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.

Microsatellite Instability, Tumor Mutational Burden, and Response to Immune Checkpoint Blockade in Patients with Prostate Cancer.

Purpose: Patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) and high tumor mutational burden (TMB-H) prostate cancers are candidates for pembrolizumab. We define the genomic features, clinical course, and response to immune checkpoint blockade (ICB) in patients with MSI-H/dMMR and TMB-H prostate cancers without MSI [TMB-H/microsatellite stable (MSS)].

Experimental Design: We sequenced 3,244 tumors from 2,257 patients with prostate cancer.

Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma.

Purpose: Vascular-targeted photodynamic therapy with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma. This Phase I trial (NCT03617003) evaluated the safety of vascular-targeted photodynamic therapy with WST-11 in upper tract urothelial carcinoma.

Materials And Methods: Nineteen patients underwent up to 2 endoscopic vascular-targeted photodynamic therapy treatments, with follow-up for up to 6 months.

Targeted Therapies in Advanced and Metastatic Urothelial Carcinoma.

This review describes the current landscape of targeted therapies in urothelial carcinoma. The standard of care for advanced urothelial carcinoma patients remains platinum-based combination chemotherapy followed by immunotherapy. However, median overall survival for these patients is still <1 year and there is an urgent need for alternative therapies.

Gene-based Confirmatory Germline Testing Following Tumor-only Sequencing of Prostate Cancer.

Background: Tumor-only genomic profiling is an important tool in therapeutic management of men with prostate cancer. Since clinically actionable germline variants may be reflected in tumor profiling, it is critical to identify which variants have a higher risk of being germline in origin to better counsel patients and prioritize genetic testing.

Objective: To determine when variants found on tumor-only sequencing of prostate cancers should prompt confirmatory germline testing.

Germline Variants Identified in Patients with Early-onset Renal Cell Carcinoma Referred for Germline Genetic Testing.

Background: Despite guidelines recommending genetic counseling for patients with early-onset renal cell carcinoma (RCC), studies interrogating the spectrum of germline mutations and clinical associations in patients with early-onset RCC are lacking.

Objective: To define the germline genetic spectrum and clinical associations for patients with early-onset RCC diagnosed at age ≤46 yr who underwent genetic testing.

Design, Setting, And Participants: We retrospectively identified patients with early-onset RCC who underwent germline testing at our institution from February 2003 to June 2020.

Developments in Vascular-Targeted Photodynamic Therapy for Urologic Malignancies.

With improved understanding of cancer biology and technical advancements in non-invasive management of urological malignancies, there is renewed interest in photodynamic therapy (PDT) as a means of focal cancer treatment. The application of PDT has also broadened as a result of development of better-tolerated and more effective photosensitizers. Vascular-targeted PDT (VTP) using padeliporfin, which is a water-soluble chlorophyll derivative, allows for tumor-specific cytotoxicity and has demonstrated efficacy in the management of urologic malignancies.

Assessing the Quality of Surgical Care for Clinically Localized Prostate Cancer: Results from the CEASAR Study.

Purpose: Prior studies suggest that nationally endorsed quality measures for prostate cancer care are not linked closely with outcomes. Using a prospective, population based cohort we measured clinically relevant variation in structure, process and outcome measures in men undergoing radical prostatectomy.

Materials And Methods: The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) Study enrolled men with clinically localized prostate cancer diagnosed from 2011 to 2012 with 1,069 meeting the final inclusion criteria.

Management of High-grade T1 Urothelial Carcinoma.

Purpose Of Review: The optimal management of high-grade T1 (HGT1) urothelial carcinoma (UC) is complex given its high rate of recurrence, progression, and cancer-specific mortality as well as its clinical variability. Our current treatment paradigm has been supplemented by recent data describing the expanding options for salvage intravesical therapy, bladder preservation, and the promising role of molecular epidemiology. In the current review, we attempt to summarize and critically analyze these studies.

Fibromyxoid Nephrogenic Adenoma in the Ureter.

Nephrogenic adenoma is a benign lesion found in the genitourinary tract, often at sites of prior inflammation, and is characterized by tubular, papillary, or tubulopapillary structures. It is thought to arise from distal migration and implantation of renal tubular cells into the renal pelvis, ureter, bladder, or urethra. These tumors often resemble malignant neoplasms.

Reversibility of Murine Motor Deficits Following Hemi-Craniectomy and Cranioplasty.

Background: Hemi-craniectomy is a common surgical procedure which allows the brain to swell and herniate and is often utilized to treat traumatic brain injury. When left untreated the scalp skin typically sinks on the side of the craniectomy creating a phenotype termed "sinking skin flap syndrome." In addition, these same patients often develop long-term neurocognitive deficits termed "syndrome of the trephined" as a result of their craniectomy which reverse when the cranial skull is replaced.