Citations

421 Background: Reported rates of adherence to post-radical cystectomy (RC) surveillance guidelines in real-world practice have been as low as 9%, in part reflecting a nihilistic view held by many of the value of routine follow-up. Indeed, conflicting data exist regarding the outcomes of patients with cancer recurrence detected by scheduled surveillance versus symptom-directed evaluation. Herein, we assessed comparative outcomes of patients with symptomatic recurrence (SR) versus asymptomatic recurrence (AR) after RC. Methods: We reviewed our Institutional Registry of RC patients to identify patients with cancer recurrence following RC. Presenting symptoms in the SR cohort included pain, constitutional symptoms, gastrointestinal symptoms, and hematuria/voiding symptoms, whereas AR was defined as recurrence detected on routine surveillance in the absence of symptoms. Baseline demographic and clinical characteristics were compared between study groups using chi-square and t-test. Kaplan-Meier and Cox survival analyses were performed to compare cancer-specific survival (CSS) and overall survival (OS) between AR and SR groups. Results: Of 3822 patients who underwent RC from 1980-2018 (with a median follow-up after RC of 2.4 years (IQR 1.1,5.5), a total of 1100 were subsequently diagnosed with recurrence, including 311 (28.3%) with AR and 789 (71.7%) with SR. Median time from RC to recurrence was longer in the AR group (13.2 months) than in the SR group (10.8 months; p = 0.01). Presenting symptoms included pain (70.2%), constitutional symptoms (50.7%), gastrointestinal symptoms (23.3%), and urinary symptoms (23.3%). Median follow-up after recurrence was 2.4 years (IQR 1.1-5.5), during which time 997 patients died, including 840 who died of bladder cancer. Compared to patients with SR, patients with AR had a longer median CSS (54.5 months vs 27.3 months, p < 0.001) and OS (43.0 months vs 25.8 months, p < 0.001). On multivariable Cox proportional hazards models adjusting for demographic and clinical factors, SR was associated with a significantly increased risk of cancer-specific (hazard ratio [HR] 1.66 [95% confidence interval 1.41-1.96], p < 0.0001) and all-cause mortality (HR 1.48 [1.23-1.71], p < 0.0001). Conclusions: SR after RC is associated with worse oncologic outcomes than post-RC recurrence detected by routine surveillance. As such, continued surveillance is warranted, while further study is needed to determine the optimal follow-up regimen balancing patient and disease risks.

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.

TPS3172 Background: Bladder cancer is a leading cause of cancer death in the United States. Over 90% of bladder cancer cases are urothelial carcinomas (UC) that may present as a non-muscle-invasive (NMIBC) or muscle-invasive disease (MIBC). Standard of care for NMIBC includes transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and immunotherapy with Bacillus Calmette-Guerin (BCG). Patients (pts) with high-grade BCG-refractory NMIBC or MIBC undergo RC, which involves complete bladder removal and pelvic lymphadenectomy. RC severely impacts quality of life with significant morbidity. Oncolytic viruses are showing promise in UC, and MV-NIS has proven efficacy in other tumor types. MV-NIS is an investigational oncolytic measles virus with an excellent safety profile, irrespective of route of administration (n > 100). MV-NIS-related adverse events are limited to infusion reactions and transient CBC changes, and little local toxicity is anticipated with intravesical therapy. Clinical efficacy of this oncolytic may be related to absence of measles immunity. Based on this, the clinical strategy for MV-NIS is focused on targeting immune-privileged sites via intra-tumoral or intravesical routes, alone or in combination with checkpoint inhibitors. We hypothesize that intravesical therapy with oncolytic MV-NIS can improve clinical outcomes for (a) BCG refractory NMIBC pts to avoid or delay the need for RC; and (b) MIBC pts undergoing RC. Methods: This study is enrolling pts undergoing RC who are ineligible to receive neoadjuvant chemotherapy. The trial has 2 stages to (a) determine the safety and tolerability of intravesical MV-NIS, and (b) assess preliminary efficacy. Part (a) includes 4-24 pts in a timing cohort with doses administered at increasing durations (1-4 weeks) prior to RC to establish safety of a single MV-NIS dose. Part (b) includes an expansion cohort (n = 12) to evaluate the safety and efficacy of 2 intravesical doses of MV-NIS at 2-week intervals prior to RC. Safety is assessed using NCI-CTCAE V5 and Clavien-Dindo grading of operative complications. The efficacy endpoint is pathologic stage at time of RC (pT0 rate), which can be compared to pre-study TURBT stage. Additional exploratory studies include PK and PD analyses in urine, blood and tumor. Enrollment is ongoing at 2 Mayo Clinic sites (Rochester, MN and Jacksonville, FL) and the study has now progressed from the timing cohort into the expansion cohort. Clinical trial information: NCT03171493 .

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non–muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non–muscle-invasive bladder cancer in the event of a bacillus Calmette-Guérin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org . Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

TPS594 Background: The standard treatment for upper tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU) with bladder cuff resection. Subsequent intravesical recurrence is common and results in patient morbidity and increased healthcare cost. Level 1 evidence has demonstrated reduction of intravesical recurrence with instillation of intravesical Mitomycin C at 10 days following RNU. However, there has been limited adoption of Mitomycin C due to concerns for toxicity and logistics of postoperative drug delivery. Meanwhile, immediate intravesical gemcitabine has been shown to reduce intravesical recurrence following transurethral resection of bladder cancers without increasing toxicity compared to placebo. Moreover, small series have suggested improved efficacy of intraoperative intravesical chemotherapy for RNU. The purpose of the GEMINI trial, therefore, is to prospectively establish the safety and efficacy of intraoperative instillation of intravesical gemcitabine in patients undergoing RNU for UTUC. Methods: GEMINI is a multi-center open-label, single-arm, Phase II study that aims to enroll 90 patients with cTa-T4N0M0 UTUC. Patients receive intraoperative intravesical instillation of gemcitabine at the beginning of RNU, to be held in the bladder for at least 1 hour. The instilled drug will be drained prior to resection of the bladder cuff. Patients will undergo standard of care postoperative surveillance, including cystoscopy at 3, 6, 12, 18, and 24 months. The primary endpoint is 1-year intravesical recurrence-free survival. The historical event rate for no treatment is 30%, and we estimated a 40% relative reduction in event rate with gemcitabine. The study is powered to provide 80% power to detect this difference based on a one-sided exact test of proportions with alpha level 0.05. Secondary endpoints include time to recurrence and stratification of recurrence free survival by tumor grade, tumor stage, neoadjuvant chemotherapy, ureteral tumor location, and history of bladder cancer. Safety and adverse event endpoints will be evaluated. Complete accrual is expected within 3 years.