Genomic landscape and evolution of metastatic chromophobe renal cell carcinoma

Chromophobe renal cell carcinoma (chRCC) typically shows ~7 chromosome losses (1, 2, 6, 10, 13, 17, and 21) and ~31 exonic somatic mutations, yet carries ~5%-10% metastatic incidence. Since extensive chromosomal losses can generate proteotoxic stress and compromise cellular proliferation, it is intriguing how chRCC, a tumor with extensive chromosome losses and a low number of somatic mutations, can develop lethal metastases. Genomic features distinguishing metastatic from nonmetastatic chRCC are unknown. An integrated approach, including whole-genome sequencing (WGS), targeted ultradeep cancer gene sequencing, and chromosome analyses (FACETS, OncoScan, and FISH), was performed on 79 chRCC patients including 38 metastatic (M-chRCC) cases. We demonstrate that TP53 mutations (58%), PTEN mutations (24%), and imbalanced chromosome duplication (ICD, duplication of ≥ 3 chromosomes) (25%) were enriched in M-chRCC. Reconstruction of the subclonal composition of paired primary-metastatic chRCC tumors supports the role of TP53, PTEN, and ICD in metastatic evolution. Finally, the presence of these 3 genomic features in primary tumors of both The Cancer Genome Atlas kidney chromophobe (KICH) (n = 64) and M-chRCC (n = 35) cohorts was associated with worse survival. In summary, our study provides genomic insights into the metastatic progression of chRCC and identifies TP53 mutations, PTEN mutations, and ICD as high-risk features

Confronting hidden COVID-19 burden: a telemedical solution for elective urological outpatient clinics

Maintaining high-quality care for urological patients is a challenge during and after the Coronavirus disease 2019 (COVID-19) pandemic. We observe an increasing volume of postponed elective visits at our tertiary care hospital, holding the risk for deterioration of non-emergency disease conditions. As it is unclear for how long the pandemic will last, we propose to implement telehealth as a solution to provide regular symptom monitoring compatible with social distancing guidelines during the pandemic and beyond. Telemedical assessment and prioritizing of high-risk patients for individual consults at outpatient services will have to be aligned with available outpatient capacity and local outbreak severity

Gender Bias in Urology: How Do Patients Really Choose Their Urologist?

Purpose: The present study aimed to investigate the influence of patients’ and urologists’ gender when choosing a urologist. With rising population diversity through immigration and generational differences, patient-centered healthcare has recently moved to the focus of European healthcare systems. As healthcare in urology often concentrates on sensitive topics, and often involves gender-specific diseases, research on the influence of gender on decision-making processes is of high importance. Understanding influence of gender on patients’ choices in real life would provide patients, and physicians alike, with the means to provide better resources to achieve greater satisfaction from visits to a urologist. Patients and Methods: A questionnaire was prepared, and patients at our tertiary referral center were given the opportunity to voluntarily participate in our survey. We collected questionnaires from 1012 patients during their visits from June 2021 to October 2021. Results: Patients were divided into groups according to their gender: male (n=763), female (n=246), and non-binary (n=3). Our patient cohort consisted of more men than women (75% vs 24%), with only three patients identifying as non-binary. Irrespective of the patients’ own gender, patients preferred a male urologist when problems were considered embarrassing, limiting daily activities, or when worrisome. When problems were considered painful, all patients preferred a female urologist. When patients had had a previous positive experience with a female or male urologist, they preferred to be treated by a female or male urologist, respectively. Overall, 65% of patients stated a gender preference for at least one given situation, or consultation scenario. Conclusion: As the majority of our patients stated a gender preference, urological departments should be considerate of potential patients’ preferences for urologist gender that may be based on the individual patient’s history, taking a comprehensive approach to fulfill the patients’ need for same gender urologists in educational hospitals and health care services

Expression of Nectin-4 in Variant Histologies of Bladder Cancer and Its Prognostic Value-Need for Biomarker Testing in High-Risk Patients?

Simple Summary Variant histologies of bladder cancer present at advanced stage and are often treated with radical cystectomy. As Nectin-4 appears to be a promising target for novel therapies in conventional bladder cancer, we aimed to analyze the expression of Nectin-4 and its prognostic value in variant histologies of bladder cancer. We found a high expression of Nectin-4 in squamous cell carcinoma and adenocarcinoma and a low expression in sarcomatoid urothelial carcinoma. No impact of Nectin-4 expression on survival has been detected in our study. Our study reveals the need to perform further biomarker testing for Nectin-4 in prospective trials including patients with variant histologies. 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 0.05). 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

Identification of the Tumor Infiltrating Lymphocytes (TILs) Landscape in Pure Squamous Cell Carcinoma of the Bladder

Simple Summary Treatment options in squamous cell carcinoma (SCC) of the bladder are limited and prognosis is poor. In this report we investigated the impact of tumor-infiltrating lymphocytes (TILs) in SCC of the bladder in patients undergoing radical cystectomy. We found that subsets of TILs hold predictive value for OS and PFS. We conclude that TILs might stratify patients with bladder SCC for immunotherapy. Background: Tumor infiltrating lymphocytes (TILs) are known as important prognostic biomarkers and build the fundament for immunotherapy. However, the presence of TILs and its impact on outcome in pure squamous cell carcinoma (SCC) of the bladder remains uncertain. Methods: Out of 1600 patients undergoing radical cystectomy, 61 patients revealed pure bladder SCC in the final histopathological specimen. Retrospectively, immunohistochemical staining was performed on a subset of TILs (CD3+, CD4+, CD8+, CD20+). Endpoints were overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). The Kaplan-Meier method was used to evaluate survival outcomes. Results: Strong infiltration of CD3+ was found in 27 (44%);of CD4+ in 28 (46%);of CD8+ in 26 (43%);and of CD20+ in 27 tumors (44%). Improved OS was observed for strong CD3+ (p < 0.001);CD4+ (p = 0.045);CD8+ (p = 0.001);and CD20+ infiltration (p < 0.001). Increased rates of PFS were observed for CD3+ (p = 0.025) and CD20+ TILs (p = 0.002). In multivariate analyses, strong CD3+ (HR: 0.163, CI: 0.044-0.614) and strong CD8+ TILs (HR: 0.265, CI: 0.081-0.864) were revealed as predictors for OS and the strong infiltration of CD20+ cells (HR: 0.095, CI: 0.019-0.464) for PFS. Conclusions: These first results of TILs in bladder SCC revealed predictive values of CD3+, CD8+ and CD20+

Whole pelvis vs. hemi pelvis elective nodal radiotherapy in patients with PSMA-positive nodal recurrence after radical prostatectomy - a retrospective multi-institutional propensity score analysis.

PURPOSE Despite growing evidence for bilateral pelvic radiotherapy (whole pelvis RT, WPRT) there is almost no data on unilateral RT (hemi pelvis RT, HPRT) in patients with nodal recurrent prostate cancer after prostatectomy. Nevertheless, in clinical practice HPRT is sometimes used with the intention to reduce side effects compared to WPRT. Prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA-PET/CT) is currently the best imaging modality in this clinical situation. This analysis compares PSMA-PET/CT based WPRT and HPRT. METHODS A propensity score matching was performed in a multi-institutional retrospective dataset of 273 patients treated with pelvic RT due to nodal recurrence (214 WPRT, 59 HPRT). In total, 102 patients (51 in each group) were included in the final analysis. Biochemical recurrence-free survival (BRFS) defined as prostate specific antigen (PSA) < post-RT nadir + 0.2ng/ml, metastasis-free survival (MFS) and nodal recurrence-free survival (NRFS) were calculated using the Kaplan-Meier method and compared using the log rank test. RESULTS Median follow-up was 29 months. After propensity matching, both groups were mostly well balanced. However, in the WPRT group there were still significantly more patients with additional local recurrences and biochemical persistence after prostatectomy. There were no significant differences between both groups in BRFS (p = .97), MFS (p = .43) and NRFS (p = .43). After two years, BRFS, MFS and NRFS were 61%, 86% and 88% in the WPRT group and 57%, 90% and 82% in the HPRT group, respectively. Application of a boost to lymph node metastases, a higher RT dose to the lymphatic pathways (> 50 Gy EQD2α/β=1.5 Gy) and concomitant androgen deprivation therapy (ADT) were significantly associated with longer BRFS in uni- and multivariate analysis. CONCLUSIONS Overall, this analysis presents the outcome of HPRT in nodal recurrent prostate cancer patients and shows that it can result in a similar oncologic outcome compared to WPRT. Nevertheless, patients in the WPRT may have been at a higher risk for progression due to some persistent imbalances between the groups. Therefore, further research should prospectively evaluate which subgroups of patients are suitable for HPRT and if HPRT leads to a clinically significant reduction in toxicity

Confronting hidden COVID-19 burden: a telemedical solution for elective urological outpatient clinics

Maintaining high-quality care for urological patients is a challenge during and after the Coronavirus disease 2019 (COVID-19) pandemic. We observe an increasing volume of postponed elective visits at our tertiary care hospital, holding the risk for deterioration of non-emergency disease conditions. As it is unclear for how long the pandemic will last, we propose to implement telehealth as a solution to provide regular symptom monitoring compatible with social distancing guidelines during the pandemic and beyond. Telemedical assessment and prioritizing of high-risk patients for individual consults at outpatient services will have to be aligned with available outpatient capacity and local outbreak severity