Radioligand treatment with [Lu]Lu-PSMA I&T in elderly Patients - Safety, efficacy, and prognostic factors for survival.

Purpose: We aimed to evaluate the safety and efficacy to explore predictors of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with [¹⁷⁷Lu]Lu-PSMA I&T in metastatic castration-resistant prostate cancer (mCRPC) patients aged ≥ 75 and explored baseline predictors of overall survival (OS).

Materials And Methods: 56 men (median age 78, range 75-95) were treated with RLT. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.

[Molecular Tumour Boards for Urological Tumours: Hope or Disappointment?].

In addition to the traditional, evidence-based, guideline-driven 'one-size-fits-all' treatment approach, personalised oncological therapy has been gaining increasing importance over the past decade. The central element in this process is a comprehensive molecular pathological analysis of the patient's tumour tissue, followed by interdisciplinary evaluation of the results and their translation into a patient-specific, therapeutic strategy within the framework of the molecular tumour board. These specialised molecular tumour boards are associated with substantial financial, time and personnel resources, as well as highly specialised expertise, and are therefore typically established only at university hospitals or major cancer centres.

Metastatic renal cell carcinoma: Synchronous vs. metachronous metastatic disease and its impact on cancer control in the IO-combination era-Real world experiences from a multi-institutional cohort.

Purpose: The association of metastatic timing (synchronous vs. metachronous) in metastatic renal cell carcinoma (mRCC) with survival outcomes in the immunooncology (IO) combination therapy era is not well understood to date. To assess progression-free survival (PFS) and overall survival (OS) based on the time to metastasis in mRCC patients treated with IO therapy combination therapies.

Propensity-Score-Based Comparative Analysis of Transperitoneal and Retroperitoneal Approaches in Open and Minimally Invasive Renal Surgery: Impact on Operative Outcomes.

Introduction: Renal cancer is among the ten most common cancers in western societies, with renal cell carcinoma (RCC) accounting for 95% of malignant renal neoplasms. Recent advances in surgical techniques and approaches have expanded treatment options, necessitating an evaluation of optimal approaches.

Methods: A retrospective, propensity-matched cohort with 814 patients (1999-2021) was conducted comparing open and minimally invasive (laparoscopic and robotic-assisted) nephrectomy and partial nephrectomy techniques, focusing on operative time, blood loss, hospital stay, complications, and perioperative complications.

Adjuvant Therapy with Pembrolizumab in Renal Cell Carcinoma: Real-World Experiences from a Retrospective, Multi-Institutional Cohort.

Introduction: Adjuvant pembrolizumab versus placebo significantly improved disease-free survival (DFS) in renal cell carcinoma (RCC) patients at high risk (HR) of recurrence following nephrectomy in KEYNOTE-564 trial (NCT03142334). The objective of this study was to evaluate efficacy and safety of adjuvant pembrolizumab in a real-world setting.

Methods: In this multicenter retrospective study, RCC patients receiving adjuvant pembrolizumab between 01/22 and 10/23 at seven tertiary referral centers were included.

An Analysis of Renal and Surgical Outcomes of Patients with and without Preoperative Ureteral Stenting before Nephron-Sparing Surgery for Renal Malignancies of Higher Complexity by Using a Propensity Score-Based Approach.

Introduction: This study aims to evaluate the impact of preoperative ureteral stenting on post-operative outcomes, especially the incidence of urinoma, in patients with complex renal tumours undergoing nephron-sparing surgery (NSS).

Methods: A retrospective analysis of 35 patients received preoperative ureteral stenting prior to NSS for complex tumours at the University Hospital of Würzburg between 2002 and 2021. A control group of 115 patients was established through 1:3 propensity score matching based on age, gender, T-stage, and RENAL score.

A Propensity Score-Based Comparison regarding Renal, Functional, and Surgical Outcome of Continent Cutaneous Urinary Diversions in Patients with Benign Chronic Bladder Diseases and Patients with Bladder Cancer.

Introduction: Continent cutaneous urinary diversion post-cystectomy is an established approach addressing both oncological and functional indications. However, there is a noticeable gap of evidence when it comes to comparing outcomes between these indications, especially concerning the technique of Mainz pouch I (MPI). This study aimed to close the gap by analyzing the long-term functional and renal outcomes of patients with MPI after cystectomy due to both benign and malign bladder pathologies.

Refluxing versus Non-Refluxing Ureteric Implantation in Continent Cutaneous Urinary Diversion: A Propensity-Scored Comparison regarding Long-Term Renal, Metabolic, and Functional Outcomes of Patients with Ileocecal Pouch.

Introduction: Studies comparing refluxing versus non-refluxing ureteric implantation in continent cutaneous urinary diversion (CCUD) are scarce and often characterized by heterogeneous study populations. This work therefore aimed at comparing both techniques regarding long-term outcomes in a propensity-scored approach.

Methods: We identified n = 19 patients, totaling n = 38 renal units (RU), who underwent CCUD surgery at our hospital out of a pool of 120 patients.

First-Line Immune Combination Therapies for Nonclear Cell Versus Clear Cell Metastatic Renal Cell Carcinoma: Real-World Multicenter Data From Germany.

Introduction: The aim was to compare treatment outcomes of clear cell metastatic renal cell carcinoma (ccmRCC) versus non-ccmRCC (nccmRCC) patients who received first-line immune combination therapies.

Materials And Methods: Within our retrospective multi-institutional consecutive database of eight tertiary-care centers, we identified mRCC patients treated with first-line immune combination therapies between 11/2017 and 12/2022. Using log-rank analysis and multivariable Cox regression, we tested for differences in overall survival (OS) and progression-free survival (PFS) of nccmRCC versus ccmRCC patients.

Metformin Regulates the miR-205/VEGFA Axis in Renal Cell Carcinoma Cells: Exploring a Clinical Synergism with Tyrosine Kinase Inhibitors.

Introduction: Metformin (MF) intake could be associated with a favorable outcome in sunitinib (SUT)- and axitinib (AX)-treated clear cell renal cell carcinoma (ccRCC) patients. Functionally, MF induces miR-205, a microRNA serving as a tumor suppressor in several cancers.

Methods: Real-time quantitative PCR, viability assays, and Western blotting analyzed MF and SUT/AX effects in RCC4 and 786-O cells.

[New forms of immunotherapy in uro-oncology : HLA-independent therapeutic approaches with bispecific antibodies and CAR T cells].

Immunotherapies using bispecific antibodies and chimeric antigen receptor (CAR) T cells do not depend on previous activation of T cells by the human leukocyte antigen (HLA) system. These HLA-independent approaches displayed groundbreaking clinical results in hematological malignancies-leading to drug approvals for diseases like acute lymphocytic leukemia (ALL), B-cell Non-Hodgkin's lymphoma and multiple myeloma. Currently, several phase I/II trials are investigating the transferability of these results to solid tumors-especially prostate cancer.

Critical Evaluation of a microRNA-Based Risk Classifier Predicting Cancer-Specific Survival in Renal Cell Carcinoma with Tumor Thrombus of the Inferior Vena Cava.

(1) Background: Clear cell renal cell carcinoma extending into the inferior vena cava (ccRCC) represents a clinical high-risk setting. However, there is substantial heterogeneity within this patient subgroup regarding survival outcomes. Previously, members of our group developed a microRNA(miR)-based risk classifier-containing miR-21-5p, miR-126-3p and miR-221-3p expression-which significantly predicted the cancer-specific survival (CSS) of ccRCC patients.

Clinical validation and assessment of feasibility of volumetric absorptive microsampling (VAMS) for monitoring of nilotinib, cabozantinib, dabrafenib, trametinib, and ruxolitinib.

Volumetric absorptive microsampling (VAMS) has emerged as a minimally invasive alternative to conventional sampling. However, the applicability of VAMS must be investigated clinically. Therefore, the feasibility of at-home sampling was investigated for the kinase inhibitors nilotinib, cabozantinib, dabrafenib, trametinib and ruxolitinib and evaluated regarding the acceptance of at-home microsampling, sample quality of at-home VAMS and incurred sample stability.

Development and preclinical evaluation of a cable-clamp fixation device for a disrupted pubic symphysis.

Background: Traumatic separation of the pubic symphysis can destabilize the pelvis and require surgical fixation to reduce symphyseal gapping. The traditional approach involves open reduction and the implantation of a steel symphyseal plate (SP) on the pubic bone to hold the reposition. Despite its widespread use, SP-fixation is often associated with implant failure caused by screw loosening or breakage.

Tin-filtered 100 kV Ultra-low-dose Abdominal CT for Calculi Detection in the Urinary Tract: A Comparative Study of 510 Cases.

Objectives: For detection of urinary calculi, unenhanced low-dose computed tomography is the method of choice, outperforming radiography and ultrasound. This retrospective monocentric study aims to compare a clinically established, dedicated low-dose imaging protocol for detection of urinary calculi with an ultra-low-dose protocol employing tin prefiltration at a standardized tube voltage of 100 kVp.

Methods: Two study arms included a total of 510 cases.

Comparison of a newly developed high performance liquid chromatography method with diode array detection to a liquid chromatography tandem mass spectrometry method for the quantification of cabozantinib, dabrafenib, nilotinib and osimertinib in human serum - Application to therapeutic drug monitoring.

Objective: Liquid chromatography tandem mass spectrometry (LC-MS/MS) is a highly selective and sensitive method for the quantification of kinase inhibitors, yet not widely available in clinical routine for therapeutic drug monitoring (TDM). To provide a more accessible alternative, a high-performance liquid chromatography method with ultraviolet/diode array detection (HPLC-UV/DAD) to quantify cabozantinib, dabrafenib, nilotinib and osimertinib, was developed and validated. Results were compared to LC-MS/MS.

C-reactive protein flare predicts response to anti-PD-(L)1 immune checkpoint blockade in metastatic urothelial carcinoma.

Purpose: Robust biomarkers to predict response to immune checkpoint blockade (ICB) in metastatic urothelial carcinoma (mUC) are still in demand. Recently, early C-reactive protein (CRP) kinetics and especially the novel CRP flare-response phenomenon has been associated with immunotherapy response.

Methods: We conducted a multicentre observational study comprising 154 patients with mUC treated with ICB to evaluate the predictive value of a previously described on-treatment CRP kinetics: CRP flare responders (at least doubling of baseline CRP within the first month after initiation of ICB followed by a decline below baseline within three months), CRP responders (decline in baseline CRP by ≥ 30% within three months without a prior flare) and the remaining patients as CRP non-responders.

Acute systemic knockdown of is lethal and causes pancreatic destruction in shRNA transgenic mice.

The notion that macroautophagy/autophagy is a potentially attractive therapeutic target for a variety of diseases, including cancer, largely stems from pre-clinical mouse studies. Most of these examine the effects of irreversible and organ confined autophagy deletion using site specific -loxP recombination of the essential autophagy regulating genes or . Model systems with the ability to impair autophagy systemically and reversibly at all disease stages would allow a more realistic approach to evaluate the consequences of authophagy inhibition as a therapeutic concept and its potential side effects.

Angiogenesis as Therapeutic Target in Metastatic Prostate Cancer - Narrowing the Gap Between Bench and Bedside.

Angiogenesis in metastatic castration-resistant prostate cancer (mCRPC) has been extensively investigated as a promising druggable biological process. Nonetheless, targeting angiogenesis has failed to impact overall survival (OS) in patients with mCRPC despite promising preclinical and early clinical data. This discrepancy prompted a literature review highlighting the tumor heterogeneity and biological context of Prostate Cancer (PCa).

Volumetric absorptive microsampling (VAMS) for the quantification of ten kinase inhibitors and determination of their in vitro VAMS-to-plasma ratio.

Personalized dosing of kinase inhibitors (KI) might be beneficial in oral anti-cancer therapy to overcome individual pharmacokinetic variability. Volumetric absorptive microsampling (VAMS) has emerged as an attractive alternative compared to conventional invasive sampling methods enabling remote and frequent specimen collection. Therefore, an LC-MS/MS VAMS method was developed and validated to monitor drug exposure of ten KI from 20 µL dried capillary blood.