Shah, Paras

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.

AbstractBackgroundThe clinical course in metastatic castrate‐resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after prior treatment with second generation hormone therapy (second HT), such as enzalutamide or abiraterone. Currently, limited data exist regarding the optimal choice of chemotherapy for mCRPC after failing second generation hormone therapy. We sought to evaluate three common chemotherapy regimens in this setting.MethodsWe retrospectively identified 150 mCRPC patients with disease progression on enzalutamide or abiraterone. Of these 150 patients, 92 patients were chemo‐naïve while 58 patients had previously received docetaxel chemotherapy before being started on second HT. After failing second HT, 90 patients were assigned for docetaxel‐alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel‐alone (Group C). A favorable response was defined by more than or equal to 50% reduction in prostate‐specific antigen from the baseline level after a complete course of chemotherapy. Survival outcomes were assessed for 30‐month overall survival.ResultsPatients in group (B) were 2.6 times as likely to have a favorable response compared to patients in group (A) (OR = 2.625, 95%CI: 1.15‐5.99) and almost three times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04–8.54) (P = .0442). 30‐month overall survival was 70.7%, 38.9% and 30.3% for group (B), (A), and (C), respectively (P = .008). We report a Hazard Ratio of 3.1 (95% CI, 1.31‐7.35; P = .0037) between patients in group (A) versus those in group (B) and a Hazard Ratio of 4.18 (95% CI, 1.58‐11.06; P = .0037) between patients in group (C) compared to those in group (B)ConclusionThis data demonstrates improved response and overall survival in treatment‐refractory mCRPC with a chemotherapy regimen of docetaxel plus carboplatin when compared to docetaxel alone or cabazitaxel alone. Further investigations are required.

AbstractObjectives: To determine the usefulness of social media for rapid communication with experts to discuss strategies for prioritization and safety of deferred treatment for urologic malignancies during COVID‐19 pandemic, and to determine whether the discourse and recommendations made through discussions on social media (Twitter) were consistent with the current peer‐reviewed literature regarding the safety of delayed treatment. Methods: We reviewed and compiled the responses to our questions on Twitter regarding the management and safety of deferred treatment in the setting of COVID‐19 related constraints on non‐urgent care. We chronicled the guidance published on this subject by various health authorities and professional organizations. Further, we analyzed peerreviewed literature on the safety of deferred treatment (surgery or systemic therapy) to make made evidence‐based recommendations. Results: Due to the rapidly changing information about epidemiology and infectious characteristics of COVID‐19, the health authorities and professional societies guidance required frequent revisions which by design take days or weeks to produce. Several active discussions on Twitter provided real‐time updates on the changing landscape of the restrictions being placed on non‐urgent care. For separate discussion threads on prostate cancer and bladder cancer, dozens of specialists with expertise in treating urologic cancers could be engaged in providing their expert opinions as well as share evidence to support their recommendations. Our analysis of published studies addressing the safety and extent to which delayed cancer care does not compromise oncological outcome revealed that most prostate cancer care and certain aspects of the bladder and kidney cancer care can be safely deferred for 2‐6 months. Urothelial bladder cancer and advanced kidney cancer require a higher priority for timely surgical care. We did not find evidence to support the idea of using nonsurgical therapies, such as hormone therapy for prostate cancer or chemotherapy for bladder cancer for safer deferment of previously planned surgery. We noted that the comments and recommendations made by the participants in the Twitter discussions were generally consistent with our evidence‐based recommendations for safely postponing cancer care for certain types of urologic cancers. Conclusion: The use of social media platforms, such as Twitter, where the comments and recommendations are subject to review and critique by other specialists is not only feasible but quite useful in addressing the situations requiring urgent resolution, often supported by published evidence. In circumstances such as natural disasters, this may be a preferable approach than the traditional expert panels due to its ability to harness the collective intellect to available experts to provide responses and solutions in real‐time. These real‐time communications via Twitter provided sound guidance which was readily available to the public and participants, and was generally in concordance with the peerreviewed data on safety of deferred treatment.

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.

725 Background: The impact of surgical resection of renal tumors on peripheral immune related cells is not well characterized, and has potential implications as biomarkers for systemic immune therapy are being developed. We sought to assess the effect of surgical resection on circulating cytotoxic T-cells (CTLs) for patients with renal tumors. Methods: We prospectively enrolled 40 patients undergoing partial, radical, or cytoreductive nephrectomy (PN, RN, CN) for unilateral primary renal tumors between 2016 and 2018. Blood draws were performed pre-op, 1 day post-op, and 3 months post-op. Flow cytometry was performed on peripheral blood mononuclear cells (PBMCs). The % of PBMCs expressing CD11a/CD8 (CTLs) were assessed. The % of CTLs expressing PD-1, Bim (a downstream PD-1 pathway pro-apoptotic mediator), CX3CR1/GZMB (an effector memory T-cell phenotype), and Ki67 (a proliferation marker) were assessed. Median changes in % of CTLs were evaluated with the Wilcoxon signed rank test. Comparisons between aggressive (pT3-4, N1, M1, or aggressive histology (high-grade, coagulative necrosis, sarcomatoid dedifferentiation, or specific RCC-variant histologies)) versus indolent tumors were assessed using the Wilcoxon rank sum test. Results: Twenty, 12, and 8 patients underwent RN, PN, and CN, respectively. Thirty, 7, and 3 patients had clear-cell RCC, non-clear cell RCC, and oncocytoma, respectively. Twenty-three and 17 patients had aggressive and indolent tumors, respectively. While there was no significant change at 1 day, by 3 months there were significantly increased CTLs among PBMCs (+1.3%; p=0.004). There was significant decrease in CX3CR1+GZMB+ CTLs (-2.9%; p<0.001) and significant increase in Bim+ CTLs (+3.0%; p=0.03) at 1 day but not 3 months. Interestingly, Ki67+ CTLs increased at day 1 (+0.6%; p<0.001) but decreased by 3 months (-0.6%; p=0.001). There were no significant changes in PD-1+ CTLs at either time point. There were no significant changes in any CTL characteristics at 1 day or 3 months between aggressive and indolent tumors. Conclusions: These findings characterize changing CTL profiles over time with surgical resection of renal tumors which may help guide biomarker development.

631 Background: For most clear cell renal cell carcinoma (ccRCC) patients with early stage disease, surgical resection offers definitive cure. However, for the small percentage of tumors that metastasize, analyzing gene expression profiles from the primary site at the time of nephrectomy can serve as a model to understand the molecular aberrations behind a metastatic phenotype. Differences in gene expression profiles between patients with Stage I and II ccRCC who experience metastasis versus patients who maintain cure after surgery may help elucidate significant molecular targets and stratify patients at higher risk for metastasis. Methods: Nineteen Stage I and twenty Stage II ccRCC tumors preserved in FFPE blocks after nephrectomy were included in this study. Patients were matched for age, gender, tumor size and grade. In both stages, approximately half the patients that experienced metastasis within 5 years of surgery were part of the experimental group, whereas the control group had > 5 years of follow-up without evidence of disease. Extracted RNA for Stage I patients was sequenced using Illumina TruSeq RNA Access Library. Gene counts were assessed by ht-seq counts and differential expression using DESeq2. Significant genes found were validated in the Stage II group using RT-qPCR. Results: In the Stage I experimental group, statistically significant upregulation of several genes associated with unfavorable prognosis in RCC were found: COL1A1, NUMBL, and STEAP3. Random forest classification accurately separated Stage I control versus experimental patients based on expression of COL1A1. Affected genes were consistent with molecular changes seen in TCGA analysis. In the Stage II group, a double-blinded analysis correctly identified the clinical outcome for the majority of the patients using qPCR expression of COL1A1, NUMBL, and STEAP3. Conclusions: Differences in gene expression profiles harbored in the primary site of early stage ccRCC may be employed to predict patients at high risk for developing metastasis. Validating these findings in a larger study carries the potential to better understand mechanisms of metastasis and identify an at risk cohort of patients with early stage disease.