Analysis of preoperative nutrition, immunity and inflammation correlation index on the prognosis of upper tract urothelial carcinoma surgical patients: a retrospective single center study.

BACKGROUND: SII, PNI, SIRI, AAPR, and LIPI are prognostic scores based on inflammation, nutrition, and immunity. The purpose of this study was to examine the prognostic value of the SII, PNI, SIRI, AAPR, and LIPI in patients with UTUC who underwent radical nephroureterectomy with bladder cuff excision. MATERIALS AND METHODS: Data of UTUC patients in Sichuan Provincial People's Hospital from January 2017 to December 2021 were collected. The optimal critical values of SII, PNI, SIRI, and AAPR were determined by ROC curve, and LIPI was stratified according to the dNLR and LDH. The Kaplan-Meier method was used to draw the survival curve, and Cox proportional hazard model was used to analyze the factors affecting the prognosis of UTUC patients. RESULTS: A total of 81 patients with UTUC were included in this study. The optimal truncation value of PNI, SII, SIRI and AAPR were determined to be 48.15, 596.4, 1.45 and 0.50, respectively. Univariate Cox proportional hazard regression showed that low PNI, high SII, high SIRI, low AAPR and poor LIPI group were effective predictors of postoperative prognosis of UTUC patients. Multivariate Cox proportional hazard regression showed that high SII was an independent risk factor for postoperative prognosis of UTUC patients. According to ROC curve, the prediction efficiency of fitting indexes of PNI, SII, SIRI, AAPR and LIPI is better than that of using them alone. CONCLUSIONS: The SII, PNI, SIRI, AAPR, and LIPI was a potential prognostic predictor in UTUC patients who underwent radical nephroureterectomy with bladder cuff excision.

Perioperative management of upper tract urothelial carcinoma in the Nordic countries.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare malignancy, with typically only few new cases annually per urological department. Adherence to European association of urology (EAU) guidelines on UTUC in the Nordic countries is unknown. The objective of this survey was to examine the implementation of EAU guidelines, the perioperative management and organization of the treatment of UTUC in the Nordic countries. METHODS: The electronic survey was distributed to 93 hospitals in the Nordic countries performing radical nephroureterectomy (NU). The survey consisted of 57 main questions and data was collected between December 1st, 2021 and April 23rd, 2022. RESULTS: Overall response rate was 47/93 (67%) with a completion rate of 98%. Five out of the 6 examined subjects on diagnostic practice are applied by ≥ 72% of the participating centers. NU as treatment for high-risk UTUC is performed by 37/47 (79%), and 91% include a bladder cuff excision. CONCLUSIONS: Adherence to EAU guidelines is high on diagnostic practice in the Nordic countries, whereas disease management is less coherent.

Robotic distal ureterectomy for high-risk distal ureteral urothelial carcinoma: a retrospective multicenter comparative analysis (ROBUUST 2.0 collaborative group).

BACKGROUND: The role of kidney-sparing surgery in patients with high-risk upper urinary tract urothelial carcinoma is controversial. The present study aimed to assess oncological and functional outcomes of robot-assisted distal ureterectomy in patients with high-risk distal ureteral tumors. METHODS: The ROBUUST 2.0 multicenter international (2015-2022) dataset was used for this retrospective cohort analysis. High-risk patients with distal ureteral tumors were divided based on type of surgery: robot-assisted distal ureterectomy or robot-assisted nephroureterectomy. A survival analysis was performed for local recurrence-free survival, distant metastasis-free survival, and overall survival. After adjusting for clinical features of the high-risk prognostic group, Cox proportional hazard model was plotted to evaluate significant predictors of time-to-event outcomes. RESULTS: Overall, 477 patients were retrieved, of which 58 received robot-assisted distal ureterectomy and 419 robot-assisted nephroureterectomy, respectively, with a mean (±SD) follow-up of 29.6 months (±2.6). The two groups were comparable in terms of baseline features. At survival analysis, no significant difference was observed in terms of recurrence-free survival (P=0.6), metastasis-free survival (P=0.5) and overall survival (P=0.7) between robot-assisted distal ureterectomy and robot-assisted nephroureterectomy. At Cox regression analysis, type of surgery was never a significant predictor of worse oncological outcomes. At last follow-up patients undergoing robot-assisted distal ureterectomy had significantly better postoperative renal function. CONCLUSIONS: Comparable outcomes in terms of recurrence-free survival, metastasis-free survival, and overall survival between robot-assisted distal ureterectomy and robot-assisted nephroureterectomy patients, and better postoperative renal function preservation in the former group were observed. Kidney-sparing surgery should be considered as a potential option for selected patients with high-risk distal ureteral UTUC.

Violation of onco-surgical principles is associated with survival outcomes in upper tract urothelial carcinomas after radical nephroureterectomy.

OBJECTIVE: Disease recurrence, particularly intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC), is common. We investigated whether violations of onco-surgical principles before or during RNU, collectively referred to as surgical violation (SV), were associated with survival outcomes.  Material and methods: Data from a consecutive series of patients who underwent RNU for UTUC 2001-2012 at Skåne University Hospital Lund/Malmö were collected. Preoperative insertion of a nephrostomy tube, opening the urinary tract during surgery or refraining from excising the distal ureter were considered as SVs. Survival outcomes in patients with and without SV (IVR-free [IVRFS], disease-specific [DSS] and overall survival [OS]) were assessed using multivariate Cox regression analyses (adjusted for tumour stage group, prior or concomitant bladder cancer, comorbidity and preoperative urinary cytology). RESULTS: Of 150 patients, 47 (31%) were subjected to at least one SV. Overall, SV was not associated with IVRFS (HR 0.81, 95% CI 0.4-1.6) but with worse DSS (HR 1.9, 95% CI 1.03-3.7) and OS (HR 1.9, 95% CI 1.2-3) in multivariable analysis. Additional analyses with a broader definition of SV including also preoperative instrumentation of the upper urinary tract (ureteroscopy and/or double J stenting) showed similar outcomes for DSS (HR 2.1, 95% CI 1.1-4.3). CONCLUSION: Worse survival outcomes, despite no difference in IVR, for patients that were subjected to the violation of sound onco-surgical principles before or during RNU for UTUC strengthen the notion that adhering to such principles is a cornerstone in upper tract urothelial cancer surgery.

Using machine learning to develop preoperative model for lymph node metastasis in patients with bladder urothelial carcinoma.

BACKGROUND: Lymph node metastasis (LNM) is associated with worse prognosis in bladder urothelial carcinoma (BUC) patients. This study aimed to develop and validate machine learning (ML) models to preoperatively predict LNM in BUC patients treated with radical cystectomy (RC). METHODS: We retrospectively collected demographic, pathological, imaging, and laboratory information of BUC patients who underwent RC and bilateral lymphadenectomy in our institution. Patients were randomly categorized into training set and testing set. Five ML algorithms were utilized to establish prediction models. The performance of each model was assessed by the area under the receiver operating characteristic curve (AUC) and accuracy. Finally, we calculated the corresponding variable coefficients based on the optimal model to reveal the contribution of each variable to LNM. RESULTS: A total of 524 and 131 BUC patients were finally enrolled into training set and testing set, respectively. We identified that the support vector machine (SVM) model had the best prediction ability with an AUC of 0.934 (95% confidence interval [CI]: 0.903-0.964) and accuracy of 0.916 in the training set, and an AUC of 0.855 (95%CI: 0.777-0.933) and accuracy of 0.809 in the testing set. The SVM model contained 14 predictors, and positive lymph node in imaging contributed the most to the prediction of LNM in BUC patients. CONCLUSIONS: We developed and validated the ML models to preoperatively predict LNM in BUC patients treated with RC, and identified that the SVM model with 14 variables had the best performance and high levels of clinical applicability.

Adoption of robot-assisted radical nephroureterectomy permits a minimally invasive option for management of upper tract urothelial carcinoma in geriatric patients: comparison with non-geriatric patients with intermediate-term oncologic follow-up.

To assess the oncologic efficacy and safety of robot-assisted approach to radical nephroureterectomy (RARNU) in geriatric versus younger patients with upper tract urothelial carcinoma (UTUC). A single-center, retrospective cohort study was conducted from 2009 to 2022 of 145 patients (two cohorts: < 75 and ≥ 75 years old) with non-metastatic UTUC who underwent RARNU. Primary endpoint was UTUC-related recurrence of disease during surveillance (bladder-specific and metastatic). Safety was assessed according to 30-day, modified Clavien-Dindo (CD) classifications (Major: C.D. III-V). Survival estimates were performed using Kaplan-Meier method. There were 89 patients < 75 years (median 65 years) and 56 patients ≥ 75 years (median 81 years). Comparing the young versus geriatric cohorts: median follow-up 38 vs 24 months (p = 0.03, respectively) with similar 3-year bladder-specific recurrence survival (60% vs 67%, HR 0.70, 95% CI [0.35, 1.40], p = 0.31) and metastasis-free survival (79% vs 70%, HR 0.71, 95% CI [0.30, 1.70], p = 0.44). Expectedly, the younger cohort had a significant deviation in overall survival compared to the geriatric cohort at 1-year (89% vs 76%) and 3-years (72% vs 41%; HR 3.29, 95% CI [1.88, 5.78], p < 0.01). The 30-day major (1% vs 0) and minor complications (8% vs 14%, p = 0.87). Limitations include retrospective study design of a high-volume, single-surgeon experience. Compared to younger patients with UTUC, geriatric patients undergoing RARNU have similar oncologic outcomes at intermediate-term follow-up with no increased risk of 30-day perioperative complications. Thus, age alone should not be used to disqualify patients from definitive surgical management of UTUC with RARNU.

Endoscopic intervention versus radical nephroureterectomy for the management of localized upper urinary tract urothelial carcinoma: a systematic review and meta-analysis of comparative studies.

OBJECTIVE: Localized Upper Urinary Tract Urothelial Carcinoma (UTUC) is an uncommon cancer typically detected at an advanced stage. Currently, radical nephroureterectomy (RNU) with bladder cuff excision is the standard treatment for high-risk UTUC. This meta-analysis aims to evaluate the 5-year overall and cancer-specific survival and bladder recurrence rates in studies comparing endoscopic kidney-sparing surgeries (E-KSS) with RNU in localized UTUC. EVIDENCE ACQUISITION: We performed a literature search on 20th April 2023 through PubMed, Web of Science, and Scopus. The PICOS model was used for study inclusion: P: adult patients with localized UTUC; I: E-KSS. C: RNU; O: primary: overall survival (OS); secondary: cancer-specific survival (CSS), bladder recurrence rate, and metastasis-free survival (MFS). S: retrospective, prospective, and randomized studies. EVIDENCE SYNTHESIS: Overall, 11 studies involving 2284 patients were eligible for this meta-analysis, 737 in the E-KSS group and 1547 in the RNU group. E-KSS showed a similar overall 5-year OS between E-KSS and RNU, and for low-grade tumors, while 5-year OS favored RNU for high-grade tumors (RR 1.84, 95% CI 1.26-2.69, p = 0.002). No difference emerged for 5-year CSS between the two groups, even when the results were stratified for low- and high grade tumors. Bladder recurrence rate and 5-year MFS were also similar between the two groups. CONCLUSIONS: Our review showed that E-KSS is a viable option for patients with localized UTUC with non-inferior oncological outcomes as compared with RNU, except for 5-year OS in high-grade tumors which favoured RNU.

Survival benefit of nephroureterectomy in systemic therapy exposed metastatic upper tract urinary urothelial carcinoma patients.

BACKGROUND: It is unknown whether the stage of the primary may influence the survival (OS) of metastatic upper tract urothelial carcinoma (mUTUC) patients treated with nephroureterectomy (NU) and systemic therapy (ST). We tested this hypothesis within a large-scale North American cohort. METHODS: Within Surveillance Epidemiology and End Results database 2000-2020, all mUTUC patients treated with ST+NU or with ST alone were identified. Kaplan-Maier plots depicted OS. Multivariable Cox regression (MCR) models tested for differences between ST+NU and ST alone predicting overall mortality (OM). All analyses were performed in localized (T1-T2) and then repeated in locally advanced (T3-T4) patients. RESULTS: Of all 728 mUTUC patients, 187 (26%) harbored T1-T2 vs 541 (74%) harbored T3-T4. In T1-T2 patients, the median OS was 20 months in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU independently predicted lower OM (HR 0.37, p < 0.001). Conversely, in T3-T4 patients, the median OS was 12 in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU was not independently associated with lower OM (HR 0.85, p = 0.1). CONCLUSIONS: In mUTUC patients, treated with ST, NU drastically improved survival in T1-T2 patients, even after strict methodological adjustments (multivariable and landmark analyses). However, this survival benefit did not apply to patients with locally more advanced disease (T3-T4).

Totally retroperitoneal approach for robot-assisted nephroureterectomy with bladder cuff without repositioning.

INTRODUCTION: Robot-assisted nephroureterectomy (RANU) for upper urinary tract urothelial carcinoma is typically performed via the transperitoneal approach because of limited surgical space. However, a retroperitoneal approach may be preferable in patients with a history of abdominal surgery or in those in whom pelvic lymph node dissection is unnecessary. MATERIALS AND SURGICAL TECHNIQUES: RANU via the retroperitoneal approach was selected for two patients diagnosed with high-grade upper urothelial carcinoma with a history of abdominal surgery. Nephrectomy was performed in the 90° flank position, and the bed was tilted at 20°. The retroperitoneal space was extended, and the robot trocar was subsequently repositioned in the left lower quadrant. After redocking the robot, the distal ureter was dissected, and the bladder cuff was resected en bloc along with the kidney and the ureter. Neither patient had any complications within 3 months postoperatively. DISCUSSION: By devising a new technique for trocar placement, total retroperitoneal RANU without repositioning was possible, even in a small patient.

Unmarried Status Effect on Stage at Presentation and Treatment Patterns in Non-Metastatic Upper Tract Urothelial Carcinoma Patients.

BACKGROUND: Unmarried status has been associated with higher proportions of locally advanced stage and lower treatment dose intensification rates in several urological and non-urological malignancies. However, no previous investigators focused on the association between unmarried status and advanced stage (T3-4N0-2) at presentation and lower nephroureterectomy (RNU) and systemic therapy (ST) rates in non-metastatic upper tract urothelial carcinoma (UTUC) patients. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020, all non-metastatic UTUC patients were identified. Multivariable logistic regression models (LRMs) tested for differences in stage at presentation and treatment (RNU and ST) according to marital status (married vs unmarried), in a sex-specific fashion. RESULTS: Of all 8544 non-metastatic UTUC patients, 4748 (56%) were male vs 3190 (44%) were female. Of all 4748 male UTUC patients, 1191 (25%) were unmarried. Of all 3190 female UTUC patients, 1608 (50%) were unmarried. In multivariable LRMs predicting RNU, unmarried status was an independent predictor of lower RNU rates in male (Odds Ratio [OR]: 0.56; P < .001), but not in female (OR: 0.81; P = .1) non-metastatic UTUC patients. In multivariable LRMs predicting ST exposure, unmarried status was an independent predictor of lower ST rates in both male (OR:0.73; P = .03) and female (OR:0.64; P < .001) UTUC patients. In multivariable LRMs predicting locally advanced stage (T3-4N0-2), unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male (OR: 0.95; P = .5) or female (OR: 0.99; P = .9) UTUC patients. CONCLUSIONS: Unmarried male UTUC patients appear at risk of less being able to access RNU, relative to their married counterparts. Moreover, unmarried UTUC patients appear to less benefit from ST, regardless of sex. Conversely, unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male or female UTUC patients.

Decisional and prognostic impact of diagnostic ureteroscopy in high-risk upper tract urothelial carcinoma: A multi-institutional collaborative analysis (ROBUUST collaborative group).

BACKGROUND: Diagnostic ureteroscopy (URS) with or without biopsy remains a subject of contention in the management of upper tract urothelial carcinoma (UTUC), with varying recommendations across different guidelines. The study aims to analyse the decision-making and prognostic role of diagnostic ureteroscopy (URS) in high-risk UTUC patients undergoing curative surgery. MATERIALS AND METHODS: In this retrospective multi-institutional analysis of high-risk UTUC patients from the ROBUUST dataset, a comparison between patients who received or not preoperative URS and biopsy before curative surgery was carried out. Logistic regression analysis evaluated differences between patients receiving URS and its impact on treatment strategy. Survival analysis included 5-year recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS). After adjusting for high-risk prognostic group features, Cox proportional hazard model estimated significant predictors of time-to-event outcomes. RESULTS: Overall, 1,912 patients were included, 1,035 with preoperative URS and biopsy and 877 without. Median follow-up: 24 months. Robot-assisted radical nephroureterectomy was the most common procedure (55.1%), in both subgroups. The 5-year OS (P = 0.04) and CSS (P < 0.001) were significantly higher for patients undergoing URS. The 5-year RFS (P = 0.6), and MFS (P = 0.3) were comparable between the 2 groups. Preoperative URS and biopsy were neither a significant predictor of worse oncological outcomes nor of a specific treatment modality. CONCLUSIONS: The advantage in terms of OS and CSS in patients undergoing preoperative URS could derive from a better selection of candidates for curative treatment. The treatment strategy is likely more influenced by tumor features than by URS findings.

Efficacy of BCG for non-muscle invasive bladder cancer following nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: To evaluate the efficacy of intravesical (IVe) Bacillus Calmette-Guerin (BCG) to treat non-muscle invasive bladder cancer (NMIBC) recurrences in patients who have previously undergone nephroureterectomy for upper tract urothelial carcinoma (UTUC). METHODS: We performed a single institution retrospective review of patients who underwent nephroureterectomy for UTUC from 2009 to 2021. Patients who subsequently developed NMIBC treated with transurethral resection followed by IVe BCG were included in the study group. A control cohort was formed by retrospective review of patents with primary NMIBC treated with BCG during the same period. Patients in the control cohort were matched by stage of bladder cancer at a 2:1 ratio of control to study subjects. Demographic data, pathology of bladder tumors prior to and following BCG, use of maintenance BCG (mBCG), time to recurrence, time to progression, progression to cystectomy, and progression to metastatic disease were collected on all patients. Descriptive statistics were utilized to compare the 2 groups. The primary outcome was progression to muscle invasive disease. Secondary outcomes included intravesical recurrence free survival, disease free survival, and progression to metastatic disease. Univariable and multivariable logistic regression analysis was performed to elucidate independent variables associated with bladder tumor recurrence. Multivariable Cox regression analysis was used to assess the impact of prior UTUC on time to bladder tumor recurrence. RESULTS: One-hundred and ninety-one patients underwent nephroureterectomy at our institution from 2009 to 2021 for UTUC. Twenty-five patients were identified to have subsequently developed NMIBC recurrences treated with inductions BCG. The control group was comprised of 50 patients with primary NMIBC matched by stage of bladder cancer for which BCG was indicated in the study group. Median (interquartile range [IQR]) follow-up was significantly longer in the control group relative to the study group (64.8 [50.1-85.6] vs 25 months [17-35]; P = 0.001). There were no significant differences in demographics between the study and control groups. The rate of progression to muscle invasive disease was 17% vs 0% in the study group and control group respectively (P = 0.0521). History of UTUC was associated with increased risk of intravesical bladder tumor recurrence post BCG on multivariable analysis (HR 2.5; P = 0.017) and Kaplan Meier survival analysis (P = 0.039). The mean time to bladder tumor recurrence after treatment with BCG was significantly worse in the study group at (7.9 vs. 23.9 months; P = 0.0322). Similarly, the rate of progression to metastatic disease was worse in the study group (24% vs 2%; P = 0.0047). Overall disease-free survival was also noted to be significantly worse on Kaplan Meier survival analysis in the study group (P = 0.0074). No statistically significant differences in the stage grade of bladder tumor recurrence, grade of bladder tumor recurrence, or rate of progression to cystectomy were identified. CONCLUSIONS: Our study suggests reduced efficacy of BCG for NMIBC in patients with a history of UTUC. Patients in this population should be counseled accordingly. Research into alternative treatments for bladder tumor recurrence and more aggressive prophylactic regimens after nephroureterectomy for prevention of bladder tumor recurrence in this population is encouraged.

Adjuvant Chemotherapy and Survival After Radical Cystectomy in Histologic Subtype Bladder Cancer.

OBJECTIVES: Patients with histologic subtype bladder cancer (HSBC) suffer worse outcomes than those with conventional urothelial carcinoma (UC). We sought to characterize the use of adjuvant chemotherapy (AC) in HSBC after radical cystectomy (RC) using the National Cancer Database (NCDB). MATERIALS AND METHODS: We retrospectively queried the NCDB (2006-2019) for patients with non-metastatic bladder cancer (BC) who underwent RC (N = 45,797). Patients were stratified by histologic subtype and receipt of AC. Multivariable logistic regression determined associations of demographic and clinicopathologic features with receipt of AC. Multivariable Cox regression evaluated associations between receipt of any AC and overall survival (OS). RESULTS: We identified 4,469 patients with HSBC classified as squamous, adenocarcinoma, small cell, sarcomatoid, micropapillary, or plasmacytoid. Squamous comprised 31% of the HSBC cohort, followed by small cells and micropapillary. Black patients were presented with a higher prevalence of adenocarcinoma (119/322, 37.0%). Use of AC was highest in plasmacytoid and small cell (30% each) and lowest in squamous (11%). Neuroendocrine histology was independently associated with greater odds of receiving AC (HR 1.6, 95% CI 1.37-1.87), while squamous cell histology was associated with lower odds (HR 0.61, 95% CI 0.53-0.71). On multivariable Cox regression analysis, treatment with AC was associated with significantly longer OS (HR 0.69, 95% CI 0.59-0.81) and for squamous, sarcomatoid, and micropapillary cohorts after stratified by subtype. CONCLUSIONS: AC was variably used among patients with HSBC and was associated with OS benefit in such patients.

Increased risk of bladder cancer recurrence due to bacillus Calmette-Guérin shortage in Brazil.

OBJECTIVE: Our study aimed to evaluate the impact of bacillus Calmette-Guérin shortage on recurrence and progression in patients with non-muscle invasive bladder cancer in a Brazilian cohort. METHODS: We retrospectively reviewed the clinicopathological data of 409 patients who had their first transurethral resection of the bladder tumor for intermediate or high-risk non-muscle invasive bladder cancer between June 2014 and May 2021 in a tertiary public hospital in Brazil. Patients included had non-muscle-invasive urothelial carcinoma of the bladder resected completely for the first time, regardless of bacillus Calmette-Guérin use. Low-risk disease patients were excluded from the analysis. Demographic, clinicopathological, and bacillus Calmette-Guérin use data were collected from our database. Recurrence and progression data were obtained from patient records or through telephone interviews. Recurrence-free survival and progression-free survival were calculated from the date of transurethral resection of the bladder tumor until the events of recurrence, progression, last office visit, or phone interview. RESULTS: Within a median follow-up period of 26.7 months, 168 (41.1%) patients experienced a recurrence in a median time of 27 months (95%CI 16.1-38). Bacillus Calmette-Guérin was administered to 57 (13.9%) individuals after transurethral resection of the bladder tumor. Patients with ≥3 lesions (p<0.001), those with lesions >3 cm (p=0.02), and those without bacillus Calmette-Guérin treatment (p<0.001) had shorter recurrence-free survival. According to a Cox multivariate regression model, bacillus Calmette-Guérin use was independently associated with a reduced recurrence rate, with an HR of 0.43 (95%CI 0.25-0.72). Out of the patients studied, 26 (6.4%) experienced progression. T1 stage (p<0.001) and high-grade (p<0.001) were associated with shorter progression-free survival. Bacillus Calmette-Guérin did not influence bladder cancer progression. In the Cox multivariate analysis, high-risk disease was independently associated with progression (p<0.001). CONCLUSION: Our study confirms that non-muscle invasive bladder cancer exhibits a high recurrence rate. The use of adjuvant bacillus Calmette-Guérin in intermediate and high-risk patients significantly reduces this rate. Furthermore, the bacillus Calmette-Guérin shortage could have negatively impacted these patients.

Phase 1b Trial Evaluating Tolerability and Activity of Targeted Fibroblast Growth Factor Receptor Inhibition in Localized Upper Tract Urothelial Carcinoma.

PURPOSE: We initiated a biomarker-informed preoperative study of infigratinib, a fibroblast growth factor receptor (FGFR) inhibitor, in patients with localized upper tract urothelial carcinoma (UTUC), a population with high unmet needs and tumor with a high frequency of FGFR3 alterations. MATERIALS AND METHODS: Patients with localized UTUC undergoing ureteroscopy or nephroureterectomy/ureterectomy were enrolled on a phase 1b trial (NCT04228042). Once-daily infigratinib 125 mg by mouth × 21 days (28-day cycle) was given for 2 cycles. Tolerability was monitored by Bayesian design and predefined stopping boundaries. The primary endpoint was tolerability, and the secondary endpoint was objective response based on tumor mapping, done after endoscopic biopsy and post-trial surgery. Total planned enrollment: 20 patients. Targeted sequencing performed using a NovaSeq 6000 solid tumor panel. RESULTS: From May 2021 to November 2022, 14 patients were enrolled, at which point the trial was closed due to termination of all infigratinib oncology trials. Two patients (14.3%) had treatment-terminating toxicities, well below the stopping threshold. Responses occurred in 6 (66.7%) of 9 patients with FGFR3 alterations. Responders had median tumor size reduction of 67%, with 3 of 5 patients initially planned for nephroureterectomy/ureterectomy converted to ureteroscopy. Median follow-up in responders was 24.7 months (14.9-28.9). CONCLUSIONS: In this first trial of targeted therapy for localized UTUC, FGFR inhibition was well tolerated and had significant activity in FGFR3 altered tumors. Renal preservation was enabled in a substantial proportion of participants. These data support the design of a biomarker-driven phase 2 trial of FGFR3 inhibition in this population with significant unmet clinical needs.

Effectiveness of Adjuvant Chemotherapy in Variant Histology Upper Tract Urothelial Carcinoma Following Radical Nephroureterectomy: Stabilized Inverse Probability Treatment Weighting Analysis of Single Center Experience.

PURPOSE: The study aimed to investigate the impact of adjuvant chemotherapy on time to recurrence (TTR) and overall survival (OS) in patients with histologic variants of upper tract urothelial carcinoma (VUTUC) following radical nephroureterectomy (RNU). MATERIALS AND METHODS: A retrospective review of 131 VUTUC patients' medical records, from a pool of 368 non-metastatic localized or locally advanced UTUC cases, treated at a single tertiary referral center between January 2011 and January 2021. The intervention was adjuvant chemotherapy administration post-RNU. TTR and OS were evaluated using Kaplan-Meier and Cox proportional hazard regression, covariates adjusted for age, postoperative GFR, history of neoadjuvant chemotherapy, T and N stage with stabilized inverse probability of treatment weighting (sIPTW). RESULTS: The application of adjuvant chemotherapy showed a significant extension in TTR (P = .01), but no substantial impact on OS (P = .19) after sIPTW adjustment for covariates. Multivariate analysis revealed adjuvant chemotherapy, tumor size, and lymphovascular invasion as significant prognostic factors for TTR. In contrast, only tumor size and perineural invasion were significant for OS. Adjuvant chemotherapy reduced the progression risk in certain VUTUC subtypes (squamous or glandular/micropapillary), but not in sarcomatoid variants. CONCLUSIONS: Adjuvant chemotherapy appears to improve TTR, albeit without a significant effect on OS, in nonmetastatic localized and locally advanced VUTUC patients post-RNU. While beneficial to some VUTUC subtypes, it did not yield significant advantages for sarcomatoid variants. Despite adjustments for known confounders, the study's findings may be subject to potential selection bias and unmeasured confounding factors.

Impact of Preoperative Plasma Potassium Levels on Oncological Outcomes, Major Complications, and 30-Day Mortality in Bladder Cancer Patients Undergoing Radical Cystectomy.

INTRODUCTION AND OBJECTIVES: We examined the impact of preoperative plasma potassium levels (PPLs) on outcomes in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB), hypothesizing that potassium imbalances might influence outcomes. PATIENTS AND METHODS: In this retrospective study, 501 UCB patients undergoing RC from 2009 to 2017 at a tertiary center were analyzed. Blood samples collected a week prior to surgery defined normal and abnormal PPL based on institutional standards. We assessed overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), postoperative complications, 30-day mortality, and non-organ confined disease. Kaplan-Meier estimates, Cox proportional hazards, logistic regression, and decision curve analyses (DCA) were employed. RESULTS: 63 (13%) patients had abnormal preoperative PPLs, with 50 (10%) elevated and 13 (2.5%) decreased. In a 59 months median follow-up, 152 (31%) had disease recurrence, 197 (39%) died from any cause, and 119 (24%) from UCB. Multivariable cox regression analyses adjusting for perioperative parameters demonstrated abnormal PPL was associated with worse OS (HR=1.9, P=0.009), CSS (HR=2.8, P<0.001) and RFS (HR=2.1; P=0.007). Elevated preoperative PPLs also demonstrated significant associations with adverse outcomes in OS, CSS, and RFS (all P<0.05). In multivariable logistic regression analyses, abnormal and elevated PPLs were not associated with 30-day mortality, major 30-day postoperative complications, positive nodal disease, pT3/4 stage, and non-organ confined disease (all P>0.05). CONCLUSION: Abnormal and elevated preoperative PPLs correlate with adverse oncologic outcomes in UCB patients treated with RC. Pending external validation, preoperative PPLs might be a cost-effective, easily obtainable supplemental biomarker for enriching accuracy of outcome prediction in this highly variable maladie.