TROPHY-U-01 Cohort 2: A Phase II Study of Sacituzumab Govitecan in Cisplatin-Ineligible Patients With Metastatic Urothelial Cancer Progressing After Previous Checkpoint Inhibitor Therapy.

Purpose: Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate with an SN-38 payload, approved for patients with locally advanced (LA) or metastatic urothelial cancer (mUC) who progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report results from Cohort 2 of TROPHY-U-01 trial, evaluating the efficacy and safety of SG in patients with mUC.

Methods: TROPHY-U-01 (ClinicalTrials.

Perioperative Immune Checkpoint Blockade for Muscle-Invasive and Metastatic Bladder Cancer.

Checkpoint inhibitors offer promise in treating muscle-invasive and metastatic bladder cancer, but the optimal timing of their administration-neoadjuvant or adjuvant-remains unclear. To determine the efficacy of combining checkpoint inhibition with standard cisplatin-based chemotherapy, we conducted a phase II trial of neoadjuvant anti-PD-1 (αPD-1) and anti-CTLA-4 (αCTLA-4), in combination with cisplatin-gemcitabine, for patients with muscle-invasive bladder cancer prior to radical cystectomy. In addition, a novel murine model of spontaneous metastatic bladder cancer was used to compare the efficacy of neoadjuvant versus adjuvant anti-PD-L1 (αPD-L1) treatment.

Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3.

Purpose: Pembrolizumab is standard therapy for patients with metastatic urothelial cancer (mUC) who progress after first-line platinum-based chemotherapy; however, only approximately 21% of patients respond. Sacituzumab govitecan (SG) is a trophoblast cell surface antigen-2-directed antibody-drug conjugate with US Food and Drug Administration-accelerated approval to treat patients with locally advanced or mUC who previously received platinum-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report the primary analysis of TROPHY-U-01 cohort 3.

Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab.

Purpose: Locally advanced/metastatic urothelial cancer (la/mUC) affects patients' quality of life (QOL) and functioning. We describe the impact of first-line (1L) enfortumab vedotin (EV) alone or with pembrolizumab (P) on QOL/functioning/symptoms in patients with la/mUC who were cisplatin-ineligible from EV-103 Cohort K.

Methods: In this phase Ib/II trial, patients were randomly assigned 1:1 to EV + P or EV monotherapy (mono).

Cost-Effectiveness Analysis for Therapy Sequence in Advanced Cancer: A Microsimulation Approach with Application to Metastatic Prostate Cancer.

Purpose: Patients with advanced cancer may undergo multiple lines of treatment, switching therapies as their disease progresses. We developed a general microsimulation framework to study therapy sequence and applied it to metastatic prostate cancer.

Methods: We constructed a discrete-time state transition model to study 2 lines of therapy.

Effects of vortioxetine on hippocampal-related cognitive impairment induced in rats by androgen deprivation as a model of prostate cancer treatment.

Advances in prostate cancer treatment have significantly improved survival, but quality of life for survivors remains an under-studied area of research. Androgen deprivation therapy (ADT) is a foundational treatment for advanced prostate cancer and is used as an adjuvant for prolonged periods in many high-risk, localized tumors. More than half of patients treated with ADT experience debilitating cognitive impairments in domains such as spatial learning and working memory.

Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer.

Purpose: Patients with locally advanced or metastatic urothelial cancer (la/mUC) who are ineligible for cisplatin-based therapy have limited first-line (1L) treatment options and significant need for improved therapies. Enfortumab vedotin (EV) and pembrolizumab (Pembro) individually have shown a survival benefit in urothelial cancer in second-line + la/mUC settings. Here, we present data from the pivotal trial of EV plus Pembro (EV + Pembro) in the 1L setting.

A Decade of Robotic-Assisted Radical Nephrectomy with Inferior Vena Cava Thrombectomy: A Systematic Review and Meta-Analysis of Perioperative Outcomes.

Purpose: Open radical nephrectomy with inferior vena cava thrombectomy (O-CT) is standard management for renal cell carcinoma with inferior vena cava thrombus. First reported a decade ago, robotic-assisted radical nephrectomy with inferior vena cava thrombectomy (R-CT) is a minimally invasive option for this disease. W aimed to perform a systematic review to assess the safety and feasibility of R-CT in terms of perioperative outcomes and compare the outcomes between R-CT and O-CT.

Disparities in Cancer Genetic Testing and Variants of Uncertain Significance in the Hispanic Population of South Texas.

Purpose: Racial and ethnic disparities have included a lack of access to both genetic testing and research, resulting in poor understanding of the genomic architecture in under-represented populations. The South Texas population is primarily of Hispanic background and has been largely devoid of genetic services. We extended access to this underserved population and uncovered genetic variants previously not observed, emphasizing the need to continually improve both genomic databases and clarification of variant significance to provide meaningful patient counseling.

Hereditary Cancer Gene Variants in Hispanic Men With a Personal or Family History of Prostate Cancer.

Background: Mutations in several common hereditary cancer genes are associated with prostate cancer, but there is limited information on the prevalence of these mutations in Hispanic men.

Materials And Methods: We selected men at high risk for genetic mutations from 1515 Hispanic men enrolled in the San Antonio Biomarkers of Risk for prostate cancer (SABOR) cohort. Inclusion criteria included men with a diagnosis of prostate cancer or a first-degree family history of prostate cancer.

Prevalence of pathogenic germline cancer risk variants in testicular cancer patients: Identifying high risk groups.

Background: Germline studies in testicular cancer have focused on unselected populations but so far have not led to recommendations for testicular cancer screening.

Objective: Herein, we hypothesized that men with testicular cancer and an additional risk factor for hereditary cancer predisposition carry a higher rate of pathogenic variants than men with testicular cancer without another risk factor.

Methods And Results: 187 patients with a personal history of testicular cancer underwent germline testing via Invitae.

Impact of facility type and volume on survival in patients with metastatic renal cell carcinoma.

Introduction: To investigate the impact of facility type and volume on survival in patients with metastatic renal cell carcinoma (mRCC).

Materials And Methods: We investigated the National Cancer Database for patients with mRCC. Patients were stratified according to treatment facility type (academic vs.

Rapamycin enhances BCG-specific γδ T cells during intravesical BCG therapy for non-muscle invasive bladder cancer: a randomized, double-blind study.

Background: Although intravesical BCG is the standard treatment of high-grade non-muscle invasive bladder cancer (NMIBC), response rates remain unsatisfactory. In preclinical models, rapamycin enhances BCG vaccine efficacy against tuberculosis and the killing capacity of γδ T cells, which are critical for BCG's antitumor effects. Here, we monitored immunity, safety, and tolerability of rapamycin combined with BCG in patients with NMIBC.

Correlates of refusal of radical cystectomy in patients with muscle-invasive bladder cancer.

Purpose: To evaluate factors associated with radical cystectomy (RC) refusal, subsequent treatment decisions, and their influence on overall survival (OS).

Materials And Methods: We queried the National Cancer Database for patients with non-metastatic muscle-invasive bladder cancer (MIBC), cT2-T4M0. Patients who refused recommended RC were further stratified by treatment into chemotherapy, radiation therapy, chemoradiotherapy, and no treatment groups.

Pathological downstaging following radical cystectomy for muscle-invasive bladder cancer: Survival outcomes in the setting of neoadjuvant chemotherapy versus transurethral resection only.

Introduction: Neoadjuvant chemotherapy (NAC) improves survival for patients undergoing radical cystectomy for muscle-invasive bladder cancer (MIBC). The overall survival (OS) advantage with NAC is primarily seen in patients who achieve pathological downstaging. However, a substantial number of patients achieve pathological downstaging following transurethral resection (TUR) without NAC.

Cost-effectiveness of abiraterone versus docetaxel in the treatment of metastatic hormone naïve prostate cancer.

Purpose: Prostate cancer is the second leading cause of cancer death in men in the US. Since 2015, landmark studies have demonstrated improved survival outcomes with the use of docetaxel (DCT) or abiraterone (AA) in addition to androgen deprivation therapy (ADT) in the metastatic hormone-naïve setting. These treatment strategies have not been prospectively compared but have similar overall survival benefits despite differing mechanisms of action, toxicity, and cost.

Managing adverse effects of immunotherapy.

Remarkable efficacy has been achieved in a variety of cancer types by targeting immune checkpoints. The cytotoxic T-lymphocyte-associated antigen 4 inhibitor ipilimumab, the programmed death 1 inhibitors nivolumab and pembrolizumab, and the programmed death ligand 1 inhibitors atezolizumab, avelumab, and durvalumab are the agents currently approved by the US Food and Drug Administration for the treatment of certain advanced malignancies. These agents mark a departure from both standard cytotoxic chemotherapy and targeted therapy.

Impact of tumor microenvironment composition on therapeutic responses and clinical outcomes in cancer.

The tumor microenvironment (TME) plays an important role in cancer growth and progression. Paradoxically, the TME is capable of acting as both a potential barrier and facilitator of tumor proliferation by affecting various processes including local growth resistance, immune system interactions, and the formation of distant metastases. This important interaction between cancer cells and their local environment, composed of immune cells, angiogenic cells, lymphatic endothelial cells and cancer-associated fibroblasts is paramount to determine a cancer cell's ability to grow and ultimately metastasize.

Randomized Controlled Trials in Hereditary Cancer Syndromes.

Conducting randomized controlled trials (RCTs) in patients with germline mutations in genes that predispose to adult-onset cancer is hampered by the rarity of these mutations, barriers to their identification, and challenges inherent to randomizing high-risk individuals as part of a clinical trial. Most of the clinically relevant RCTs have been conducted in 3 syndromes in only some of the high-risk genes for which clinical testing is currently available. This article reviews the surgical, screening, and chemoprevention RCTs in each of the syndromes in clinically relevant studies conducted in the past 10 years.