The use of focal therapy for the treatment of prostate cancer in Canada: Where are we, how did we get here, and where are we going?

Introduction: Focal therapy is an emerging treatment for localized prostate cancer. The objectives of this review were to: 1) review how focal therapies are regulated and approved; 2) summarize the scope and quality of the literature regarding safety, efficacy, and side-effects; and 3) outline ongoing clinical trials of focal therapy in Canada.

Methods: Using the PRISMA framework for scoping reviews, we searched PubMed, Embase, and Cochrane from 2021-2024, complementing Hopstaken et al's search up functional and oncologic outcomes.

Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.

Purpose: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up.

Materials And Methods: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50).

Multiomics profiling of urothelial carcinoma reveals CIS-specific gene signature and immune characteristics.

Urothelial carcinoma (CIS) is an aggressive phenotype of non-muscle-invasive bladder cancer. Molecular features unique to CIS compared to high-grade papillary tumors are underexplored. RNA sequencing of CIS, papillary tumors, and normal urothelium showed lower immune marker expression in CIS compared to papillary tumors.

Whole exome sequencing analysis of canine urothelial carcinomas without BRAF V595E mutation: Short in-frame deletions in BRAF and MAP2K1 suggest alternative mechanisms for MAPK pathway disruption.

Molecular profiling studies have shown that 85% of canine urothelial carcinomas (UC) harbor an activating BRAF V595E mutation, which is orthologous to the V600E variant found in several human cancer subtypes. In dogs, this mutation provides both a powerful diagnostic marker and a potential therapeutic target; however, due to their relative infrequency, the remaining 15% of cases remain understudied at the molecular level. We performed whole exome sequencing analysis of 28 canine urine sediments exhibiting the characteristic DNA copy number signatures of canine UC, in which the BRAF V595E mutation was undetected (UDV595E specimens).

A Phase 1b/2 Study of Atezolizumab with or Without Bacille Calmette-Guérin in Patients with High-risk Non-muscle-invasive Bladder Cancer.

Background: Bacille Calmette-Guérin (BCG) is the standard therapy after transurethral resection of bladder tumour for high-risk non-muscle-invasive bladder cancer (NMIBC). However, post-BCG recurrence/progression occurs frequently, and noncystectomy options are limited.

Objective: To evaluate the safety and clinical activity of atezolizumab ± BCG in high-risk BCG-unresponsive NMIBC.

Advanced chronic kidney disease; A comparison between nephroureterectomy and nephron-sparing surgery for upper tract urothelial carcinoma.

Purpose: Renal function outcomes between radical nephroureterectomy (RNU) and nephron-sparing surgery (NSS) for upper tract urothelial carcinoma (UTUC) patients are not well established. We sought to compare the incidence and factors associated with development of advanced chronic kidney disease (CKD) between RNU and NSS and examine the role of acute kidney injury (AKI) on renal function outcomes.

Methods: We retrospectively analyzed an institutional database for patients who underwent either RNU or NSS for UTUC.

Hyperthermic Mitomycin C in Intermediate-risk Non-muscle-invasive Bladder Cancer: Results of the HIVEC-1 Trial.

Background: Optimising therapeutic strategies of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC) is needed.

Objective: To compare recurrence-free survival (RFS) with adjuvant intravesical mitomycin C (MMC) at normothermia or hyperthermia using the COMBAT bladder recirculation system at 43 °C for 30 and 60 min.

Design, Setting, And Participants: A prospective open-label, phase 3 randomised controlled trial (HIVEC-1) accrued across 13 centres between 2014 and 2020 in Spain.

Intravital optical imaging for immune cell tracking after photoimmunotherapy with plasmonic gold nanostars.

Bladder cancer has been ranked as one of the most commonly occurring cancers in men and women with approximately half of the diagnoses being the late stage and/or metastatic diseases. We have developed a novel cancer treatment by combining gold nanostar-mediated photothermal therapy with checkpoint inhibitor immunotherapy to treat bladder cancer. Experiment results with a murine animal model demonstrated that our developed photoimmunotherapy therapy is more efficacious than any individual studied treatment.

Automated versus manual analysis of body composition measures on computed tomography in patients with bladder cancer.

Purpose: Manual measurement of body composition on computed tomography (CT) is time-consuming, limiting its clinical use. We validate a software program, Automatic Body composition Analyzer using Computed tomography image Segmentation (ABACS), for the automated measurement of body composition by comparing its performance to manual segmentation in a cohort of patients with bladder cancer.

Method: We performed a retrospective analysis of 285 patients treated for bladder cancer at the Duke University Health System from 1996 to 2017.

Genomic Sequencing Should Not be Part of the Standard of Care for Most Urologic Cancers.

There are currently few situations in which genomic testing is actionable for genitourinary tumors. Without clear indications or treatment paradigms, genomic sequencing cannot be recommended as a standard of care for genitourinary tumors.

Pre-existing Castration-resistant Prostate Cancer-like Cells in Primary Prostate Cancer Promote Resistance to Hormonal Therapy.

Background: Hormonal therapy targeting the androgen receptor inhibits prostate cancer (PCa), but the tumor eventually recurs as castration-resistant prostate cancer (CRPC).

Objective: To understand the mechanisms by which subclones within early PCa develop into CRPC.

Design, Setting, And Participants: We isolated epithelial cells from fresh human PCa cases, including primary adenocarcinoma, locally recurrent CRPC, and metastatic CRPC, and utilized single-cell RNA sequencing to identify subpopulations destined to become either CRPC-adeno or small cell neuroendocrine carcinoma (SCNC).

Recirculating hyperthermic intravesical chemotherapy with mitomycin C (HIVEC) versus BCG in high-risk non-muscle-invasive bladder cancer: results of the HIVEC-HR randomized clinical trial.

Purpose: The purpose of the study was to compare the outcomes of high-risk non-muscle-invasive bladder cancer (HR-NMIBC) patients treated with BCG vs recirculating hyperthermic intravesical chemotherapy (HIVEC) with mitomycin C (MMC).

Methods: A pilot phase II randomized clinical trial was conducted including HR-NMIBC patients, excluding carcinoma in situ. Patients were randomized 1:1 to receive intravesical BCG for 1 year (once weekly for 6 weeks plus subsequent maintenance) or HIVEC with 40 mg MMC, administered using the Combat BRS system (once weekly instillations were given for 6 weeks, followed by once monthly instillation for 6 months).

Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non-muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial.

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders).

Characterization of a castrate-resistant prostate cancer xenograft derived from a patient of West African ancestry.

Background: Prostate cancer is a clinically and molecularly heterogeneous disease, with highest incidence and mortality among men of African ancestry. To date, prostate cancer patient-derived xenograft (PCPDX) models to study this disease have been difficult to establish because of limited specimen availability and poor uptake rates in immunodeficient mice. Ancestrally diverse PCPDXs are even more rare, and only six PCPDXs from self-identified African American patients from one institution were recently made available.

Plasmonic gold nanostars for synergistic photoimmunotherapy to treat cancer.

Cancer is the second leading cause of death and there is an urgent need to improve cancer management. We have developed an innovative cancer therapy named Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) by combining gold nanostars (GNS)-mediated photothermal ablation with checkpoint inhibitor immunotherapy. Our previous studies have demonstrated that SYMPHONY photoimmunotherapy not only treats the primary tumor but also dramatically amplifies anticancer immune responses in synergy with checkpoint blockade immunotherapy to treat remote and unresectable cancer metastasis.

Active surveillance of metastatic renal cell carcinoma: Results from a prospective observational study (MaRCC).

Background: Systemic therapy (ST) can be deferred in patients who have metastatic renal cell carcinoma (mRCC) and slow-growing metastases. Currently, this subset of patients managed with active surveillance (AS) is not well described in the literature.

Methods: This was a prospective observational study of patients with mRCC across 46 US community and academic centers.

Videos of Sipuleucel-T Programmed T Cells Lysing Cells That Express Prostate Cancer Target Antigens.

Sipuleucel-T, an autologous cellular immunotherapy, was approved to treat metastatic castration-resistant prostate cancer in 2010 in the United States. Treatment with sipuleucel-T primes the immune system to target prostate acid phosphatase, which is expressed by prostate cancer cells, potentially leading to lysis of cancer cells. Expanding on previously reported indirect evidence of cell killing with sipuleucel-T treatment, we sought to provide direct evidence of cell lysis through visualization.

Clinical trial of high dose hyperthermic intravesical mitomycin C for intermediate and high-risk non-muscle invasive bladder cancer during BCG shortage.

Purpose: Intravesical Bacillus Calmette-Guérin (BCG) is the gold standard for intermediate and high-risk non-muscle invasive bladder cancer (NMIBC), but availability is limited by global shortages. We present the first North American clinical experience using intravesical hyperthermia (HIVEC) with high-dose mitomycin C (MMC) during BCG shortage.

Materials And Methods: Single arm intermediate size expanded access protocol for high dose HIVEC MMC in patients with intermediate and high-risk NMIBC during BCG shortage.

The nephroureterectomy: a review of technique and current controversies.

The nephroureterectomy (NU) is the standard of care for invasive upper tract urothelial carcinoma (UTUC) and has been around for well over one hundred years. Since then new operative techniques have emerged, new technologies have developed, and the surgery continues to evolve and grow. In this article, we review the various surgical techniques, as well as present the literature surrounding current areas of debate surrounding the NU, including the lymphatic drainage of the upper urinary tract, management of UTUC involvement with the adrenals and caval thrombi, surgical management of the distal ureter, the use of intravesical chemotherapy as well as perioperative systemic chemotherapy, as well as various outcome measures.