapinarof cream 1% QD demonstrated rapid and clinically meaningful improvements in patient-reported pruritus and disease impact as early as Week 1, the first assessment, with continued improvement through Week 12. Patients reported high rates of satisfaction and positive perceptions of tapinarof.Funding Support: Dermavant Sciences, Inc.