Faculty Bibliography

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/METHODS: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/METHODS: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/CONCLUSIONS: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/RESULTS: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.

Localized upper tract urothelial carcinoma (UTUC) is a difficult disease for clinicians to treat, due to the multitude of oncological and patient factors to consider. Despite the challenges of diagnostic staging, endoscopic management, and disease recurrence, there is still a need for local therapeutic options that do not subject patients to the morbidities of radical nephroureterectomy (RNU). Intraluminal chemotherapies have allowed for improved oncological control in patients with low-grade disease receiving renal-sparing treatment approaches. This narrative review discusses the treatment modalities available for localized low-grade UTUC, with a focus on the current status of chemoablation. The OLYMPUS trial was a pivotal study that lead to the Food and Drug Administration (FDA) approval of UGN-101 (mitomycin-C) in April 2020 for the treatment of low-grade UTUC, and intraluminal chemotherapy is now a widely used modality for managing this disease. The trial reported a complete response (CR) rate of 59%, and an estimated treatment durability of 82% at 1 year. However, a concern was the reported 44% ureteral stricture rate using the retrograde approach. More research is currently underway to determine the ideal instillation method for intraluminal therapies (e.g., retrograde vs. antegrade). Lastly, we discuss upcoming treatment options. Newer novel agents like padeliporfin vascular targeted photodynamic (VTP) therapy (brand name TOOKAD) are currently being studied, which will in hope provide additional treatment options for UTUC patients.

PURPOSE:Ureteroscopy is a commonly performed procedure, with postoperative pain that can lead to revisits and opioid prescribing. Perioperative gabapentinoids have shown promise in decreasing pain and opioid use. We hypothesized that single-dose perioperative pregabalin would be safe and efficacious for decreasing pain after ureteroscopy. MATERIALS AND METHODS:This was an Institutional Review Board-approved and registered blinded, placebo-controlled trial conducted at a single institution. Patients undergoing ureteroscopy without histories that would limit use of opioids, gabapentinoids, and nonsteroidal medications were enrolled. Either 300 mg pregabalin or placebo was administered 1 hour before ureteroscopy. Pain was assessed using a visual analogue scale before administration and 1 hour after surgery. Clinical factors, pain scores, a proxy for cognition, patient satisfaction, and opioid prescribing were assessed in the first 30 postoperative days. RESULTS:= .004), a finding that remained statistically significant when accounting for patient age and preoperative pain scores. There was no difference in the measure of cognition or in reports of adverse events. CONCLUSIONS:In this trial evaluating the efficacy of single-dose perioperative pregabalin in ureteroscopy, pregabalin did not decrease postoperative pain when compared to placebo. Urologists should not routinely use this adjunctive medication in ureteroscopy, as it is unlikely to provide benefit.

BACKGROUND:Intracavitary UGN-101 is approved for the treatment of low-grade noninvasive upper tract urothelial carcinoma (UTUC). Post-commercialization studies underscore the benefit of UGN-101 administration for patients with imperative indications for whom radical nephroureterectomy (RNU) is not a viable option. OBJECTIVE:To describe the use, efficacy, and safety of UGN-101 in patients with UTUC with imperative indications for renal preservation, including high-grade disease. DESIGN, SETTING, AND PARTICIPANTS/METHODS:Patients receiving UGN-101 with imperative indications were retrospectively analyzed using a multicenter centralized registry from 15 high-volume academic and community centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:We defined imperative indications as patients with a solitary kidney, the presence of chronic kidney disease (CKD) with a glomerular filtration rate <30 ml/min, bilateral UTUC, and patients unfit for or unwilling to undergo surgical extirpation. Tumor characteristics, disease progression/recurrence, and adverse events were recorded on a per-renal-unit basis. RESULTS AND LIMITATIONS/CONCLUSIONS:UGN-101 was instilled into 52 renal units (38%) in 48 patients for imperative indications, including 29 patients (56%) with a solitary kidney, 11 kidneys (21%) in the setting of bilateral UTUC, six patients (12%) with CKD, and six patients (12%) who were unfit for or unwilling to undergo RNU. Twelve renal units had biopsy-proven high-grade papillary disease. Tumors were completely ablated before induction therapy in 34% of cases, while 66% had tumor present. Following induction therapy, 17 patients (40%) had no evidence of disease (NED) on ureteroscopy, 88% of whom maintained this status at median follow-up of 10.8 mo. In the cohort with high-grade disease, five patients (45%) had NED at initial post-induction primary disease evaluation. Adverse events included pyelonephritis (8%), ureteral stenosis (8%), anemia (6%), and acute renal failure (4%). Limitations include the retrospective study design, the lack of long-term follow up, and patient selection bias. CONCLUSIONS:Intracavitary therapy with UGN-101 in patients with UTUC and imperative indications shows promise as a kidney-sparing treatment modality. While long-term follow-up is needed, this intracavitary treatment may help in prolonging time to RNU and delaying the morbidity of hemodialysis in this comorbid population. PATIENT SUMMARY/RESULTS:We reviewed results for patients with cancer in the upper urinary tract and an additional condition that would not allow kidney removal who received treatment with a gel called UGN-101. Our results suggest that UGN-101 shows promise as a kidney-sparing treatment. It may delay the time until kidney removal is needed in these patients and avoid the negative effects associated with dialysis.

OBJECTIVES/OBJECTIVE:To assess the safety profile of antegrade mitomycin gel instillation through a percutaneous nephrostomy tube (PCNT) for upper tract urothelial carcinoma (UTUC), with aims to decrease morbidity associated with therapy. PATIENTS AND METHODS/METHODS:Patients undergoing antegrade administration of mitomycin gel via PCNT were retrospectively included for analysis from four tertiary referral centers between 2020 and 2022. The primary outcome was safety profile graded by Common Terminology Criteria for Adverse Events (v5.0). Post-therapy disease burden was assessed by primary disease evaluation (PDE) via ureteroscopy. RESULTS:Thirty-two patients received at least one dose of mitomycin gel via PCNT for UTUC, 29 of whom completed induction and underwent PDE. Thirteen (41%) patients had residual tumor present prior to induction therapy. At a median follow up of 15.0 months following first dose of induction therapy, ureteral stenosis occurred in 3 (9%) patients, all of which were treated without later recurrence or chronic stenosis. Other adverse events included fatigue (27%), flank pain (19%), UTI (12%), sepsis (8%), and hematuria (8%). No patients had impaired renal function during follow up and there were no treatment related deaths. Seventeen patients (59%) had no evidence of disease at PDE, and have not recurred at a median follow up of 13.0 months post-induction CONCLUSIONS: Administration of mitomycin gel via a percutaneous nephrostomy tube offers a low rate of ureteral stenosis, demonstrates a favorable safety profile, and is administered without general anesthesia.

BACKGROUND:Gender disparities in editorial board composition exist across a variety of surgical subspecialties. OBJECTIVE:To investigate temporal variation in gender representation on the editorial boards of urology journals and assess the relationship between editorial board composition and female authorship. DESIGN, SETTING, AND PARTICIPANTS/METHODS:We analyzed female authorship and editorial board composition between 2002 and 2020 among eight high-impact urology journals. Female publication status was assessed using publication records retrieved from PubMed. Editorial board information was manually extracted and titles were grouped for comparison as Editor-in-Chief, mid-level editor, and consulting editors. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS/METHODS:Female representation across different editorial levels was analyzed via hierarchical logistic regression with additional terms to test for between-journal differences in overall representation and change over time. The relationship between representation on editorial boards and as publication authors was assessed at the journal level via correlation. RESULTS AND LIMITATIONS/CONCLUSIONS:Eight journals and 49 412 articles were analyzed. No female has held the title of Editor-in-Chief for any of these eight journals in 18 yr. Significant growth was seen for mid-level editors, whereas no growth was seen for consulting editors. Neurourology and Urodynamics and Journal of Sexual Medicine had significantly higher than average female editorial board representation (p < 0.05). Across the eight journals, there was a statistically significant correlation between the proportion of overall female authors and female editors (r = 0.93, 95% confidence interval 0.65-0.99). For all journals, the proportion of female contributing authors is greater than the proportion of female editorial board members. CONCLUSIONS:Women in urology represent a small but increasing presence as editorial board members. Clear differences exist between journals, potentially attributable to specialty-specific demographics. Despite increasing representation, no female has ever been appointed Editor-in-Chief for any of the eight journals evaluated. At the journal-specific level, a positive correlation was observed between female editorial staff and female authorship. Given the implication of both academic authorship and editorial board assignment on academic advancement, actionable changes are outlined to guide improvement in gender diversity at the journal level. PATIENT SUMMARY/RESULTS:Females are under-represented on the editorial boards for urology journals, although some roles have seen growth over time. Moreover, female editorial board membership is associated with representation of females among article authors. Gender disparities in both are noteworthy because they affect career paths and contribute to the gender gap in urology.

Renal cryoablation (CA) has become an accepted treatment option for patients with small renal tumors and co-morbidities that make them less favorable for surgical intervention. Complications from renal CA have been previously reported and are generally associated with increasing size and central location of the tumor. Ureteral injury from renal CA, although rare, can be difficult to manage and may require complex surgeries in patients who are poor surgical candidates to begin with. We report a case of a renal mass CA complicated by proximal ureteral necrosis and transection, treated with multiple minimally invasive procedures ultimately resulting in successful bridging of the necrotic segment with nephroureteral stent and thus avoiding major surgery.

Background and Objective/UNASSIGNED:Glucocorticoids, secreted from the adrenal gland, are commonly used in the treatment of castration-resistant prostate cancer (CRPC) because of their anti-inflammatory and anti-toxic effects. However, glucocorticoids have been reported to have the opposite effects within the course of treatment. Many studies have shown that glucocorticoid receptors (GRs) are involved in the establishment of a dominant population of androgen-independent malignant cells, which may result in CRPC. In this review, we summarized the mechanisms of GRs in CRPC and the clinical application of glucocorticoids based on the present evidence. Methods/UNASSIGNED:We summarized the isoforms of GRs and the mechanisms involved in CRPC. An updated literature search was performed from the ClinicalTrials database, the National Center for Biotechnology Information database and European Union Drug Regulating Authorities Clinical Trials database. The focus was on the timeframe from 2017 to 2022. At least one primary or secondary outcome [prostate-specific antigen (PSA) response rate, progression-free survival (PFS) or overall survival (OS) and median time to PSA progression] according to studies should be included. Key Content and Findings/UNASSIGNED:, guidelines of CSCO, etc.). Based on the collected data, prednisone appears to be the most widely used steroid hormone, followed by dexamethasone. Comparisons of the PSA response rate and the median time to PSA progression revealed that the efficacy of the 2 hormones is similar; however, further research on the effect of steroid hormone in CRPC is still required. Conclusions/UNASSIGNED:Various GR isoforms may play an important part in the development of CRPC, whose mechanism remains unclear. Most clinical trials have focused on the use of prednisone in the last 5 years. The efficacy of prednisone and dexamethasone is similar.