Pathological Downstaging and Survival Outcomes Associated with Neoadjuvant Chemotherapy for Variant Histology Muscle Invasive Bladder Cancer.

PURPOSE: Patients with muscle invasive bladder cancer (MIBC) of variant histology have a poor prognosis. It is unclear if neoadjuvant chemotherapy prior to radical cystectomy is associated with pathological downstaging or improved overall survival (OS) for patients with variant histology. Our objective was to assess for associations between receipt of neoadjuvant chemotherapy, pathological downstaging and OS for patients with variant histology MIBC. MATERIALS AND METHODS: Patients were identified in the National Cancer Database from 2004 to 2017 with MIBC, without metastases, who underwent radical cystectomy. Patients were stratified by histological subgroup, and receipt or nonreceipt of neoadjuvant chemotherapy. Pathological downstaging was defined as pT0N0 or pT ≤1N0, and OS from the time of diagnosis to date of death or censoring at last followup. Multivariable logistic regression analysis determined associations between neoadjuvant chemotherapy and pathological downstaging. Multivariable Cox regression analysis determined associations between neoadjuvant chemotherapy and OS. RESULTS: A total of 31,218 patients were included in the final study population (urothelial carcinoma [UC]: 27,779; sarcomatoid UC: 501; micropapillary UC: 418; squamous cell carcinoma: 1,141; neuroendocrine carcinoma: 629; adenocarcinoma: 750). Neoadjuvant chemotherapy was associated with pathological downstaging to pT0N0 in all histological subgroups (UC: OR 5.1 [4.6-5.6]; sarcomatoid UC: OR 13.8 [5.5-39.0]; micropapillary UC: OR 9.7 [2.8-46.8]; squamous cell carcinoma: OR 7.4 [2.1-24.5]; neuroendocrine: OR 4.7 [2.6-9.2]; adenocarcinoma: OR 23.3 [8.0-74.2]). Neoadjuvant chemotherapy was associated with improved OS for UC (HR 0.8 [0.77-0.84]), sarcomatoid UC (HR 0.64 [0.44-0.91]) and neuroendocrine carcinoma (HR 0.55 [0.43-0.70]). CONCLUSIONS: Neoadjuvant chemotherapy was associated with pathological downstaging for all MIBC histological variants, with improved OS for patients with UC, sarcomatoid variant UC and neuroendocrine carcinoma.

Perioperative stroke and myocardial infarction in urologic surgery.

INTRODUCTION Perioperative stroke and myocardial infarction are uncommon but devastating thromboembolic complications. There is no comprehensive study detailing these complications for urologic procedures. The primary aim of this study is to determine which urologic procedures and patients carry the highest risk of perioperative stroke and myocardial infarction. MATERIALS AND METHODS: The National Surgical Quality Improvement Program data set was reviewed from 2008-2017. Procedures coded under the urology specialty were included and patients who had a perioperative stroke or myocardial infarction were identified. CPTs were stratified into clinically relevant procedure groups. Two multivariable logistic regression analyses were performed to determine preoperative and procedural risk factors for developing perioperative stroke or myocardial infarction. A multivariable logistic regression analysis was performed to determine the association between these complications and 30-day mortality. RESULTS: A total of 281,744 cases were included, identifying 392 strokes (0.14%) and 1,016 myocardial infarctions (0.36%). Age ≥ 70, hypertension, and disseminated cancer were the strongest preoperative risk factors for perioperative stroke or myocardial infarction. Cystectomy was the highest risk urologic procedure (stroke: OR 3.3, 95%CI 2.3-4.8; MI: OR 7.2, 95%CI 5.6-9.1). Thirty-day mortality was dramatically worse for patients who had a perioperative stroke or myocardial infarction. CONCLUSIONS: Perioperative stroke and myocardial infarction were confirmed to be uncommon but devastating complications of urologic surgery, with incidence of 0.14% and 0.36%, respectively. Cystectomy was the highest risk urologic procedure. Perioperative stroke and myocardial infarction were strongly associated with age ≥ 70, hypertension, and disseminated cancer.

Educational value of the transplant experience in urology residency.

INTRODUCTION To evaluate the educational value of transplant rotation in urology residency. In the United States, exposure to kidney transplantation during urology residency has declined significantly over the past few decades. At our institution, transplantation has been a core component of urology residency since its inception in 1959. MATERIALS AND METHODS: A 15-question anonymous survey was developed. The first 8 questions queried demographics and the last 7 were a set of questions with a Likert Scale response. The survey was electronic- mailed to past and current urology residents who had completed the transplant rotation, dating back to 1972. RESULTS: A total of 61 out of 98 (62%) individuals responded. The majority (59%) were general urologists, and one (2%) had completed a transplant fellowship. In their practices, 17% performed kidney transplants and 28% performed donor nephrectomies. Overall, 100% responded that the skills learned on the transplant rotation were beneficial for urology training, 100% had learned valuable vascular surgical techniques, and 93% felt that urology residents should have clinical transplant experience during their training. There was no statistical difference between the younger and older graduates in Likert scale responses. CONCLUSION: The majority of graduates did not perform transplants in their practice, yet, all of responders agreed that the skills learned on the transplant rotation were beneficial and 93% expressed that urology residents should have clinical transplant experience during residency. Kidney transplantation should be an integral part of urology residency training.

Relative Value Units do Not Adequately Account for Operative Time of Urological Surgery.

PURPOSE: Physician work relative value units are determined based on operative time, technical skill, mental effort and stress. In theory, work relative value units should account for the operative time involved in a procedure, resulting in similar work relative value units per unit time for short and long procedures. We assessed whether operative time is adequately accounted for by the current work relative value units assignments. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was reviewed from 2015 to 2017. The 50 most frequently coded urology CPT codes were included in the study. The primary variable was work relative value units per hour of operative time (work relative value units per hour). Linear regression analysis was used to assess the associations between work relative value units, operative time and the work relative value units per hour variable. RESULTS: A total of 105,931 cases were included in the study. Among the included urology CPTs the median work relative value units was 15.26, median operative time was 48 minutes and median work relative value units per hour was 11.2. CPTs with operative time less than 90 minutes had higher work relative value units per hour compared with longer procedures (12.2 vs 8.7, p <0.001). Univariable analysis revealed that each additional hour of operative time was associated with a decrease in work relative value units per hour by 1.32 (-0.022 per minute, 95% CI -0.037 - -0.001, p <0.001) and that work relative value units were not statistically associated with work relative value units per hour (-0.093, 95% CI -0.193 - 0.007, p=0.07). CONCLUSIONS: This analysis of large population, national level data suggests that the current work relative value units assignments do not proportionally compensate for longer operative times.

Comparative effectiveness analysis of first-line immunotherapy versus chemotherapy in metastatic urothelial carcinoma of the bladder.

BACKGROUND: Clinical trials have not shown a significant overall survival (OS) difference between chemotherapy and immunotherapy as first-line agents in metastatic urothelial carcinoma (UC). However, the generalizability of these findings in a real-world setting has not yet been evaluated in comparative effectiveness studies. OBJECTIVE: To assess the effectiveness of first-line immunotherapy compared with chemotherapy regimens on OS in patients with metastatic UC of the bladder. DESIGN, SETTING, AND PARTICIPANTS: This retrospective propensity-matched study identified metastatic bladder UC patients in the National Cancer Database from 2014 to 2017 who received either first-line immunotherapy-monotherapy or multi-agent chemotherapy, and who were not treated on a clinical trial protocol. OUTCOME MEASURES AND ANALYSIS: The primary outcome was OS from the date of diagnosis to date of death or censoring at last follow-up. Patients were stratified into first-line immunotherapy and chemotherapy treatment groups. After 1:1 nearest-neighbor caliper-matching of propensity scores, the survival analysis was conducted using Cox regression modeling and Kaplan-Meier estimates. RESULTS AND LIMITATIONS: A total of 2,796 patients were included in the final study population, and 960 in the matched cohort (480 per treatment group). Utilization of immunotherapy increased over the time period studied as chemotherapy decreased (Immunotherapy: 3%-37%; Chemotherapy: 97%-63%; P < 0.001). In the overall cohort, patients who received first-line immunotherapy were older and more comorbid than those who received first-line chemotherapy (Age: 73 v. 67, respectively, P < 0.001; Charlson-Deyo score ≥2: 17% v. 11.5%, respectively, P < 0.001). In the matched cohort, patients who were treated with first-line immunotherapy had similar OS to those who were treated with first-line chemotherapy (HR: 0.91, 95CI 0.72-1.15). Due to the retrospective nature of the study, interpretation is limited by potential selection bias from unmeasured confounding. CONCLUSIONS AND RELEVANCE: Metastatic bladder UC patients who received first-line immunotherapy had similar OS to those who received first-line chemotherapy.

Survival Outcomes Associated With Cytoreductive Nephrectomy in Patients With Metastatic Clear Cell Renal Cell Carcinoma.

Importance: Level I evidence has failed to demonstrate an overall survival (OS) advantage for cytoreductive nephrectomy in patients with metastatic clear cell renal cell carcinoma (ccRCC) in the modern era, which is at odds with observational studies reporting a marked OS benefit associated with these operations. These observational studies were not designed to adjust for unmeasured confounding. Objective: To assess whether cytoreductive nephrectomy is associated with improved OS in patients with metastatic ccRCC. Design, Setting, and Participants: This cohort study identified patients with metastatic ccRCC in the National Cancer Database from January 1, 2006, to December 31, 2016, who received systemic targeted therapy. The analysis was finalized on July 23, 2021. Exposures: Receipt of cytoreductive nephrectomy. Main Outcomes and Measures: The primary outcome was OS from the date of diagnosis to death or censoring at last follow-up. Distance from the patients' zip code of residence to the treating facility was identified as a valid instrument and was used in a 2-stage residual inclusion instrumental variable analysis. Conventional adjustments for selection bias, multivariable Cox proportional hazards regression, and propensity score matching were performed for comparison. Measured covariates adjusted for in all analyses included age, sex, race, Charlson-Deyo score, facility type, year of diagnosis, clinical T stage, and clinical N stage. Results: The final study population included 12 766 patients (median age, 63 years; IQR, 56-70 years; 8744 [68%] male; 11 206 [88%] White). Cytoreductive nephrectomy was performed in 5005 patients (39%). Conventional adjustments for selection bias demonstrated a significant OS benefit associated with cytoreductive nephrectomy (multivariable Cox proportional hazards regression: hazard ratio [HR], 0.49; 95% CI, 0.47-0.51; propensity score matching: HR, 0.48; 95% CI, 0.46-0.50). Instrumental variable estimates did not demonstrate an association between cytoreductive nephrectomy and OS (HR, 0.92; 95% CI, 0.78-1.09). Conclusions and Relevance: Instrumental variable analysis did not demonstrate a survival advantage associated with cytoreductive nephrectomy for patients with metastatic ccRCC. This discrepancy likely reflects the fact that surgical indication for cytoreductive nephrectomy is primarily driven by factors that are not commonly measured or available in observational data sets.

Misaligned Incentives in Benign Prostatic Enlargement Surgery: More Complex and Efficacious Procedures Are Earning Fewer Relative Value Units.

Background: Relative value units (RVUs) are the measure of value used in US Medicare reimbursement. Medicare determines physician work RVUs (wRVUs) from the Relative Value Update Committee (RUC) for a procedure based on operative time, technical skill and effort, mental effort and judgment, and stress. In theory, work RVUs should account for the complexity and operative time involved in a procedure. The aim of this study was to assess whether major procedures for treatment of benign prostatic enlargement (BPE) are fairly compensated based on complexity and operative time in the RVU system and compare them with the intended reimbursement. Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database and the Centers for Medicare and Medicaid Services (CMS) Medicare Physician Fee Schedule were queried from 2015 to 2017. Single, current, procedural terminology codes associated with BPE treatments were included: transurethral resection of the prostate (TURP), photovaporization of the prostate (PVP), holmium laser enucleation of the prostate (HoLEP), retropubic simple prostatectomy (RSP), and suprapubic simple prostatectomy (SSP). The CMS operative times and the NSQIP real data were used in turn to calculate separate values for wRVUs per hour (wRVUs/hr) of operative time. The wRVUs/hr derived from CMS operative times represent RUC-estimated wRVUs/hr and wRVUs/hr derived from NSQIP represent actual wRVUs/hr. Results: A total of 27,664 cases were included from the NSQIP dataset. Median wRVU was 15.3 (interquartile range [IQR] 12.2-15.3), median operative time 50 minutes (IQR 33-74), and median wRVUs/hr 17.0 (IQR 11.6-26.2). RUC-estimated wRVUs/hr were TURP 12.2, PVP 12.2, RSP 9, SSP 9.3, and HoLEP 7.3. The actual wRVUs/hr were TURP 19.1, PVP 15.5, RSP 10.2, HoLEP 9.4, and SSP 7.6. Conclusions: Laser enucleation and simple prostatectomy are highly complex and efficacious procedures for treating BPE, yet the current payment schedule assigns these procedures the least amount of wRVUs/hr. Financial incentives for performing BPE surgeries are clearly misaligned.

Relative value units do not adequately account for operative time in pediatric urology.

BACKGROUND: Relative value units (RVUs) are the measure of value used in United States Medicare and Medicaid reimbursement. The Relative Update Committee (RUC) determines physician work RVU (wRVUs) based on operative time, technical skill and effort, mental effort and judgment, and stress. The primary aim of this study was to assess whether operative time is adequately accounted for in the wRVU system in pediatric urology. METHODS: The American College of Surgeons National Surgical Quality Improvement Program Pediatric Participant User File (ACS-NSQIPP-PUF) was reviewed from 2012 to 2017. Most common single pediatric urology current procedural terminology (CPT) codes were included. The primary variable was wRVU per hour of operative time (wRVU/h). Linear regression analysis was used to assess the relative influence that operative time had on wRVU/h. RESULTS: 25,432 cases were included in the final study population from 45 unique CPT codes. The median operative time was 79 min, and the median RVU/h was 12.2. Procedures with operative time less than 79 min had higher wRVU/h compared with procedures longer than 79 min (14.5 vs 10.5, p < 0.001). Procedures with higher than average incidence of any complications had a lower wRVU/h (9.0 vs. 14.6 p < 0.001). Linear regression analysis revealed that each additional hour of operative time was expected to decrease wRVU/h by 4.2 (-0.70 per 10 min, 95% CI: -0.71 to -0.69, p < 0.001; R2 = 0.39). CONCLUSION: This analysis of contemporary large pediatric population national-level data suggests that the wRVU system significantly favors shorter and less complex procedures in Pediatric Urology. Pediatric urologists performing longer and more complex procedures are not adequately compensated for the increase in complexity. EVIDENCE LEVEL III: Retrospective comparative study.

Real-World Survival Outcomes Associated With First-Line Immunotherapy, Targeted Therapy, and Combination Therapy for Metastatic Clear Cell Renal Cell Carcinoma.

Importance: Clinical trials have shown an overall survival (OS) benefit associated with first-line immunotherapy (IT) and combination targeted therapy (TT) and IT regimens compared with TT among patients with metastatic clear cell renal cell carcinoma (RCC). Generalizability of these findings in a real-world cohort outside of a clinical trial setting is unclear. Objective: To assess the association of first-line TT, IT, and combination TT and IT regimens with OS in a real-world cohort of patients with metastatic clear cell RCC. Design, Setting, and Participants: This retrospective propensity-matched cohort study identified 5872 patients with metastatic clear cell RCC in the National Cancer Database from January 1, 2015, to December 31, 2017, who received first-line TT, IT, or combination TT and IT and were not treated on a clinical trial protocol. Patients were stratified by first-line systemic treatment. Statistical analysis was conducted from October 1 to December 1, 2020. Main Outcomes and Measures: The primary outcome was OS from the date of diagnosis to death or censoring at last follow-up. After 1:1:1 nearest-neighbor caliper matching of propensity scores, survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates. Results: The final study population included 5872 patients (TT group: n = 4755 [81%]; 3332 men [70%]; median age, 64 years [interquartile range, 57-71 years]; IT group: n = 638 [11%]; 475 men [74%]; median age, 61 years [interquartile range, 54-69 years]; and combination TT and IT group: n = 479 [8%]; 321 men [67%]; median age, 62 years [interquartile range, 55-69 years]), and the matched cohort included 1437 patients (479 per treatment group). Patients in the IT and combination TT and IT groups were younger than those in the TT group, had fewer comorbid conditions (Charlson-Deyo score of 0, 480 of 638 [75%] in the TT group, 356 of 479 [74%] in the IT group, and 3273 of 4755 [69%] in the combination TT and IT group), and were more often treated at academic centers (315 of 638 [49%], 216 of 479 [45%], and 1935 of 4755 [41%], respectively). Both first-line IT and combination TT and IT were associated with improved OS compared with first-line TT for patients with metastatic clear cell RCC (IT group: hazard ratio [HR], 0.60 [95% CI, 0.48-0.75]; P < .001; combination TT and IT group: HR, 0.74 [95% CI, 0.60-0.91]; P = .005). No survival difference was seen between the IT and combination TT and IT groups (combination TT and IT: HR, 1.24 [95% CI, 0.98-1.56]; P = .08). Conclusions and Relevance: This study suggests that both first-line IT and combination TT and IT were associated with improved OS compared with first-line TT for patients with metastatic clear cell RCC. These findings are similar to those identified in recently reported clinical trials, lending confidence to the broader applicability of these findings outside of a clinical trial setting.

RUC Operative Time Estimates are Inaccurate, Resulting in Decreased Work RVU Assignments for Longer Urologic Procedures.

OBJECTIVE: To assess whether inaccurate operative time estimates utilized by the Relative Value Update Committee (RUC) contribute to the undervaluation of longer urologic procedures. METHODS: The National Surgical Quality Improvement Program (NSQIP) and Centers for Medicare and Medicaid Services (CMS) data sets were reviewed from 2015 to 2017. NSQIP operative time is directly measured, contrasting with CMS times which are determined by the RUC via survey-generated estimates. The 50 most frequently coded urology current procedural terminologies were included. Operative time difference was compared between the 2 data sets, and Spearman's correlation coefficient was utilized to assess differences in wRVU/h. RESULTS: A total of 105,931 cases were included. Overall, RUC operative time estimates were longer than NSQIP (124.4 vs 103.5 minutes, P < .001). RUC data overestimated operative time by 42.9% for procedures ≤90 minutes and 16.4% for longer procedures (P < .001). Using NSQIP, procedures ≤90 minutes had higher wRVU/h than longer procedures (12.2 vs 8.7, P < .001), but this was not statistically different using RUC estimates (8.4 vs 7.7, P = .13). Spearman's correlation coefficient confirmed a statistically significant negative relationship between wRVU/h and operative time using NSQIP data (r = -0.57, 95% confidence interval: -7.4 to -0.36), and no statistically significant relationship using RUC data (r = -0.24, 95% confidence interval: -0.49 to 0.04). CONCLUSION: The RUC-intended wRVU/h is more equitable than the NSQIP real-world wRVU/h with regard to operative time. Inaccurate RUC operative time estimates contribute to the undervaluation of longer urologic procedures.

Work relative value units do not account for complexity and operative time in hypospadias surgery.

INTRODUCTION: Relative value units (RVU) are the measure of value used in United States Medicare and Medicaid reimbursement. The Relative Update Committee (RUC) determine physician work RVU (wRVU) based on operative time, technical skill and effort, mental effort and judgement, and stress. In theory, wRVU should account for the complexity and operative time involved in a procedure. OBJECTIVE: The primary aim of this study is to assess if operative time and complexity of hypospadias surgery is adequately accounted for by the current wRVU assignments. STUDY DESIGN: The American College of Surgeons National Surgical Quality Improvement Program Participant User File (ACS-NSQIP PUF) database was utilized from 2012 to 2017. Single stage hypospadias current procedural terminology (CPT) codes (including acceptable secondary CPT codes) were extracted. Using total wRVU and total operative time, the primary variable of wRVU per hour was calculated (wRVU/hr). Multivariable linear regression analysis was used to assess the relative influence that wRVU and operative time had on the wRVU/hr variable. RESULTS: 9810 cases were included in the final study population divided into four categories: simple distal (eg. MAGPI, V-Flap), single stage distal, single stage mid, single stage proximal. On analysis of variance, there was statistically significant different wRVU/hr for the four different types of hypospadias repairs with simple distal having the highest mean wRVU/hr of 19.5 and the lowest being proximal hypospadias repairs at 13.2. Simple distal, distal and midshaft hypospadias had statistically significantly higher wRVU/hr compared to proximal hypospadias (16.2, 95% CI: 15.8-16.5 vs. 13.2, 95% CI 10.9-15.5; p<0.001). Multivariable linear regression revealed that each additional hour of operative time was expected to decrease wRVU/hr by 10.5 (-10.5, 95% CI: -11.0 to -10.1, p < 0.001); total work wRVU had a statistically significant independent association with wRVU/hr (0.6, 95%CI: 0.5-0.7, p <0.001). DISCUSSION: This the first objective assessment of the current wRVU assignments with regards to one stage hypospadias repairs. More complex and longer hypospadias procedures are not adequately compensated by wRVU. Most notably, simple distal procedures are reimbursed at a mean of 19.5 wRVU/hr compared to 13.2 wRVU/hr for one stage proximal repairs. CONCLUSION: This analysis of national-level data suggests that the current wRVU assignments significantly favor shorter and simpler procedures in hypospadias surgery.

Perioperative complications within 30 days of hypospadias surgery: Results from NSQIP-Pediatrics.

INTRODUCTION: There are no large multi-institutional studies reporting on perioperative complications of hypospadias repairs. We sought to determine perioperative complications of hypospadias repairs from the National Surgical Quality Improvement Program Pediatrics (NSQIP-P) to aid in patient counseling. STUDY DESIGN: This cohort study from 2012 to 2017 was conducted using NSQIP-P database. Pediatric patients undergoing hypospadias surgery were identified and compared based on 4 major categories: distal/midshaft repair, one-stage repair proximal, stage one repair, and stage two repair. Baseline demographics between the four groups and perioperative parameters were compared. Multivariable logistic regression analysis models including type of repair was used to determine associations with overall complications, infectious complications, and dehiscence. DISCUSSION: There were 11,292 patients identified in the study population. Overall, 78% underwent distal/midshaft hypospadias repair, 12% underwent one-stage proximal repair, 1.4% underwent proximal first stage repair and 9% underwent proximal second stage repair. Multivariable logistic regression analysis revealed that proximal first stage procedures had similar overall complications to distal/mid repairs but proximal one-stage and proximal second stage procedures were associated with significantly more overall complications, local infectious complications, and dehiscence. Age, race, operative time, prematurity were also independently associated with increased overall complications. As expected, complication rates are higher in those with proximal hypospadias. In staged hypospadias, first stage has a lower complication rate compared to second stage. All complications, especially of infectious and dehiscence are the highest in the one-stage proximal and proximal second stage repairs. CONCLUSION: We report large multi-institutional analysis of 30-day peri-operative hypospadias repair complications; this information is useful for patient counseling and education.