Primary bladder neck obstruction in men: The importance of urodynamic assessment and cystourethrography in measuring its severity.

OBJECTIVE: Primary bladder neck obstruction (PBNO) is a condition primarily affecting young men, characterized by obstruction at the bladder neck, leading to lower urinary tract symptoms. The aim of this study was to identify a correlation between the severity of bladder neck opening impairment and urinary symptoms by means of urodynamic studies. MATERIALS AND METHODS: A retrospective analysis was conducted in adult males diagnosed with PBNO at a university neurourology department between 2015 and 2022 who underwent voiding cystourethrography (VCUG) and pressure-flow studies. The cohort was divided into two groups: absence of bladder neck opening on VCUG (Group A) and incomplete bladder neck opening (Group B). RESULTS: Out of the 82 patients with PBNO screened, 53 were included in the analysis. Nocturia was the only symptom more prevalent in Group A (65% in Group A vs. 30% in Group B, p = 0.02) but scores and subscores of the Urinary Symptom Profile questionnaire were not different between groups. In addition, the detrusor pressure at a maximum flow rate (PdetQmax), bladder outlet obstruction index (BOOI), and bladder contractility index (BCI) were higher in Group A than in Group B [PdetQmax (A = 93.7 ± 53.7 cmH2O vs. B = 65.7 ± 26.4 cmH2O; p = 0.01)-BOOI (A = 77 ± 58.3 vs. B = 48 ± 25.7; p = 0.03)-BCI (A = 136 ± 51.3 vs. B = 110 ± 41.7; p = 0.04)]. CONCLUSION: This study demonstrates a significant association between the extent of bladder neck opening impairment observed on VCUG and obstruction and contraction urodynamic parameters, but no association with the severity of urinary symptoms. Future studies should evaluate the predictive value of treatment response and the occurrence of complications based on clinical and urodynamic parameters.

Perioperative and oncological outcomes of distal ureter management during nephroureterectomy for upper urinary tract urothelial carcinoma: a systematic review and meta-analysis.

INTRODUCTION: The best approach of the bladder cuff (i.e., transvesical, extravesical, endoscopic) during radical nephroureterectomy (RNU) remains an unsolved question. The aim of this review is to compare the oncological and perioperative outcomes among three different approaches of the distal ureter during RNU. EVIDENCE ACQUISITION: A literature search was conducted through June 2022 using PubMed/Medline, Embase, and Web of Science databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. The primary outcome was bladder recurrence-free survival and secondary outcomes included: perioperative outcomes, metastasis-free survival, and cancer-specific survival. EVIDENCE SYNTHESIS: A total of 19 non-randomized studies comprising 6581 patients met our inclusion criteria. The risk of bladder recurrence, metastasis and cancer-related death did not differ significantly between each approach (all P>0.05). In subgroup analysis excluding patients with history of bladder cancer, the risk of bladder recurrence remained similar between each approach (all P>0.05). There was no significant difference in terms of operative time, estimated blood loss, length of hospital stay, and postoperative complications between each approach (all P>0.05). The main limitation is the retrospective design of 18/19 included studies. CONCLUSIONS: The present systematic review and meta-analysis highlights the lack of high-level evidence on distal ureter management during RNU. On the basis of the available data, the present review supports the equivalence of different techniques of bladder cuff excision during RNU. The extravesical approach seems non-inferior to the transvesical approach in terms of oncological and perioperative outcomes.

Large-scale analysis of cell-cell communication reveals angiogenin-dependent tumor progression in clear cell renal cell carcinoma.

Cellular crosstalk in the tumor microenvironment (TME) is still largely uncharacterized, while it plays an essential role in shaping immunosuppression or anti-tumor response. Large-scale analyses are needed to better decipher cell-cell communication in cancer. In this work, we used original and publicly available single-cell RNA sequencing (scRNAseq) data to characterize in-depth the communication networks in human clear cell renal cell carcinoma (ccRCC). We identified 50 putative communication channels specifically used by cancer cells to interact with other cells, including two novel angiogenin-mediated interactions. Expression of angiogenin and its receptors was validated at the protein level in primary ccRCC. Mechanistically, angiogenin enhanced ccRCC cell line proliferation and down-regulated secretion of IL-6, IL-8, and MCP-1 proinflammatory molecules. This study provides novel biological insights into molecular mechanisms of ccRCC, and suggests angiogenin and its receptors as potential therapeutic targets in clear cell renal cancer.

Quinolone Prophylaxis in Conjunction with Bacillus Calmette-Guérin Instillations for Bladder Cancer: Time To Reconsider the Evidence and Open the Quinolone Box?

Adjuvant bacillus Calmette-Guérin (BCG) instillations represent a cornerstone in the treatment of non-muscle-invasive bladder cancer. Instillation schedule and dose modifications have been evaluated in efforts to reduce the incidence of adverse events (AEs), but none so far has the same treatment efficacy as the full-dose recommended schedule. It has been shown that prophylactic quinolone use in conjunction with BCG instillations reduces AE incidence and improves timely completion of instillation regimens and patient survival. However, the European Medicines Agency imposed restrictions on the use of quinolones in 2019 because of side effects. Nevertheless, rational use of quinolone prophylaxis could be considered for selected individuals treated with BCG without risk factors for quinolone-associated side effects in conjunction with patient information about side-effect symptoms. PATIENT SUMMARY: Bladder instillations of BCG (bacillus Calmette-Guérin) are used in the treatment of non-muscle-invasive bladder cancer. Antibiotics from the quinolone class can reduce the adverse effects of BCG and help patients in completing the treatment course; however, these antibiotics have their own side effects. Our mini review suggests that the antibiotics could be used in selective cases if patients are given adequate information on these side effects and their symptoms.

Optimizing outcomes for high-risk, non-muscle-invasive bladder cancer: The evolving role of PD-(L)1 inhibition.

Transurethral resection of bladder tumor followed by intravesical Bacillus Calmette-Guérin (BCG) is the standard of care in high-risk, non-muscle-invasive bladder cancer (NMIBC). Although many patients respond, recurrence and progression are common. In addition, patients may be unable to receive induction + maintenance due to intolerance or supply issues. Therefore, alternative treatment options are urgently required. Programmed cell death (ligand) 1 (PD-[L]1) inhibitors show clinical benefit in phase 1/2 trials in BCG-unresponsive NMIBC patients. This review presents the status of PD-(L)1 inhibition in high-risk NMIBC and discusses future directions. PubMed and Google scholar were searched for articles relating to NMIBC immunotherapy and ClinicalTrials.gov for planned and ongoing clinical trials. Preclinical and early clinical studies show that BCG upregulates PD-L1 expression in bladder cancer cells and, when combined with a PD-(L)1 inhibitor, a potent antitumor response is activated. Based on this mechanism, several PD-(L)1 inhibitors are in phase 3 trials in BCG-naïve, high-risk NMIBC in combination with BCG. Whereas PD-(L)1 inhibitors are well characterized in patients with advanced malignancies, the impact of immune-related adverse events (irAE) on the benefit/risk ratio in NMIBC should be determined. Alternative routes to intravenous administration, like subcutaneous and intravesical administration, may facilitate adherence and access. The outcomes of combination of PD-(L)1 inhibitors and BCG in NMIBC are highly anticipated. There will be a need to address treatment resources, optimal management of irAEs and education and training related to use of this therapy in clinical practice.

The effect of cisplatin-based neoadjuvant chemotherapy on the renal function of patients undergoing radical cystectomy.

INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both. METHODS: We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context. RESULTS: We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m2) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m2). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m2), and the proportion of those with stage ≥3 CKD increased from 37% to 51%. CONCLUSIONS: Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.

Can Simplified PADUA Renal (SPARE) Nephrometry scoring system help predict renal function outcomes after robot-assisted partial nephrectomy? (UroCCR study 93).

BACKGROUND: The SPARE Nephrometry Score (NS) is described as easier to implement than the RENAL and PADUA NSs, currently more widely used. Our objective was to compare the accuracy of SPARE NS in predicting renal function outcomes following RAPN. METHODS: A multicentric retrospective study was conducted using French kidney cancer network (UroCCR, NCT03293563) database. All patients included had RAPN for cT1 renal tumors between May 2010 and March 2021. SPARE was compared to RENAL, PADUA and Tumor Size to predict postoperative acute kidney injury (AKI), chronic kidney disease (CKD) upstaging, de novo CKD at 3-6 months follow-up and Trifecta failure. The ability of the different NSs and tumor size to predict renal function outcomes was evaluated using uni- and multivariate logistic regression models. RESULTS: According to our study criteria, 1171 patients were included. Mean preoperative tumor size and estimated glomerular filtration rate (eGFR) were 3.4±1.4 cm and 85.8 mL/min/1.73 m2. In total, 266 (22.7%), 87 (7.4%), 94 (8%), and 624 (53.3%) patients had AKI, de novo CKD, CKD upstaging, and Trifecta failure, respectively. In multivariate analysis, all three NSs and tumor size were independent predictors of AKI, CKD de novo, CKD upgrade and Trifecta failure. There was no significant difference between all three NS and tumor sizes in predicting renal function outcomes. CONCLUSIONS: SPARE Score seems to be a valid alternative to predict renal function outcomes after RAPN. Nevertheless, in our study, tumor size was as accurate as NSs in predicting postoperative outcomes and, therefore, seems to be the logical choice for surgical decisions.

Design and rationale of a single-arm phase II study of neoadjuvant Durvalumab and Gemcitabine associated with Cisplatin or Carboplatin for upper urinary tract urothelial cancer: the iNDUCT trial (NCT04617756).

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) is often locally advanced at initial diagnosis and is associated with high recurrence and mortality rates after radical nephroureterectomy (RNU). Adjuvant platinum-based chemotherapy has shown a recurrence-free survival benefit in a randomised phase III trial, while neoadjuvant treatment seems promising in retrospective series. On the contrary, little is known about the role of perioperative immunotherapy and its combination with chemotherapy for UTUC patients, although initial positive results have been published for muscle-invasive bladder cancer. STUDY DESIGN AND ENDPOINTS: Against this backdrop, we are running a multi-centre single-arm phase 2 trial of neoadjuvant Durvalumab, a monoclonal antibody targeting programmed cell death ligand 1, combined with Gemcitabine and Cisplatin or Carboplatin for high-risk UTUC patients. The primary outcome is pathological complete response rate at RNU. Secondary endpoints include the partial pathological response rate, safety, as well as disease-free and overall survival. A biomarker analysis is also planned. PATIENTS AND INTERVENTIONS: Included patients must have a good performance status and harbour a non-metastatic UTUC, considered at high risk of progression, defined as either biopsy-proven high-grade disease or invasive features at imaging with or, more recently, without high-grade cytology at the multidisciplinary team discretion, as specified in the latest amendment. Enrolled patients receive 3 cycles of neoadjuvant immuno-chemotherapy before RNU, and the standard of care thereafter. The trial is registered as NCT04617756 and is supervised by an independent data monitoring committee.

Safety and efficacy of preoperative chemotherapy for muscle-invasive bladder cancer in elderly patients.

PURPOSE: This study aimed at describing the feasibility and oncological outcomes of standard cisplatin-based neoadjuvant chemotherapy (C-NAC) for muscle-invasive bladder cancer (MIBC) in patients aged ≥ 75 and assess the impact of baseline geriatric parameters. METHODS: This retrospective study included patients with stage cT2-4NanyM0 MIBC aged 75 and older treated with ≥ 1 cycle of C-NAC from 2011 to 2021 at a high-volume academic center. Primary outcome was overall survival (OS). Secondary outcomes were chemotherapy feasibility (administration of ≥ 4 cycles), safety, and pathological downstaging. RESULTS: Fifty-six patients were included. Median age was 79 (range 75-90). C-NAC regimen was ddMVAC in 41 patients and GC in 15. Seventy-three percent of patients received ≥ 4 cycles of C-NAC. Grade ≥ 3 toxicity was observed in 55% of patients. The febrile neutropenia rate was 7%. Thirty patients underwent cystectomy, and 13 underwent chemoradiotherapy. Three-year OS was 63%. Geriatric parameters polypharmacy, undernutrition, and age-adjusted Charlson comorbidity index ≥ 8 predicted worse OS. CONCLUSION: Standard-of-care C-NAC and local treatments are feasible in selected elderly MIBC patients, with efficacy and safety findings similar to that observed in pivotal trials with younger patients. The prognostic impact of geriatric parameters underlines the need for specialized evaluation before treatment initiation.

En Bloc Versus Conventional Resection of Primary Bladder Tumor (eBLOC): A Prospective, Multicenter, Open-label, Phase 3 Randomized Controlled Trial.

BACKGROUND: En bloc transurethral resection of the bladder (eTURB) might improve the surgical management of non-muscle-invasive bladder cancer (NMIBC) in comparison to conventional TURB (cTURB). OBJECTIVE: To evaluate whether eTURB is superior to cTURB in resection of NMIBC and specimen retrieval. DESIGN, SETTING, AND PARTICIPANTS: This was a randomized, multicenter trial in patients with up to three cTa-T1 NMIBC tumors of 1-3 cm in size, who were enrolled from January 2019 to January 2022. INTERVENTION: Participants were randomized 1:1 to undergo eTURB (n = 192) or cTURB (n = 192). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the prevalence of detrusor muscle (DM) in the specimen retrieved. Secondary endpoints included bladder perforation, persistent disease at second-look TURB, positive lateral resection margin, positive deep resection margin, operation time, perforation rate, obturator reflex, conversion from eTURB to cTURB, recurrence-free survival, and disease recurrence at 3 mo. RESULTS AND LIMITATIONS: A total of 384 patients were randomized to undergo eTURB or cTURB. A total of 452 tumors were resected and analyzed for the primary outcome. eTURB was superior to cTURB in retrieval of DM (80.7% vs 71.1%; mixed-model p = 0.01). Bladder perforation (5.6% vs 12%; difference -6.4%; 95% confidence interval [CI] -12.2% to -0.6%) and obturator reflex (8.4% vs 16%; difference -7.6%; 95% CI -14.3% to -0.9%) were less frequent in the eTURB arm than in the cTURB arm. Operation time did not differ between the two techniques (26 min, interquartile range [IQR] 20-38 for eTURB vs 25 min, IQR 17-35 for cTURB; difference 1 min, 95% CI -25.9 to 4.99). Second-look TURB was performed in 24 patients in the eTURB arm and 34 in the cTURB arm, with no difference in the rate of residual papillary disease (pTa/pT1: 56% vs 55.9%; difference 0.1%, 95% CI -25.5% to 25.7%). At median follow-up of 13 mo (IQR 7-20), 18.4% of the patients in the eTURB arm and 16.7% in the cTURB arm had experienced bladder cancer recurrence (Cox hazard ratio 0.87, 95% CI 0.49-1.52; p = 0.6). CONCLUSIONS: In patients with clinical NMIBC with up to three tumors of 1-3 cm in size, tumor removal via eTURB resulted in a higher rate of DM in the pathologic specimen in comparison to cTURB. Moreover, eTURB was associated with lower frequency of obturator reflex and bladder perforation than cTURB was. While improving on the quality indicators for NMIBC, the long-term differential oncologic benefits of eTURB remain uncertain. PATIENT SUMMARY: We compared two techniques for removal of bladder tumors and found that tumor removal in a single piece, called en bloc resection, provides a better-quality specimen for pathology analysis and fewer complications in comparison to the conventional method. This trial is registered at ClinicalTrials.gov as NCT03718754.

Transcriptomic Profiling of Upper Tract Urothelial Carcinoma: Bladder Cancer Consensus Classification Relevance, Molecular Heterogeneity, and Differential Immune Signatures.

Analyses of large transcriptomics data sets of muscle-invasive bladder cancer (MIBC) have led to a consensus classification. Molecular subtypes of upper tract urothelial carcinomas (UTUCs) are less known. Our objective was to determine the relevance of the consensus classification in UTUCs by characterizing a novel cohort of surgically treated ≥pT1 tumors. Using immunohistochemistry (IHC), subtype markers GATA3-CK5/6-TUBB2B in multiplex, CK20, p16, Ki67, mismatch repair system proteins, and PD-L1 were evaluated. Heterogeneity was assessed morphologically and/or with subtype IHC. FGFR3 mutations were identified by pyrosequencing. We performed 3'RNA sequencing of each tumor, with multisampling in heterogeneous cases. Consensus classes, unsupervised groups, and microenvironment cell abundance were determined using gene expression. Most of the 66 patients were men (77.3%), with pT1 (n = 23, 34.8%) or pT2-4 stage UTUC (n = 43, 65.2%). FGFR3 mutations and mismatch repair-deficient status were identified in 40% and 4.7% of cases, respectively. Consensus subtypes robustly classified UTUCs and reflected intrinsic subgroups. All pT1 tumors were classified as luminal papillary (LumP). Combining our consensus classification results with those of previously published UTUC cohorts, LumP tumors represented 57.2% of ≥pT2 UTUCs, which was significantly higher than MIBCs. Ten patients (15.2%) harbored areas of distinct subtypes. Consensus classes were associated with FGFR3 mutations, stage, morphology, and IHC. The majority of LumP tumors were characterized by low immune infiltration and PD-L1 expression, in particular, if FGFR3 mutated. Our study shows that MIBC consensus classification robustly classified UTUCs and highlighted intratumoral molecular heterogeneity. The proportion of LumP was significantly higher in UTUCs than in MIBCs. Most LumP tumors showed low immune infiltration and PD-L1 expression and high proportion of FGFR3 mutations. These findings suggest differential response to novel therapies between patients with UTUC and those with MIBC.

Survival after sequential neoadjuvant chemotherapy followed by trimodal treatment or radical cystectomy for muscle-invasive bladder cancer.

PURPOSE: to assess the respective outcomes of patients with localized muscle-invasive bladder cancer (MIBC) treated by either radical cystectomy (RC) or trimodal treatment (TMT) depending on pathological response to previous neoadjuvant chemotherapy (NAC) assessed on cystectomy specimen or post-NAC transurethral resection (TURB) specimen, respectively. PATIENT AND METHODS: We retrospectively included all consecutive patients treated in one academic center with cisplatin-based NAC followed by RC or TMT for cT2-3N0M0 MIBC between 2014 and 2021. Primary endpoint was metastasis-free survival (MFS) in both treatment groups and according to pathological response to NAC. Local recurrence-free survival and conservative management failure (metastasis-free bladder-intact survival) for patients treated with TMT were assessed. RESULTS: 104 patients were included, 26 treated with TMT and 78 with RC. The rate of complete pathological response was 47.4% in patients treated with RC (ypT0) and 66.7% in patients treated with TMT (ycT0). Median follow-up was 34.9 months. Four-year MFS was 72% in both treatment groups. Four-year MFS was 85% in both ypT0 RC patients and ycT0 TMT patients. ycT0 stage was associated with low rates of intravesical recurrence and conservative management failure. CONCLUSION: Patients with post-NAC ycT0 stage treated with TMT have favorable oncological outcomes similar to those of ypT0 patients treated with RC. Assessment of complete histological response with TURB after NAC may help in selecting the best candidates for bladder preservation with TMT.

Urethral Diverticulum During Pregnancy Managed With Primum Non Nocere Principle: Conservative Treatment During Pregnancy and Diverticulectomy After Child Birth.

OBJECTIVE: To report our referral single institution experience of the management of urethral diverticulum (UD) in female during pregnancy (UDp), which is a rare condition, not standardized and sparsely reported in the current literature. METHODS: The charts of 12 female patients treated for UDp between 2010 and 2020 were screened retrospectively. Baseline demographics, management strategies, delivery complications, and surgical outcomes were specifically analyzed and compared to our historical cohort of UD patients (n = 54). RESULTS: Overall, 7/12 (58%) patients were primiparous and 5/12 (42%) had previous pregnancy with no history of UD. Symptoms at diagnosis were respectively urinary tract infections (7/12, 58%), urethral purulent discharge (6/12, 50%), vaginal bulging (4/12, 33%), and dyspareunia (4/12, 33%). Compared to UD outside pregnancy, UDp patients were younger and were more likely to bear asymptomatic UD. Conservative management until delivery was elected in all patients. Vaginal delivery was possible in all but one patient. There was not any reported infectious mother-to-child transmission. Diverticulectomy through vaginal route were performed 3 months after delivery. Low-grade Clavien Dindo complications were reported in up to 25% (3/12) of the cases. No recurrence was reported. CONCLUSION: Our report showed UDp could be managed conservatively during pregnancy without jeopardizing vaginal delivery and increasing infectious mother-to-child transmission. Surgical diverticulectomy could safely be performed after child birth using similar technique and care pathways generally used for the management of UD outside pregnancy.

Minimally invasive nephron-sparing treatments for T1 renal cell cancer in patients over 75 years: a comparison of outcomes after robot-assisted partial nephrectomy and percutaneous ablation.

PURPOSE: To compare the oncological and perioperative outcomes of robot-assisted partial nephrectomy (RPN) and percutaneous thermal ablation (PTA) for treatment of T1 renal cell cancer (RCC) in patients older than 75 years. MATERIALS AND METHODS: Retrospective national multicenter study included all patients older than 75 years treated for a T1 RCC by RPN or PTA between January 2010 and January 2021. Patients' characteristics, tumor data, and perioperative and oncological outcomes were compared. RESULTS: A total of 205 patients for 209 procedures (143 RPN and 66 PTA) were included. In the PTA group, patients were older (80.4 ± 3.7 vs. 79 ± 3.7 years (p = 0.01)); frailer (ASA score (2.43 ± 0.6 vs. 2.17 ± 0.6 (p < 0.01)); and more frequently had a history of kidney surgery (16.7% [11/66] vs. 5.6% [8/143] (p = 0.01)) than in the RPN group. Tumors were larger in the RPN group (2.7 ± 0.7 vs. 3.2 ± 0.9 cm (p < 0.01)). Operation time, length of hospital stay, and increase of creatinine serum level were higher in RPN (respectively 92.1 ± 42.7 vs. 150.7 ± 61.3 min (p < 0.01); 1.7 ± 1.4 vs. 4.2 ± 3.4 days (p < 0.01); 1.9 ± 19.3% vs. 10.1 ± 23.7 (p = 0.03)). Disease-free survival and time to progression were similar (respectively, HR 2.2; 95% CI 0.88-5.5; p = 0.09; HR 2.1; 95% CI 0.86-5.2; p = 0.1). Overall survival was shorter for PTA that disappeared after Cox adjusting model (HR 3.3; 95% CI 0.87-12.72; p = 0.08). CONCLUSION: Similar oncological outcomes are observed after PTA and RPN for T1 RCC in elderly patients. CLINICAL RELEVANCE STATEMENT: Robot-assisted partial nephrectomy and percutaneous thermal ablation have similar oncological outcomes for T1a kidney cancer in patients over 75 years; however, operative time, decrease in renal function, and length of hospital stay were lower with ablation. KEY POINTS: • After adjusting model for age and ASA score, similar oncological outcomes are observed after percutaneous thermal ablation and robot-assisted partial nephrectomy for T1 renal cell cancer in elderly patients. • Operation time, length of hospital stay, and increase of creatinine serum level were higher in the robot-assisted partial nephrectomy group.

Carboplatin Induction Chemotherapy in Clinically Lymph Node-positive Bladder Cancer.

Background: There are currently no guideline recommendations regarding the treatment of cisplatin-ineligible, clinically lymph node-positive (cN+) bladder cancer (BCa). Objective: To investigate the oncological efficacy of gemcitabine/carboplatin induction chemotherapy (IC) in comparison to cisplatin-based regimens in cN+ BCa. Design setting and participants: This was an observational study of 369 patients with cT2-4 N1-3 M0 BCa. Intervention: IC followed by consolidative radical cystectomy (RC). Outcome measurements and statistical analysis: The primary endpoints were the pathological objective response (pOR; ypT0/Ta/Tis/T1 N0) rate and the pathological complete response (pCR; ypT0N0) rate. We applied 3:1 propensity score matching (PSM) to reduce selection bias. Overall survival (OS) and cancer-specific survival (CSS) were compared across groups using the Kaplan-Meier method. Associations between the treatment regimen and survival endpoints were tested in multivariable Cox regression analyses. Results and limitations: After PSM, a cohort of 216 patients was available for analysis, of whom 162 received cisplatin-based IC and 54 gemcitabine/carboplatin IC. At RC, 54 patients (25%) had a pOR and 36 (17%) had a pCR. The 2-yr CSS was 59.8% (95% confidence interval [CI] 51.9-69%) for patients who received cisplatin-based IC versus 38.8% (95% CI 26-57.9%) for those who received gemcitabine/carboplatin. For the pOR (p = 0.8), ypN0 status at RC (p = 0.5), and cN1 BCa subgroups (p = 0.7), there was no difference in CSS between cisplatin-based IC and gemcitabine/carboplatin. In the cN1 subgroup, treatment with gemcitabine/carboplatin was not associated with shorter OS (p = 0.2) or CSS (p = 0.1) on multivariable Cox regression analysis. Conclusions: Cisplatin-based IC seems to be superior to gemcitabine/carboplatin and should be the standard for cisplatin-eligible patients with cN+ BCa. Gemcitabine/carboplatin may be an alternative treatment for selected cisplatin-ineligible patients with cN+ BCa. In particular, selected cisplatin-ineligible patients with cN1 disease may benefit from gemcitabine/carboplatin IC. Patient summary: In this multicenter study, we found that selected patients with bladder cancer and clinical evidence of lymph node metastasis who cannot receive standard cisplatin-based chemotherapy before surgery to remove their bladder may benefit from chemotherapy with gemcitabine/carboplatin. Patients with a single lymph node metastasis may benefit the most.

Age represents the main driver of surgical decision making in patients candidate to radical cystectomy.

BACKGROUND AND OBJECTIVES: Age might influence the choice of surgical approach, type of urinary diversion (UD) and lymph node dissection (LND) in patients candidate to radical cystectomy (RC) for urothelial bladder cancer (UBC). Similarly, age may enhance surgical morbidity and worsen perioperative outcomes. We tested the impact of age (octogenarian vs. younger patients) on surgical decision making and peri- and postoperative outcomes of RC. METHODS: Non-metastatic muscle-invasive UBC patients treated with RC at 18 high-volume European institutions between 2006 and 2021 were identified and stratified according to age (≥80 vs. <80 years). Intraoperative Complications Assessment and Reporting with Universal Standards and European Association of Urology guidelines recommendations were accomplished in collection and reporting of, respectively, intraoperative and postoperative complications. Multivariable logistic regression models (MVA) tested the impact of age on outcomes of interest. Sensitivity analyses after 1:3 propensity score matching were performed. RESULTS: Of 1955 overall patients, 251 (13%) were ≥80-year-old. Minimally invasive RC was performed in 18% and 40% of octogenarian and younger patients, respectively (p < 0.001). UD without bowel manipulation (ureterocutaneostomy, UCS) was performed in 31% and 7% of octogenarian and younger patients (p < 0.001). LND was delivered to 81% and 93% of octogenarian and younger patients (p < 0.001). At MVA, age ≥80 years independently predicted open approach (odds ratio [OR]: 1.55), UCS (OR: 3.70), and omission of LND (OR: 0.41; all p ≤ 0.02). Compared to their younger counterparts, octogenarian patients experienced higher rates of intraoperative (8% vs. 4%, p = 0.04) but not of postoperative complications (64% vs. 61%, p = 0.07). At MVA, age ≥80 years was not an independent predictor of length of stay, intraoperative or postoperative transfusions and complications, and readmissions (all p values >0.1). These results were replicated in sensitivity analyses. CONCLUSIONS: Age ≥80 years does not independently portend worse surgical outcomes for RC. However, octogenarians are unreasonably more likely to receive open approach and UCS diversion, and less likely to undergo LND.

European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2023 Update.

CONTEXT: The European Association of Urology (EAU) guidelines panel on upper urinary tract urothelial carcinoma (UTUC) has updated the guidelines to aid clinicians in evidence-based management of UTUC. OBJECTIVE: To provide an overview of the EAU guidelines on UTUC as an aid to clinicians. EVIDENCE ACQUISITION: The recommendations provided in these guidelines are based on a review of the literature via a systematic search of the PubMed, Ovid, EMBASE, and Cochrane databases. Data were searched using the following keywords: urinary tract cancer, urothelial carcinomas, renal pelvis, ureter, bladder cancer, chemotherapy, ureteroscopy, nephroureterectomy, neoplasm, (neo)adjuvant treatment, instillation, recurrence, risk factors, metastatic, immunotherapy, and survival. The results were assessed by a panel of experts. EVIDENCE SYNTHESIS: Even though data are accruing, for many areas there is still insufficient high-level evidence to provide strong recommendations. Patient stratification on the basis of histology and clinical examination (including imaging) and assessment of patients at risk of Lynch syndrome will aid management. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk UTUC and two functional kidneys. In particular, for patients with high-risk or metastatic UTUC, new treatment options have become available. In high-risk UTUC, platinum-based chemotherapy after radical nephroureterectomy, and adjuvant nivolumab for unfit or patients who decline chemotherapy, are options. For metastatic disease, gemcitabine/carboplatin chemotherapy is recommended as first-line treatment for cisplatin-ineligible patients. Patients with PD-1/PD-L1-positive tumours should be offered a checkpoint inhibitor (pembrolizumab or atezolizumab). CONCLUSIONS: These guidelines contain information on the management of individual patients according to the current best evidence. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen according to the risk stratification of these tumours. PATIENT SUMMARY: Cancer of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, timely and appropriate diagnosis is most important. A number of known risk factors exist.