Downstaging and Survival Associated with Neoadjuvant Immunotherapy Before Radical Cystectomy for Muscle-invasive Bladder Cancer.

BACKGROUND: Neoadjuvant cisplatin-containing chemotherapy before radical cystectomy is the standard of care for patients with localized muscle-invasive bladder cancer (MIBC). However, a large proportion of patients are ineligible for cisplatin. Single-arm phase 2 neoadjuvant immunotherapy trials have reported promising tumor response rates, but interpretation is limited owing to lack of a comparator arm. OBJECTIVE: To compare rates of pathologic downstaging and overall survival between patients receiving neoadjuvant immunotherapy (NAI), neoadjuvant chemotherapy (NAC), or no neoadjuvant therapy (NNAT). DESIGN, SETTING, AND PARTICIPANTS: We identified 18 483 patients in the National Cancer Data Base who were diagnosed with clinically localized MIBC and underwent radical cystectomy from 2014 to 2019. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Nearest-neighbor propensity-score caliper matching was used to create three demographically similar and equally sized cohorts stratified by NAT receipt. Logistic regression was used to examine the association of treatment received with pathologic downstaging to pT0N0 and pT < 2N0. Cox proportional-hazards regression was used to assess the association of treatment received with overall survival (OS). RESULTS AND LIMITATIONS: Propensity score matching yielded three equally sized cohorts without significant differences in baseline characteristics (n = 840). The NAI group had a higher rate of pathologic downstaging to pT0N0 than the NNAT group and a similar rate to the NAC group (NNAT 6.7% vs NAC 26.4%, odds ratio 5.0, 95% confidence interval [CI] 2.9-8.3; NAI 22.5%, odds ratio 4.0, 95% CI 2.4-7.1). The NAI group had better OS than the NNAT group and similar OS to the NAC group (NAC: hazard ratio 0.62, 95% CI 0.42-0.92; NAI: hazard ratio 0.68, 95% CI 0.46-0.97, with NNAT as the reference). The primary limitation is selection bias from confounding by clinical indication. CONCLUSIONS: NAI is a promising alternative to NAC for patients with clinically localized MIBC, as evidenced by similar pathologic downstaging rates and OS benefits in comparison to no NAT. Phase 3 trials should be conducted to test the noninferiority of NAI to NAC. PATIENT SUMMARY: We compared outcomes for patients with muscle-invasive bladder cancer according to whether they received chemotherapy, immunotherapy, or no medical therapy before surgical removal of their bladder. We found that preoperative immunotherapy improved patient survival and regression of the cancer stage in comparison to no medical therapy, similar to the outcomes seen with preoperative chemotherapy. Randomized clinical trials are needed to confirm these findings.

Clinical Impact of the CARMENA Trial on Cytoreductive Nephrectomy Practices in the USA: A Difference-in-differences Analysis.

BACKGROUND AND OBJECTIVE: It is unclear whether cytoreductive nephrectomy (CN) practices have changed in the USA after the publication of the Cancer du Rein Métastatique Nephrectomie et Antiangiogéniques (CARMENA) trial in 2018. Our primary objective is to determine the effect of the CARMENA trial on CN rates in the USA. METHODS: Patients were identified in the National Cancer Database from 2004 to 2020. A quasiexperimental difference-in-differences analysis was used to test the primary outcome, as follows: the change in CN rate was assessed among metastatic clear cell renal cell carcinoma (ccRCC) patients diagnosed before versus after 2018, while using the localized nephrectomy (LN) rate performed in the setting of nonmetastatic ccRCC as a control group. KEY FINDINGS AND LIMITATIONS: The difference-in-differences analysis identified a statistically significant decrease in CN rate after CARMENA (ß-coefficient [standard error]: -0.06 [0.025], p = 0.028), with a 10.2% absolute and a 31.8% relative rate reduction when compared with the counterfactual (expected) value (34.7% â†’ 21.9% [actual] vs 32.1% [expected]). Primarily, relative differences in CN and LN rates before and after 2018 may be attributable to additional factors, aside from CARMENA publication, not tested in this quasiexperimental model. CONCLUSIONS AND CLINICAL IMPLICATIONS: CN rates decreased significantly after the publication of the CARMENA trial in 2018, with a minimal difference in regional or demographic practice patterns. Overall, the publication of the CARMENA trial results is seemingly associated with substantial alteration of clinical practice in the USA, with relatively broad and nonspecific adoption across facilities, regions, and demographics. PATIENT SUMMARY: For decades, the immediate surgical removal of the kidney tumor (cytoreductive nephrectomy) was a mainstay of metastatic kidney cancer treatment. In 2018, the CARMENA study showed that patients treated with systemic therapy alone had similar outcomes to patients who underwent cytoreductive nephrectomy first. In this study, we show that fewer cytoreductive nephrectomies were performed after the CARMENA trial results were published.

Evaluating Adherence to Guideline-based Injury Grading in Pediatric Renal Trauma: How Are Patients Being Worked Up Prior to Transfer to a Level 1 Trauma Center?

OBJECTIVE: To determine whether children with renal trauma who are transferred to a level I trauma center (TC) receive appropriate imaging studies before transfer and whether this impacts care. The American Urologic Association (AUA) Urotrauma guidelines state clinicians should perform IV contrast-enhanced CT with immediate and delayed images when renal trauma is suspected. Adherence to these guidelines in pediatric patients is unknown. METHODS: Children treated for renal trauma at our TC between 2005 and 2019 were identified. Comparisons between patients with initial imaging at a transferring hospital (TH) and patients with initial imaging at our TC were performed using logistic regression. RESULTS: Of the included 293 children, 67% (197/293) were transferred into our TC and 61% (180/293) received initial imaging at the TH. Patients with initial imaging at the TH were more likely to have higher-grade renal injuries (P = .001) and were less likely to have guideline-recommended imaging (31% vs 82%, P < .001). Of patients who were imaged at the TH, 28% (50/180) underwent an additional CT imaging shortly after transfer. When imaging was incomplete at the TH, having an additional scan upon transfer was associated with emergent urologic surgery (P = .004). CONCLUSION: Adherence to the AUA Urotrauma guidelines is low, with most pediatric renal trauma patients not receiving complete staging with delayed-phase imaging before transfer to a TC. Furthermore, patients initially imaged at THs were more likely to receive more CT scans per admission and were exposed to higher amounts of radiation. There is a need to improve imaging protocols for complete staging of renal trauma in children before transfer.

The incidence of hypertension among children after renal trauma: A matched cohort analysis.

PURPOSE: To describe the intermediate-term incidence of hypertension following pediatric renal trauma relative to that in an extremity (control group) trauma cohort. METHODS: This was a single-institution matched cohort study of pediatric patients presenting to a Level I trauma center between 2010 and 2019. The primary cohort included patients who sustained renal trauma, and a comparator cohort of sex- and age-matched patients with isolated extremity fracture was identified. The primary outcome was new hypertension, and a sensitivity analysis was conducted of any elevated blood pressure (EBP). Conditional logistic regression was performed and adjusted for overweight/obese status. RESULTS: There were 62 renal trauma patients included, representing 35% of all eligible patients seen in the study period. Hypertension was not found to be more prevalent with renal trauma (OR 1.18, 95% CI: 0.41, 3.39). The incidence of hypertension (9.7-11.3%) and EBP (22.6-32.3%) was comparable between renal trauma and control groups. CONCLUSION: Despite a high incidence of EBP and hypertension in pediatric patients after renal or extremity trauma, we did not observe an association between renal trauma and postinjury hypertension. We identified no cases of malignant or symptomatic hypertension, and no surgical interventions for renovascular hypertension was performed. Our findings suggest that only select patients, rather than most renal trauma patients, may benefit from monitoring for postinjury hypertension.

Routine repeat imaging may be avoidable for asymptomatic pediatric patients with renal trauma.

INTRODUCTION: AUA Urotrauma guidelines for renal injury recommend initial nonoperative management followed by repeat CT imaging for stable patients with deep lacerations or clinical signs of complications. Particularly in pediatric patients where caution is taken to limit radiation exposure, it is not known whether routine repeat imaging affects clinical outcomes. OBJECTIVE: Our objective was to determine whether routine repeat imaging is associated with urologic intervention or complications in nonoperatively managed pediatric renal trauma. METHODS: We retrospectively analyzed 337 pediatric patients with blunt and penetrating renal trauma from a prospectively collected database from 2005 to 2019 at a Level I trauma center. Exclusion criteria included age >18 years old, death during admission (N = 39), immediate operative intervention (N = 28), and low-grade renal injury (AAST grades I-II, N = 91). Routine repeat imaging was defined as reimaging in asymptomatic patients within 72 h of initial injury. Patients were placed into three imaging groups consisting of: (A) those with routine repeat imaging, (B) those reimaged for symptoms, or (C) those not reimaged. Comparisons were made using logistic regression controlling for grade of renal injury. RESULTS: Of the included 179 children, 44 (25%) underwent routine repeat imaging, 20 (11%) were reimaged for symptoms, and 115 patients (64%) were managed without reimaging. Compared to patients who were reimaged for symptoms, asymptomatic patients in the routine repeat imaging group and without reimaging group were significantly less likely to develop a complication (16% and 7% vs. 55%, p < 0.001) or require delayed urologic procedure (5% and 1% vs. 25%, p = 0.007). Comparing the routine repeat imaging group to those without reimaging, we found no difference in complications (p = 0.47), readmissions (p = 0.75), or urologic interventions (p = 0.50). CONCLUSION: Despite suffering high-grade (III-IV) renal injuries, the majority of pediatric patients who remained asymptomatic during the first three days of hospitalization did not require a urologic intervention. Foregoing repeat imaging was not associated with a higher rate of complications or delayed procedures, supporting that routine repeat imaging may expose these children to unnecessary radiation and may be avoidable in the absence of signs or symptoms of concern.

Experiences and attitudes of young adults with congenital bowel and bladder conditions.

INTRODUCTION: Young adults with complex congenital bowel and bladder anomalies are a vulnerable population at risk for poor health outcomes. Their experiences with the healthcare system and attitudes towards their health are understudied. OBJECTIVE: Our objective was to describe how young adults with congenital bladder and bowel conditions perceive their current healthcare in the domains of bladder and bowel management, reproductive health, and transition from pediatric to adult care. STUDY DESIGN: At a camp for children with chronic bowel and bladder conditions, we offered a 50-question survey to the 62 adult chaperones who themselves had chronic bowel and bladder conditions. Of the 51 chaperones who completed the survey (a response rate of 82%), 30 reported a congenital condition and were included. RESULTS: The cohort of 30 respondents had a median age of 23 years and almost half of the subjects (46%) reported not having transitioned into adult care. Most reported bowel (81%) and bladder (73%) management satisfaction despite high rates of stool accidents (85%), urinary accidents (46%), and recurrent urinary tract infections (70%). The majority of respondents (90%) expressed interest in having a reproductive health provider as part of their healthcare team. The median ages of the first conversation regarding transition to adult care and feeling confident in managing self-healthcare were 18 and 14 years, respectively. Most (85%) reported feeling confident in navigating the medical system. DISCUSSION: In this cohort of young adults who reported confidence with self-care and navigating the medical system, the proportion who had successfully transitioned into to adult care was low. These data highlight the need for improved transitional care and the importance of patient-provider and provider-provider communication throughout the transition process. CONCLUSION: These data highlight the need to understand the experience of each individual patient in order to provide care that aligns with their goals.