Lyon, Timothy D.

Objectives: To characterize 30-day morbidity of upper ureteral reconstruction (UUR) and lower ureteral reconstruction (LUR) surgery by comparing open and minimally invasive surgery (MIS) approaches using a national surgical outcomes registry. Methods: The American College of Surgeons National Surgical Quality Improvement Program database was reviewed for patients who underwent UUR and LUR between 2007 and 2017. Primary endpoints included 30-day complications, transfusion, readmission, return to operating room (ROR), and prolonged postoperative length of stay (LOS). Multivariable logistic regression was performed to observe the association of MIS approach on 30-day outcomes. Results: Three thousand forty-two patients were identified with 2116 undergoing UUR and 926 undergoing LUR. Of 2116 patients undergoing UUR, 1733 (82%) were performed through an MIS approach. On multivariable analysis, open approach for UUR was associated with increased odds of any 30-day complication (odds ratio (OR) 1.6 [1.1–2.4]; p = 0.014), major complication (OR 1.8 [1.04–3.0]; p = 0.034), transfusion (OR 3.7 [1.2–11.5]; p = 0.025), ROR (OR 2.0 [1.0–3.9]; p = 0.047), and prolonged LOS (OR 5.4 [3.9–7.6]; p < 0.001). Of the 926 patients undergoing LUR, 458 (49%) were performed through an MIS approach. On multivariable analysis, open approach for LUR was associated with increased odds of any 30-day complication (OR 1.5 [1.1–2.1]; p = 0.028), minor complication (OR 1.7 [1.1–2.6]; p = 0.02), transfusion (OR 8.1 [2.7–23.7]; p < 0.001), and prolonged LOS (OR 4.2 [2.4–7.3]; p < 0.001). Conclusion: Utilization of a national surgical database revealed an open approach was associated with increased 30-day morbidity across multiple postoperative outcome measures. These findings suggest an MIS approach should be considered, when feasible, for upper and lower ureteral reconstruction.

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 .

Ambiguity exists regarding the definition of a level III inferior vena cava tumor thrombus (IVC-TT), limiting comparisons between open and minimally-invasive series. We assessed 253 patients who underwent radical nephrectomy with IVC-TT from 2000-2015 and proposed a modified classification based on associations between intraoperative IVC clamp position and need for cardiopulmonary bypass with complications, length of stay, and blood transfusions. Predictive ability of the modified system was not meaningfully improved (AUCs 0.59–0.58; 0.61–0.61; 0.72–0.72). Nevertheless, we advocate for standardization of the border of a level III thrombus at or above the major hepatic veins to facilitate meaningful comparisons between techniques.

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.