The extent of lymph node dissection (LND) at the time of radical cystectomy (RC) for bladder cancer (BC) may affect oncologic outcomes. We present updated long-term data from a prospective, multicenter, phase 3 trial involving patients with locally resectable, high-risk T1 grade 3 or muscle-invasive urothelial BC (T2-T4a M0) without neoadjuvant treatment (trial LEA AUO AB 25/02; NCT01215071). A total of 401 patients were randomly assigned 1:1 to either standard LND (sLND: obturator, internal, and external iliac nodes) or extended LND (eLND), which also included the deep obturator, common iliac, presacral, paracaval, interaortocaval, and para-aortic nodes up to the inferior mesenteric artery. Median follow-up for patients alive without disease recurrence was 58.4 mo. The primary endpoint was recurrence-free survival (RFS). Overall survival (OS) and cancer-specific survival (CSS) were secondary endpoints. eLND failed to show superiority over sLND for RFS (5-yr rate: 68% vs 60%; hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.56-1.14; p = 0.2) and OS (5-yr rate: 57% vs 51%; HR 0.84, 95% CI 0.64-1.12; p = 0.2). The CSS rate was significantly higher in the eLND arm (5-yr rate: 76% vs 65%; HR 0.65, 95% CI 0.43-0.96; p = 0.031), which is clinically meaningful. With long-term follow-up, this randomized controlled trial remains negative for the primary endpoint of RFS, but was positive for CSS. Therefore, meticulous LND using at least a standard template remains the recommended surgical approach for patients undergoing RC for BC.

Die Bevölkerungsentwicklung in Deutschland ist für die kommenden Jahrzehnte vorgezeichnet. Bis zum Jahr 2030 wird die Anzahl derer in der Altersgruppe 65+ um rund ein Drittel auf 22,3 Mio. Personen angestiegen sein. Die Zunahme an Lebensjahren geht häufig auch mit einer Zunahme an (urologischen) Gesundheitsstörungen einher. Vor allem beim alternden Mann kommt die Diskussion um Überdiagnostik und Übertherapie in der Vorsorge zum Tragen. Bei der Therapie des Prostatakarzinoms spielt das Konzept der aktiven Überwachung eine zunehmend größere Rolle. Ein großer Teil der älteren und alten Männer mit Prostatakarzinom scheint nicht (mehr) von einer direkten kurativen Therapie zu profitieren.

Background: To evaluate whether stone extraction with a loop ureteral catheter (LUC) in distal ureteral stones is associated with a higher frequency of ureteral strictures compared to treatment with primary ureteroscopic stone removal (p-URS) or ureteroscopic laser lithotripsy (I-URS). Methods: Five hundred and forty-seven consecutive patients were primarily endourologically treated for distal ureteral stones in our department between 2005 and 2019 and included in the study protocol. Data was retrospectively obtained from the patients' charts and medical reports as well as from office-based urologists. Data analysis was performed using Fisher's exact test, Mann-Whitney test or Student's t-test as appropriate. A level of P<0.05 was assigned statistical significance. Results: Four hundred and twelve patients were treated by URS (p-URS n=304, 1-URS n=108) and another 135 by LUC stone extraction. Median follow-up was 41 [2-159] months. There was no difference between the groups concerning age, gender, proportion of patients with ureteral stenting, operating time, hospitalization or readmission rates. The number of ureteric strictures was small in all procedures [n=3 (1.0%) in p-URS, n=2 (1.9%) in 1-URS and n=2 (1.5%) in LUC] and there was no difference between the groups concerning this serious complication (p-URS vs. LUC: P=0.6465; I-URS vs. LUC: P=0.9999). Conclusions: In small distal stones, LUC stone extraction still is an alternative to URS procedures in stone management with comparable results concerning postinterventional ureteral strictures. In experienced hands, it still has its value in accurately selected patients.

To compare clinical outcome and quality of life (QoL) in octogenarian patients with muscle-invasive urothelial carcinoma (MIBC) either treated by radical cystectomy (RC) or transurethral resection of the tumor (TURBT). We identified octogenarian patients with MIBC in our institutions since 2005. Clinical treatment outcomes and QoL were analyzed. Uni- and multivariable Cox regression analyses, two-tailed Wilcoxon test, Mann–Whitney test and Fisher’s exact test were assessed as appropriate. QoL was evaluated using FACT-G (Functional Assessment of Cancer Therapy-General) questionnaire. 143 patients were identified (RC: 51 cases, TURBT: 92 cases). Mean follow-up was 14 months (0–100 months). Median overall survival (OS) was 12 months in the RC group and 7 months in the TURBT group. TURBT and low preoperative hemoglobin were independent risk factors for reduced cancer-specific survival (CSS) (TURBT: p = 0.019, Hb: p = 0.008) and OS (TURBT: p = 0.026, Hb: p = 0.013) in multivariable analyses. Baseline QoL was low throughout the whole cohort. There was no difference in baseline FACT-G scoring comparing RC and TURBT (FACT-G total score (median): RC 43.7/108 vs. TURBT 44.0/108, p = 0.7144). Increased FACT-G questionnaire scoring was assessed for RC patients (median percentage score change RC 22.9%, TURBT 2.3%, p < 0.0001). RC and TURBT are feasible treatment options for MIBC in octogenarian patients. In our cohort, RC was associated with increased CSS, OS and QoL. QoL in general was low throughout the whole cohort. Interdisciplinary decision-making has to be improved for these critically ill patients.

In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.

Das metastasierte Urothelkarzinom ist eine Erkrankung mit ungünstiger Prognose. Jahrzehntelang war eine Chemotherapie die einzige Behandlungsoption. Als Referenzbehandlung gilt die polychemotherapeutische Behandlung nach dem MVAC-Schema (Methotrexat, Vinblastin, Doxorubicin und Cisplatin), mit einem progressionsfreien Überleben von 10,0 Monaten und einem Gesamtüberleben von 12,5 Monaten. Cisplatin haltige Chemotherapien sind nach wie vor wichtiger Bestandteil der systemischen Behandlung dieser seltenen Erkrankung. Als Alternative zur Chemotherapie gilt heute die Immuntherapie. Ihr Einsatz in der Erst- und Zweitlinientherapie war ein großer evolutionärer Schritt der Systemtherapie des metastasierten Urothelkarzinoms. Das vorliegenden Kapitel ist eine Zusammenfassung über die notwendigen Voraussetzungen der Behandlung, Behandlungsdetails und Nebenwirkungsspektren aktueller Substanzen in der systemischen Therapie, sowie der Stellenwert operativer Optionen bei oligometastasierter Erkrankung.

Introduction: The aim of the study is to compare length of hospital stay, transfusion rates, and re-intervention rates during hospitalization for transurethral resection of the prostate (TUR-P), open prostatectomy (OP), and laser therapy (LT) for surgical treatment of benign prostatic obstruction (BPO). Methods: URO-Cert is an organization, in which clinical data of prostatic diseases from 2 university, 19 public, and 3 private hospitals and 270 office-based urologists are collected in order to document treatment quality. Data on diagnostics, therapy, and course of disease are recorded web based. The analysis includes datasets from 2005 to 2017. Results: Of 10,420 patients, 8,389 were treated with TUR-P, 1,334 with OP, and 697 with LT. Median length of hospital stay was 6 days (IQR: 4–7) for TUR-P, 9 days (IQR: 7–11) for OP, and 5 days (IQR: 4–6) for LT (p < 0.001). Risk for a hospital stay ≥7 days was higher for OP versus TUR-P (OR: 7.25; 95% CI = 6.27–8.36; p < 0.001) and LT (OR: 17.89; 95% CI = 14.12–22.65; p < 0.001) and higher for TUR-P versus LT (OR: 2.47; 95% CI = 2.03–3.01; p < 0.001). OP had a significantly higher risk for transfusions than TUR-P (OR: 2.44; 95% CI = 1.74–3.41; p < 0.001) and LT (OR: 3.32; 95% CI = 1.56–7.01; p < 0.001). Transfusion rates were not significantly different between TUR-P and LT (OR: 1.36; 95% CI = 0.66–2.79; p = 0.51). Risk of re-intervention was not different between all 3 approaches. Conclusion: OP was associated with higher transfusion rates and longer hospital stay than TUR-P and LT. Risk of transfusion was not different between TUR-P and LT, but TUR-P was inferior to LT concerning length of hospital stay. Re-intervention rates during hospitalization did not differ between the groups.

Metastatic renal cell carcinoma (RCC) remains largely incurable. Up to 30% of patients show metastasis at the time of the initial diagnosis. Prognostic criteria developed by the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium) and MSKCC (Memorial Sloan Kettering Cancer Center) are used to classify patients based on certain pretreatment factors. The prognosis of patients with metastatic disease varies depending on these risk factors. Anti-angiogenic agents targeting the vascular endothelial growth factor (VEGF) and its receptors are standard treatments based on improved clinical outcomes in randomized phase III trials. Standard of care therapies now include multitargeted tyrosine kinase inhibitors (TKIs) such as sunitinib, axitinib, pazopanib, and cabozantinib, as well as the mTOR inhibitors temsirolimus and everolimus. Tumor-associated PD-L1 expression has been detected in RCC and is associated with a worse prognosis. Immune checkpoint inhibitors such as the PD-1 inhibitor nivolumab have shown promising results in treatment of the metastatic disease. Future developments including novel combinations and attempts to find the optimal position of immunotherapy in the disease pathway are subject of ongoing clinical trials.

Urachal cancer (UrC) is a rare but aggressive malignancy often diagnosed in advanced stages requiring systemic treatment. Although cytotoxic chemotherapy is of limited effectiveness, prospective clinical studies can hardly be conducted. Targeted therapeutic treatment approaches and potentially immunotherapy based on a biological rationale may provide an alternative strategy. We therefore subjected 70 urachal adenocarcinomas to targeted next-generation sequencing, conducted in situ and immunohistochemical analyses (including PD-L1 and DNA mismatch repair proteins [MMR]) and evaluated the microsatellite instability (MSI) status. The analytical findings were correlated with clinicopathological and outcome data and Kaplan-Meier and univariable/multivariable Cox regression analyses were performed. The patients had a mean age of 50 years, 66% were male and a 5-year overall survival (OS) of 58% and recurrence-free survival (RFS) of 45% was detected. Sequence variations were observed in TP53 (66%), KRAS (21%), BRAF (4%), PIK3CA (4%), FGFR1 (1%), MET (1%), NRAS (1%), and PDGFRA (1%). Gene amplifications were found in EGFR (5%), ERBB2 (2%), and MET (2%). We detected no evidence of MMR-deficiency (MMR-d)/MSI-high (MSI-h), whereas 10 of 63 cases (16%) expressed PD-L1. Therefore, anti-PD-1/PD-L1 immunotherapy approaches might be tested in UrC. Importantly, we found aberrations in intracellular signal transduction pathways (RAS/RAF/PI3K) in 31% of UrCs with potential implications for anti-EGFR therapy. Less frequent potentially actionable genetic alterations were additionally detected in ERBB2 (HER2), MET, FGFR1, and PDGFRA. The molecular profile strengthens the notion that UrC is a distinct entity on the genomic level with closer resemblance to colorectal than to bladder cancer.

BACKGROUND:The extent of lymph node dissection (LND) in bladder cancer (BCa) patients at the time of radical cystectomy may affect oncologic outcome. OBJECTIVE:To evaluate whether extended versus limited LND prolongs recurrence-free survival (RFS). DESIGN, SETTING, AND PARTICIPANTS:Prospective, multicenter, phase-III trial patients with locally resectable T1G3 or muscle-invasive urothelial BCa (T2-T4aM0). INTERVENTION:Randomization to limited (obturator, and internal and external iliac nodes) versus extended LND (in addition, deep obturator, common iliac, presacral, paracaval, interaortocaval, and para-aortal nodes up to the inferior mesenteric artery). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:The primary endpoint was RFS. Secondary endpoints included cancer-specific survival (CSS), overall survival (OS), and complications. The trial was designed to show 15% advantage of 5-yr RFS by extended LND. RESULTS AND LIMITATIONS:In total, 401 patients were randomized from February 2006 to August 2010 (203 limited, 198 extended). The median number of dissected nodes was 19 in the limited and 31 in the extended arm. Extended LND failed to show superiority over limited LND with regard to RFS (5-yr RFS 65% vs 59%; hazard ratio [HR]=0.84 [95% confidence interval 0.58-1.22]; p=0.36), CSS (5-yr CSS 76% vs 65%; HR=0.70; p=0.10), and OS (5-yr OS 59% vs 50%; HR=0.78; p=0.12). Clavien grade ≥3 lymphoceles were more frequently reported in the extended LND group within 90d after surgery. Inclusion of T1G3 tumors may have contributed to the negative study result. CONCLUSIONS:Extended LND failed to show a significant advantage over limited LND in RFS, CSS, and OS. A larger trial is required to determine whether extended compared with limited LND leads to a small, but clinically relevant, survival difference (ClinicalTrials.gov NCT01215071). PATIENT SUMMARY:In this study, we investigated the outcome in bladder cancer patients undergoing cystectomy based on the anatomic extent of lymph node resection. We found that extended removal of lymph nodes did not reduce the rate of tumor recurrence in the expected range.

Zusammenfassung Einleitung: Die spezifische Lebensqualität (LQ) transidenter Menschen ist bislang unzureichend untersucht worden, zudem existiert bislang kein Messverfahren zur Erfassung der transidentitätsspezifischen LQ. Forschungsziele: Ziel der Studie war es, das Essener Transidentität Lebensqualitäts-Inventar (ETLI), bestehend aus 30 Items, zu entwickeln und zu validieren. Methoden: Bei 158 Mann-zu-Frau (MzF) transidenten Personen wurden neben dem ETLI Instrumente zur Erfassung von LQ, sozialer Unterstützung, individueller Ressourcen und psychischer Belastung eingesetzt. Es wurde eine explorative Faktorenanalyse durchgeführt. Ergebnisse: Mittels der explorativen Faktorenanalyse wurden die vier Dimensionen psychische, körperliche und soziale LQ sowie LQ durch Offenheit identifiziert. Die Subskalen zeigten eine gute Reliabilität mit Werten von Cronbachs α zwischen α = .75 und α = .89, die Gesamtreliabilität betrug α = .89. Positive Korrelationen des ETLI mit generischer LQ und Ressourcen sowie negative Korrelationen mit psychischer Belastung weisen auf eine sehr gute Konstruktvalidität hin. Schlussfolgerung: Das ETLI als Instrument zur Erfassung der transidentitätsspezifischen LQ stellt eine wichtige Ergänzung zu Messinstrumenten der generischen LQ dar. Es kann im Forschungs- und Versorgungskontext sowie bei der retrospektiven Evaluation von Veränderungen der LQ und bei der Therapieplanung zum Einsatz kommen.

PURPOSE:To evaluate diagnostic accuracy of integrated 68Gallium labelled prostate-specific membrane antigen (68Ga-PSMA)-11 positron emission tomography (PET)/MRI in patients with primary prostate cancer (PCa) as compared to multi-parametric MRI.MATERIAL AND METHODS:A total of 22 patients with recently diagnosed primary PCa underwent clinically indicated 68Ga-PSMA-11 PET/CT for initial staging followed by integrated 68Ga-PSMA-11 PET/MRI. Images of multi-parametric magnetic resonance imaging (mpMRI), PET and PET/MRI were evaluated separately by applying Prostate Imaging Reporting and Data System (PIRADSv2) for mpMRI and a 5-point Likert scale for PET and PET/MRI. Results were compared with pathology reports of biopsy or resection. Statistical analyses including receiver operating characteristics analysis were performed to compare the diagnostic performance of mpMRI, PET and PET/MRI.RESULTS:PET and integrated PET/MRI demonstrated a higher diagnostic accuracy than mpMRI (area under the curve: mpMRI: 0.679, PET and PET/MRI: 0.951). The proportion of equivocal results (PIRADS 3 and Likert 3) was considerably higher in mpMRI than in PET and PET/MRI. In a notable proportion of equivocal PIRADS results, PET led to a correct shift towards higher suspicion of malignancy and enabled correct lesion classification.CONCLUSION:Integrated 68Ga-PSMA-11 PET/MRI demonstrates higher diagnostic accuracy than mpMRI and is particularly valuable in tumours with equivocal results from PIRADS classification.

Introduction: Research investigating the specific aspects of quality of life (QoL) of transgender people is scarce. Furthermore, no instruments for the assessment of transgender-specific QoL exist. Objectives: The aim of the study was the development and validation of the Essen Transgender Quality of Life Inventory consisting of 30 items. Methods: A total of 158 male-to-female transgender persons completed the ETLI questionnaire and instruments for the assessment of QoL, social support, individual resources and psychological stress. An exploratory factor analysis was performed. Results: The exploratory factor analysis revealed the following four dimensions: mental, physical and social QoL, and QoL through openness. Reliability analyses showed good internal consistencies for the four subscales with values between Cronbachs alpha=.75 and alpha=.89. Additionally, there was a good overall reliability of a=.89. Positive correlations of the ETLI with generic QoL and psychosocial resources and negative correlations with measures of psychological strain indicated very good construct validity. Conclusion: As an instrument for the assessment of transgender-specific QoL, the ETLI complements generic QoL questionnaires. Its application can be recommended for research as well as for clinical care contexts. It can be used to evaluate changes in QoL throughout the transitional process or to identify a need for psychotherapy or counseling.