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.

Background: [⁶⁸Ga]Ga-FAPI-46 is a novel positron emission tomography (PET) ligand that targets fibroblast activation protein (FAP) expression as FAP inhibitor (FAPI) and could already show promising results in several tumor entities. It could be demonstrated that an increased FAP expression correlates with tumor aggressivity in urothelial carcinoma (UC). Given the limited value of [¹⁸F]FDG in UC, [⁶⁸Ga]Ga-FAPI-46 could add diagnostic information in staging and response assessment in UC. We present the first data of [⁶⁸Ga]Ga-FAPI-46 PET imaging in a pilot cohort of UC patients evaluating uptake characteristics in metastases and primary tumors. Methods: Fifteen patients with UC prior to or after local treatment underwent [⁶⁸Ga]Ga-FAPI-46 PET/CT imaging for detection of metastatic spread. We compared the biodistribution in non-affected organs and tumor uptake of UC lesions by standard uptake value measurements (SUV_mean and SUV_max). Additionally, metastatic sites on PET were compared to its morphological correlate on contrast-enhanced computed tomography (CT). Results: Overall, 64 tumor sites were detected on PET and/or CT. The highest uptake intensity was noted at the primary site (SUV_max 20.8 (range, 8.1–27.8)) followed by lymph node metastases (SUV_max 10.6 (range, 4.7–29.1)). In 4/15 (26.7%) patients there were [⁶⁸Ga]Ga-FAPI-46-positive lesions that were missed on standard routine CT imaging. On the other hand, 2/15 patients had suspicious prominent bipulmonary nodules as well as pelvic lymph nodes previously rated as suspicious for metastatic spread on CT, but without increased FAPI expression; here histopathology excluded malignancy. Conclusion: [⁶⁸Ga]Ga-FAPI-46 PET shows distinctly elevated uptake in UC lesions. Therefore, the tracer has potential as a promising new biomarker in metastatic UC patients, as [⁶⁸Ga]Ga-FAPI-46 PET might improve detection of metastatic sites compared to CT alone. These findings highly emphasize larger studies investigating FAPI imaging in UC patients.

Background: This study investigates the effect of classical music, music of patients’ own choice, or no music on pain reduction during elective cystoscopy. Objectives: The aim of the study was to describe the effect of listening to classical music, music of patients’ own choice, or no music on patient’s pain and satisfaction rates when carrying out an elective cystoscopy and the effect on the assessment capability of the performing urologist. Design, Setting, and Participants: This randomized trial included 127 patients undergoing elective cystoscopy at the Urological Department of the University Clinic of Munich between June 2019 and March 2020. Outcome Measurements and Statistical Analysis: Patients were assigned randomly to 3 groups: group I: listening to standardized classical music (n = 35), group II: listening to music according to the patients’ choice (n = 34), and control group III: no music (n = 44). Prior to cystoscopy, anxiety levels were assessed by the Beck Anxiety Inventory (BAI). The Visual Analog Scale (VAS, range 1–100) was used for a self-assessment of pain, discomfort, and satisfaction. Statistical analysis was done with Spearman’s rank correlation and t-tests. Results and Limitations: The median age was 63 (range 27–91) years. The duration of cystoscopy was 5.7 (1–30) min. Patients had undergone a median of 2.3 cystoscopies in the past. Between giving informed consent and cystoscopy, patients had to wait for a median of 64 (0–260) min. The median VAS pain score was significantly lower in group I at 1.7 and group II at 2.3 versus 5.2 in the control group III (p < 0.001). The control group III had significantly worse pain and patient satisfaction rates compared with groups I and II. Group I had a significant lower VAS pain score than groups II and III (p < 0.001). Classical music also increased the assessment capability of the preforming urologist. Conclusions: Listening to music during elective cystoscopy significantly reduces pain and distress and leads to higher patient and surgeon satisfaction. We recommend listening to classical music or music chosen by the patients during outpatient flexible/rigid cystoscopy in daily clinical routine. Patient Summary: In this study, we found that patients who listened to classical music or music of their own choice while undergoing a cystoscopy showed significant reduction of pain and distress.

Objectives: Patients’ oncological outcome after radical cystectomy (RC) due to urothelial carcinoma of the urinary bladder (UCB) is always up for debate. There is accumulating evidence on the influence of routine blood parameters. We aimed to identify reasonable and easy-to-detect biomarkers, such as preoperative C-reactive protein (CRP) and hemoglobin (Hb) levels, as predictors of overall survival (OS) and cancer-specific survival (CSS) in patients undergoing RC for UCB. Materials and Methods: This is a large single-center study in which both preoperative CRP and Hb levels were available in 1,043 patients undergoing RC for UCB from 2004 to 2018 with a median follow-up time of 22 months (mean 38, max. 170). We used the Kaplan-Meier method, log-rank test, and Cox regression models for assessment of OS and CSS. Using our data, we validated an existing outcome prediction score (TNR-C). Results: Median CRP level was 0.5 mg/dL (IQR 0.2–1.4), and median Hb level was 13.4 g/dL (IQR 11.9–14.7). We found that patients with CRP values above the median reached a significantly lower median survival than those with CRP values below the median (23 vs. 83 months, p < 0.001). The TNR-C score was successfully validated, and we discriminated between 3 risk groups (5-year CSS: 76, 40, and 16% for low, intermediate, and high risk, respectively). We observed a similar outcome for patients with a Hb level below the median: CSS was significantly poorer than with Hb levels above the median (median CSS 27 vs. 91 months, p < 0.001). Multivariant analysis showed CRP and Hb levels to be independent prognostic parameters for CSS and OS. Conclusions: We found elevated preoperative CRP levels and decreased Hb levels to be independent prognostic factors indicating an unfavorable outcome in patients undergoing RC for UCB and were able to validate the TNR-C score in a large patient cohort. We propose using these routine biomarkers for individual risk stratification and optimization of therapeutic strategies in patients undergoing RC for UCB.

Background: Radical cystectomy (RC) with the formation of an ileal orthotopic neobladder (ONB) may adversely affect long-term health-related quality of life (HRQOL). An advanced age at the time of ONB construction could further exacerbate the decline in HRQOL. This study aims to establish an evidence-based age threshold at the time of RC with ONB, beyond which a significant deterioration in HRQOL is observed. Methods: We retrospectively analyzed all bladder cancer patients in our department between 2013 and 2022 that fulfilled the EORTC-QLQ-C30 questionnaire preoperatively, as well as at 3 and 12 months after RC with ONB. Patients receiving neoadjuvant or adjuvant chemotherapy or benign/palliative RC were excluded. Results: Overall, 120 patients (81% males) with a mean age of 66 ± 9.6 years underwent RC with ONB and fulfilled the selection criteria. The Global Health Status (GHS) of the EORTC-QLQ-C30 was 64 ± 23 preoperatively, was 64 ± 20 three months postoperatively, and was 68 ± 23 twelve months postoperatively. Overall, 80 (67%) patients presented an increase in GHS at twelve months compared to their preoperative values. The perioperative complications did not differ between patients with decreased and increased GHS. Patients with increased GHS had values of 58 ± 24 preoperatively, 67 ± 19 at 3 months, and 77 ± 16 at 12 months. Patients with decreased GHS had values of 76 ± 16 preoperatively, 57 ± 21 at 3 months, and 50 ± 25 at 12 months. Using ROC analyses with Youden’s index, we defined a threshold of 70 years, after which RC with ONB may lead to worse GHS twelve months postoperatively. Worse continence outcomes were the only perioperative and long-term parameters that predicted worse HRQOL in elderly patients. Conclusions: Based on HRQOL, we suggest that RC with an ileal conduit as a urinary diversion should be recommended in patients older than 70 years.

Purpose: With a median age at diagnosis of 73 years, bladder cancer has the highest median age of all cancers. Age alone seems to be an independent risk factor for developing the disease with peak age advancing into the range of 85 years. As demographic changes will lead to an ever more aging population in western countries, incidence of advanced age malignancies will rise. We, therefore, analyzed a contemporary radical cystectomy (RC) series at a single high-volume center on patients undergoing RC for urothelial carcinoma of the bladder (UCB). We aim to evaluate the feasibility of RC in the oldest-old patient cohort by assessing perioperative complications and long-term outcome. Materials and Methods: We retrospectively analyzed data of 1,278 consecutive patients who underwent RC for UCB at our tertiary referral center between 2004 and 2019. A total of 408 patients were aged 75–97 years at the time of RC and were further divided into 2 groups: 75–84 years of age (group 1) and ≥85 years of age (group 2). Median follow-up was 23 months. Outcome was analyzed using the χ² test, Mann-Whitney U test, Kaplan-Meier method, and log-rank test. Results: Perioperative Clavien-Dindo grade ≥III complications were seen in 25.1% (92/366) of group 1 patients and 35.7% (15/42) of group 2 patients (p = 0.073). Thirty- and 90-day mortality was 3.3 and 8.7% in group 1 and 4.8 and 14.3% in group 2 (p = 0.617 and p = 0.242, respectively). Three-year overall survival was 54.6% in group 1 and 31.3% in group 2 (p = 0.03). Three-year cancer-specific survival was 64.8% in group 1 and 38.8% in group 2 (p = 0.037). Recurrence-free survival was 105 months in group 1 and 12 months in group 2 (p = 0.039). Conclusion:In light of increasing life expectancy in western nations, we sought to evaluate the impact of age in a large series of elderly patients undergoing RC for UCB. We found that RC offers acceptable perioperative complication rates in the oldest-old patient cohort (≥85 years). Therefore, RC for UCB can be offered as a viable treatment option even in the oldest patients.