Sharma, Vidit

416 Background: Urethral recurrence (UR) has been reported to occur in up to 5% of patients following radical cystectomy (RC). Debate continues regarding the utility of screening for UR after RC. Moreover, oncologic outcomes of patients with UR remain incompletely described, and reports have been limited by small cohort sizes. Herein, we evaluated risk factors for UR as well as cancer-specific survival (CSS) and overall survival (OS) among patients with UR. Methods: We reviewed our institutional RC registry to identify patients with UR following RC. Logistic regression was used to assess risk factors for UR. Kaplan-Meier and Cox proportional hazard regression were used to compare outcomes in those with UR diagnosis prompted by symptoms versus those with asymptomatic UR diagnosed on surveillance cytology. Results: Overall, 2930 patients underwent RC from 1980-2018, with a median post-operative follow-up of 4.9 years (IQR 1.6-11.0), of whom 144 (4.9%) were subsequently diagnosed with UR. Prostatic urethral involvement at RC (odds ratio [OR] 5.75 [3.67-9.01], p < 0.0001) and higher pT-stage (OR 3.57 [2.07-6.14], p < 0.0001) were associated with an increased risk of UR, whereas receipt of continent urinary diversion (OR 0.34 [0.20-0.58], p < 0.0001) was associated with a decreased risk of UR. A total of 72/144 (50%) patients were diagnosed with UR based on symptoms, and 104/144 (72.2%) patients with UR underwent subsequent urethrectomy. Patients with symptomatic recurrence had higher tumor stage on urethrectomy than those with asymptomatic recurrence (≥pT2 in 13.1% vs 3.1%, p = 0.007). At a median follow-up of 2.6 years (IQR 1.0-7.1) after UR, 68 of the patients with UR died of urothelial carcinoma. Kaplan-Meier analyses suggest longer median overall and cancer-specific survival for patients with UR detected by cytology than those presenting with symptoms (p = 0.05 for both). On multivariable analyses, patients who experienced UR had significantly increased risk of cancer-specific (hazard ratio [HR] 1.93 [95% confidence interval 1.50-2.50), p < 0.0001) and all-cause mortality (HR 1.34 [1.13-1.65], p = 0.001). Conclusions: Approximately 5% of patient undergoing RC experience UR, with higher pT-stage and prostatic urethral involvement increasing the risk of UR. Asymptomatic detection of UR was associated with lower pathologic stage at urethrectomy as well as longer cancer-specific and overall survival, supporting urethral surveillance after RC.

405 Background: The diagnosis of upper tract urothelial carcinoma (UTUC) is frequently obtained via diagnostic ureteroscopy (URS) with biopsy. In a recent meta-analysis of five retrospective series comparing UTUC RNU patients with and without prior diagnostic URS, prior URS was associated with intravesical recurrence of urothelial carcinoma. However, there remains an incomplete understanding of the risks of URS on intravesical recurrence after RNU, and existing studies have not examined the risks of URS without endoscopic biopsy or percutaneous biopsy alone. Here, we query our institutional RNU registry to determine if UTUC diagnostic modality influences post-RNU intravesical recurrence risk. Methods: Years 1995 to 2019 of our institutions RNU registry were queried. Patients with UTUC were divided into four groups: 1) URS with endoscopic biopsy; 2) URS without endoscopic biopsy (visual confirmation alone); 3) percutaneous biopsy without any URS; 4) no URS and no percutaneous biopsy. Exclusion criteria included pure non-urothelial histology, RNU for benign indications, and prior/concomitant cystectomy. The primary outcome was intravesical recurrence of urothelial carcinoma compared across the four groups using Kaplan-Meier log-rank analyses and Cox-proportional hazard modeling (hazard ratio = HR). Results: In a cohort of 878 patients (mean post-RNU follow-up 43 months), 461 (53%) had URS with biopsy, 130 (15%) had URS without biopsy, 229 (26%) had no URS or percutaneous biopsy, and 58 (7%) had percutaneous biopsy alone. The 3-year intravesical recurrence rate was 27%, 22%, 18%, 12% for groups 1-4, respectively. Covariates associated with intravesical recurrence on univariable analysis included age (HR 1.03, p < 0.01), female gender (HR 0.76, p = 0.06), history of bladder cancer (HR 1.39, p = 0.01), current smoker (HR 1.49, p = 0.04), and multifocality (HR 1.34, p = 0.03). After adjusting for these covariates, multivariable analysis found that group 1 (URS with biopsy) was associated with increased intravesical recurrence (HR 1.41, p = 0.03) relative to group 3 (no URS or percutaneous biopsy). Compared to group 1, the hazard ratio for intravesical recurrence was not significantly different for group 2 (HR 1.18, p = 0.45) or group 4 (HR 1.11, p = 0.79). Conclusions: Patients undergoing ureteroscopic biopsy to diagnose UTUC prior to RNU had a higher risk of intravesical recurrence after RNU compared to patients who did not undergo any URS or percutaneous biopsy. This agrees with prior literature and suggests that aggressive ureteroscopic manipulation of UTUC tumors via biopsy may promote shedding of urothelial carcinoma cells capable of seeding the bladder. Our study does support the initiation of a randomized trial to determine if intravesical chemotherapy after ureteroscopic biopsy can reduce intravesical urothelial carcinoma recurrences.

395 Background: Patients with BCG-unresponsive carcinoma in situ (CIS) are treated with radical cystectomy (RCx) or salvage intravesical chemotherapy (SIC). Recently, the FDA approved pembrolizumab for BCG-unresponsive CIS +/- papillary tumors. Given the costs and toxicities of pembrolizumab, it remains unclear whether its benefits are sufficient to warrant widespread use for BCG-unresponsive CIS. To that end, we conducted a cost-effectiveness analysis comparing pembrolizumab with RCx and SIC (using gemcitabine-docetaxel as the prototypical regimen) for patients with BCG-unresponsive CIS. Methods: A decision-analytic Markov model compared pembrolizumab, SIC (with gemcitabine-docetaxel), and RCx for patients with BCG-unresponsive CIS +/- papillary tumors who are RCx candidates (index patient 1) or are unwilling/unable to undergo RCx (index patient 2). Each treatment option was a Markov node containing distinct variations of the following health states: surveillance, recurrence, progression to MIBC, progression to metastasis, treatment toxicity, and death. Incremental Cost-Effectiveness Ratios (ICERs) were compared using a willingness-to-pay threshold of $100,000/Quality-adjusted life year (QALY). The model used a US Medicare perspective with a 5-year time horizon for the base case. One-way and probabilistic sensitivity analyses were performed for all model parameters. Results: For index patient 1, pembrolizumab was not cost-effective vs. RCx (ICER $1,403,008) or SIC (ICER $2,011,923). One-way sensitivity analysis revealed that pembrolizumab only became cost-effective relative to RCx with a > 93% price reduction. Relative to RCx, SIC was cost-effective for time horizons < 5 years and nearly cost-effective at 5 years (ICER $118,324). One-way sensitivity analysis revealed that SIC became cost-effective relative to RCx if its risk of recurrence or metastasis at 2 years was less than 55% or 5.9%, respectively. For index patient 2, pembrolizumab required > 90% price reduction to be cost-effective vs. RCx (ICER $1,073,240). Probabilistic sensitivity analyses revealed that pembrolizumab was unlikely to be cost-effective even at high willingness-to-pay thresholds. Further sensitivity analyses found that no two-way combination of extrapolated values resulted in pembrolizumab being favored over RCx or SIC for either index patient. Conclusions: Based on decision-analytic Markov modeling of treatment options for patients with BCG-unresponsive CIS, pembrolizumab was unlikely to be cost-effective without a > 90% price reduction. While both RCx and SIC were more cost-effective than pembrolizumab, further studies may validate the cost-effectiveness of gemcitabine-docetaxel relative to RCx if the recurrence and metastasis thresholds are met. Overall, our model supports the preferential use of RCx and SIC over pembrolizumab for BCG-unresponsive CIS.

430 Background: Malignant melanoma of the female urethra accounts for less than 1% of all melanoma and less than 4% of urethral cancer. Due to limited data regarding management and outcomes of this condition, we evaluated the management and outcomes of urethral melanoma in females over the last 20 years at our institution. Methods: Patients were identified via retrospective review of the medical record. Those with metastatic disease at initial diagnosis were excluded. We evaluated primary and adjuvant treatments, disease recurrence and overall survival. Results: Fifteen women (median age 71, range 55, 82) were identified. Majority of masses involved the distal urethra (86.6%). All patients underwent primary surgical resection (60.0% partial urethrectomy, 40.0% radical urethrectomy). Disease recurrence and metastatic spread occurred in 73.3% (median 7 months, IQR 4, 12) and 60% (median 6 months, IQR 3, 9) of patients, respectively. 90.9% of patients with recurrence received adjuvant therapy: 5 chemotherapy and radiation, 4 chemotherapy only, 1 anterior exenteration. Of the 9 patients undergoing chemotherapy, treatment regimens were varied and included checkpoint inhibitors (2/9), platinum-based chemotherapy (3/9), tyrosine kinase inhibitors (2/9), taxels (2/9), and alkylating agents (1/9). Median overall survival was 27 months (IQR 7.5, 57.5). Conclusions: Malignant melanoma of the urethra is locally aggressive with a high likelihood of recurrence and metastases resulting in poor long-term survival. Despite high recurrence rates, our data highlight the lack of consensus adjuvant treatment regimens. Future research is required to identify neoadjuvant, combination, and adjuvant treatment approaches to improve disease outcomes.

Abstract Background: We report the first case of instillation of alteplase, a tissue plasminogen activator, to dissolve occlusive upper urinary tract blood clot. Case Presentation: A 67-year-old Caucasian man with a solitary kidney became dialysis dependent because of upper urinary tract clot obstruction after ureteral stent placement for obstructing ureterolithiasis. After failure of more conservative measures, 10 mg of alteplase was instilled through nephrostomy tube daily for 2 consecutive days 30 minutes before manual irrigation with physiologic saline. After alteplase instillation, the occlusive blood clot dissolved with rapid improvement in urinary output and creatinine. Conclusions: Alteplase instillation through nephrostomy tube is a viable option to dissolve obstructing upper urinary tract blood clots.