Eligibility and Endpoints for Clinical Trials in Trimodality Therapy for Bladder Cancer.

Background: Trimodality therapy (TMT) is a viable option for muscle-invasive localized bladder cancer, providing an alternative to radical cystectomy in properly selected patients. The approval of novel therapeutics in different stages of bladder cancer treatment has sparked interest in exploring concurrent systemic therapies with radiation in clinical trials to enhance long-term outcomes. Achieving uniformity in trial eligibility criteria and endpoint definitions is imperative in describing clinical significance, comparing trials, and changing standard of care guidelines.

Approaches to Treating High Risk and Advanced Renal Cell Carcinoma (RCC): Key Trial Data That Impacts Treatment Decisions in the Clinic.

The treatment paradigm for high risk localized and advanced kidney cancer has been characterized by ongoing changes, with the introduction of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR TKIs) and later with immune checkpoint blockade. In this article, we review how current evidence informs our decision-making on post-checkpoint inhibitor systemic therapies, the role of adjuvant and/or neoadjuvant therapies, and the role of cytoreductive nephrectomy in the evolving systemic therapy landscape. While some studies support a post-checkpoint inhibitor benefit from the VEGFR TKIs cabozantinib or axitinib, the benefit of doublet therapies including a VEGF receptor inhibitor and a checkpoint inhibitor remains an area of active investigation, with the combination of lenvatinib plus pembrolizumab showing promise but with a Phase III trial of the combination of atezolizumab plus cabozantinib showing no benefit over cabozantinib alone.

Vaccine approaches to treat urothelial cancer.

Bladder cancer (BC) accounts for about 4% of all malignancies. Non-muscle-invasive BC, 75% of cases, is treated with transurethral resection and adjuvant intravesical instillation, while muscle-invasive BC warrants cisplatin-based perioperative chemotherapy. Although immune-checkpoint inhibitors, antibody drug conjugates and targeted agents have provided dramatic advances, metastatic BC remains a generally incurable disease and clinical trials continue to vigorously evaluate novel molecules.

Impact of Angiotensin Converting Enzyme Inhibitors on Pathologic Complete Response With Neoadjuvant Chemotherapy for Muscle Invasive Bladder Cancer.

Introduction: The renin-angiotensin system (RAS) has been demonstrated to modulate cell proliferation, desmoplasia, angiogenesis and immunosuppression. We examined the association of RAS inhibitors (RASi)-namely angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB)-with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) preceding radical cystectomy (RC).

Patients And Methods: We retrospectively investigated concurrent RASi use with NAC prior to RC in 302 patients with MIBC from 3 academic institutions.

Factors predictive of recurrence, metastasis and death in node-negative penile squamous cell carcinoma: A retrospective multicentre cohort study.

Background: Penile squamous cell carcinoma (PSCC) carries significant morbidity and mortality. Literature is limited regarding prognostic factors, especially prognostic factors for development of metastasis.

Objectives: To identify independent prognostic factors associated with poor outcomes, defined as local recurrence (LR), metastasis and disease-specific death (DSD) in clinically node-negative PSCC undergoing local therapy.

Real-World Multicenter Study of PD-1 Blockade in HIV-Associated Classical Hodgkin Lymphoma Across the United States.

Background: Despite a higher risk of classical Hodgkin lymphoma (cHL) in people with HIV and the demonstrated safety and efficacy of PD-1 blockade in cHL, there are limited data on the use of these agents in HIV-associated cHL (HIV-cHL).

Patients/methods: We retrospectively identified patients with HIV-cHL from the "Cancer Therapy using Checkpoint inhibitors in People with HIV-International (CATCH-IT)" database who received nivolumab or pembrolizumab, alone or in combination with other agents, and reviewed records for demographics, disease characteristics, immune-mediated adverse events (imAEs), and treatment outcomes. Changes in CD4 T-cell counts with treatment were measured via Wilcoxon signed-rank tests.

The evolving treatment landscape of metastatic urothelial cancer.

Cisplatin-based chemotherapy is currently the first-line standard of care for patients with metastatic urothelial cancer (mUC); however, up to 50% of patients are ineligible for cisplatin, necessitating alternative treatment options. Immune checkpoint inhibitors have been shown to be effective in cisplatin-ineligible patients. However, despite advances in the first-line setting, the prognosis remains poor, and challenges persist in selecting optimal therapies, treatment sequences and combination regimens.

Health-related Quality of Life in Patients with Previously Treated Advanced Urothelial Carcinoma from EV-301: A Phase 3 Trial of Enfortumab Vedotin Versus Chemotherapy.

Background And Objective: In comparison to chemotherapy, enfortumab vedotin (EV) prolonged overall survival in patients with previously treated advanced urothelial carcinoma in EV-301. The objective of the present study was to assess patient experiences of EV versus chemotherapy using patient-reported outcome (PRO) analysis of health-related quality of life (HRQoL).

Methods: For patients in the phase 3 EV-301 trial randomized to EV or chemotherapy we assessed responses to the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, weekly for the first 12 wk, and then every 12 wk until discontinuation.

Comparative real-world survival outcomes of muscle-invasive bladder cancer treated with bladder-only vs. whole-pelvis concurrent chemoradiation.

Introduction: Elective pelvic nodal irradiation for patients with muscle-invasive bladder cancer (MIBC) undergoing trimodal therapy (TMT ) is controversial. In patients with node-negative (N0) MIBC, the benefit of elective whole-pelvis concurrent chemoradiation (WP-CCR) compared to bladder-only (BO )-CCR has not been demonstrated. Using real-world data from the National Cancer Database (NCDB ), we sought to compare the overall survival (OS ) between BO-CCR and WP-CCR for MIBC.

Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma.

Purpose: Effective treatment of locally advanced or metastatic urothelial carcinoma (mUC) remains an unmet need. Antibody-drug conjugates (ADC) providing targeted drug delivery have shown antitumor activity in this setting. AGS15E is an investigational ADC that delivers the cytotoxic drug monomethyl auristatin E to cells expressing SLITRK6, a UC-associated antigen.

Total Margin Control Is Superior to Traditional Margin Assessment for Treatment of Low-Stage Penile Squamous Cell Carcinoma.

Purpose: Penile cancer is rare, with significant morbidity and limited literature assessing utility of peripheral and deep en face margin assessment (PDEMA) vs traditional margin assessment (vertical sections) on treatment outcomes.

Materials And Methods: This was a 32-year retrospective multicenter cohort study at 3 academic tertiary care centers. The cohort consisted of 189 patients with histologic diagnosis of in situ or T1a cutaneous squamous cell carcinoma of the penis at Brigham and Women's, Massachusetts General Hospital (1988-2020), and Memorial Sloan Kettering Cancer Center (1995-2020) treated with PDEMA surgical excision, excision/circumcision, or penectomy/glansectomy.

Pretest Video Education Versus Genetic Counseling for Patients With Prostate Cancer: ProGen, A Multisite Randomized Controlled Trial.

Purpose: Germline genetic testing (GT) is recommended for men with prostate cancer (PC), but testing through traditional models is limited. The ProGen study examined a novel model aimed at providing access to GT while promoting education and informed consent.

Methods: Men with potentially lethal PC (metastatic, localized with a Gleason score of ≥8, persistent prostate-specific antigen after local therapy), diagnosis age ≤55 years, previous malignancy, and family history suggestive of a pathogenic variant (PV) and/or at oncologist's discretion were randomly assigned 3:1 to video education (VE) or in-person genetic counseling (GC).

Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors.

Background: Treatment options for penile squamous cell carcinoma are limited. We sought to investigate clinical outcomes and safety profiles of patients with penile squamous cell carcinoma receiving immune checkpoint inhibitors.

Methods: This retrospective study included patients with locally advanced or metastatic penile squamous cell carcinoma receiving immune checkpoint inhibitors between 2015 and 2022 across 24 centers in the United States, Europe, and Asia.

Circulating tumor DNA as a Predictive and Prognostic Biomarker in the Perioperative Treatment of Muscle-invasive Bladder Cancer: A Systematic Review.

Context: Predictive and prognostic biomarkers in the perioperative treatment of muscle-invasive bladder cancer (MIBC) are an unmet need. Circulating tumor DNA (ctDNA) holds promise as a biomarker in this setting.

Objective: To review the evidence of ctDNA as a prognostic and predictive biomarker in the perioperative treatment of MIBC.

Precision Medicine to Treat Urothelial Carcinoma-The Way Forward.

The treatment of urothelial carcinoma (UC) is challenging given its molecular heterogeneity and variable response to current therapies. To address this, many tools, including tumor biomarker assessment and liquid biopsies, have been developed to predict prognosis and treatment response. Approved therapeutic modalities for UC currently include chemotherapy, immune checkpoint inhibitors, receptor tyrosine kinase inhibitors, and antibody drug conjugates.

Real-world treatment patterns and clinical outcomes with first-line therapy in patients with locally advanced/metastatic urothelial carcinoma by cisplatin-eligibility.

Introduction: Patients with locally advanced/metastatic urothelial carcinoma (la/mUC) have a poor prognosis. With recent therapeutic advances, data on real-world treatment patterns and overall survival (OS) in patients with la/mUC treated with first-line therapy are limited, particularly when comparing patients who are cisplatin-ineligible versus cisplatin-eligible.

Methods: This was a retrospective observational study of real-world first-line treatment patterns and OS in patients with la/mUC stratified by cisplatin-eligibility and treatment.