First analysis of the safety and efficacy of UGN-101 in the treatment of ureteral tumors.

OBJECTIVE: UGN-101 has been approved for the chemoablation of low-grade upper tract urothelial cancer (UTUC) involving the renal pelvis and calyces. Herein is the first reported cohort of patients with ureteral tumors treated with UGN-101. PATIENTS AND METHODS: We performed a retrospective review of patients treated with UGN-101 for UTUC at 15 high-volume academic and community centers focusing on outcomes of patients treated for ureteral disease. Patients received UGN-101 with either adjuvant or chemo-ablative intent. Response rates are reported for patients receiving chemo-ablative intent. Adverse outcomes were characterized with a focus on the rate of ureteral stenosis. RESULTS: In a cohort of 132 patients and 136 renal units, 47 cases had tumor involvement of the ureter, with 12 cases of ureteral tumor only (8.8%) and 35 cases of ureteral plus renal pelvic tumors (25.7%). Of the 23 patients with ureteral involvement who received UGN-101 induction with chemo-ablative intent, the complete response was 47.8%, which did not differ significantly from outcomes in patients without ureteral involvement. Fourteen patients (37.8%) with ureteral tumors had significant ureteral stenosis at first post-treatment evaluation, however, when excluding those with pre-existing hydronephrosis or ureteral stenosis, only 5.4% of patients developed new clinically significant stenosis. CONCLUSIONS: UGN-101 appears to be safe and may have similar efficacy in treating low-grade urothelial carcinoma of the ureter as compared to renal pelvic tumors.

Route of Administration for UGN-101 and Impact on Oncological and Safety Outcomes.

BACKGROUND: UGN-101 can be used for chemoablation of low-grade upper tract urothelial carcinoma (UTUC). The gel can be administered via a retrograde route through a ureteral catheter or an antegrade route via a nephrostomy tube. OBJECTIVE: To report outcomes of UGN-101 by route of administration. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of 132 patients from 15 institutions who were treated with UGN-101 for low-grade UTUC via retrograde versus antegrade administration. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Survival outcomes are reported per patient. Treatment, complications, and recurrence outcomes are reported per renal unit. Statistical analysis was performed for primary endpoints of oncological response and ureteral stricture occurrence. RESULTS AND LIMITATIONS: A total of 136 renal units were evaluated, comprising 78 retrograde and 58 antegrade instillations. Median follow-up was 7.4 mo. There were 120 cases (91%) of biopsy-proven low-grade UTUC. Tumors were in the renal pelvis alone in 89 cases (65%), in the ureter alone in 12 cases (9%), and in both in 35 cases (26%). Seventy-six patients (56%) had residual disease before UGN-101 treatment. Chemoablation with UGN-101 was used in 50/78 (64%) retrograde cases and 26/58 (45%) antegrade cases. A complete response according to inspection and cytology was achieved in 31 (48%) retrograde and 30 (60%) antegrade renal units (p = 0.1). Clavien grade 3 ureteral stricture occurred in 21 retrograde cases (32%) and only six (12%) antegrade cases (p < 0.01). Limitations include treatment bias, as patients in the antegrade group were more likely to undergo endoscopic mechanical ablation before UGN-101 instillation. CONCLUSIONS: These preliminary results show a significantly lower rate of stricture occurrence with antegrade administration of UGN-101, with no apparent impact on oncological efficacy. PATIENT SUMMARY: We compared results for two different delivery routes for the drug UGN-101 for treatment of cancer in the upper urinary tract. For the antegrade route, a tube is inserted through the skin into the kidney. For the retrograde route, a catheter is inserted past the bladder into the upper urinary tract. Our results show a lower rate of narrowing of the ureter (the tube draining urine from the kidney into the bladder) using the antegrade route, with no difference in cancer control.

The ablative effect of mitomycin reverse thermal gel: Expanding the role for nephron preservation therapy in low grade upper tract urothelial carcinoma.

PURPOSE: Assess the real-world ablative effect of mitomycin reverse thermal gel for low-grade upper tract urothelial carcinoma (UTUC) in patients who undergo biopsy only or partial ablation and evaluate utility of complete ablation prior to UGN-101. MATERIAL AND METHODS: We retrospectively reviewed low-grade UTUC patients treated with UGN-101 from 15 high-volume centers. Patients were categorized based on initial endoscopic ablation (biopsy only, partial ablation, or complete ablation) and by size of remaining tumor (complete ablation, <1cm, 1-3cm, or >3cm) prior to UGN-101. The primary outcome was rendered disease free (RDF) rate at first post-UGN-101 ureteroscopy (URS), defined as complete response or partial response with minimal mechanical ablation to endoscopically clear the upper tract of visible disease. RESULTS: One hundred and sixteen patients were included for analysis after excluding those with high-grade disease. At first post-UGN-101 URS, there were no differences in RDF rates between those who at initial URS (pre-UGN-101) had complete ablation (RDF 77.0%), partial ablation (RDF 55.9%) or biopsy only (RDF 66.7%) (P = 0.14). Similarly, a complimentary analysis focusing on tumor size (completely ablated, <1cm, 1-3cm or >3cm) prior to UGN-101 induction did not demonstrate significant differences in RDF rates (P = 0.17). CONCLUSION: The results of the early real-world experience suggest that UGN-101 may play a role in initial chemo-ablative cytoreduction of larger volume low-grade tumors that may not initially appear to be amenable to renal preservation. Further studies will help to better quantify the chemo-ablative effect and to identify clinical factors for patient selection.

Understanding Prescribing Differences Between Urologists and Medical Oncologists in the Management of Advanced Prostate Cancer.

INTRODUCTION: The availability of oral therapies for advanced prostate cancer allows urologists to continue to care for their patients who develop castration resistance. We compared the prescribing practices of urologists and medical oncologists in treating this patient population. METHODS: The Medicare Part D Prescribers data sets were utilized to identify urologists and medical oncologists who prescribed enzalutamide and/or abiraterone from 2013 to 2019. Each physician was assigned to one of 2 groups: enzalutamide prescriber (physicians that wrote more 30-day prescriptions for enzalutamide than abiraterone) or abiraterone prescriber (opposite). We ran a generalized linear regression to determine factors influencing prescribing preference. RESULTS: In 2019, 4,664 physicians met our inclusion criteria: 23.4% (1,090/4,664) urologists and 76.6% (3,574/4,664) medical oncologists. Urologists were more likely to be enzalutamide prescribers (OR 4.91, CI 4.22-5.74, P < .001) and this held in all regions. Urologists with greater than 60 prescriptions of either drug were not shown to be enzalutamide prescribers (OR 1.18, CI 0.83-1.66, P = .349); 37.9% (5,702/15,062) of abiraterone fills by urologists were for generic compared to 62.5% (57,949/92,741) of abiraterone fills by medical oncologists. CONCLUSIONS: There are dramatic prescribing differences between urologists and medical oncologists. A greater understanding of these differences is a health care imperative.

Efficacy and Safety of Mitomycin Gel (UGN-101) as an Adjuvant Therapy After Complete Endoscopic Management of Upper Tract Urothelial Carcinoma.

PURPOSE: We describe a novel application of the reverse thermal polymer gel of mitomycin C (UGN-101) as adjuvant therapy after complete endoscopic ablation of upper tract urothelial carcinoma. MATERIALS AND METHODS: We retrospectively reviewed patients treated with UGN-101 from 15 high-volume centers. Adjuvant therapy was defined as treatment administered following visually complete endoscopic ablation. Response at primary endoscopic evaluation was defined as no visual tumor or negative biopsy. Ipsilateral disease-free and progression-free survival were estimated by the Kaplan-Meier method. Ureteral stenosis and other adverse events were abstracted from the medical records. Ureteral stenosis was defined as a condition requiring ureteral stent or nephrostomy, or that would typically warrant stent or nephrostomy. RESULTS: Adjuvant UGN-101 after complete endoscopic ablation was used in 52 of 115 (45%) renal units in the oncologic analysis. At first endoscopic evaluation, 36/52 (69%) were without visible disease. At 6.8 months' median follow-up, the ipsilateral disease-free rate was 63%. Recurrence after adjuvant UGN-101 therapy was more likely in multifocal tumors compared to unifocal (HR 3.3, 95% CI 1.07-9.91). Compared with UGN-101 treatment for chemoablation of measurable disease, there were significantly fewer disease detections with adjuvant therapy (P < .001). Ureteral stenosis after UGN-101 was diagnosed in 10 patients (19%) undergoing adjuvant therapy compared to 17 (29%) undergoing chemoablative therapy (P = .28). CONCLUSIONS: In patients being considered for UGN-101, maximal endoscopic ablation prior to UGN-101 treatment may result in fewer patients with disease at first endoscopy and possibly fewer adverse events than primary chemoablative therapy. Longer follow-up is needed to determine if UGN-101 after complete endoscopic ablation will lead to durable disease-free interval.

Early experience with UGN-101 for the treatment of upper tract urothelial cancer - A multicenter evaluation of practice patterns and outcomes.

BACKGROUND: UGN-101 is a novel delivery system for intracavitary treatment of upper tract urothelial cancer (UTUC). UGN-101 was approved based on a pivotal trial for small volume residual low-grade UTUC. Our aim was to report our experience with UGN-101 in a more heterogenous and real-world setting. METHODS: We performed a retrospective review of all UGN-101 cases from 15 institutions with a focus on practice patterns, efficacy, and adverse effects. We include UGN-101 utilization in both the chemoablative and adjuvant setting. RESULTS: There were a total 136 renal units treated from 132 patients. The majority of cases were biopsy proven low-grade UTUC. Practice patterns varied considerably - the most common administration technique was antegrade instillation via a percutaneous nephrostomy. When utilized in the adjuvant setting, 69% of patients were disease free at the time of their first endoscopic evaluation, while in the chemoablative setting, 37% were endoscopically clear on the first evaluation (P < 0.001). Complete response was higher in patients with smaller tumor size prior to UGN-101 induction; low volume (<1 cm) residual disease was associated with a 70% complete response, similar to disease free rate at first endoscopic evaluation when UGN-101 was used in the adjuvant setting. The use of maintenance doses of UGN-101 was reported in 27% of cases. The overall incidence of new onset, clinically significant ureteral stenosis was 23%. CONCLUSIONS: This study represents the largest review of patients treated with UGN-101 and can serve as a basis of ongoing hypotheses regarding treatment with UGN-101 for UTUC.

Clinicopathological analysis of recurrence and progression of low-grade papillary urothelial carcinoma of the urinary bladder: Predicting the outcome.

BACKGROUND: Urothelial carcinoma of the urinary bladder is the most common malignancy of the urinary system. Patients with low grade papillary urothelial carcinoma (LGPUC) usually have a low risk for tumor recurrence and progression; yet a subset of patients develop recurrence or grade/stage progression to high-grade papillary urothelial carcinoma (HGPUC). The clinicopathological and molecular factors that contribute to this progression are yet to be determined. OBJECTIVES: In our study, we aimed to assess the incidence and clinicopathological factors associated with tumor recurrence/progression of LGPUC. METHODS: Using a pathological database of surgical specimens from patients who underwent bladder biopsies and/or transurethral resection of bladder tumors (TURBTs) between August 01, 2011, and July 31, 2021, at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed. RESULTS: Of the total 258 patients included, 157 (60.9 %) had "no recurrence", 85 (32.9 %) had ≥1 "recurrence of LGPUC", and 16 (6.2 %) had "grade progression to HGPUC". The mean follow-up time was 31.5 ± 32 months. Patients with "grade progression" and "recurrence of LGPUC" had larger mean tumor size on initial biopsy and multiple lesions on initial cystoscopy compared to those with "no recurrence." Interestingly, former smokers had 2.5- and 8.5-times higher risk of recurrence of LGPUC and grade progression, respectively. CONCLUSION: Since the majority of our patients did not develop recurrence, we question whether there is tendency to overclassify the papillomas as LGPUC based on the 2004 WHO/ISUP consensus grading classification.

Variations in Opioid Use Following Robotic Radical Prostatectomy in South Florida.

Introduction: Opioid dependency has been a persistent issue in the United States over the past two decades. Increased efforts have been made to reduce opioid prescribing. Our objective was to quantify at-home opioid requirements following radical prostatectomy. Methods: Written questionnaires were administered to patients 1 week following robot-assisted laparoscopic radical prostatectomy (RALP). Patients provided data on opioid use, pain levels, and demographic characteristics. Results: Sixty-five patients were included. Median age (interquartile range [IQR]) was 69 (62-72) years. The majority were white (85%) and hispanic (67%). Prescriptions ranged from 6 to 15 pills of 5-mg oxycodone equivalents. Twenty-two percent (145/663) of the prescribed pills in the study were consumed. Fifty-four percent (35/65) of patients did not take opioids. Of the 30 patients who took opioids, median use (IQR) was 4.5 (3-6) pills. Forty-six percent (30/65) reported catheter-related pain. Patients who took opioids reported higher levels of pain. On generalized linear regression, younger age, lower levels of education, and living with a family member were factors associated with increased risk for opioid use (all p < 0.05). Conclusions: Despite the Florida Department of Health's restriction on narcotic prescriptions to 3-day supplies, opioids are still overprescribed in our region. The majority of patients do not require opioids after RALP, and patients who do require an opioid analgesic can be adequately managed with less than 6 pills of 5-mg oxycodone equivalents.

Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing.

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An alternative way to treat PCa is by repurposing of existing drugs that were initially intended for other conditions. By extrapolating the effects of previously approved drugs to the intracellular processes of PCa, treatment options will expand. In addition, drug repurposing is cost-effective and efficient because it utilizes drugs that have already demonstrated safety and efficacy. This review catalogues the drugs that can be repurposed for PCa in preclinical studies as well as clinical trials.

The Role of Health Literacy in Prostate Cancer Screening.

OBJECTIVE: To determine if there is an association between self-reported health literacy and rates of prostate cancer screening through PSA testing. METHODS: This secondary data analysis utilized information from the 2016 Behavioral Risk Factor Surveillance System (BRFSS). The primary exposure was self-reported health literacy, and the primary outcome was whether patients underwent prior PSA testing. Males 55-69 years old from 13 states were included in the study and were excluded if they had any missing data. Participants were categorized into low, moderate, or high level of health literacy. Confounders were adjusted for using binary logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: A total of 12,149 participants were included. Five percent of participants reported low health literacy, 54% moderate health literacy, and 41% high health literacy. Compared with study participants who self-reported high levels of health literacy, the odds of undergoing PSA testing were 59% lower in those with low health literacy (OR 0.41; 95% CI 0.28-0.64) and 30% lower in those with moderate health literacy (OR 0.70; 95% CI 0.60-0.83). CONCLUSIONS: Our research demonstrates a positive association between self-reported health literacy and the likelihood of PSA screening. While PSA screening can be controversial, health literacy may serve as a window into which patients are more likely to be proactive in their urologic care. Future studies examining how health literacy effects other urologic conditions is necessary.

Trends in Positioning for Robotic Prostatectomy: Results From a Survey of the Endourological Society.

PURPOSE: most robot-assisted laparoscopic prostatectomies (RALP) are performed with the patient in lithotomy, carrying risks of positioning-related complications. Newer robot models have allowed for supine positioning, potentially avoiding these pitfalls. We gauged the current sentiment on patient positioning among surgeons who perform robot-assisted surgery. METHODS: we surveyed members of the Endourological Society regarding their practice settings and their opinions on positioning for robot-assisted laparoscopic prostatectomy. Summary statistics were reviewed and data were analyzed using chi-square tests and t-tests. RESULTS: our survey had 92 eligible respondents. The majority were fellowship-trained, with 51% trained in robotics and 57% practicing in the U.S. with a mean of 13 years of practice. Most were working in an academic setting (69%) and performing at least 25 robotic prostatectomies yearly. 28 respondents used the Intuitive Surgical Inc. da Vinci® Xi™ exclusively (30%), and nearly two-thirds used it sometimes. Although 54% of respondents considered using supine positioning, less than half of these surgeons used it regularly, while 75% overall preferred lithotomy. A majority attributed this choice to surgical team familiarity with lithotomy positioning. Surgeons in the U.S. and those using the da Vinci® Xi™ were more likely to consider supine positioning. CONCLUSIONS: lithotomy position is the standard for RALP procedures; nonetheless, it poses significant risks that might be avoided with supine positioning. Our survey suggests that, although supine positioning has been considered, it has not gained momentum in practice. Addressing factors of inertia in training practices and one's surgical team might allow for novel and safer approaches.

The Association Between Race and 5-year Survival in Patients With Clear Cell Renal Cell Carcinoma: A Cohort Study.

OBJECTIVE: To determine if race was associated with 5-year cause-specific survival in patients with clear cell renal cell carcinoma. MATERIALS AND METHODS: Outcomes were investigated using the Surveillance Epidemiology and End Results database with data from 13 states between the years 2007-2015. Covariates included age, sex, insurance, marital status, and tumor stage at diagnosis. Patients <18 years old or with missing data for race, survival time or insurance status were excluded. Cox regression models were used to determine associations through hazard ratios (HR) with 95% confidence intervals (CI) and to adjust for covariates. RESULTS: A total of 8421 subjects were included in the analysis. After adjustment, there was no association between race and 5-year cause-specific survival in patients with ccRCC (Black- HR: 0.96, 95%CI: 0.83,1.12; American Indian/Alaskan- HR: 1.01, 95%CI: 0.75,1.36; Asian Pacific Islander- HR: 0.99, 95%CI: 0.82,1.12). Older individuals and those with regional or distant tumors showed an increased hazard of death, while females and insured patients showed decreased hazard. CONCLUSION: Our study found that race was not associated with 5-year cause-specific survival from clear cell renal cell carcinoma. However inferior overall survival in Blacks with RCC has been well demonstrated in the literature. Our findings suggest that differences in survival may not be driven by cause-specific factors such as renal cell carcinoma, but rather social determinants of health which disproportionality affect Black patients. Further studies with more power that incorporate information on income, comorbidities, education status, and access to care are therefore necessary.

A Comparison Between AMS 700 and Coloplast Titan: A Systematic Literature Review.

There are only two three-piece inflatable penile prostheses (IPP) available to patients in the American market: the AMS (American Medical Systems) 700TM series (Boston Scientific, Massachusetts) and the Coloplast Titan® series (Coloplast, Minnesota), and data comparing the two are scant. The aim of our study was to summarize the current scientific evidence comparing the two. A systematic literature review was conducted on PubMed. A 10-year filter was placed to include only studies published after Coloplast launched the Titan Touch® release pump. Eligibility criteria included articles discussing specifically the AMS 700TM and Coloplast Titan® models. Further searches for studies on patient/partner satisfaction were conducted. Abstracts were reviewed to include studies focusing specifically on the models we are studying and studies on patient satisfaction using the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire. The Coloplast device demonstrated slightly greater resistance to the stimulated forces of penetration and gravity. Coloplast implants coated with vancomycin/gentamicin had the highest infection rate followed by the AMS penile prosthesis and the rifampin/gentamicin coating had the lowest infection rate. Prosthesis durability and survival were similar between both brands. Overall satisfaction was high but comparisons are inconsistent. The literature is inconclusive about which device is superior. We suggest randomized, multicenter, prospective studies to help further elucidate the highlights of each product.

Does Health Insurance Modify the Association Between Race and Cancer-Specific Survival in Patients with Urinary Bladder Malignancy in the U.S.?

Background: Scientific evidence on the effect of health insurance on racial disparities in urinary bladder cancer patients' survival is scant. The objective of our study was to determine whether insurance status modifies the association between race and bladder cancer specific survival during 2007-2015. Methods: The 2015 database of the cancer surveillance program of the National Cancer Institute (n = 39,587) was used. The independent variable was race (White, Black and Asian Pacific Islanders (API)), the main outcome was cancer specific survival. Health insurance was divided into uninsured, any Medicaid and insured. An adjusted model with an interaction term for race and insurance status was computed. Unadjusted and adjusted Cox regression analysis were applied. Results: Health insurance was a statistically significant effect modifier of the association between race and survival. Whereas, API had a lower hazard of death among the patients with Medicaid insurance (HR 0.67; 95% CI 0.48-0.94 compared with White patients, no differences in survival was found between Black and White urinary bladder carcinoma patients (HR 1.24; 95% CI 0.95-1.61). This may be due a lack of power. Among the insured study participants, Blacks were 1.46 times more likely than Whites to die of bladder cancer during the 5-year follow-up (95% CI 1.30-1.64). Conclusions: While race is accepted as a poor prognostic factor in the mortality from bladder cancer, insurance status can help to explain some of the survival differences across races.

Insurance status as a modifier of the association between race and stage of prostate cancer diagnosis in Florida during 1995 and 2013.

BACKGROUND: Cancer stage at diagnosis is a critical prognostic factor regarding a patient's health outcomes. It has yet to be shown whether insurance status across different race has any implications on the stage of disease at the time of diagnosis. This study aimed to investigate whether insurance status was a modifier of the association between race and stage of previously undetected prostate cancer at the time of diagnosis in Florida between 1995 and 2013. METHODS: Secondary data analysis of a cross-sectional survey using information from the Florida Cancer Data System (n = 224,819). Study participants included black and white males diagnosed with prostate cancer in Florida between 1995 and 2013. The main outcome variable was stage of prostate cancer at diagnosis. The main independent variable was race (black vs white). Adjusted logistic regression models were used to explore the association between race, insurance status and stage at diagnosis. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. RESULTS: Black males were more likely to be diagnosed with late stage prostate cancer (OR 1.31; 95% CI 1.27-1.35). Being uninsured (OR 2.28; 95% CI 2.13-2.45) or having Medicaid (OR 1.84; 95% CI 1.70-1.98) was associated with a diagnosis of late stage cancer. Stratified analysis for health insurance revealed that blacks had an increased risk for late stage cancer if uninsured (OR 1.29; 95% CI 1.07-1.55) and if having Medicare (OR 1.39; 95% CI 1.31-1.48). CONCLUSION: Insurance status may modify the effect of race on late stage prostate cancer in black patients.