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The treatment options for high-risk non-muscle invasive bladder cancer (NMIBC), particularly following BCG, remain limited. We highlight recent, promising therapies for high-risk NMIBC.Several therapies utilizing different mechanisms of action have demonstrated favorable results in the BCG-naïve and BCG-unresponsive settings. These treatments include intravenous and intravesical immunotherapy, viral- and bacterial-based intravesical therapies, combination intravesical chemotherapy regimens, and novel intravesical chemotherapy administration. Overall, the efficacy and tolerability of emerging treatments for NMIBC appear promising and provide potential alternatives to radical cystectomy. As the landscape of managing BCG-unresponsive disease evolves, clinical trials will explore future options and determine effective alternatives.

Many patients with recurrent high-risk non-muscle invasive bladder cancer after intravesical bacillus calmette-guerin (BCG) face a difficult decision between radical cystectomy (RC) or salvage intravesical therapy (IVT). We sought to determine if there is a difference in overall survival RC and IVT after previous treatment with BCG.We performed a retrospective cohort study of patients with Ta, T1, and Tis bladder cancer treated with induction BCG in the SEER-Medicare dataset from 2000 to 2015. We used a proportional hazards regression model to compare differences in survival between patients having RC and IVT. We adjusted for confounding using a propensity score and stratified our analysis according to timing of treatment and stage at diagnosis.We identified 3940 patients who received either IVT (79%) or RC (21%) following induction BCG. Among patients treated within 12 months of BCG, there was no significant difference in survival between RC and IVT (HR 0.92, 95% CI 0.81-1.04) and 17% of patients having early IVT ultimately required RC. Among patients treated at least 12 months after BCG, RC was associated with worse survival than IVT (HR 1.19, 95% CI 1.06-1.35) and 10% of patients having late IVT ultimately required RC.Among patients with bladder cancer who required additional treatments after induction BCG, we did not observe a difference in overall survival between IVT and RC within 12 months of starting BCG. While RC remains the gold-standard for high risk recurrent NMIBC after BCG, bladder preservation with IVT may be appropriate for well-selected patients.

ImportanceSpecialist palliative care benefits patients undergoing medical treatment of cancer; however, data are lacking on whether patients undergoing surgery for cancer similarly benefit from specialist palliative care.ObjectiveTo determine the effect of a specialist palliative care intervention on patients undergoing surgery for cure or durable control of cancer.Design, Setting, and ParticipantsThis was a single-center randomized clinical trial conducted from March 1, 2018, to October 28, 2021. Patients scheduled for specified intra-abdominal cancer operations were recruited from an academic urban referral center in the Southeastern US.InterventionPreoperative consultation with palliative care specialists and postoperative inpatient and outpatient palliative care follow-up for 90 days.Main Outcomes and MeasuresThe prespecified primary end point was physical and functional quality of life (QoL) at postoperative day (POD) 90, measured by the Functional Assessment of Cancer Therapy–General (FACT-G) Trial Outcome Index (TOI), which is scored on a range of 0 to 56 with higher scores representing higher physical and functional QoL. Prespecified secondary end points included overall QoL at POD 90 measured by FACT-G, days alive at home until POD 90, and 1-year overall survival. Multivariable proportional odds logistic regression and Cox proportional hazards regression models were used to test the hypothesis that the intervention improved each of these end points relative to usual care in an intention-to-treat analysis.ResultsA total of 235 eligible patients (median [IQR] age, 65.0 [56.8-71.1] years; 141 male [60.0%]) were randomly assigned to the intervention or usual care group in a 1:1 ratio. Specialist palliative care was received by 114 patients (97%) in the intervention group and 1 patient (1%) in the usual care group. Adjusted median scores on the FACT-G TOI measure of physical and functional QoL did not differ between groups (intervention score, 46.77; 95% CI, 44.18-49.04; usual care score, 46.23; 95% CI, 43.08-48.14; P = .46). Intervention vs usual care group odds ratio (OR) was 1.17 (95% CI, 0.77-1.80). Palliative care did not improve overall QoL measured by the FACT-G score (intervention vs usual care OR, 1.09; 95% CI, 0.75-1.58), days alive at home (OR, 0.87; 95% CI, 0.69-1.11), or 1-year overall survival (hazard ratio, 0.97; 95% CI, 0.50-1.88).Conclusions and RelevanceThis randomized clinical trial showed no evidence that early specialist palliative care improves the QoL of patients undergoing nonpalliative cancer operations.Trial RegistrationClinicalTrials.gov Identifier: NCT03436290

When it comes to the treatment of patients with non-muscle-invasive bladder cancer (NMIBC) with intravesical bacillus Calmette-Guérin (BCG), two questions must be considered: 1) what dose to give, and 2) for how long? The issue of optimal dose and duration has been the subject of several randomized trials and is especially pertinent in the context of a global BCG shortage. Despite this, there appears to be uncertainty as to whether BCG dose or duration may be compromised in the event of shortage. As such, we wish to summarize the available evidence as an aid to the practicing urologist.

This AUA Guideline focuses on evaluation/counseling/management of adult patients with clinically-localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions.The Renal Mass and Localized Renal Cancer guideline underwent an update literature review which resulted in the 2021 amendment. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]).Great progress has been made regarding the evaluation/management of clinically-localized renal masses. These guidelines provide updated, evidence-based recommendations regarding evaluation/counseling including the evolving role of renal-mass-biopsy (RMB). Given great variability of clinical/oncologic/functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Options for intervention (partial-nephrectomy (PN), radical-nephrectomy (RN), and thermal-ablation (TA)) are reviewed including recent data about comparative-effectiveness/potential morbidities. Oncologic issues are prioritized while recognizing the importance of functional-outcomes for survivorship. Granular criteria for RN are provided to help reduce overutilization of RN while also avoiding imprudent PN. Priority for PN is recommended for clinical T1a lesions, along with selective utilization of TA, which has good efficacy for tumors≤3.0 cm. Recommendations for genetic-counseling have been revised and considerations for adjuvant-therapies are addressed. Active-surveillance and follow-up after intervention are discussed in an adjunctive article.Several factors require consideration during counseling/management of patients with clinically-localized renal masses including general health/comorbidities, oncologic-considerations, functional-consequences, and relative efficacy/potential morbidities of various management-strategies.

Neoadjuvant chemotherapy (NAC) prior to surgery and immune checkpoint therapy (ICT) have revolutionized bladder cancer management. However, stratification of patients that would benefit most from these modalities remains a major clinical challenge. Here, we combine single nuclei RNA sequencing with spatial transcriptomics and single-cell resolution spatial proteomic analysis of human bladder cancer to identify an epithelial subpopulation with therapeutic response prediction ability. These cells express Cadherin 12 (CDH12, N-Cadherin 2), catenins, and other epithelial markers. CDH12-enriched tumors define patients with poor outcome following surgery with or without NAC. In contrast, CDH12-enriched tumors exhibit superior response to ICT. In all settings, patient stratification by tumor CDH12 enrichment offers better prediction of outcome than currently established bladder cancer subtypes. Molecularly, the CDH12 population resembles an undifferentiated state with inherently aggressive biology including chemoresistance, likely mediated through progenitor-like gene expression and fibroblast activation. CDH12-enriched cells express PD-L1 and PD-L2 and co-localize with exhausted T-cells, possibly mediated through CD49a (ITGA1), providing one explanation for ICT efficacy in these tumors. Altogether, this study describes a cancer cell population with an intriguing diametric response to major bladder cancer therapeutics. Importantly, it also provides a compelling framework for designing biomarker-guided clinical trials., The identification of response biomarkers for surgery, chemotherapy and immune checkpoint therapy in bladder cancer is crucial. Here, single nuclei RNA sequencing and spatial profiling identify a cancer cell population expressing Neural Type Cadherin 2 that associates with distinct treatment outcomes.

Biodynamic signatures (temporal patterns of microscopic motion within a 3-dimensional tumor explant) offer phenomic biomarkers that are highly predictive for therapeutic response.By utilizing motility contrast tomography, which provides a simple, fast assessment of motion patterns in living tissue, we evaluated the predictive accuracy of a biodynamic drug response classifier in muscle-invasive bladder cancer (MIBC) patients undergoing neoadjuvant chemotherapy (NAC).One hundred five consecutive bladder cancer patients suspected of having MIBC were screened in a multi-institutional prospective observational study (NCT03739177) from July 2018 to June 2020, of whom, 30 completed NAC and radical cystectomy.Biodynamic signatures from treatment-naïve fresh bladder tumor specimens obtained after transurethral resection were measured in living tumor fragments challenged by standard-of-care cytotoxins. Patients received gemcitabine and cisplatin or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin per institutional guidelines and were followed through radical cystectomy.A 4-level classifier was developed to predict pathologic complete response (pCR) vs. incomplete response utilizing a one-left-out cross-validation protocol to minimize over-fitting. Area under the curve evaluated predictive utility.Thirty percent (9 of 30) achieved pCR. Utilizing the 4-level classifier, biodynamically "favored" (scoring ≥ 3) and "strongly favored" (scoring 4) regimens accurately predicted pCR at rates of 66.7% (4 of 6 patients) and 100% (4 of 4 patients), respectively. Biodynamically "favored" scores predicted pCR with 88% sensitivity and 95% negative predictive value, P0.0001. Only 5.0% (1 of 20 patients) achieved pCR from regimens scoring 1 or 2, indicating poor to no response from NAC. Area under the receiver operating curve was 96% (95% Confidence Interval: 79%-99%, P0.0001). Future direction involves validating this model prospectively.Biodynamic scoring accurately predicts response in MIBC patients receiving NAC and holds promise to substantially improve the scope of appropriate management intervention.

Nonmuscle-invasive bladder cancer is treated by resection within the bladder and bladder instillment with bacillus Calmette-Guérin or chemotherapy. For bacillus Calmette-Guérin-refractory disease, systemic anti-PD-1 (programmed cell death protein 1) immune checkpoint inhibition is a treatment. Our aim is to test whether intravesical instillment with anti-PD-1 inhibitor treats localized bladder cancer as effectively as systemic administration.We investigated an orthotopic mouse model of urothelial bladder cancer using MBT2 cells instilled into the bladders of syngeneic, wild-type C3H mice. Groups of 10 mice received each treatment for comparison of intravesical anti-PD-1, intraperitoneal anti-PD1, and intravesical chemotherapy. The primary outcome was overall survival and secondary outcomes included long-term immunity and toxicity.Anti-PD-1 administered by bladder instillment (intravesical route) successfully treats localized bladder cancer and has similar overall survival to anti-PD-1 by systemic route. Anti-PD-1 by either route provides a significant survival advantage over control antibody. Anti-PD-1 increases CD8+ cell infiltration in tumors, particularly when administered intravesically. Antibody treatment avoids toxicity observed for intravesical chemotherapy. Mice who cleared their tumors after initial treatment were rechallenged with tumor engraftment 3-9 months later without any additional treatment. Initial anti-PD-1-treated mice did not grow tumors when rechallenged, which suggests long-term immunity exists, but initial mitomycin-treated mice readily grew tumors indicating no immunity occurred by chemotherapy treatment.Intravesical administration of anti-PD-1 is a promising treatment route for localized bladder cancer, with comparable overall survival to systemic anti-PD-1 in this mouse model. Intravesical anti-PD-1 increases CD8+ T cells in treated tumors and long-term immunity was seen to tumor rechallenge.

Intravesical therapy for nonmuscle invasive bladder cancer decreases recurrence and progression but carries a high risk of side effects, which limit patient adherence. Appropriate management of the toxicities from intravesical therapy requires consideration of the agent used, the side effects experienced, and the timing of those side effects. Management strategies for intravesical toxicities ideally improve patient tolerance without sacrificing oncologic outcomes. This review aims to provide a comprehensive overview of the available evidence regarding the side effects of intravesical therapies for nonmuscle invasive bladder cancer and to propose practical strategies for toxicity management.

Coordinated preoperative optimization programs for radical cystectomy (RC) are limited and non-comprehensive. We evaluated the feasibility and acceptability of a coordinated, multi-faceted prehabilitation program for RC patients at a high-volume bladder cancer referral center.We performed a narrative literature review for prehabilitation in bladder cancer management as of December 1, 2020, with specific emphasis on examining higher-level evidence sources. We selected domains with the highest level of evidence and recruited a multidisciplinary team of experts to design our program. We implemented a comprehensive prehabilitation program with a pre-defined order set as standard of care for all patients undergoing RC beginning February 1, 2021. Demographic and clinicopathologic data were collected prospectively. Rates of adherence to the prehabilitation program services were analyzed using Stata version 13.A total of 82 patients were enrolled between February - December 2021, of which 67 (81%) had undergone RC at data cutoff. Mean age was 68 years (SD 11) and 63 (76%) identified as male. Neoadjuvant chemotherapy (NAC) was utilized in 48 (59%) patients. The mean Charlson Comorbidity Index was 3.8 (SD 2.3). 100% of patients were screened for malnutrition, with 82% consuming nutritional supplements. Fifty-two percent of patients attended physical therapy pre-op. The 30-day and 30- to 90-day rates of complications were 56% and 40%, respectively. Resource length of stay (RLOS) declined after implementation of prehabilitation.Implementation of a comprehensive prehabilitation program at a high-volume bladder cancer referral center is feasible and has a modest effect on resource consumption and complications in our early experience.

OBJECTIVES To examine the effect of hospital volume on short and long-term outcomes for radical nephroureterectomy (RNUx). Upper tract urothelial carcinoma is a rare malignancy that few surgeons have experience with. The hospital volume-outcome relationship has been well established for other cancers but not RNUx. METHODS The National Cancer Database was queried for all cases of upper tract urothelial carcinoma that underwent RNUx from 2004 to 2016. Average annual hospital volume for radical nephroureterectomy was stratified into tertiles. The upper tertile, defined as 6 or more RNUx per year, was considered high volume while low volume was less than 6 RNUx per year. Kaplan-Meier and Cox proportional hazards regression were used to identify independent predictors of overall survival, and logistic regression was used to identify predictors of perioperative outcomes. RESULTS We identified 37,479 RNUx performed across 1290 hospitals. There were no differences in baseline health or cancer staging between patients who presented at low- versus high-volume centers. Both peri-operative survival (30- and 90-day mortality) and long-term overall survival were improved in patients treated at high-volume centers. On multivariable survival analysis, treatment at a high-volume center was associated with improved hazards of survival. This relationship for long-term survival remained consistent on landmark analysis where patients who died within 90 days of surgery were removed. CONCLUSIONS Treatment at a high-volume hospital was associated not only with improved short-term perioperative outcomes but also with improved overall long-term survival. The mechanism behind this is likely multifactorial with surgeon volume, and ancillary support services all playing critical roles.

Non-muscle invasive bladder cancer is a heterogeneous disease with widely varying risks of recurrence and progression to muscle invasion. Risk stratification within current treatment guidelines are an attempt to address this heterogeneity. This heterogeneity stems from a number of pathologic characteristics as well as recurrence status. Radical cystectomy, while the definitive, curative therapy for muscle invasive disease, is not often utilized for non-muscle invasive disease, even when it may be a superior option to bladder-sparing therapy. A majority of American Urologists have been reported to defer cystectomy for less invasive therapies when it is a guideline driven option. Both cystectomy and bladder-sparing therapy have excellent oncologic outcomes, but very different morbidity and mortality profiles. Timely, initial cystectomy provides improved oncologic outcomes for patients with high-risk non-muscle invasive bladder cancer, as opposed to delayed cystectomy following prolonged, failed bladder-sparing therapy. Patient selection is paramount when considering timely, initial cystectomy, given the increased rates of morbidity and mortality. The heterogeneity of non-muscle invasive pathologic characteristics includes a number of factors that may help differentiate patients who would benefit from a timely, initial cystectomy as opposed to bladder-sparing therapy. A rapidly evolving understanding of bladder cancer biology may help improve risk stratification and further aid in the selection of patients for timely, initial cystectomy.

495 Background: Patients (pts) with BCG-unresponsive NMIBC have limited treatment options and are at an increased risk for cystectomy. Nogapendekin alfa inbakicept (NAI, also known as N-803), is an interleukin-15 superagonist (IL-15RαFc), which synergizes with BCG to elicit innate immune memory resulting in durable complete responses (CRs) in this patient population. In an open-label, 3-cohort, multicenter Phase 2/3 study of intravesical BCG plus NAI in BCG-unresponsive high-grade NMIBC (QUILT 3.032; NCT03022825), pts with carcinoma in situ (CIS; Cohort A) have a CR rate of 71% (median duration 26.6 months), 89.2% cystectomy avoidance and 100% bladder cancer specific survival at 24 months. We submit here the first quality of life (QOL) data report in the same pts cohort. Methods: Cohort A: 86 pts (median age 73 years; 87% male) with histologically confirmed BCG-unresponsive CIS with or without Ta/T1 disease, treated with intravesical BCG 50 mg plus NAI 400 μg. Mean baseline ECOG score was 0.183, with 82% of pts having score = 0. QOL was measured by the EORTC QOL Questionnaire Core 30 (QLQ-C30) and QOL NIMBC-Specific 24 Questionnaire (QLQ-NMIBC24). Results: Multivariate analyses have shown no significant changes over time for any of the measured QOL domains. Mild worsening vs. baseline in feeling ill was reported by 6% and 3% of pts by week 27 and 52, while 4% and 6% reported improvement. By week 78 and 104, 7% and 9% of pts reported improvement vs. baseline in their wellbeing with the majority being stable (non-significant). No statistically significant variations were detected in the physical function (PF) score (baseline vs. week 27, 52, 78 and 104). Higher PF scores were observed in pts responding to the therapy vs. non-responders; however, baseline value of PF was also higher in responders vs. non-responders. In contrast to historical results of BCG alone, week 27 physical function scores were numerically higher than baseline, with a subsequent nadir at week 78 and recovery to baseline by week 104 (non-significant). Hospitalizations for any reason remained low (0% - 6% per assessments) during the study. Conclusions: QOL measurement supports good tolerability of the intravesical NAI plus BCG in BCG-unresponsive, high-grade NMIBC pts with CIS. These results further strengthen the evidence of a favorable benefit: risk ratio of this novel combination immunotherapy, in a challenging disease. Clinical trial information: NCT03022825 .

Significance: Tissue birefringence is an important parameter to consider when designing realistic, tissue-mimicking phantoms. Options for suitable birefringent materials that can be used to accurately represent tissue scattering are limited. Aim: To introduce a method of fabricating birefringent tissue phantoms with a commonly used material—polydimethylsiloxane (PDMS)—for imaging with polarization-sensitive optical coherence tomography (PS-OCT). Approach: Stretch-induced birefringence was characterized in PDMS phantoms made with varying curing ratios, and the resulting phantom birefringence values were compared with those of biological tissues. Results: We showed that, with induced birefringence levels up to 2.1×10−4, PDMS can be used to resemble the birefringence levels in weakly birefringent tissues. We demonstrated the use of PDMS in the development of phantoms to mimic the normal and diseased bladder wall layers, which can be differentiated by their birefringence levels. Conclusions: PDMS allows accurate control of tissue scattering and thickness, and it exhibits controllable birefringent properties. The use of PDMS as a birefringent phantom material can be extended to other birefringence imaging systems beyond PS-OCT and to mimic other organs.

Extraction site incisional hernia (IH) has been recognized as an important complication in minimally invasive procedures but has not been as well characterized following robotic-assisted laparoscopic prostatectomy (RALP). Approximately 29% of IH required surgical repair. A number of techniques have been utilized to reduce the rates of IH following minimally invasive procedures. First, off-midline extraction was investigated, this did not demonstrate a reduction in incisional hernia rates. Recently, supra-umbilical transverse incisions have been utilized to extract prostate specimen and this method decreased the extraction site IH rate compared to the vertical midline incision. In addition, the choice of fascial closure technique and choice of the suture may influence the incidence of extraction site IH. For example, studies showed that abdominal fascial closure using a nonabsorbable suture and a continuous running suture technique decreased IH rate from 32 to 17%. Finally, “the small bites technique” has been recommended to reduce hernia incidence after midline fascial closure following a randomized controlled trial (RCT) which demonstrated the superiority of the small-bite technique. In summary, a supra-umbilical transverse incision to extract the specimen was shown to decrease the rate of extraction site IH. In vertical midline incisional closure, the small bites technique with slowly- or non-absorbable suture, such as #0 or 2–0 PDS II with SH or CT-2 needle (26 mm arch length), reduces the IH rate. Urologists should consider this data to reduce the risk of IH following RALP.

INTRODUCTION AND OBJECTIVE:Patients with NMIBC CIS unresponsive to BCG have limited treatment options. N-803 (Anktiva) is an mutant IL-15-based immunostimulatory fusion protein complex (IL-15RαFc) ...

To characterize training and practice factors that influence early career stability and satisfaction in urology residency and fellowship graduates.A computer-based survey was distributed to residency and fellowship graduates from a single, large US training program from 1992 to 2015. Queries encompassed training program specifics, post-training practice characteristics, and a validated burnout assessment.Of 108 surveyed individuals there were 77 (71.3%) respondents. Fifty-one (67.1%) remained in their first position after residency. While 52 (67.5%) urologists reported that the program did not formally assist in finding their first post-residency position, no respondent reported difficulty securing a position. Proximity to family was a major factor in selecting a post-residency position in 40 (51.9%) of respondents. Twenty-nine (37.7%) participants joined practices with at least one other graduate of the same urology training program on staff and 24 remain in this position (82%).Urology graduates from a large US training program did not have difficulty finding employment after training and most remain in their first post-training position. While proximity to family was a strong consideration for graduates, the perceived importance of first-position characteristics varied widely. 37.7% of our cohort took initial positions at a practice already employing a graduate from the same training program with80% staying in this position. Surveying a broader range of programs may help future graduates and training programs better tailor their mentorship curricula and alumni networks to trainee goals.

Purpose:We designed a prospective randomized, controlled pilot trial to investigate the effects of an enriched oral nutrition supplement on body composition and clinical outcomes following radical cystectomy.Materials and Methods:A total of 61 patients were randomized to an oral nutrition supplement or a multivitamin multimineral supplement twice daily during an 8-week perioperative period. Body composition was determined by analyzing abdominal computerized tomography images at the L3 vertebra. Sarcopenia was defined as a skeletal muscle index of less than 55 cm2/m2 in males and less than 39 cm2/m2 in females. The primary outcome was the difference in 30-day hospital free days. Secondary outcomes included hospital length of stay, complications, readmissions and mortality.Results:The oral nutrition supplement group lost less weight (–5 vs –6.5 kg, p = 0.04) compared to the multivitamin multimineral supplement group. The proportion of patients with sarcopenia did not change in the oral nutrition supplement ...

Objectives To investigate the relationship between gender, body mass index (BMI), and prognosis in renal cell carcinoma (RCC) patients. Materials and Methods We retrospectively reviewed 1353 patients with RCC who underwent a partial or radical nephrectomy between 1988 and 2015. The association among sex, BMI, stage, grade, overall survival (OS), and recurrence-free survival (RFS) was analyzed. Results The median age of the patients was 59.4 ± 11.9 years. Female patients had proportionally lower grade tumors than male patients (Grade I-II in 75.5% vs. 69.3% in women and men, respectively, P = 0.022). There was no relationship between Fuhrman grade and BMI when substratified by gender (p > 0.05). There was a nonsignificant trend toward more localized disease in female patients (p = 0.058). There was no relationship between T stage and BMI when stratified by gender (p > 0.05). Patients with higher BMI had significantly better OS (p = 0.0004 and P = 0.0003) and RFS (P = 0.0209 and P =0.0082) whether broken out by lower 33rd or 25th percentile. Male patients with higher BMI had significantly better OS and RFS rates. However, there was no relationship between BMI and OS or RFS for female patients (P > 0.05). Multivariate analysis of the entire cohort demonstrated that a BMI in the lower quartile independently predicts OS (hazard ratio 1.604 [95% confidence interval: 1.07-2.408], P = 0.022) but not RFS (P > 0.05). When stratified by gender, there was no relationship between BMI and either OS or RFS (P > 0.05). Conclusions Increasing BMI was associated with RCC prognosis. However, the clinical association between BMI and oncologic outcomes may be different between men and women.

This AUA Guideline focuses on active surveillance (AS) and follow-up after intervention for adult patients with clinically-localized renal masses suspicious for cancer, including solid enhancing tumors and Bosniak 3/4 complex cystic lesions.In January 2021, the Renal Mass and Localized Renal Cancer guideline underwent additional amendment based on a current literature-search. This literature search retrieved additional studies published between July 2016 to October 2020 using the same Key Questions and search criteria from the Renal Mass and Localized Renal Cancer guideline. When sufficient evidence existed, the body of evidence was assigned strength-rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]).AS with potential delayed intervention should be considered for patients with solid, enhancing renal masses2cm or Bosniak 3-4 lesions that are predominantly-cystic. Shared decision-making about AS should consider risks of intervention/competing mortality versus the potential oncologic benefits of intervention. Recommendations for renal mass biopsy and considerations for periodic clinical/imaging-based surveillance are discussed. After intervention, risk-based surveillance protocols are defined incorporating clinical/laboratory evaluation and abdominal/chest imaging designed to detect local/systemic recurrences and possible treatment-related sequelae, such as progressive renal-insufficiency.AS is a potential management strategy for some patients with clinically-localized renal masses that requires careful risk-assessment, shared decision-making and periodic-reassessment. Follow-up after intervention is designed to identify local/systemic recurrences and potential treatment-related sequelae. A risk-based approach should be prioritized with selective use of laboratory/imaging resources.

Objective To examine the relationship between hospital volume and the management of bladder cancer variant histology. Variant histologies of bladder cancer are rare which limits the ability for providers to develop expertise however there is a clear hospital and/or surgeon-volume relationship for management of rare or complex surgical and/or medical diseases. Methods We queried the National Cancer Database from 2004-2016 for all cases of bladder cancer, identifying cases of variant histology. Our primary outcome was overall survival while secondary outcomes included identifying treatment patterns. Hospitals were stratified into those that managed ≤2, >2-4, >4-6, and ≥6 cases per year of variant histology. Results We identified 23,284 patients with bladder cancer of variant histology who were treated at 1301 hospitals. Few institutions had high volume experience with this disease: 18.5% (n = 241) treated >2 patients annually and 5.7% (n = 76) treated >4 cases annually. Hospital volume positively correlated with utilization of early radical cystectomy (RC) in non–muscle invasive disease and neoadjuvant chemotherapy in muscle-invasive disease. On multivariable analysis, increased hospital volume was associated with improved survival. After stratifying by sub-type, hospital volume continued to be associated with improved survival for squamous, small cell, and sarcomatoid cancers. Conclusion Management of variant histology urothelial carcinoma at high-volume centers is associated with improved overall survival. The mechanisms of this are multifactorial, and future research should focus on improvement opportunities for low-volume hospitals, centralization of care, and/or increased access to care at high-volume centers.

4508 Background: Patients with NMIBC CIS unresponsive to BCG have limited treatment options. N-803 (Anktiva) is a mutant IL-15-based immunostimulatory fusion protein complex (IL15RaFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. Phase 1b data in BCG-naïve patients with NMIBC demonstrate that intravesical administration of N-803 with BCG induced complete response in all patients, without recurrences for the study duration of 24 months. Pembrolizumab was approved in 2020 with a 41% complete response (CR) rate in a single arm phase 2 trial of 96 patients. We report data on 160 subjects from an open-label, 3 cohort multicenter study (QUILT 3.032) of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825). Methods: All treated patients received intravesical N-803 plus BCG, consistent with the standard induction/maintenance treatment schedule. The primary endpoint for Cohort A (CIS) is incidence of CR of CIS at any time. The primary endpoint for Cohort B (Papillary) is disease-free rate (DFS) at 12 months. Results: To date, we enrolled 160 patients (83 CIS, 77 Papillary). In the overall population, median age is 72.3 years, 81% male, with mean number of prior TURBT = 4. Median number of prior BCG doses = 12. CIS patients have a CR rate of 71% (59/83), with a mediation duration of CR of 24.1 months in responders; 91% avoided cystectomy and 96% 24 month bladder cancer specific progression free survival (defined as progression to MIBC). Papillary patients have a 57% 12 month DFS rate, 48% 24 month DFS rate, and 95% avoided cystectomy. Median time to cystectomy in responders (N = 4) is 12.9 months versus 7.8 in non-responders (N = 8) for a 5.1 month delay in cystectomy. PK data shows no systemic levels of N-803; activity is confined to the bladder. Low grade treatment related AEs (grade 1-2) include dysuria (22%), pollakiurua (19%), hematuria (18%), fatigue (16%), and urgency (12%), all other AEs were seen at 7% or less. No treatment related grade 4 or 5 AE were seen. No SAE's were considered treatment related. No immune related SAE's have been seen. Conclusions: In 160 patients with BCG-unresponsive NMIBC, there is a 99% bladder cancer specific overall survival at 2 years. In CIS patients 71% CR rate with 24.1 months median duration of response, and 53% DFS rate at 18 months in Papillary disease. Cystectomy was avoided in over 90% of patients with 2 years of follow-up. The efficacy and safety profile of N-803+BCG exceeds that of other available intravesical and systemic options for BCG-unresponsive NMIBC. Clinical trial information: NCT03022825.

e17053 Background: 18F-DCFPyL (piflufolastat F 18) is a PSMA-targeted agent FDA-approved for PET imaging in men with prostate cancer. Given the recent availability for clinical use, we sought to evaluate the impact and potential changes in management after the incorporation of 18F-DCFPyL (PyL) PET/CT at an academic medical center. Methods: We reviewed the first 100 PyL PET/CT scans performed at the Vanderbilt-Ingram Cancer Center for men with prostate adenocarcinoma. Patient demographics, treatment history, and prior imaging results were recorded, along with PyL PET results, most recent PSA, and clinical management plans. Management changes were designated as change in systemic therapy, radiation, or surgery and were determined by two independent reviewers with a third reviewer for any discordant cases. Results: There were 100 men included with PyL PET scans dating from 9/1/21 to 12/31/21. The median age was 69 years, 76% of patients were white and 13% were black. The median Gleason sum at diagnosis was 7 (4+3), 55% of men had prior prostatectomy, and 38% had prior radiation to the prostate/pelvis. The median PSA prior to PyL PET scan was 1.86 (IQR 0.53-9.95 ng/mL), 32% of men had previous ADT exposure, and 15% were on ADT at the time of PyL PET scan. The clinical setting prior to PyL PET scan was initial staging 22%, biochemical recurrence 59%, m1HSPC 14%, m0CRPC 2%, and m1CRPC 3%. There were 16 patients who had a prior 18F-fluciclovine within six months of PyL PET; of these 69% (11/16) had additional disease on PyL PET not previously identified. Activity in lymph nodes was observed in 48%, bone 37%, visceral sites 3%, prostate/prostate bed 46%, and 15% had no PSMA-avid disease. Clinical staging was altered after the PyL PET scan in 55% of patients, with the most common change being from BCR to m1HSPC (40/55). Clinical management was altered in 59% of cases: systemic therapy 38%, radiation planning 46%, and surgical planning 6% (Table). Conclusions: Clinical management was affected in 59% of cases after implementation of PyL PET in this retrospective, single center review. Given the rapid adoption of PSMA-targeted PET imaging agents, further studies are needed to evaluate the clinical impact of subsequent changes to management planning, as well as to develop multidisciplinary consensus statements and protocols to guide management.[Table: see text]

Extraction site incisional hernia (IH) has been recognized as an important complication in minimally invasive procedures but has not been as well characterized following robotic-assisted laparoscopic prostatectomy (RALP). Approximately 29% of IH required surgical repair. A number of techniques have been utilized to reduce the rates of IH following minimally invasive procedures. First, off-midline extraction was investigated, this did not demonstrate a reduction in incisional hernia rates. Recently, supra-umbilical transverse incisions have been utilized to extract prostate specimen and this method decreased the extraction site IH rate compared to the vertical midline incision. In addition, the choice of fascial closure technique and choice of the suture may influence the incidence of extraction site IH. For example, studies showed that abdominal fascial closure using a nonabsorbable suture and a continuous running suture technique decreased IH rate from 32 to 17%. Finally, "the small bites technique" has been recommended to reduce hernia incidence after midline fascial closure following a randomized controlled trial (RCT) which demonstrated the superiority of the small-bite technique. In summary, a supra-umbilical transverse incision to extract the specimen was shown to decrease the rate of extraction site IH. In vertical midline incisional closure, the small bites technique with slowly- or non-absorbable suture, such as #0 or 2-0 PDS II with SH or CT-2 needle (26 mm arch length), reduces the IH rate. Urologists should consider this data to reduce the risk of IH following RALP.

INTRODUCTION AND OBJECTIVE: Readmission rates after radical cystectomy are among the highest of any surgery. The Hospital Readmissions Reduction Program (HRRP) penalizes hospitals with excess readmissions for certain targeted conditions, including total hip and knee arthroplasty. We examined whether changes made by hospitals in response to the HRRP had spillover effects on radical cystectomy readmissions. METHODS: We used a 20% sample of Medicare data to identify patients undergoing cystectomy from 2010 to 2014 and measured 30-day adjusted cystectomy readmission rates. To determine the effect of the HRRP, we calculated adjusted readmission rates following total hip or knee arthroplasty and stratified hospitals into quartiles (most improved, middle quartiles, least improved) based on their improvement in reducing those targeted readmissions. Multivariable logistic regression was used to identify factors associated with spillover effects from the targeted joint surgery to cystectomy. RESULTS: We identified 2,394 patients undergoing radical cystectomy. Of these, 606 were treated at hospitals in the “most improved” quartile and 522 in the “least improved.” Patients undergoing cystectomy were similar in age, comorbidity, and SEC independent of hospital performance quartile. The readmission rate following cystectomy was 26% in the most improved quartile and 24% in the least improved. No spillover effect was identified between readmission reduction after major joint surgery and radical cystectomy (adjusted OR 0.90, p=0.42). CONCLUSIONS: Hospitals that succeeded in reducing readmissions following major joint surgery targeted by the HRRP did not have similar reductions in readmissions following radical cystectomy. This lack of spillover effect suggests that each surgical condition may require tailored interventions to prevent readmissions.

INTRODUCTION AND OBJECTIVE:Upper tract urothelial carcinoma (UTUC) is a rare genitourinary malignancy that represents only 5-10% of all urothelial carcinoma (UC). While the majority of these cancer...

The heterogenous nature of high-risk nonmuscle invasive bladder cancer encompasses a wide range of tumor biologies with varying recurrence and progression risks. Radical cystectomy provides excellent oncologic outcomes but is often underutilized. Timing for these patients is critical, however, to its effectiveness. Certain unfavorable tumor characteristics predict worse outcomes and may help select the most appropriate patients for more aggressive initial therapy. This manuscript aims to outline factors that predict worse outcomes in high-risk nonmuscle invasive bladder cancer and proposes which patients may benefit most from a timely radical cystectomy.

PURPOSE: The RAZOR (Randomized Open versus Robotic Cystectomy) trial revealed noninferior 2-year progression-free survival for robotic radical cystectomy. This update was performed with extended followup for 3 years to determine potential differences between the approaches. We also report 3-year overall survival and sought to identify factors predicting recurrence, and progression-free and overall survival. MATERIALS AND METHODS: We analyzed the per protocol population of 302 patients from the RAZOR study. Cumulative recurrence was estimated using nonbladder cancer death as the competing risk event and the Gray test was applied to assess significance in differences. Progression-free survival and overall survival were estimated by the Kaplan-Meier method and compared with the log rank test. Predictors of outcomes were determined by Cox proportional hazard analysis. RESULTS: Estimated progression-free survival at 36 months was 68.4% (95% CI 60.1–75.3) and 65.4% (95% CI 56.8–72.7) in the robotic and open groups, respectively (p=0.600). At 36 months overall survival was 73.9% (95% CI 65.5–80.5) and 68.5% (95% CI 59.8–75.7) in the robotic and open groups, respectively (p=0.334). There was no significant difference in the cumulative incidence rates of recurrence (p=0.802). Patient age greater than 70 years, poor performance status and major complications were significant predictors of 36-month progression-free survival. Stage and positive margins were significant predictors of recurrence, and progression-free and overall survival. Surgical approach was not a significant predictor of any outcome. CONCLUSIONS: This analysis showed no difference in recurrence, 3-year progression-free survival or 3-year overall survival for robotic vs open radical cystectomy. It provides important prospective data on the oncologic efficacy of robotic radical cystectomy and high level data for patient counseling.