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

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

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

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+

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

Strategies to successfully prevent COVID-19 outbreak in vulnerable uro-oncology patient population

Purpose As COVID-19 pandemic persists with variants, and despite effective vaccination campaigns, breakthrough infections surge. We implemented strategies to protect vulnerable patients of the uro-oncologic outpatient clinic. We adopted proactive non-symptomatic risk reduction measures, which include non-symptomatic testing requirements for both patients and health care professionals (HCP), intensified patient tracing and contact reduction by implementation of digital health options. Here, we present our best practice example to safely guide oncology professionals and patients with metastasized genitourinary cancers through the current and future pandemics. Methods Solely for this purpose, we created a registry of collected data (current telephone numbers, e-mail addresses, vaccination status). We collected a nasopharyngeal swab from every patient upon presentation for treatment. We implemented bi-weekly RNA-PCR assay tests for HCP with patient contact, and limited personal contact at our facility through digital patient consultations. Results We started implementing our COVID prevention model at the beginning of the second wave in September 2020 and included 128 patients with urologic malignancies requiring systemic treatment. After COVID vaccination became available in December 2020, all of our HCP were fully vaccinated within 6 weeks and 97% of our patients (125/128) within 9 months. We performed 1410 nasopharyngeal swabs during in-house visits, thereby detecting two COVID-19 infections among our patients, who both survived and successfully continued treatment. To further reduce personal contact, half of our consultations were fully operated digitally, with 76% (97/128) of our patients participating in our digital health offers. Conclusion The willingness of patients and HCPs to participate in the study allowed us to implement strict standards to prepare for the ongoing and future pandemics in outpatient cancer units. Next to general preventive measures such as frequent hand disinfection, wearing facial masks, and keeping distance, an important measure to protect vulnerable uro-oncology patients is the capability to perform virus genome sequencing to trace transmission chains

Image-Guided Robotic Radiosurgery for the Treatment of Lung Metastases of Renal Cell Carcinoma&mdash;A Retrospective, Single Center Analysis

Pulmonary metastases are the most frequent site of metastases in renal cell carcinoma (RCC). Metastases directed treatment remains an important treatment option despite advances in systemic therapies. However, the safety and efficacy of robotic radiosurgery (RRS) for the treatment of lung metastases of RCC remains unclear. Patients with metastatic RCC and lung metastases treated by RRS were retrospectively analyzed for overall survival (OS), progression-free survival (PFS), local recurrence free survival (LRFS) and adverse events. The Kaplan&ndash;Meier method was used for survival analysis and the common terminology criteria for adverse events (CTCAE; Version 5.0) classification for assessment of adverse events. A total of 50 patients were included in this study. Median age was 64 (range 45&ndash;92) years at the time of RRS. Prior to RRS, 20 patients (40.0%) had received either tyrosine kinase inhibitors or immunotherapy and 27 patients (54.0%) were treatment na&iuml;ve. In our patient cohort, the median PFS was 13 months (range: 2&ndash;93). LRFS was 96.7% after two years with only one patient revealing progressive disease of the treated metastases 13 months after RRS. Median OS was 35 months (range 2&ndash;94). Adverse events were documented in six patients (12%) and were limited to grade 2. Fatigue (n = 4) and pneumonitis (n = 2) were observed within 3 months after RRS. In conclusion, RRS is safe and effective for patients with metastatic RCC and pulmonary metastases. Radiation induced pneumonitis is specific in the treatment of pulmonary lesions, but not clinically relevant and survival rates seem favorable in this highly selected patient cohort. Future directions are the implementation of RRS in multimodal treatment approaches for oligometastatic or oligoprogressive disease