Variant histologies of bladder cancer (BC) often present with advanced tumor stage and the status of perioperative therapy is unclear. Thereby, squamous cell carcinoma (SCC), adenocarcinoma (ADENO), and sarcomatoid urothelial carcinoma (SARCO) are the most frequent variants. Nectin-4 has emerged as a highly interesting target in BC and might guide therapeutic application of antibody–drug conjugates (ADC). We therefore aimed to investigate expression patterns and prognostic value of Nectin-4 in variant histologies of BC. A single-center retrospective analysis was conducted of patients who underwent radical cystectomy (RC) for BC and revealed variant histologies of BC in the final specimens. Immunohistochemical staining for Nectin-4 was performed on tissue microarrays with 59 SCC, 22 ADENO, and 24 SARCO, and Nectin-4 expression was scored using the histochemical scoring system (H-score). Overall survival (OS) and progression-free survival (PFS) was calculated by Kaplan–Meier method. Median expression of Nectin-4 was 150 (range 0–250) in SCC, 140.5 (range 30–275) in ADENO, and 10 (0–185) in SARCO, with significantly lower levels for SARCO compared to SCC or ADENO (p < 0.001). For SCC, ADENO or SARCO no differences regarding OS or PFS were observed based on Nectin-4 expression levels (p > 0.05). Multivariate analysis revealed nodal stage as an independent prognostic factor for OS and PFS and metastases for PFS but not Nectin-4 expression. In conclusion, Nectin-4 was not prognostic in histological subtypes of BC in our study cohort. However, the high expression of Nectin-4 in SCC and ADENO might guide future treatment with novel Nectin-4-directed ADCs and provide this high-risk patient collective with a new promising therapeutic option. Testing Nectin-4 expression as a biomarker should be considered in trials with SARCO, where low Nectin-4 expression has been observed.

Introduction/Objective: Contrast-enhanced ultrasound (CEUS) is a promising modality for differentiating benign and malignant lesions in various organs, including the testis. Testicular tumors, common in young men, are often treated with radical orchiectomy, which can have significant consequences. This study aimed to analyze CEUS parameters and their association with malignant testicular tumors. Materials and Methods: Between May 2009 and September 2020, 342 patients with suspected testicular lesions underwent CEUS at a tertiary referral center. Multiparametric ultrasound, including B-mode, Color Doppler, CEUS, and elastography, was performed. Exclusion criteria were the absence of a testicular lesion in the CEUS examination. Histological results, CEUS parameters, and elastography data were analyzed, and statistical correlations were evaluated using chi-square and Mann–Whitney U tests, with multivariate logistic regression for significant findings. Results: Of the 342 patients, 114 (33.3%) had suspicious CEUS findings, and 84 underwent surgical exploration. Malignancy was confirmed in 48 cases (57.1%). The sensitivity and specificity of CEUS for detecting malignancy were 93.8% and 85.2%, respectively. Contrast enhancement was observed in 93.3% of malignant tumors, but not statistically significant compared to benign lesions (p = 0.107). However, elastography revealed higher tissue stiffness in 77.8% of malignant tumors versus 41.0% in benign lesions (p = 0.009). Multivariate analysis indicated that tissue stiffness was significantly associated with malignancy (HR 8.29, 95%CI 1.26–54.58, p = 0.028). Conclusions: CEUS is a valuable tool for testicular lesion evaluation, with elastography showing strong potential in predicting malignancy through tissue stiffness. However, contrast enhancement and “wash-in/-out” were not reliable malignancy indicators. Further research is needed to standardize CEUS and elastography techniques for routine clinical use.

Immune checkpoint inhibitor (ICI) therapies have been established as the standard-of-care in various uro-oncological cancers. Immune-related adverse events (irAEs) are frequent, but their degree rarely leads to the discontinuation of immunotherapies. Unplanned permanent treatment discontinuation may negatively impact the outcomes of patients, but there are emerging data about a positive correlation between emergence of severe irAEs and therapeutic cancer responses. In this study, a retrospective analysis of patients treated for urothelial carcinoma (UC) with ICI-based immunotherapy was conducted. irAEs were classified according to the Common Terminology Criteria for Adverse Events (CTCAEs) and radiological responses according to the Response Evaluation Criteria In Solid Tumors (RECISTs). Out of 108 patients with metastatic urothelial cancer that underwent immunotherapy, 11 experienced a severe irAE that required permanent discontinuation of ICI therapy. The most frequent irAEs leading to discontinuation were hepatitis (n = 4), pneumonitis (n = 2), and gastritis or colitis (n = 2). Prior to discontinuation (R1), the radiological best response was complete remission (CR) in three patients, partial response (PR) in six, and stable disease (SD) in wo patients. After the discontinuation of ICI therapy (R2), the best responses were CR in six, PR in three, and SD in two patients. Following discontinuation, the majority of these patients showed a sustained treatment response, despite not receiving any cancer-specific treatment. The median time of response after discontinuation of ICI therapy was 26.0 (5.2–55.8) months. We propose accurate counseling and close follow-ups of patients following their discontinuation of ICI therapy due to irAEs, as responses can be durable and deep, and many patients do not require immediate subsequent therapies, even in urothelial cancer. More data are required to find predictors of the length of response to appropriately counsel patients.

Zusammenfassung: Laser haben ein umfangreiches Anwendungsspektrum in der endourologischen Therapie. Nicht nur in der Therapie von Steinen, auch in der Behandlung des benignen Prostatasyndroms (BPS) nimmt ihr Stellenwert immer weiter zu. Auf die endourologische Behandlung der BPS mit verschiedenen Laser-Techniken wird im weiteren Verlauf näher eingegangen. Dabei werden zuerst die physikalischen Unterschiede der einzelnen Laser erklärt, im weiteren Verlauf die Behandlungsmöglichkeiten an sich, die mit einem Laser durchgeführt werden können. Hauptaugenmerk soll auf dem konkreten Vergleich der Behandlungsmethoden vor allem im klinischen Kontext liegen. Insbesondere die OP-Dauer, Hospitalisierungsdauer, das Nachblutungsrisiko, die DK(Dauerkatheter)-Zeit, das Risiko eines Harnverhalts und das Risiko für postoperative Komplikationen wie retrograde Ejakulation, BH (Blasenhals)-Sklerose, HR (Harnröhren)-Striktur, Adenomrezidive sollen für die wichtigsten Methoden aufgeführt und miteinander verglichen werden. Dennoch liegt weiterhin die Verteilung von TURP zu Laser mit 30:1 zu Gunsten der TURP [1].