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.
View Article and Find Full Text PDFPurpose: 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.
View Article and Find Full Text PDFClinical 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.
View Article and Find Full Text PDFBackground: 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.
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.
View Article and Find Full Text PDFSacituzumab 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.
View Article and Find Full Text PDFObjective: 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.
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.
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.
View Article and Find Full Text PDFF-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.
View Article and Find Full Text PDFBackground: 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.
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.
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.
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).
View Article and Find Full Text PDFDue to significant risks of cancer recurrence and progression, and limited options after intravesical Bacillus Calmette Guerin (BCG) therapy, there is a critical unmet need to identify novel treatments for those patients with BCG-unresponsive bladder cancer. There is active investigation of immunotherapies which provide both biologic and clinical rationales for indoleamine-2,3- dioxygenase inhibitors in salvage therapy for non-muscle invasive bladder cancer.
View Article and Find Full Text PDFBackground. Hepatitis C virus (HCV) treatment access among human immunodeficiency virus (HIV)/HCV-coinfected people who inject drugs is poor, despite a high burden of disease in this population. Understanding barriers and facilitators to HCV treatment uptake is critical to the implementation of new direct-acting antivirals.
View Article and Find Full Text PDFAIDS Res Hum Retroviruses
January 2015
Our objective was to explore the social meaning of HIV and perceptions of an HIV cure among people who inject drugs (PWID) in Guangzhou, China, which speaks to ethical and resource challenges to development in this field. We conducted a qualitative research study using in-depth interviews. We analyzed interview transcripts from 29 PWID, eight physicians, and three social workers from an outpatient HIV clinic and two methadone maintenance treatment centers.
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