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: Erectile dysfunction (ED) is a highly common sexual dysfunction of men but often undertreated as patients experience high treatment barriers. Aim: The aims of this study were to characterize patients with ED using an online prescription platforms (OPPs) and determine treatment barriers that might prevent patients from seeking care in conventional health care settings. Methods: Data from a German OPP were retrospectively analyzed with focus on patients suffering from ED with at least one online prescription of phosphodiesterase-5 (PDE5) inhibitors between May 2019 and November 2019. In addition, a voluntary questionnaire was used to assess additional social features and prior treatment barriers. Main Outcome Measure: The main outcome measures were the epidemiological data, prescription metadata, and follow-up questionnaires. Results: A total of 11,456 male patients received prescriptions via the OPP (mean age: 49 years [95% CI 46.92–47.45]). Patients lived mainly in rural areas (69%) and frequently sought prescriptions outside the average office times of German urologists (49%). From all patients that responded to a follow-up questionnaire (n = 242), the majority were employed full-time (81%), married (50%), and native German (94%); 63.5% had not used PDE5 inhibitors before. From all repeat users, 41% had received them from unreliable sources. Reasons to seek treatment via the OPP were convenience (48%), shame (23%), and lack of discretion (13%). Conclusion: In this first study, to epidemiologically characterize ED patients of an OPP, it was confirmed that inconvenience is a treatment barrier, along with shame and perceived lack of discretion. This is the first evidence that OPPs reduce treatment barriers and ease access for patients to the medical system.