Molecular Heterogeneity and Immune Infiltration Drive Clinical Outcomes in Upper Tract Urothelial Carcinoma.

Background And Objective: Molecular classification of upper tract urothelial carcinoma (UTUC) can provide insight into divergent clinical outcomes and provide a biological rationale for clinical decision-making. As such, we performed multi-omic analysis of UTUC tumors to identify molecular features associated with disease recurrence and response to immune checkpoint blockade (ICB).

Methods: Targeted DNA and whole transcriptome RNA sequencing was performed on 100 UTUC tumors collected from patients undergoing nephroureterectomy.

HER2 overexpression in urothelial carcinoma with GATA3 and PPARG copy number gains.

HER2, encoded by the ERBB2 gene, is an important druggable driver of human cancer gaining increasing importance as a therapeutic target in urothelial carcinoma (UC). The genomic underpinnings of HER2 overexpression in ERBB2 nonamplified UC are poorly defined. To address this knowledge gap, we investigated 172 UC tumors from patients treated at the University of California San Francisco, using immunohistochemistry and next-generation sequencing.

"I think my vagina is still there?": Women's perspectives on sexual function and dysfunction following radical cystectomy for bladder cancer, a qualitative study.

Background: Women's sexual health after radical cystectomy is an important but poorly understood aspect of bladder cancer survivorship. Dedicated investigation is needed to elucidate patient perceptions on sexual function and dysfunction in this setting.

Aims: In this study we sought to qualitatively examine women's perceptions and experiences of sexual health following radical cystectomy for bladder cancer.

Clinical and Genomic Landscape of FGFR3-Altered Urothelial Carcinoma and Treatment Outcomes with Erdafitinib: A Real-World Experience.

Purpose: Erdafitinib is the only FDA-approved targeted therapy for FGFR2/3-altered metastatic urothelial cancer. We characterized the genetic landscape of FGFR-altered urothelial carcinoma and real-world clinical outcomes with erdafitinib, including on-treatment genomic evolution.

Experimental Design: Prospectively collected clinical data were integrated with institutional genomic data to define the landscape of FGFR2/3-altered urothelial carcinoma.

Cxbladder Monitor testing to reduce cystoscopy frequency in patients with bladder cancer.

Purpose: Bladder cancer surveillance is associated with high costs and patient burden. CxMonitor (CxM), a home urine test, allows patients to skip their scheduled surveillance cystoscopy if CxM-negative indicating a low probability of cancer presence. We present outcomes from a prospective multi-institutional study of CxM to reduce surveillance frequency during the coronavirus pandemic.

Scratching the Surface: NECTIN-4 as a Surrogate for Enfortumab Vedotin Resistance.

Clinical data with enfortumab vedotin (EV) suggest that most bladder cancers overexpress NECTIN-4. A recent article shows that NECTIN-4 membranous expression changes with progression to metastatic disease and that low NECTIN-4 expression in metastatic biopsies is potentially associated with EV resistance. These data argue for incorporation of NECTIN-4 expression into future biomarker strategies.

Prostate cancer disparities among American Indians and Alaskan Natives in the United States.

Background: Americans Indians and Alaska Natives face disparities in cancer care with lower rates of screening, limited treatment access, and worse survival. Prostate cancer treatment access and patterns of care remain unknown.

Methods: We used Surveillance, Epidemiology, and End Results data to compare incidence, primary treatment, and cancer-specific mortality across American Indian and Alaska Native, Asian and Pacific Islander, Black, and White patients.

Genomic heterogeneity as a barrier to precision oncology in urothelial cancer.

Precision oncology relies on the accurate molecular characterization of individual patients with cancer at the time of treatment initiation. However, tumor molecular profiles are not static, and cancers continually evolve because of ongoing mutagenesis and clonal selection. Here, we performed genomic analyses of primary tumors, metastases, and plasma collected from individual patients to define the concordance of actionable genomic alterations and to identify drivers of metastatic disease progression.

Immune mechanisms and molecular therapeutic strategies to enhance immunotherapy in non-muscle invasive bladder cancer: Invited review for special issue "Seminar: Treatment Advances and Molecular Biology Insights in Urothelial Carcinoma".

Intravesical immunotherapy with Bacillus Calmette-Guérin (BCG) has been the standard of care for patients with high-risk non non-muscle invasive bladder cancer (NMIBC) for over four decades. Despite its success as a cancer immunotherapy, disease recurrence and progression remain common. Current efforts are focused on developing effective and well-tolerated alternatives to BCG and salvage bladder preservation therapies after BCG has failed.

TROP2 Expression Across Molecular Subtypes of Urothelial Carcinoma and Enfortumab Vedotin-resistant Cells.

Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) targeting TROP2, which has recently been approved for treatment-refractory metastatic urothelial cancer (UC). However, the variability of TROP2 expression across different bladder cancer (BC) subtypes, as well as after enfortumab vedotin (EV) exposure, remains unknown. Using gene expression data from four clinical cohorts with >1400 patient samples of muscle-invasive BC and a BC tissue microarray, we found that TROP2 mRNA and protein are highly expressed across basal, luminal, and stroma-rich subtypes, but depleted in the neuroendocrine subtype.

Formal Mentorship as an Opportunity to Expand the Urology Pipeline: Under Represented Trainees Entering Residency (UReTER) Program Evaluation 2020-2021.

Objective: To rank percentages of underrepresented residents in surgical subspecialties and understand the experience of mentees and mentors who participated in the inaugural University of California, San Francisco Urology UnderRepresented Trainees Entering Residency (UReTER) Mentorship Program for Black, Indigenous, and/or LatinX medical students applying into urology.

Methods: Medical student mentees across the country were recruited via social media and email listservs. Demographic information and photos of mentors were presented on the UReTER website.

A Cross-Sectional Analysis of Barriers Associated With Non-Attendance at a Urology Telehealth Clinic in a Safety-Net Hospital.

Objective: To analyze the factors associated with non-attendance at a urology telehealth clinic in a large urban safety-net hospital after institutional-mandated transition to telehealth due to COVID-19.

Methods: We identified all encounters scheduled for telehealth after March 17, 2020 and in the subsequent 8 weeks. Logistic regression was used to identify factors associated with attendance.

CASE-based and Guidelines-based Lectures are the Most Preferred Form of Online Webinar Education: Results from the Urology Collaborative Online Video Didactics Series (COViD).

Objective To evaluate the most preferred style of online didactic lectures. The COVID-19 pandemic has had a significant impact on surgical resident education, instigating a major shift towards online webinar didactics as a major of resident teaching. We hypothesize that a case-based format of online didactics are the most preferred format for this style of lecture.

Association of Age With Risk of Adverse Pathological Findings in Men Undergoing Delayed Radical Prostatectomy Following Active Surveillance.

Objectives: To determine if older men with Gleason grade group (GG) 1 prostate cancer have a higher risk of having adverse pathology at radical prostatectomy after initially being managed with active surveillance (AS).

Methods: A total of 365 patients with GG1 prostate cancer initially managed with AS followed by delayed radical prostatectomy were identified. The primary outcome was adverse pathology after delayed radical prostatectomy in the men that were <65 years vs.

Heterogeneity in Expression Across Molecular Subtypes of Urothelial Cancer Mediates Sensitivity to Enfortumab Vedotin.

Purpose: Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) targeting NECTIN4 (encoded by the gene) approved for treatment-refractory metastatic urothelial cancer. Factors that mediate sensitivity or resistance to EV are unknown. In this study, we sought to (i) examine heterogeneity of gene expression across molecular subtypes of bladder cancer and (ii) determine whether NECTIN4 expression mediates EV sensitivity or resistance.

Prostate-specific Membrane Antigen and Fluciclovine Transporter Genes are Associated with Variable Clinical Features and Molecular Subtypes of Primary Prostate Cancer.

F-Fluciclovine-based positron emission tomography (PET) imaging is recommended in the USA for biochemical recurrence (BCR) after prostate cancer treatment. However, prostate-specific membrane antigen (PSMA)-based PET imaging is more common worldwide, supported by international guidelines, and is now approved by the Food and Drug Administration in the USA for initial staging of primary prostate cancer. Little is known about the molecular profiles of lesions detected by PSMA-targeted PET/computed tomography (CT) versus F-fluciclovine PET/CT.

Cell-free DNA concentration and fragment size as a biomarker for prostate cancer.

Prostate cancer is the most commonly diagnosed neoplasm in American men. Although existing biomarkers may detect localized prostate cancer, additional strategies are necessary for improving detection and identifying aggressive disease that may require further intervention. One promising, minimally invasive biomarker is cell-free DNA (cfDNA), which consist of short DNA fragments released into circulation by dying or lysed cells that may reflect underlying cancer.

Identifying the Best Candidates for Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography as the Primary Staging Approach Among Men with High-risk Prostate Cancer and Negative Conventional Imaging.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is an emerging imaging modality with greater sensitivity and specificity over conventional imaging for prostate cancer (PCa) staging. Using data from two prospective trials (NCT03368547 and NCT04050215), we explored predictors of overall upstaging (nodal and metastatic) by PSMA PET/CT among patients with cN0M0 National Comprehensive Cancer Network high-risk PCa on conventional imaging (n = 213). Overall, 21.

Diagnostic Accuracy and Prognostic Value of Serial Prostate Multiparametric Magnetic Resonance Imaging in Men on Active Surveillance for Prostate Cancer.

Background: Multiparametric magnetic resonance imaging (MRI) is increasingly utilized to improve the detection of clinically significant prostate cancer. Evidence for serial MRI in men on active surveillance (AS) is lacking.

Objective: To evaluate the role of MRI in detecting Gleason grade group (GG) ≥2 disease in confirmatory and subsequent surveillance biopsies for men on AS.

Liposomal Bupivacaine Decreases Postoperative Length of Stay and Opioid Use in Patients Undergoing Radical Cystectomy.

Objective: To analyze differences in length of stay, opioid use, and other perioperative outcomes in patients undergoing radical cystectomy with urinary diversion who received either liposomal bupivacaine (LB) or epidural analgesia.

Methods: This was a single center, retrospective cohort study of patients undergoing open radical cystectomy with urinary diversion from 2015-2019 in the early recovery after surgery (ERAS) pathway. Patients received either LB or epidural catheter analgesia for post-operative pain control.

The Clinical Significance of Multiple Negative Surveillance Prostate Biopsies for Men on Active Surveillance-Does Cancer Vanish or Simply Hide?

Purpose: Men with low risk prostate cancer on active surveillance undergo multiple biopsies over time. The long-term clinical significance of consecutively negative biopsies is not known.

Materials And Methods: Men with low risk prostate cancer prospectively enrolled in an active surveillance database with at least 4 biopsies were included in the study.

Multi-Institutional Collaborative Resident Education in the Era of COVID-19.

Introduction: The 2019-2020 coronavirus pandemic has had a significant impact on all aspects of health care. Decrease in clinical and operative volume and limitations for conferences has drastically decreased educational opportunities for resident trainees. We describe the formation and initial success of the Collaborative Online Video Didactics lecture series, a multi-institutional online video didactics collaboration.

Multiparametric Magnetic Resonance Imaging Alone is Insufficient to Detect Grade Reclassification in Active Surveillance for Prostate Cancer.

Multiparametric magnetic resonance imaging (mpMRI) has improved the detection of clinically significant prostate cancer. It remains unclear, however, whether mpMRI can safely replace confirmatory or surveillance biopsies in men with low-risk disease managed with active surveillance (AS). Overall, 166 men were upgraded at a median of 29 mo (interquartile range 13-54).