Robotic Resection of Spinal and Paraspinal Tumors.

BACKGROUND AND OBJECTIVES: Robotic arm surgical systems provide minimally invasive access and are commonly used in multiple surgical fields, with limited application in neurosurgery. Our institutional experience has led us to explore the benefits of a neurosurgeon trained to perform robotic surgery as part of a multidisciplinary team. The objective of this study is to evaluate the feasibility, safety, and outcomes of robotic resection for spinal nerve sheath tumors (NST). METHODS: Retrospective case series of robotic-assisted intracavitary approaches and resection of NSTs including thoracic, retroperitoneal, and transperitoneal. Surgical outcomes are compared to a historical cohort of open surgical resection of NSTs. RESULTS: Nineteen cases presented, of which 2 were combined posterior spinal followed by robotic tumor resection. One of 19 cases was converted to an open surgery. Gross total resection was achieved in all cases. There were 2 cases of postoperative Horner's syndrome, and 1 case with an intraoperative durotomy that was repaired primarily with no postoperative sequelae. Median estimated blood loss was 50 cc (range: 5-650) and median length of stay was 1 day (range: 0-6), with 9 (47.4%) patients discharged on postoperative day 1 and 3 (15.8%) patients discharged on an outpatient basis. Compared with our previously reported institutional outcomes for open resection of 25 tumors, there was a significant increase in rates of gross total resection (100 vs 60%, P = .002) and decrease in length of stay (median 1 vs 5 days, P < .0001). CONCLUSION: Robotic resection of complex paraspinal tumors appears safe and effective including for preservation of neurological function and may reduce surgical morbidity. Integration of robotic surgical platforms holds the potential to significantly affect neurological surgery.

Randomized Trial of Transverse vs Vertical Extraction Site Incision After Robotic Radical Prostatectomy.

PURPOSE: Incisional hernias are a frequent complication following robotic radical prostatectomy. Observational data in men undergoing robotic prostatectomy suggest that transverse closure resulted in lower hernia rates than vertical closure. We sought to compare the incidence of incisional hernia after robotic radical prostatectomy after vertical and transverse extraction site closure. MATERIALS AND METHODS: We conducted a clinically integrated, crossover, cluster randomized trial at a single tertiary referral center (January 2016-September 2021) comparing the rate of hernia after transverse vs vertical extraction site excision in 1356 patients treated with minimally invasive radical prostatectomy. The primary outcome was between-group incidence of incisional hernia within 15 months of prostatectomy defined by physical examination and self-reported patient surveys. RESULTS: Overall, 197 (20%) patients developed an incisional hernia within 15 months, 797 did not have an incisional hernia within this period, and 362 had missing outcome data regarding incisional hernia. We found no significant difference in hernia rates between the 2 incision types (absolute between-group difference 1.8%; 95% CI -3.4%, 6.6%; P = .5) in the primary analysis or in the 3 sensitivity analyses. Notably, because of the inclusive definition of hernia used, these data cannot be used as an estimate of the true prevalence of incisional hernia. CONCLUSIONS: Surgeons should choose the incision and closure approach they are most comfortable with when extracting specimens. Studies of modifications to the surgical technique are best conducted as randomized comparisons, and the clinically integrated, crossover, cluster randomized trial allows large trials to be completed at a single center and at low cost. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01407263.

Natural History and Genomic Landscape of Chemotherapy-Resistant Muscle-Invasive Bladder Cancer.

PURPOSE: Patients with residual invasive bladder cancer after neoadjuvant chemotherapy (NAC) and radical cystectomy have a poor prognosis. Data on adjuvant therapy for these patients are conflicting. We sought to evaluate the natural history and genomic landscape of chemotherapy-resistant bladder cancer to inform patient management and clinical trials. METHODS: Data were collected on patients with clinically localized muscle-invasive urothelial bladder cancer treated with NAC and cystectomy at our institution between May 15, 2001, and August 15, 2019, and completed four cycles of gemcitabine and cisplatin NAC, excluding those treated with adjuvant therapies. Survival was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were used to identify predictors of recurrence-free survival (RFS). Genomic alterations were identified in targeted exome sequencing (Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets) data from post-NAC specimens from a subset of patients. RESULTS: Lymphovascular invasion (LVI) was the strongest predictor of RFS (hazard ratio, 2.15 [95% CI, 1.37 to 3.39]) on multivariable analysis. Patients with ypT2N0 disease without LVI had a significantly prolonged RFS compared with those with LVI (70% RFS at 5 years). Lymph node yield did not affect RFS. Among patients with sequencing data (n = 101), chemotherapy-resistant tumors had fewer alterations in DNA damage response genes compared with tumors from a publicly available chemotherapy-naïve cohort (15% v 29%; P = .021). Alterations in CDKN2A/B were associated with shorter RFS. PIK3CA alterations were associated with LVI. Potentially actionable alterations were identified in more than 75% of tumors. CONCLUSION: Although chemotherapy-resistant bladder cancer generally portends a poor prognosis, patients with organ-confined disease without LVI may be candidates for close observation without adjuvant therapy. The genomic landscape of chemotherapy-resistant tumors is similar to chemotherapy-naïve tumors. Therapeutic opportunities exist for targeted therapies as adjuvant treatment in chemotherapy-resistant disease.

Implementation and Validation of an Automated, Longitudinal Robotic Surgical Evaluation and Feedback Program at a High-volume Center and Impact on Training.

Background: Surgical education lacks a standardized, proficiency-based approach to evaluation and feedback. Objective: To assess the implementation and reception (ie, feasibility) of an automated, standardized, longitudinal surgical skill assessment and feedback system, and identify baseline trainee (resident and fellow) characteristics associated with achieving proficiency in robotic surgery while learning robotic-assisted laparoscopic prostatectomy. Design setting and participants: A quality improvement study assessing a pilot of a surgical experience tracking program was conducted over 1 yr. Participants were six fellows, eight residents, and nine attending surgeons at a tertiary cancer center. Intervention: Trainees underwent baseline self-assessment. After each surgery, an evaluation was completed independently by the trainee and attending surgeons. Performance was rated on a five-point anchored Likert scale (trainees were considered "proficient" when attending surgeons' rating was ≥4). Technical skills were assessed using the Global Evaluative Assessment of Robotic Skills (GEARS) and Prostatectomy Assessment and Competency Evaluation (PACE). Outcome measurements and statistical analysis: Program success and utility were assessed by evaluating completion rates, evaluation completion times, and concordance rates between attending and trainee surgeons, and exit surveys. Baseline characteristics were assessed to determine associations with achieving proficiency. Results and limitations: Completion rates for trainees and attending surgeons were 72% and 77%, respectively. Fellows performed more steps/cases than residents (median [interquartile range]: 5 [3-7] and 3 [2-4], respectively; p < 0.01). Prior completion of robotics or laparoscopic skill courses and surgical experience measures were associated with achieving proficiency in multiple surgical steps and GEARS domains. Interclass correlation coefficients on individual components were 0.27-0.47 on GEARS domains. Conclusions: An automated surgical experience tracker with structured, longitudinal evaluation and feedback can be implemented with good participation and minimal participant time commitment, and can guide curricular development in a proficiency-based education program by identifying modifiable factors associated with proficiency, individualizing education, and identifying improvement areas within the education program. Patient summary: An automated, standardized, longitudinal surgical skill assessment and feedback system can be implemented successfully in surgical education settings and used to inform education plans and predict trainee proficiency.

A Quantitative Multiparametric MRI Analysis Platform for Estimation of Robust Imaging Biomarkers in Clinical Oncology.

There is a need to develop user-friendly imaging tools estimating robust quantitative biomarkers (QIBs) from multiparametric (mp)MRI for clinical applications in oncology. Quantitative metrics derived from (mp)MRI can monitor and predict early responses to treatment, often prior to anatomical changes. We have developed a vendor-agnostic, flexible, and user-friendly MATLAB-based toolkit, MRI-Quantitative Analysis and Multiparametric Evaluation Routines ("MRI-QAMPER", current release v3.0), for the estimation of quantitative metrics from dynamic contrast-enhanced (DCE) and multi-b value diffusion-weighted (DW) MR and MR relaxometry. MRI-QAMPER's functionality includes generating numerical parametric maps from these methods reflecting tumor permeability, cellularity, and tissue morphology. MRI-QAMPER routines were validated using digital reference objects (DROs) for DCE and DW MRI, serving as initial approval stages in the National Cancer Institute Quantitative Imaging Network (NCI/QIN) software benchmark. MRI-QAMPER has participated in DCE and DW MRI Collaborative Challenge Projects (CCPs), which are key technical stages in the NCI/QIN benchmark. In a DCE CCP, QAMPER presented the best repeatability coefficient (RC = 0.56) across test-retest brain metastasis data, out of ten participating DCE software packages. In a DW CCP, QAMPER ranked among the top five (out of fourteen) tools with the highest area under the curve (AUC) for prostate cancer detection. This platform can seamlessly process mpMRI data from brain, head and neck, thyroid, prostate, pancreas, and bladder cancer. MRI-QAMPER prospectively analyzes dose de-escalation trial data for oropharyngeal cancer, which has earned it advanced NCI/QIN approval for expanded usage and applications in wider clinical trials.

Evaluating residual tumor after neoadjuvant chemotherapy for muscle-invasive urothelial bladder cancer: diagnostic performance and outcomes using biparametric vs. multiparametric MRI.

BACKGROUND: Neoadjuvant chemotherapy (NAC) before radical cystectomy is standard of care in patients with muscle-invasive bladder cancer (MIBC). Response assessment after NAC is important but suboptimal using CT. We assessed MRI without vs. with intravenous contrast (biparametric [BP] vs. multiparametric [MP]) for identifying residual disease on cystectomy and explored its prognostic role. METHODS: Consecutive MIBC patients that underwent NAC, MRI, and cystectomy between January 2000-November 2022 were identified. Two radiologists reviewed BP-MRI (T2 + DWI) and MP-MRI (T2 + DWI + DCE) for residual tumor. Diagnostic performances were compared using receiver operating characteristic curve analysis. Kaplan-Meier curves and Cox proportional-hazards models were used to evaluate association with disease-free survival (DFS). RESULTS: 61 patients (36 men and 25 women; median age 65 years, interquartile range 59-72) were included. After NAC, no residual disease was detected on pathology in 19 (31.1%) patients. BP-MRI was more accurate than MP-MRI for detecting residual disease after NAC: area under the curve = 0.75 (95% confidence interval (CI), 0.62-0.85) vs. 0.58 (95% CI, 0.45-0.70; p = 0.043). Sensitivity were identical (65.1%; 95% CI, 49.1-79.0) but specificity was higher in BP-MRI compared with MP-MRI for determining residual disease: 77.8% (95% CI, 52.4-93.6) vs. 38.9% (95% CI, 17.3-64.3), respectively. Positive BP-MRI and residual disease on pathology were both associated with worse DFS: hazard ratio (HR) = 4.01 (95% CI, 1.70-9.46; p = 0.002) and HR = 5.13 (95% CI, 2.66-17.13; p = 0.008), respectively. Concordance between MRI and pathology results was significantly associated with DFS. Concordant positive (MRI+/pathology+) patients showed worse DFS than concordant negative (MRI-/pathology-) patients (HR = 8.75, 95% CI, 2.02-37.82; p = 0.004) and compared to the discordant group (MRI+/pathology- or MRI-/pathology+) with HR = 3.48 (95% CI, 1.39-8.71; p = 0.014). CONCLUSION: BP-MRI was more accurate than MP-MRI for identifying residual disease after NAC. A negative BP-MRI was associated with better outcomes, providing complementary information to pathological assessment of cystectomy specimens.

Multiparametric MRI in Era of Artificial Intelligence for Bladder Cancer Therapies.

This review focuses on the principles, applications, and performance of mpMRI for bladder imaging. Quantitative imaging biomarkers (QIBs) derived from mpMRI are increasingly used in oncological applications, including tumor staging, prognosis, and assessment of treatment response. To standardize mpMRI acquisition and interpretation, an expert panel developed the Vesical Imaging-Reporting and Data System (VI-RADS). Many studies confirm the standardization and high degree of inter-reader agreement to discriminate muscle invasiveness in bladder cancer, supporting VI-RADS implementation in routine clinical practice. The standard MRI sequences for VI-RADS scoring are anatomical imaging, including T2w images, and physiological imaging with diffusion-weighted MRI (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI). Physiological QIBs derived from analysis of DW- and DCE-MRI data and radiomic image features extracted from mpMRI images play an important role in bladder cancer. The current development of AI tools for analyzing mpMRI data and their potential impact on bladder imaging are surveyed. AI architectures are often implemented based on convolutional neural networks (CNNs), focusing on narrow/specific tasks. The application of AI can substantially impact bladder imaging clinical workflows; for example, manual tumor segmentation, which demands high time commitment and has inter-reader variability, can be replaced by an autosegmentation tool. The use of mpMRI and AI is projected to drive the field toward the personalized management of bladder cancer patients.

Open vs. robot-assisted radical cystectomy with extracorporeal or intracorporeal urinary diversion for bladder cancer A pairwise meta-analysis of outcomes and a network meta-analysis of complications.

INTRODUCTION: There are no meta-analyses of randomized controlled trials (RCTs) comparing open radical cystectomy (OR C) with robot-assisted radical cystectomy (RARC), inclusive of both intracorporeal (iRARC) and extracorporeal (hybrid RARC, hRARC) urinary reconstruction. METHODS: MEDL INE, Embase, Scopus, the International Clinical Trials Registry Platform and ClinicalTrials.gov registries were searched in May 2022. Outcomes of interest included recurrence- or progression-free survival (RFS/PFS), margin status and lymph node yield, mean estimated blood loss (EBL) and operating room time (ORT ), hospital length of stay (LOS ), 90-day complications and readmissions, and quality of life (QoL). Pairwise meta-analyses and network meta-analyses were performed using random-effects models and Bayesian hierarchical random-effects models, respectively. RESULTS: We found no significant differences between RARC and OR C for oncological and most perioperative outcomes: RFS/PFS (hazard ratio [HR ] 0.91, 95% confidence interval [CI] 0.67-1.23); positive surgical margins (odds ratio [OR ] 1.05, 95% CI 0.60-1.85); lymph node yield (mean difference [MD ] -0.63, 95% CI -2.63-1.37); LOS (MD -0.22, 95% CI -1.10-0.65); overall complications (OR 0.81, 95% CI 0.61-1.07); major complications (OR 0.94, 95% CI 0.69-1.30); readmissions (OR 0.90, 95% CI 0.60-1.35); and QoL (standardized MD -0.02, 95% CI -0.17-0.14). We found significantly lower EBL for RARC compared to OR C (MD -312.61, 95% CI -447 to -178.22) at the expense of significantly prolonged ORT (MD 82.34 minutes, 95% CI 44.82-119.86). Network meta-analysis did not find significant differences in complications between hRARC and iRARC. CONCLUSIONS: This meta-analysis confirms the equivalence of RARC and OR C with respect to oncological outcomes.

A Novel Expert Coaching Model in Urology, Aimed at Accelerating the Learning Curve in Robotic Prostatectomy.

INTRODUCTION/BACKGROUND: The surgical residency model assumes that upon completion, a surgeon is ready to practice and grow independently. However, many surgeons fail to improve after reaching proficiency, which in certain instances has correlated with worse clinical outcomes. Coaching addresses this problem and furthers surgeons' education post-residency. Currently, surgical coaching programs focus on medical students and residents, and have been shown to improve residents' and medical students' technical and non-technical abilities. Coaching programs also increase the accuracy of residents, fellows, and attendings in self-assessing their surgical ability. Despite the potential benefits, coaching remains underutilized and poorly studied. We developed an expert-led, face-to-face, video-based surgical coaching program at a tertiary medical center among specialized attending surgeons. Our goal was to evaluate the feasibility of such a program, measure surgeons' attitudes towards internal peer coaching, determine whether surgeons found the sessions valuable and educational, and to subjectively self-assess changes in operative technique. METHODS/MATERIALS: Surgeons who perform robot-assisted laparoscopic prostatectomies were chosen and grouped by number of cases completed: junior (<100 cases), intermediate (100-500 cases), and senior (>500 cases). Surgeons were scheduled for 3 1-hour coaching sessions 1-2 months apart (February-October 2019), meeting individually with the coach (PS), an expert Urologic Oncologist with thousands of cases of experience performing radical prostatectomy. He received training on coaching methodology prior to beginning the coaching program. Before each session, surgeons selected 1 of their recent intraoperative videos to review. During sessions, the coach led discussion on topics chosen by the surgeon (i.e. neurovascular bundle dissection, apical dissection, bladder neck); together, they developed goals to achieve before the next session. Subsequent sessions included presentation and discussion of a case occurring subsequent to the prior session. Sessions were coded by discussion topics and analyzed based on level of experience. Surgeons completed a survey evaluating the experience. RESULTS: All 6 surgeons completed 3 sessions. Five surgeons completed the survey; most respondents evaluated themselves as having improved in desired areas and feeling more confident performing the discussed steps of the operation. Discussed surgical principles varied by experience group; when subjectively quantifying the difficulty of surgical steps, the more difficult steps were discussed by the higher experience groups compared to the junior surgeons. The senior surgeons also focused more on oncologic potency, continence outcomes, and more theory-driven questions while the junior surgeons tended to focus more on anatomic and technique-based questions such as tissue handling and the use of cautery and clips. Overall, the surgeons thought this program provoked critical discussion and subsequently modified their technique, and "agreed" or "strongly agreed" that they would seek further sessions. CONCLUSIONS: Surgical coaching at a large medical center is not only feasible but was rated positively by surgeons across all levels of experience. Coaching led to subjective self-improvement and increased self-confidence among most surgeons. Surgeons also felt that this program offered a safe space to acquire new skills and think critically after finishing residency/fellowship. Themes discussed and takeaways from the sessions varied based on surgeon experience level. While further research is needed to more objectively quantify the impact coaching has on surgeon metrics and patient outcomes, the results of this study supports the initial "proof-of-concept" of peer-based surgical coaching and its potential benefits in accelerating the learning curve for surgeons' post-residency.

Uretero-enteric stricture outcomes: secondary analysis of a randomised controlled trial comparing open versus robot-assisted radical cystectomy.

OBJECTIVES: To analyse the risk of uretero-enteric anastomotic stricture in patients randomised to open (ORC) or robot-assisted radical cystectomy (RARC) with extracorporeal urinary diversion. PATIENTS AND METHODS: We included 118 patients randomised to RARC (n = 60) or ORC (n = 58) at a single, high-volume institution from March 2010 to April 2013. Urinary diversion was performed by experienced open surgeons. Stricture was defined as non-malignant obstruction on imaging, corroborated by clinical status, and requiring procedural intervention. The risk of stricture within 1 year was compared between groups using Fisher's exact test. RESULTS: In all, 58 and 60 patients were randomised to RARC and ORC, respectively. We identified five strictures, all in the ORC group. In patients with ≥1 year of follow-up, the increase in risk of stricture from open surgery was 9.3% (95% confidence interval 1.5%, 17%). Of the five strictures, three were managed endoscopically while two required open revision. There was no evidence that perioperative Grade 3-5 complications were associated with development of a stricture (P = 1) and no evidence of a difference in 24-month estimated glomerular filtration rate between arms (P = 0.15). CONCLUSIONS: In this study at a high-volume centre, RARC with extracorporeal urinary diversion achieved excellent ureteric anastomotic outcomes. Purported increased risk of stricture is not a reason to avoid RARC. Future research should examine the impact of different surgical techniques and operator experience on the risk of stricture, especially as more intracorporeal diversions are performed.

Long-term Outcomes of Local and Metastatic Small Cell Carcinoma of the Urinary Bladder and Genomic Analysis of Patients Treated With Neoadjuvant Chemotherapy.

INTRODUCTION: Small cell carcinoma of the bladder (SCCB) is a rare variant of bladder cancer with poor outcomes. We evaluated long-term outcomes of nonmetastatic (M0) and metastatic (M1) SCCB and correlated pathologic response with genomic alterations of patients treated with neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: Clinical history and pathology samples from SCCB patients diagnosed at our institution were reviewed. RESULTS: One hundred and ninety-nine SCCB patients were identified. (M0: 147 [74%]; M1: 52 [26%]). Among M0 patients, 108 underwent radical cystectomy (RC) (NAC: 71; RC only: 23; adjuvant chemotherapy: 14); 14 received chemoradiotherapy; the rest received chemotherapy alone or no cancer-directed therapy. RC-only patients had a median follow-up of 9.1 years, and median disease-free survival (DFS) and overall survival (OS) were 1.1 and 1.2 years, respectively. NAC patients had pathologic response (

Clinical and Genomic Characterization of Bladder Carcinomas With Glandular Phenotype.

PURPOSE: To compare oncologic outcomes and genomic alteration profiles in patients with bladder and urachal adenocarcinoma, urothelial carcinoma (UC) with glandular differentiation, and UC, not otherwise specified (NOS) undergoing surgical resection, with emphasis on response to systemic therapy. METHODS: We identified patients with bladder cancer with glandular variants who underwent surgical resection at Memorial Sloan Kettering from 1995 to 2018 (surgical cohort) and/or patients who had tumor sequencing using a targeted next-generation sequencing platform (genomics cohort). Pathologic complete and partial response rates to neoadjuvant chemotherapy (NAC) and recurrence-free and cancer-specific survival were measured. Alteration frequencies between histologic subtypes were compared. RESULTS: Thirty-seven patients with bladder adenocarcinoma, 46 with urachal adenocarcinoma, 84 with UC with glandular differentiation, and 1,049 with UC, NOS comprised the surgical cohort. Despite more advanced disease in patients with bladder and urachal adenocarcinoma, no significant differences in recurrence or cancer-specific survival by histology were observed after adjusting for stage. In patients with UC with glandular differentiation, NAC resulted in partial (≤ pT1N0) and complete (pT0N0) responses in 28% and 17%, respectively. Bladder and urachal adenocarcinoma genomic profiles resembled colorectal adenocarcinoma with frequent TP53, KRAS, and PIK3CA alterations while the genomic profile of UC with glandular differentiation more closely resembled UC, NOS. Limitations include retrospective nature of analysis and small numbers of nonurothelial histology specimens. CONCLUSION: The genomic profile of bladder adenocarcinomas resembled colorectal adenocarcinomas, whereas UC with glandular differentiation more closely resembled UC, NOS. Differences in outcomes among patients with glandular bladder cancer variants undergoing surgical resection were largely driven by differences in stage. Cisplatin-based NAC demonstrated activity in UC with glandular differentiation, suggesting NAC should be considered for this histologic variant.

Value of MRI in evaluating urachal carcinoma: A single center retrospective study.

OBJECTIVES: Urachal carcinomas (UrC) are rare non-urothelial bladder neoplasms, however the potential role for MR imaging in UrC has not been well established. Our objective was to assess the value of magnetic resonance imaging (MRI) in primary and recurrent UrC. METHODS AND MATERIALS: This retrospective single-center study included all patients with UrC that underwent MRI between January 2005 and May 2020. Two radiologists reviewed MRIs independently followed by consensus with a third radiologist. For primary UrC, tumor location, size, morphology, invasion of peritoneum and/or local structures other than bladder and concordance between Mayo stage on MRI and pathology were assessed. MRI performed for recurrent UrC evaluated the pattern of recurrence. The reference standard was histopathological analysis. RESULTS: Ninety-six patients with UrC were identified of which 17 were included (9 men and 8 women, median age 50 years [IQR 42-62]). At initial MR staging (n = 10), all primary UrC were located at the bladder dome with median longest axis dimension of 6.0 cm. Most (70%) were mixed solid-and-cystic. Invasion of the peritoneum and/or local structures other than bladder was identified in 30%. Concordance between consensus MRI Mayo stage and final pathologic Mayo stage was 90%. At MR restaging (n = 7), UrC recurrence was most commonly seen at the bladder dome (71%). Overall, MRI showed a sensitivity of 85% and specificity of 50% for detecting recurrent tumor. CONCLUSION: MRI demonstrates value in evaluation of disease extent in primary and recurrent UrC, with high concordance between Mayo stage at MRI and pathology, and in the detection of local recurrences.

Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in Patients With Muscle-Invasive Bladder Cancer: A Multicenter, Single-Arm, Phase II Trial.

PURPOSE: Neoadjuvant gemcitabine and cisplatin (GC) followed by radical cystectomy (RC) is standard for patients with muscle-invasive bladder cancer (MIBC). On the basis of the activity of atezolizumab (A) in metastatic BC, we tested neoadjuvant GC plus A for MIBC. METHODS: Eligible patients with MIBC (cT2-T4aN0M0) received a dose of A, followed 2 weeks later by GC plus A every 21 days for four cycles followed 3 weeks later by a dose of A before RC. The primary end point was non-muscle-invasive downstaging to < pT2N0. RESULTS: Of 44 enrolled patients, 39 were evaluable. The primary end point was met, with 27 of 39 patients (69%) < pT2N0, including 16 (41%) pT0N0. No patient with < pT2N0 relapsed and four (11%) with ≥ pT2N0 relapsed with a median follow-up of 16.5 months (range: 7.0-33.7 months). One patient refused RC and two developed metastatic disease before RC; all were considered nonresponders. The most common grade 3-4 adverse event (AE) was neutropenia (n = 16; 36%). Grade 3 immune-related AEs occurred in five (11%) patients with two (5%) requiring systemic steroids. The median time from last dose of chemotherapy to surgery was 7.8 weeks (range: 5.1-17 weeks), and no patient failed to undergo RC because of AEs. Four of 39 (10%) patients had programmed death-ligand 1 (PD-L1)-positive tumors and were all < pT2N0. Of the patients with PD-L1 low or negative tumors, 23 of 34 (68%) achieved < pT2N0 and 11 of 34 (32%) were ≥ pT2N0 (P = .3 for association between PD-L1 and < pT2N0). CONCLUSION: Neoadjuvant GC plus A is a promising regimen for MIBC and warrants further study. Patients with < pT2N0 experienced improved relapse-free survival. The PD-L1 positivity rate was low compared with published data, which limits conclusions regarding PD-L1 as a predictive biomarker.

An Assessment Tool to Provide Targeted Feedback to Robotic Surgical Trainees: Development and Validation of the End-To-End Assessment of Suturing Expertise (EASE).

Purpose: To create a suturing skills assessment tool that comprehensively defines criteria around relevant sub-skills of suturing and to confirm its validity. Materials and Methods: 5 expert surgeons and an educational psychologist participated in a cognitive task analysis (CTA) to deconstruct robotic suturing into an exhaustive list of technical skill domains and sub-skill descriptions. Using the Delphi methodology, each CTA element was systematically reviewed by a multi-institutional panel of 16 surgical educators and implemented in the final product when content validity index (CVI) reached ≥0.80. In the subsequent validation phase, 3 blinded reviewers independently scored 8 training videos and 39 vesicourethral anastomoses (VUA) using EASE; 10 VUA were also scored using Robotic Anastomosis Competency Evaluation (RACE), a previously validated, but simplified suturing assessment tool. Inter-rater reliability was measured with intra-class correlation (ICC) for normally distributed values and prevalence-adjusted bias-adjusted Kappa (PABAK) for skewed distributions. Expert (≥100 prior robotic cases) and trainee (<100 cases) EASE scores from the non-training cases were compared using a generalized linear mixed model. Results: After two rounds of Delphi process, panelists agreed on 7 domains, 18 sub-skills, and 57 detailed sub-skill descriptions with CVI ≥ 0.80. Inter-rater reliability was moderately high (ICC median: 0.69, range: 0.51-0.97; PABAK: 0.77, 0.62-0.97). Multiple EASE sub-skill scores were able to distinguish surgeon experience. The Spearman's rho correlation between overall EASE and RACE scores was 0.635 (p=0.003). Conclusions: Through a rigorous CTA and Delphi process, we have developed EASE, whose suturing sub-skills can distinguish surgeon experience while maintaining rater reliability.

Prognostic Utility of MRI Features in Intradiverticular Bladder Tumor.

BACKGROUND: Intradiverticular bladder tumors (IDBT) are rare but clinically important, as they are difficult to assess endoscopically due to limited anatomic access and risk of perforation. MRI may be helpful in assessing IDBT and providing relevant staging and prognostic information. PURPOSE: To assess MRI findings of IDBT and their relationship with overall survival. METHODS: This retrospective study included 31 consecutive patients with IDBT undergoing MRI from 2008 to 2018 identified through electronic medical records and PACS database search. Two radiologists independently assessed the following MRI features: size (>3 vs ≤3 cm), diverticular neck involvement, Vesical Imaging-Reporting and Data System (VI-RADS) score (>3 vs ≤3), perivesical fat infiltration, additional tumors and suspicious pelvic lymph nodes. Overall survival was estimated using Kaplan-Meier analysis; and the relationship with clinicopathological and MRI features was determined using the Cox proportional-hazards regression model. Inter-reader agreement was assessed using intraclass correlation coefficients (ICC) and Cohen's kappa (K). RESULTS: Median follow-up was 1044 days (interquartile range, 474-1952 days). Twenty-six (83.9%) patients underwent surgical treatment with or without neoadjuvant chemotherapy. On MRI, greater tumor size (>3 cm), diverticular neck involvement, perivesical extension, and suspicious lymph nodes were associated with lower overall survival (HR = 3.6-8.1 and 4.3-6.3 for the 2 radiologists, p ≤ 0.03). Other clinicopathological or MRI findings were not associated with survival (p = 0.27-0.65). Inter-reader agreement was excellent for tumor size (ICC = 0.991; 95% CI 0.982-0.996), fair for VI-RADS (K = 0.52, 95% CI, 0.22-0.82), and moderate for others (K = 0.61-0.79). CONCLUSION: In patients with IDBT, several MRI features were significantly associated with overall survival. Utilizing all available clinicopathological and imaging information may improve estimation of prognosis.

Pathological and oncological outcomes in patients with sarcomatoid differentiation undergoing cystectomy.

OBJECTIVE: To evaluate whether urothelial carcinoma (UC) with sarcomatoid differentiation is associated with a lower pathological response rate to neoadjuvant chemotherapy (NAC) and worse oncological outcomes compared to UC without variant histology among patients undergoing radical cystectomy. PATIENTS AND METHODS: Patients with UC undergoing cystectomy from 1995 to 2018 at the Memorial Sloan Kettering Cancer Centre were identified. Patients with sarcomatoid differentiation at transurethral resection (TUR) or cystectomy, and patients without variant histology were selected. Downstaging from ≥cT2 to ≤pT1N0 defined partial response and pT0N0 defined complete response. Recurrence-free, cancer-specific and overall survival were modelled. RESULTS: We identified 131 patients with sarcomatoid differentiation and 1722 patients without variant histology, of whom 25 with sarcomatoid histology on biopsy and 313 without variant histology received NAC. Those with sarcomatoid differentiation presented with higher consensus tumour stage (94% ≥T2 vs 62%; P < 0.001) and were, therefore, more likely to receive NAC (29% vs 18%; P = 0.003). We found no evidence to support a difference in partial (24% vs 31%) or complete (20% vs 24%) response between patients with sarcomatoid histology and those with pure UC at TUR (P = 0.6). Among patients with sarcomatoid differentiation, 5-year recurrence-free survival was 55% (95% confidence interval [CI] 41-74) among patients receiving NAC and 40% (95% CI 31-52) among patients undergoing cystectomy alone (P = 0.1). Adjusting for stage, nodal involvement, margin status and receipt of NAC, sarcomatoid differentiation was associated with worse recurrence-free (hazard ratio [HR] 1.82, 95% CI 1.39-2.39), disease-specific (HR 1.66, 95% CI 1.23-2.22), and overall survival (HR 1.37, 95% CI 1.06-1.78). CONCLUSIONS: Sarcomatoid differentiation was associated with higher stage at presentation and independently associated with worse survival. Given similar pathological response rates if sarcomatoid differentiation is detected at initial resection, and greater survival among patients receiving NAC, treatment with NAC appears warranted. Other drivers of the poor outcomes of this histology must be investigated.

Plasmacytoid urothelial carcinoma of the bladder: MRI features and their association with survival.

OBJECTIVES: Plasmacytoid urothelial carcinomas (PUC) of the bladder are rare variants known for diffuse and infiltrative spread, however their magnetic resonance imaging (MRI) features are not well established. We aimed to evaluate MRI features of PUC of the bladder and their association with survival. METHODS AND MATERIALS: This retrospective single-center study included 41 patients with pathologically-proven bladder PUC of the bladder that underwent pre-treatment MRI between January 2000 and March 2020. Two radiologists reviewed MRIs independently followed by consensus with a third radiologist. On MRI, tumor extent, size, Vesical Imaging-Reporting and Data System (VI-RADS) scores (≥4, muscle-invasive; 5, extravesical extension [EVE]), pelvic peritoneal spread (PPS), hydronephrosis, pelvic adenopathy and clinicopathological factors of age, gender, pathological stage, and treatment type were extracted. Kaplan-Meier curves and Cox proportional-hazards models were used to evaluate association with survival. RESULTS: Thirty-two men and 9 women (median age 70 years, IQR 64-76) were included. Most were muscle-invasive (n = 30 [73.2%]). On MRI, most tumors were diffuse (n = 28 [68.3%]), >5 cm (n = 30 [73.2%]), VI-RADS 4 to 5 (n = 36 [87.8%]) with features of EVE and (n = 31 [75.6%]) and PPS (n = 25 [61.0%]). Variables associated with survival were: Larger tumors (>5 cm; hazard ratio [HR] = 5.0; 95% confidence interval [CI] 1.6-15.5; P < 0.01), diffuse extent (HR = 4.0; 95% CI 1.4-11.2; P = 0.01), EVE (HR = 4.5; 95% CI 1.5-13.6; P < 0.01), PPS (HR = 3.0; 95% CI 1.2-7.4; P = 0.01), hydronephrosis (HR = 13.7; 95% CI 3.1-60.9; P < 0.01), pathologic stage (≥pT3 vs. pT1; HR = 5.6; 95% CI 1.3-22.0; P = 0.02), and margin positivity (HR = 4.4 [95% CI 1.2-16.4], P = 0.03). CONCLUSION: PUCs of the bladder are commonly large, diffuse VI-RADS score 4 to 5 tumors with MRI features of EVE and PPS. These features and pathological stage were associated with survival.