[Enfortumab vedotin and pembrolizumab : Management of side effects during first line combined treatment for advanced or metastatic urothelial carcinoma].

The aim of this article is to raise awareness among healthcare providers about the adverse events (AEs) associated with the combined treatment with enfortumab vedotin and pembrolizumab. The differential diagnostic allocation of these AEs to the respective agents is discussed, overlaps between the side effect profiles of the two drugs are identified and strategies for an effective management of these AEs are presented. The recommendations are based on the currently valid prescription information for both drugs, the results of pivotal approval studies and the guidelines of recognized specialist organizations as well as the clinical experience of the authors.

Comprehensive genomic characterization of early-stage bladder cancer.

Understanding the molecular landscape of nonmuscle-invasive bladder cancer (NMIBC) is essential to improve risk assessment and treatment regimens. We performed a comprehensive genomic analysis of patients with NMIBC using whole-exome sequencing (n = 438), shallow whole-genome sequencing (n = 362) and total RNA sequencing (n = 414). A large genomic variation within NMIBC was observed and correlated with different molecular subtypes.

Complications of Tumor Nephrectomy with and Without Tumor Thrombus in the Vena Cava, Recorded with the Clavien-Dindo Classification: A Matched-Pair Analysis.

Background/objectives: Radical nephrectomy (RN) with inferior vena cava thrombectomy (IVCT) is indicated for the curative management of renal cell carcinoma (RCC) with tumor thrombus (TT). In the literature, any direct comparison of complications between RNs with or without IVCT is lacking. The objective of this study was to analyze and compare complications after RNs with or without IVCT.

Reasonability of Frequent Laboratory Analyses during Therapy with Nivolumab and Nivolumab+Ipilimumab in Patients with Advanced or Metastatic Renal Cell Carcinoma during the Phase 2 Clinical Trial TITAN-RCC.

In clinical trials, laboratory values are assessed with high frequency. This can be stressful for patients, resource intensive, and difficult to implement, for example in office-based settings. In the prospective, multicentre phase 2 TITAN-RCC trial (NCT02917772), we investigated how many relevant changes in laboratory values would have been missed if laboratory values had been assessed less frequently.

Nivolumab + Ipilimumab as Immunotherapeutic Boost in Metastatic Urothelial Carcinoma: A Nonrandomized Clinical Trial.

Importance: Studies with nivolumab, an approved therapy for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy, demonstrate improved outcomes with added high-dose ipilimumab.

Objective: To assess efficacy and safety of a tailored approach using nivolumab + ipilimumab as an immunotherapeutic boost for mUC.

Design, Setting, And Participants: In this phase 2 nonrandomized trial, patients with mUC composed 2 cohorts.

Treatment patterns and clinical outcomes in metastatic urothelial carcinoma: a German retrospective real-world analysis.

This study assessed real-world treatment in patients with metastatic urothelial carcinoma (mUC) in Germany. Patients diagnosed with mUC from 2015 to 2019 were identified in two claims databases: AOK PLUS and GWQ. 3226 patients with mUC were analyzed; 1286 (39.

Effect of Sex on the Oncological Outcomes in Response to Immunotherapy and Antibody-drug Conjugates in Patients with Urothelial and Kidney Cancer: A Systematic Review and a Network Meta-analysis.

Background And Objective: Immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) herald a transformative era in metastatic renal cell carcinoma (RCC) and transitional cell carcinoma (TCC) treatment, amid acknowledged sex-based disparities in these cancers. We conducted a systematic review and network meta-analysis (NMA) to identify sex-specific differences in the efficacy of ICI/ADC monotherapy or combination therapies for RCC and TCC survival, in metastatic and adjuvant settings.

Methods: A systematic search was conducted up to October 2023 for English articles on ICIs and ADCs as systemic therapies (ICIs in first-line and adjuvant treatment for RCC, ICIs and ADCs in first- and second-line treatment for TCC).

Healthcare resource utilization and associated costs in patients with metastatic urothelial carcinoma: a real-world analysis using German claims data.

Aims: This retrospective claims data study characterized real-world treatment patterns, healthcare resource utilization (HCRU), and costs in patients with metastatic urothelial carcinoma (mUC) in Germany.

Materials And Methods: Continuously insured adults with incident mUC diagnosis (=index; : C65-C68/C77-C79) in 2015-2019 were identified from two German claims databases. Patients who received first-line (1 L) treatment within 12 months of index were divided into three mutually exclusive sub-cohorts: platinum-based chemotherapy (PB-CT), non-PB-CT, and immunotherapy (IO).

Simulation of the effects of molecular urine markers in follow-up of patients with high-risk non-muscle invasive bladder cancer.

A plethora of urine markers for the management of patients with bladder cancer has been developed and studied in the past. However, the clinical impact of urine testing on patient management remains obscure. The goal of this manuscript is to identify scenarios for the potential use of molecular urine markers in the follow-up of patients with high-risk non-muscle-invasive BC (NMIBC) and estimate potential risks and benefits.

PAE planning: Radiation exposure and image quality of CT and CBCT.

Purpose: To determine accurate organ doses, effective doses, and image quality of computed tomography (CT) compared with cone beam CT (CBCT) for correct identification of prostatic arteries.

Method: A dual-energy CT scanner and a flat-panel angiography system were used. Dose measurements (gallbladder (g), intestine (i), bladder (b), prostate (p), testes (t), active bone marrow of pelvis (bmp) and femura (bmf)) were performed using an anthropomorphic phantom with 65 thermoluminescent dosimeters in the pelvis and abdomen region.

[Combination therapy with poly(adenosine diphosphate-ribose) polymerase (PARPi) and androgen receptor signaling pathway (ARPi) inhibitors for metastatic castration-resistant prostate cancer].

Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with varying clinical and molecular subtypes. Almost one-third of patients have abnormalities in homologous recombinant repair genes. Again, about one third of these mutations affect the BReast CAncer 1 or 2 (BRCA 1 or BRCA 2) genes, which generally render tumours receptive to treatment with poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi).

A Pooled Analysis of 3 Phase II Trials of Salvage Nivolumab/Ipilimumab After Nivolumab in Renal Cell Carcinoma.

Background: Nivolumab plus ipilimumab has demonstrated improved survival for treatment-naïve advanced clear cell renal cell carcinoma (RCC). A series of clinical trials evaluated the effect of salvage nivolumab plus ipilimumab in patients without an objective response to nivolumab. Given the size and heterogeneity of these studies, we performed a pooled analysis to better inform the activity of nivolumab plus ipilimumab after nivolumab.

Impact of Prior Cytoreductive Nephrectomy on Efficacy in Patients with Synchronous Metastatic Renal Cell Carcinoma Treated with Avelumab plus Axitinib or Sunitinib: Post Hoc Analysis from the JAVELIN Renal 101 Phase 3 Trial.

Data on the effects of prior cytoreductive nephrectomy (CN) in patients with renal cell carcinoma (RCC) with synchronous metastases (M1 disease) before immune checkpoint inhibitor (ICI) treatment are limited. In this post hoc analysis of treatment-naive patients with advanced RCC from the phase 3 JAVELIN Renal 101 trial, we assessed efficacy outcomes in the avelumab + axitinib and sunitinib arms in patients who were initially diagnosed with M1 disease (n = 412) grouped by prior CN (yes vs no). Progression-free survival (PFS) and overall survival (OS) were analyzed using multivariable Cox regression, and objective response rates (ORRs) were analyzed using logistic regression.

Tailored immunotherapy approach with nivolumab with or without nivolumab plus ipilimumab as immunotherapeutic boost in patients with metastatic renal cell carcinoma (TITAN-RCC): a multicentre, single-arm, phase 2 trial.

Background: Nivolumab plus ipilimumab is approved as first-line regimen for intermediate-risk or poor-risk metastatic renal cell carcinoma, and nivolumab monotherapy as second-line therapy for all risk groups. We aimed to examine the efficacy and safety of nivolumab monotherapy and nivolumab plus ipilimumab combination as an immunotherapeutic boost after no response to nivolumab monotherapy in patients with intermediate-risk and poor-risk clear-cell metastatic renal cell carcinoma.

Methods: TITAN-RCC is a multicentre, single-arm, phase 2 trial, done at 28 hospitals and cancer centres across Europe (Austria, Belgium, Czech Republic, France, Germany, Italy, Spain, and the UK).

Quality of Life in Patients with High-grade Non-muscle-invasive Bladder Cancer Undergoing Standard Versus Reduced Frequency of Bacillus Calmette-Guérin Instillations: The EAU-RF NIMBUS Trial.

Background: Adverse events induced by intravesical bacillus Calmette-Guérin (BCG) to treat high-grade non-muscle-invasive bladder cancer (NMIBC) often lead to treatment discontinuation. The EAU-RF NIMBUS trial found a reduced number of standard-dose BCG instillations to be inferior with the standard regimen. Nonetheless, it remains important to evaluate whether patients in the reduced BCG treatment arm had better quality of life (QoL) due to a possible reduction in toxicity or burden.

Optimal length and temporal resolution of dynamic contrast-enhanced MR imaging for the differentiation between prostate cancer and normal peripheral zone tissue.

The value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the detection of prostate cancer is controversial. There are currently insufficient peer reviewed published data or expert consensus to support routine adoption of DCE-MRI for clinical use. Thus, the objective of this study was to explore the optimal temporal resolution and measurement length for DCE-MRI to differentiate cancerous from normal prostate tissue of the peripheral zone of the prostate by non-parametric MRI analysis and to compare with a quantitative MRI analysis.

A paired-kidney allocation study found superior survival with HLA-DR compatible kidney transplants in the Eurotransplant Senior Program.

The Eurotransplant Senior Program (ESP) has expedited the chance for elderly patients with kidney failure to receive a timely transplant. This current study evaluated survival parameters of kidneys donated after brain death with or without matching for HLA-DR antigens. This cohort study evaluated the period within ESP with paired allocation of 675 kidneys from donors 65 years and older to transplant candidates 65 years and older, the first kidney to 341 patients within the Eurotransplant Senior DR-compatible Program and 334 contralateral kidneys without (ESP) HLA-DR antigen matching.

[Antibody-drug conjugates as new therapeutic agents in uro-oncology].

Antibody-drug conjugates represent a new class of therapeutic agents that are already being used in the field of uro-oncology. They consist of an antibody directed against a specific tumour antigen linked to a cytotoxic substance ("payload") which acts after internalisation into the tumour cell and its release. Currently, approval in the European Union is restricted to enfortumab vedotin which is directed against nectin‑4 and carries the microtubule-inhibiting active ingredient monomethyl auristatin E (MMAE).

67 Ga-PSMA I&T for Radioguided Surgery of Lymph Node Metastases in Patients With Biochemical Recurrence of Prostate Cancer.

Purpose: Radioguided lymph node dissection in patients with prostate cancer, and suffering from biochemical recurrence has been described thoroughly during the past few years. Several prostate-specific membrane antigen (PSMA)-directed ligands labeled with 111 In, 99m Tc, and 68 Ga have been published; however, limitations regarding availability, short half-life, high costs, and unfavorable high energy might restrict frequent use. This study aims at introducing 67 Ga as a promising radionuclide for radioguided surgery.

Disease-free Survival Analysis for Patients with High-risk Muscle-invasive Urothelial Carcinoma from the Randomized CheckMate 274 Trial by PD-L1 Combined Positive Score and Tumor Cell Score.

Background: The CheckMate 274 trial demonstrated improved disease-free survival (DFS) with adjuvant nivolumab versus placebo in patients with muscle-invasive urothelial carcinoma at high risk of recurrence after radical surgery in both the intent-to-treat population and the subset with tumor programmed death ligand 1 (PD-L1) expression ≥1%.

Objective: To analyze DFS by combined positive score (CPS), which is based on PD-L1 expression in both tumor and immune cells.

Design, Setting, And Participants: We randomized a total of 709 patients 1:1 to nivolumab 240 mg or placebo every 2 wk intravenously for ≤1 yr of adjuvant treatment.

Tailored immunotherapy approach with nivolumab with or without ipilimumab in patients with advanced transitional cell carcinoma after platinum-based chemotherapy (TITAN-TCC): a multicentre, single-arm, phase 2 trial.

Background: Nivolumab is used after platinum-based chemotherapy in patients with metastatic urothelial carcinoma. Studies suggest improved outcomes for dual checkpoint inhibition with high ipilimumab doses. We aimed to examine the safety and activity of nivolumab induction and high-dose ipilimumab as an immunotherapeutic boost as a second-line treatment for patients with metastatic urothelial carcinoma.