Prophylactic Use of Biologic Mesh in Ileal Conduit (PUBMIC): A Randomized Clinical Trial.

PURPOSE: We assessed the effect of prophylactic biologic mesh on parastomal hernia (PSH) development in patients undergoing cystectomy and ileal conduit (IC). MATERIALS AND METHODS: This phase 3, randomized, controlled trial (NCT02439060) included 146 patients who underwent cystectomy and IC at the University of Southern California between 2015 and 2021. Follow-ups were physical exam and CT every 4 to 6 months up to 2 years. Patients were randomized 1:1 to receive FlexHD prophylactic biological mesh using sublay intraperitoneal technique vs standard IC. The primary end point was time to radiological PSH, and secondary outcomes included clinical PSH with/without surgical intervention and mesh-related complications. RESULTS: The 2 arms were similar in terms of baseline clinical features. All surgeries and mesh placements were performed without any intraoperative complications. Median operative time was 31 minutes longer in patients who received mesh, yet with no statistically significant difference (363 vs 332 minutes, P = .16). With a median follow-up of 24 months, radiological and clinical PSHs were detected in 37 (18 mesh recipients vs 19 controls) and 16 (8 subjects in both arms) patients, with a median time to radiological and clinical PSH of 8.3 and 15.5 months, respectively. No definite mesh-related adverse events were reported. Five patients (3 in the mesh and 2 in the control arm) required surgical PSH repair. Radiological PSH-free survival rates in the mesh and control groups were 74% vs 75% at 1 year and 69% vs 62% at 2 years. CONCLUSIONS: Implementation of biologic mesh at the time of IC construction is safe without significant protective effects within 2 years following surgery.

The effect of enhanced recovery after surgery on oncologic outcome following radical cystectomy for urothelial bladder carcinoma.

INTRODUCTION: Limited data are available regarding the effect of enhanced recovery after surgery (ERAS) protocols on the long-term outcomes of radical cystectomy (RC) in bladder cancer patients. The aim of this study is to evaluate the oncological outcomes in patients who underwent RC with ERAS protocol. METHODS: We reviewed the records of patients who underwent RC for primary urothelial bladder carcinoma with curative intent from January 2003 to August 2022. The primary and secondary outcomes were recurrence-free (RFS) and overall survival (OS). Multivariable Cox regression analysis was performed to evaluate the effect of ERAS on oncological outcomes. RESULTS: A total of 967 ERAS patients and 1144 non-ERAS patients were included in this study. The RFS rates at 1, 3, and 5 years after RC were 81%, 71.5%, and 69% in the ERAS cohort, respectively. This rate in the non-ERAS group was 81%, 71%, and 67% at 1, 3, and 5 years after RC, respectively (P = 0.50). However, ERAS patients had significantly better OS with 86%, 73%, and 67% survival rates at 1, 3, and 5 years compared to 84%, 68%, and 59.5% survival rates in the non-ERAS group, respectively (P = 0.002). In multivariable analysis adjusting for other relevant factors, ERAS was no longer independently associated with recurrence-free (HR = 0.96, 95% CI 0.76-1.22, P = 0.75) or overall survival (HR = 0.84, 95% CI 0.66-1.09, P = 0.28) following RC. CONCLUSION: ERAS protocols are associated with a shorter hospital stay, yet with no impact on long-term oncologic outcomes in patients undergoing RC for bladder cancer.

Perioperative mortality for radical cystectomy in the modern Era: experience from a tertiary referral center

ABSTRACT Purpose To evaluate the perioperative mortality and contributing variables among patients who underwent radical cystectomy (RC) for bladder cancer in recent decades, with comparison between modern (after 2010) and premodern (before 2010) eras. Materials and Methods Using our institutional review board-approved database, we reviewed the records of patients who underwent RC for primary urothelial bladder carcinoma with curative intent from January 2003 to December 2019. The primary and secondary outcomes were 90- and 30-day mortality. Univariate and multivariable logistic regression models were applied to assess the impact of perioperative variables on 90-day mortality. Results A total of 2047 patients with a mean±SD age of 69.6±10.6 years were included. The 30- and 90-day mortality rates were 1.3% and 4.9%, respectively, and consistent during the past two decades. Among 100 deaths within 90 days, 18 occurred during index hospitalization. Infectious, pulmonary, and cardiac complications were the leading mortality causes. Multivariable analysis showed that age (Odds Ratio: OR 1.05), Charlson comorbidity index ≥ 2 (OR 1.82), blood transfusion (OR 1.95), and pathological node disease (OR 2.85) were independently associated with 90-day mortality. Nevertheless, the surgical approach and enhanced recovery protocols had no significant effect on 90-day mortality. Conclusion The 90-day mortality for RC is approaching five percent, with infectious, pulmonary, and cardiac complications as the leading mortality causes. Older age, higher comorbidity, blood transfusion, and pathological lymph node involvement are independently associated with 90-day mortality.

Radical cystectomy versus trimodality therapy for muscle-invasive bladder cancer: a multi-institutional propensity score matched and weighted analysis.

BACKGROUND: Previous randomised controlled trials comparing bladder preservation with radical cystectomy for muscle-invasive bladder cancer closed due to insufficient accrual. Given that no further trials are foreseen, we aimed to use propensity scores to compare trimodality therapy (maximal transurethral resection of bladder tumour followed by concurrent chemoradiation) with radical cystectomy. METHODS: This retrospective analysis included 722 patients with clinical stage T2-T4N0M0 muscle-invasive urothelial carcinoma of the bladder (440 underwent radical cystectomy, 282 received trimodality therapy) who would have been eligible for both approaches, treated at three university centres in the USA and Canada between Jan 1, 2005, and Dec 31, 2017. All patients had solitary tumours less than 7 cm, no or unilateral hydronephrosis, and no extensive or multifocal carcinoma in situ. The 440 cases of radical cystectomy represent 29% of all radical cystectomies performed during the study period at the contributing institutions. The primary endpoint was metastasis-free survival. Secondary endpoints included overall survival, cancer-specific survival, and disease-free survival. Differences in survival outcomes by treatment were analysed using propensity scores incorporated in propensity score matching (PSM) using logistic regression and 3:1 matching with replacement and inverse probability treatment weighting (IPTW). FINDINGS: In the PSM analysis, the 3:1 matched cohort comprised 1119 patients (837 radical cystectomy, 282 trimodality therapy). After matching, age (71·4 years [IQR 66·0-77·1] for radical cystectomy vs 71·6 years [64·0-78·9] for trimodality therapy), sex (213 [25%] vs 68 [24%] female; 624 [75%] vs 214 [76%] male), cT2 stage (755 [90%] vs 255 [90%]), presence of hydronephrosis (97 [12%] vs 27 [10%]), and receipt of neoadjuvant or adjuvant chemotherapy (492 [59%] vs 159 [56%]) were similar between groups. Median follow-up was 4·38 years (IQR 1·6-6·7) versus 4·88 years (2·8-7·7), respectively. 5-year metastasis-free survival was 74% (95% CI 70-78) for radical cystectomy and 75% (70-80) for trimodality therapy with IPTW and 74% (70-77) and 74% (68-79) with PSM. There was no difference in metastasis-free survival either with IPTW (subdistribution hazard ratio [SHR] 0·89 [95% CI 0·67-1·20]; p=0·40) or PSM (SHR 0·93 [0·71-1·24]; p=0·64). 5-year cancer-specific survival for radical cystectomy versus trimodality therapy was 81% (95% CI 77-85) versus 84% (79-89) with IPTW and 83% (80-86) versus 85% (80-89) with PSM. 5-year disease-free survival was 73% (95% CI 69-77) versus 74% (69-79) with IPTW and 76% (72-80) versus 76% (71-81) with PSM. There were no differences in cancer-specific survival (IPTW: SHR 0·72 [95% CI 0·50-1·04]; p=0·071; PSM: SHR 0·73 [0·52-1·02]; p=0·057) and disease-free survival (IPTW: SHR 0·87 [0·65-1·16]; p=0·35; PSM: SHR 0·88 [0·67-1·16]; p=0·37) between radical cystectomy and trimodality therapy. Overall survival favoured trimodality therapy (IPTW: 66% [95% CI 61-71] vs 73% [68-78]; hazard ratio [HR] 0·70 [95% CI 0·53-0·92]; p=0·010; PSM: 72% [69-75] vs 77% [72-81]; HR 0·75 [0·58-0·97]; p=0·0078). Outcomes for radical cystectomy and trimodality therapy were not statistically different among centres for cancer-specific survival and metastasis-free survival (p=0·22-0·90). Salvage cystectomy was done in 38 (13%) trimodality therapy patients. Pathological stage in the 440 radical cystectomy patients was pT2 in 124 (28%), pT3-4 in 194 (44%), and 114 (26%) node positive. The median number of nodes removed was 39, the soft tissue positive margin rate was 1% (n=5), and the perioperative mortality rate was 2·5% (n=11). INTERPRETATION: This multi-institutional study provides the best evidence to date showing similar oncological outcomes between radical cystectomy and trimodality therapy for select patients with muscle-invasive bladder cancer. These results support that trimodality therapy, in the setting of multidisciplinary shared decision making, should be offered to all suitable candidates with muscle-invasive bladder cancer and not only to patients with significant comorbidities for whom surgery is not an option. FUNDING: Sinai Health Foundation, Princess Margaret Cancer Foundation, Massachusetts General Hospital.

Perioperative mortality for radical cystectomy in the modern Era: experience from a tertiary referral center.

PURPOSE: To evaluate the perioperative mortality and contributing variables among patients who underwent radical cystectomy (RC) for bladder cancer in recent decades, with comparison between modern (after 2010) and premodern (before 2010) eras. MATERIALS AND METHODS: Using our institutional review board-approved database, we reviewed the records of patients who underwent RC for primary urothelial bladder carcinoma with curative intent from January 2003 to December 2019. The primary and secondary outcomes were 90- and 30-day mortality. Univariate and multivariable logistic regression models were applied to assess the impact of perioperative variables on 90-day mortality. RESULTS: A total of 2047 patients with a mean±SD age of 69.6±10.6 years were included. The 30- and 90-day mortality rates were 1.3% and 4.9%, respectively, and consistent during the past two decades. Among 100 deaths within 90 days, 18 occurred during index hospitalization. Infectious, pulmonary, and cardiac complications were the leading mortality causes. Multivariable analysis showed that age (Odds Ratio: OR 1.05), Charlson comorbidity index ≥ 2 (OR 1.82), blood transfusion (OR 1.95), and pathological node disease (OR 2.85) were independently associated with 90-day mortality. Nevertheless, the surgical approach and enhanced recovery protocols had no significant effect on 90-day mortality. CONCLUSION: The 90-day mortality for RC is approaching five percent, with infectious, pulmonary, and cardiac complications as the leading mortality causes. Older age, higher comorbidity, blood transfusion, and pathological lymph node involvement are independently associated with 90-day mortality.

Association between early postradical cystectomy kidney injury and perioperative outcome in enhanced recovery era.

OBJECTIVE: To evaluate the incidence and predictors of early postoperative acute kidney injury (EP-AKI) during index hospitalization following radical cystectomy and its association with postoperative outcomes. METHODS: All patients with bladder cancer who underwent radical cystectomy with intent-to-cure at our center between 2012 and 2020 were reviewed. EP-AKI during index hospitalization was evaluated using the Acute Kidney Injury Network criteria. The association between EP-AKI and demographics, clinicopathologic features, and perioperative outcomes, including length of hospital stay, complication rate, and readmission rate, were examined. A logistic regression analysis was performed to evaluate the predictors of EP-AKI. RESULTS: Overall, 435 patients met eligibility, of whom 112 (26%) experienced EP-AKI during index hospitalization (90 [21%] stage 1, 17 [4%] stage 2, and 5 [1%] stage 3). EP-AKI was associated with a longer mean operative time (6.8 vs. 6.1 hours; P < 0.001), higher mean length of hospital stay (6.3 vs. 5.6; P = 0.02), 30-day complication rate (71% vs. 51%; P < 0.001), 90-day complication rate (81% vs. 69%; P = 0.01) and 90-day readmission rate (37% vs. 33%; P = 0.04). The rate of complications increased at higher stages of AKI. On multivariable analysis, perioperative blood transfusion (OR: 1.84, P = 0.02) and continent diversion (OR: 3.29, P < 0.001) were independent predictors of EP-AKI. CONCLUSION: A quarter of cystectomy patients experience acute kidney injury during index hospitalization, which is associated with higher length of stay, postoperative complication, and readmission rates. Perioperative blood transfusion and continent diversion are independent predictors of such injury.

Recommendations for Intraoperative Adverse Events Data Collection in Clinical Studies and Study Protocols. An ICARUS Global Surgical Collaboration Study.

Introduction: Intraoperative adverse events (iAEs) occur and have the potential to impact the postoperative course. However, iAEs are underreported and are not routinely collected in the contemporary surgical literature. There is no widely utilized system for the collection of essential aspects of iAEs, and there is no established database for the standardization and dissemination of this data that likely have implications for outcomes and patient safety. The Intraoperative Complication Assessment and Reporting with Universal Standards (ICARUS) Global Surgical Collaboration initiated a global effort to address these shortcomings, and the establishment of an adverse event data collection system is an essential step. In this study, we present the core-set variables for collecting iAEs that were based on the globally validated ICARUS criteria for surgical/interventional and anesthesiologic intraoperative adverse event collection and reporting. Material and Methods: This article includes three tools to capture the essential aspects of iAEs. The core-set variables were developed from the globally validated ICARUS criteria for reporting iAEs (item 1). Next, the summary table was developed to guide researchers in summarizing the accumulated iAE data in item 1 (item 2). Finally, this article includes examples of the method and results sections to include in a manuscript reporting iAE data (item 3). Then, 5 scenarios demonstrating best practices for completing items 1-3 were presented both in prose and in a video produced by the ICARUS collaboration. Dissemination: This article provides the surgical community with the tools for collecting essential iAE data. The ICARUS collaboration has already published the 13 criteria for reporting surgical adverse events, but this article is unique and essential as it actually provides the tools for iAE collection. The study team plans to collect feedback for future directions of adverse event collection and reporting. Highlights: This article represents a novel, fully-encompassing system for the data collection of intraoperative adverse events.The presented core-set variables for reporting intraoperative adverse events are not based solely on our opinion, but rather are synthesized from the globally validated ICARUS criteria for reporting intraoperative adverse events.Together, the included text, figures, and ICARUS collaboration-produced video should equip any surgeon, anesthesiologist, or nurse with the tools to properly collect intraoperative adverse event data.Future directions include translation of this article to allow for the widest possible adoption of this important collection system.

Recurrence patterns in bladder cancer patients with no residual disease (pT0N0) at radical cystectomy: A 20-year experience.

OBJECTIVE: To examine the oncological outcomes and recurrence patterns in patients with no residual disease at the time of radical cystectomy (RC). METHODS: A retrospective review of our IRB-approved bladder cancer database identified patients who underwent RC between 2000 and 2019 and were found to have no residual disease (pT0N0), either following neoadjuvant chemotherapy (NAC) or transurethral resection (TURBT) alone. The primary outcome was recurrence-free survival (RFS). Regression models assessed factors influencing recurrence, and a detailed description of recurrence patterns was compiled. RESULTS: From a total of 2222 patients, 234 (10.5%) were included with a median age of 67 years. NAC was used in 89 (38%) patients and 145 (62%) cases were rendered pT0 following TURBT alone. At a median follow-up of 44 months, there were 16 (6.8%) recurrences, 10 (63%) of which occurred in the ypT0 group. None of the patients with clinical Ta/Tis disease had a recurrence after RC. The median time to recurrence was 9 months. Ninety-one percent (10/11) of recurrences in the ypT0 group were within 2 years of cystectomy, while half of the recurrences in the pT0 group occurred after 2 years. Patients with ypT0 had worse 2- and 5-year RFS compared to the pT0 group (85% and 84% vs. 99% and 95%, respectively; P = 0.003). Variant histology was noted in 49 (21%) patients; the recurrence rate was higher in this subgroup compared to those with pure urothelial carcinoma (12.2% vs. 5.4%, P = 0.02). Lung metastasis and involvement of distant organs, while rare, were noted at similar rates in both groups. CONCLUSION: Patients with pT0N0 pathology at the time of cystectomy should prudently undergo long-term surveillance as recurrence and metastasis can still develop up to 4 years after surgery. Patients achieving ypT0 after NAC exhibit worse prognosis and shorter times to recurrence, closer follow-up may be considered.

Radical cystectomy and urinary diversion outcomes in patients with single vs. double renal unit: A 2:1 matched-pair analysis.

OBJECTIVE: To evaluate perioperative and functional outcomes of radical cystectomy (RC) and urinary diversion (UD) in patients with a single kidney (SK) vs. double kidneys (DK). METHODS: We reviewed records of patients who underwent RC for bladder cancer with a history of prior or concurrent nephrectomy at USC between 2004 and 2020. Patients with chronic kidney disease who were already on dialysis were excluded. UD, perioperative complications, and postoperative glomerular filtration rate (GFR) of the SK group were compared with a group of patients who underwent RC with DK using 2:1 matching with respect to age, sex, preop GFR, and tumor stage. RESULTS: We included 186 patients (SK = 62 and DK = 124). Half of the SK patients underwent continent UD. SK patients had a higher length of hospital stay compared to the DK group; however, 90-day complications, readmission, and mortality rates were similar. In patients with continent diversion, SK vs. DK showed similar 90-day complications (71% vs. 69%, P = 1.0). SK patients had significantly lower GFRs at discharge, 3-, and 12-month following RC compared to the DK group. Postoperative GFRs of the SK patients with continent vs. incontinent UD were statistically similar. On multivariable analysis, UD (i.e. continent vs. incontinent) was not associated with post-op GFR decline at discharge, 3- and 12-month following RC. CONCLUSIONS: Perioperative outcomes of radical cystectomy patients with single kidney are similar to double kidney patients, except for more GFR decline in single kidney cases. Continent urinary diversion in single kidney is as safe as double kidney patients.

Development of a Pocket Nomogram to Predict Cancer and Disease Specific Survival After Radical Cystectomy For Bladder Cancer: The CRAB Nomogram.

OBJECTIVES: To develop an easy tool to predict cancer specific (CSS) and disease-free survival (DFS) in patients with bladder cancer treated with radical cystectomy. METHODS: Data from a consecutive series of 2395 patients with primitive or progression to muscle invasive bladder cancer (MIBC) undergone to radical cystectomy and lymph nodes dissection in 5 centers were evaluated. Using Cox proportional hazards analyses, the Cancer of the bladder risk assessment (CRAB) nomogram was generated. Accuracy of the nomogram was evaluated by Harrell's C test. Internal validation of the model was performed using 200 bootstraps. RESULTS: Median age was 66 (IQR 58/73) years; 612/2395 (26%) patients presented an advanced pathological stage (≥pT3a); 478/2395 (20%) presented positive lymph nodes. Overall, 729/2395 (30%) presented local or distant recurrence with a median DFS of 42 (IQR 14/89) months. Overall, 642/2395 (27%) died of bladder cancer with a median follow up of 48 (IQR 22/92) months. On univariate Cox proportional hazards analyses, age, stage, and lymph nodes density were a significant predictor of 3 and5 years CSS and DFS. Accuracy of the CRAB nomogram was 0.73 and 0.71 respectively. CONCLUSION: CRAB nomogram can be a practical and easily applicable tool that may help urologists to classify the long-term CSS and DFS of patients treated with radical cystectomy and to predict the oncological outcome.

Impact of Patient, Surgical, and Perioperative Factors on Discharge Disposition after Radical Cystectomy.

Radical cystectomy (RC) is a complex procedure associated with lengthy hospital stays and high complication and readmission rates. We evaluated the impact of patient, surgical, and perioperative factors on discharge disposition following RC at a tertiary referral center. From 2012 to 2019, all bladder cancer patients undergoing RC at our institution were identified (n = 1153). Patients were classified based on discharge disposition: to home or to continued facility-based rehabilitation centers (CFRs, n = 180 (15.61%) patients). On multivariate analysis of patient factors only, age [Risk Ratio (RR): 1.07, p < 0.001)], single marital status (RR: 1.09, p < 0.001), and living alone prior to surgery (RR: 2.55, p = 0.004) were significant predictors of discharge to CFRs. Multivariate analysis of patient, surgical, and perioperative factors indicated age (RR: 1.09, p < 0.001), single marital status (RR: 3.9, p < 0.001), living alone prior to surgery (RR: 2.42, p = 0.01), and major post-operative (Clavien > 3) complications (RR: 3.44, p < 0.001) were significant independent predictors of discharge to CFRs. Of note, ERAS did not significantly impact discharge disposition. Specific patient and perioperative factors significantly impact discharge disposition. Patients who are older, living alone prior to surgery, and/or have a major post-operative complication are more likely to be discharged to CFRs after RC.

Population-Based Assessment of Determining Predictors for Discharge Disposition in Patients with Bladder Cancer Undergoing Radical Cystectomy.

Objective: To assess predictors of discharge disposition­either home or to a CRF­after undergoing RC for bladder cancer in the United States. Methods: In this retrospective, cohort study, patients were divided into two cohorts: those discharged home and those discharged to CRF. We examined patient, surgical, and hospital characteristics. Multivariable logistic regression models were used to control for selected variables. All statistical tests were two-sided. Patients were derived from the Premier Healthcare Database. International classification of disease (ICD)-9 (<2014), ICD-10 (≥2015), and Current Procedural Terminology (CPT) codes were used to identify patient diagnoses and encounters. The population consisted of 138,151 patients who underwent RC for bladder cancer between 1 January 2000 and 31 December 2019. Results: Of 138,151 patients, 24,922 (18.0%) were admitted to CRFs. Multivariate analysis revealed that older age, single/widowed marital status, female gender, increased Charlson Comorbidity Index, Medicaid, and Medicare insurance are associated with CRF discharge. Rural hospital location, self-pay status, increased annual surgeon case, and robotic surgical approach are associated with home discharge. Conclusions: Several specific patient, surgical, and facility characteristics were identified that may significantly impact discharge disposition after RC for bladder cancer.

Characterization of Cellular and Acellular Analytes from Pre-Cystectomy Liquid Biopsies in Patients Newly Diagnosed with Primary Bladder Cancer.

Urinary bladder cancer (BCa) is the 10th most frequent cancer in the world, most commonly found among the elderly population, and becomes highly lethal once cells have spread from the primary tumor to surrounding tissues and distant organs. Cystectomy, alone or with other treatments, is used to treat most BCa patients, as it offers the best chance of cure. However, even with curative intent, 29% of patients experience relapse of the cancer, 50% of which occur within the first year of surgery. This study aims to use the liquid biopsy to noninvasively detect disease and discover prognostic markers for disease progression. Using the third generation high-definition single cell assay (HDSCA3.0), 50 bladder cancer patient samples and 50 normal donor (ND) samples were analyzed for circulating rare events in the peripheral blood (PB), including circulating tumor cells (CTCs) and large extracellular vesicles (LEVs). Here, we show that (i) CTCs and LEVs are detected in the PB of BCa patients prior to cystectomy, (ii) there is a high heterogeneity of CTCs, and (iii) liquid biopsy analytes correlate with clinical data elements. We observed a significant difference in the incidence of rare cells and LEVs between BCa and ND samples (median of 74.61 cells/mL and 30.91 LEVs/mL vs. 34.46 cells/mL and 3.34 LEVs/mL, respectively). Furthermore, using classification models for the liquid biopsy data, we achieved a sensitivity of 78% and specificity of 92% for the identification of BCa patient samples. Taken together, these data support the clinical utility of the liquid biopsy in detecting BCa, as well as the potential for predicting cancer recurrence and survival post-cystectomy to better inform treatment decisions in BCa care.

Management Trends and Outcomes of Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder: Evolution of the University of Southern California Experience over 3,347 Cases.

PURPOSE: There are conflicting reports on outcome trends following radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS: Evolution of modern bladder cancer management and its impact on outcomes was analyzed using a longitudinal cohort of 3,347 patients who underwent RC at an academic center between 1971 and 2018. Outcomes included recurrence-free survival (RFS) and overall survival (OS). Associations were assessed using univariable and multivariable models. RESULTS: In all, 70.9% of cases underwent open RC in the last decade, although trend for robot-assisted RC rose since 2009. While lymphadenectomy template remained consistent, nodal submission changed to anatomical packets in 2002 with increase in yield (p <0.001). Neoadjuvant chemotherapy (NAC) use increased with time with concomitant decrease in adjuvant chemotherapy; this was notable in the last decade (p <0.001) and coincided with improved pT0N0M0 rate (p=0.013). Median 5-year RFS and OS probabilities were 65% and 55%, respectively. Advanced stage, NAC, delay to RC, lymphovascular invasion and positive margins were associated with worse RFS (all, multivariable p <0.001). RFS remained stable over time (p=0.73) but OS improved (5-year probability, 1990-1999 51%, 2010-2018 62%; p=0.019). Among patients with extravesical and/or node-positive disease, those who received NAC had worse outcomes than those who directly underwent RC (p ≤0.001). CONCLUSIONS: Despite perioperative and surgical advances, and improved pT0N0M0 rates, there has been no overall change in RFS trend following RC, although OS rates have improved. While patients who are downstaged with NAC derive great benefit, our real-world experience highlights the importance of preemptively identifying NAC nonresponders who may have worse post-RC outcomes.

Bladder Recurrence Following Diagnostic Ureteroscopy in Patients Undergoing Nephroureterectomy for Upper Tract Urothelial Cancer: Is Ureteral Access Sheath Protective?

OBJECTIVE: To examine the effect of diagnostic ureteroscopy (URS) and ureteral access sheath usage on bladder recurrence following radical nephroureterectomy (RNU). METHODS: We retrospectively reviewed the records of patients who underwent RNU between 2005 - 2019. Patients with a history of bladder cancer and those without a bladder cuff resection were excluded. Bladder recurrence was the primary outcome and cox regression modeling was used to assess the impact of URS adjusting for other factors. RESULTS: Out of 271 RNU cases, 143 were included with a median age of 73 years (IQR 65 - 80). URS was performed in 104 cases (73%) and a ureteral access sheath was used in 26 (25%). With a median follow-up of 27 months, there were 36 (25%) bladder recurrences. The bladder recurrence rate (median time to recurrence) for patients who had URS vs no URS was 30.8% (9.0 months) and 7.7% (12.1 months), respectively (P = .02). A lower recurrence rate was noted in patients whom a ureteral access sheath was utilized (11.5%) vs those with no access sheath (39.7%, P = .01). Multivariable analysis revealed a significant increase in bladder recurrence if URS was performed prior to RNU (HR 5.6 [1.7 - 18.5], P <.004), however, this effect was mitigated if a ureteral access sheath was used (HR 1.3, [0.3 - 6.4], P = .76). Ureteral stent usage and performing a ureteroscopic biopsy had no significant effect on bladder recurrence. CONCLUSION: Diagnostic URS in patients undergoing RNU for UTUC significantly increases the risk of bladder recurrence. This effect may be mitigated by using a ureteral access sheath.

Risk factors and natural history of parastomal hernia after radical cystectomy and ileal conduit.

OBJECTIVE: To investigate the incidence, risk factors and natural history of parastomal hernia (PSH). MATERIALS AND METHODS: We reviewed the records of patients who underwent radical cystectomy (RC) and ileal conduit (IC) procedure between 2007 and 2020. Patients who had available follow-up computed tomography (CT) imaging were included in this study. All CT scans were re-reviewed for detection of PSH according to Moreno-Matias classification. Patients who developed hernia were followed up and classified into stable or progressive (defined as radiological upgrading and/or need for surgical intervention) groups. Multivariable Cox regression was performed to identify independent predictors of hernia development and progression. RESULTS: A total of 361 patients were included in this study. The incidence of radiological PSH was 30%, graded as I (56.5%), II (12%) and III (31.5%). The median (interquartile range [IQR]) time to radiological hernia was 8 (5-15) months. During the median (IQR) follow-up of 27 (13-47) months in 108 patients with a hernia, 26% patients progressed. The median (IQR) time to progression was 12 (6-21) months. On multivariable analysis, female gender (hazard ratio [HR] 1.86), diabetes (HR 1.81), chronic obstructive pulmonary disease (COPD; HR 1.78) and higher body mass index (BMI; HR 1.07 for each unit) were independent predictors for radiological PSH development. No significant factor was found to be associated with hernia progression. CONCLUSION: Radiological PSH after RC and IC occurred in 30% of patients, a quarter of whom progressed in a median time of 12 months. Female gender, diabetes, COPD and high BMI were independent predictors for radiological hernia development.

Prediction of Metastatic Patterns in Bladder Cancer: Spatiotemporal Progression and Development of a Novel, Web-based Platform for Clinical Utility.

BACKGROUND: Bladder cancer (BCa), the sixth commonest cancer in the USA, is highly lethal when metastatic. Spatial and temporal patterns of patient-specific metastatic spread are deemed random and unpredictable. Whether BCa metastatic patterns can be quantified and predicted more accurately is unknown. OBJECTIVE: To develop a web-based calculator for forecasting metastatic progression in individual BCa patients. DESIGN SETTING AND PARTICIPANTS: We used a prospectively collected longitudinal dataset of 3503 BCa patients who underwent a radical cystectomy following diagnosis and were enrolled continuously. We subdivided patients by their pathologic subgroup stages of organ confined (OC), extravesical (EV), and node positive (N+). We illustrated metastatic pathway progression using color-coded, circular, tree ring diagrams. We created a dynamical, data-visualization, web-based platform that displays temporal, spatial, and Markov modeling figures with predictive capability. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients underwent history and physical examination, serum studies, and liver function tests. Surveillance follow-up included computed tomography scans, chest x-rays, and radiographic evaluation of the reservoir and upper tracts, with bone scans performed only if clinically indicated. Outcomes were measured by time to clinical recurrence and overall or progression-free survival. RESULTS AND LIMITATIONS: Metastases developed in 29% of patients (n = 812; median follow-up 15.3 yr), with 5-yr overall survival of 20.2%, compared with 78.6% in those without metastases (n = 1983; median follow-up 10.9 yr). The three commonest sites of spread at the time of first progression were bone (n = 214; 26.4%), pelvis (n = 194; 23.9%), and lung (n = 194; 23.9%). The order and frequency of these sites vary when divided by pathologic subgroup stages of OC (lung [n = 65; 25.1%], urethra [n = 45; 17.4%], and bone [n = 29; 11.2%]), EV (pelvis [n = 63; 33.0%], bone [n = 45; 23.6%], and lung [n = 29; 15.2%]), and N+ (bone [n = 111; 30.7%], retroperitoneum [n = 70; 19.3%], and pelvis [n = 60; 16.6%]). Markov chain modeling indicated a higher probability of spread from bladder to bone (15.5%), pelvis (14.7%), and lung (14.2%). CONCLUSIONS: Our web-based calculator allows real-time analyses in the clinic based on individual patient-specific demographic and cancer data elements. For contrasting subgroups, the models indicated differences in Markov transition probabilities. Spatiotemporal patterns of BCa metastasis and sites of spread indicated underlying organotropic mechanisms in the prediction of response. This recognition opens the possibility of organ site-specific therapeutic targeting in the oligometastatic BCa setting. In the precision medicine era, visualization of complex, time-resolved clinical data will enhance management of postoperative metastatic BCa patients. PATIENT SUMMARY: We developed a web-based calculator to forecast metastatic progression for individual bladder cancer (BCa) patients, based on the clinical and demographic information obtained at diagnosis. This can help in predicting disease status and survival, and improving management in postoperative metastatic BCa patients. TAKE HOME MESSAGE: Future pathways of metastatic progression for individual bladder cancer patients can be determined based on currently available clinical and demographic information obtained at diagnosis. In focused subgroups of patients, these metastatic spread patterns can also portend disease status and survival.