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.

Tumor characteristics in immunosuppressed and renal dysfunction populations.

Purpose: Renal transplantation and end-stage renal disease are increasingly common. Renal dysfunction and immunosuppression are two risk factors in the development of renal cell carcinoma. Carcinomas in these patients are thought to be more indolent, however data are limited and mixed.

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.

Incidence and management of prostatic urethra recurrence in a cohort of 21 patients who received BCG induction for non-muscle invasive bladder cancer.

Purpose: To describe the incidence and management of patients who develop a prostatic urethral (PU) urothelial carcinoma recurrence after Bacillus Calmette-Guerin (BCG) induction for non-muscle invasive bladder cancer (NMIBC).

Materials And Methods: We performed a retrospective cohort study of all patients who received BCG induction at our institution from 1996 to 2021 (N = 642) for NMIBC. All patients with pathologically confirmed PU involvement following BCG induction with no known PU involvement pre-BCG were included.

Clinical and Genomic Landscape of FGFR3-Altered Urothelial Carcinoma and Treatment Outcomes with Erdafitinib: A Real-World Experience.

Purpose: Erdafitinib is the only FDA-approved targeted therapy for FGFR2/3-altered metastatic urothelial cancer. We characterized the genetic landscape of FGFR-altered urothelial carcinoma and real-world clinical outcomes with erdafitinib, including on-treatment genomic evolution.

Experimental Design: Prospectively collected clinical data were integrated with institutional genomic data to define the landscape of FGFR2/3-altered urothelial carcinoma.

Survival outcomes in patients with muscle invasive bladder cancer undergoing radical vs. partial cystectomy.

Purpose: While radical cystectomy (RC) is the standard of care for muscle invasive bladder cancer (MIBC), partial cystectomy (PC) is an effective alternative in select patients. We sought to examine differences in survival for RC and PC in a hospital-based registry.

Material And Methods: We identified patients diagnosed with cT2-4 bladder cancer who underwent RC or PC from 2003 to 2015 in the National Cancer Database (NCDB).

Readmissions after radical nephrectomy in a national cohort.

Objective: To analyze the factors and costs associated with 30-day readmissions for patients undergoing radical nephrectomy.

Materials And Methods: We used the 2014 Nationwide Readmission Database to identify adults who underwent radical nephrectomy for renal cancer, stratified by surgical approach. We determined patient factors associated with readmission rates, diagnoses, and costs using multivariate logistic regression.

Genomic heterogeneity as a barrier to precision oncology in urothelial cancer.

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.

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.

FOXA1 repression drives lineage plasticity and immune heterogeneity in bladder cancers with squamous differentiation.

Cancers arising from the bladder urothelium often exhibit lineage plasticity with regions of urothelial carcinoma adjacent to or admixed with regions of divergent histomorphology, most commonly squamous differentiation. To define the biologic basis for and clinical significance of this morphologic heterogeneity, here we perform integrated genomic analyses of mixed histology bladder cancers with separable regions of urothelial and squamous differentiation. We find that squamous differentiation is a marker of intratumoral genomic and immunologic heterogeneity in patients with bladder cancer and a biomarker of intrinsic immunotherapy resistance.

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.

Clinical and Genomic Characterization of Bladder Carcinomas With Glandular Phenotype.

Purpose: To compare oncologic outcomes and genomic alteration profiles in patients with bladder and urachal adenocarcinoma, urothelial carcinoma (UC) with glandular differentiation, and UC, not otherwise specified (NOS) undergoing surgical resection, with emphasis on response to systemic therapy.

Methods: We identified patients with bladder cancer with glandular variants who underwent surgical resection at Memorial Sloan Kettering from 1995 to 2018 (surgical cohort) and/or patients who had tumor sequencing using a targeted next-generation sequencing platform (genomics cohort). Pathologic complete and partial response rates to neoadjuvant chemotherapy (NAC) and recurrence-free and cancer-specific survival were measured.

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.

Head-to-Head Comparison of Ga-PSMA-11 PET/CT and mpMRI with a Histopathology Gold Standard in the Detection, Intraprostatic Localization, and Determination of Local Extension of Primary Prostate Cancer: Results from a Prospective Single-Center Imaging Trial.

The role of prostate-specific membrane antigen (PSMA)-targeted PET in comparison to multiparametric MRI (mpMRI) in the evaluation of intraprostatic cancer foci is not well defined. The aim of our study was to compare the diagnostic performance of Ga-PSMA-11 PET/CT (PSMA PET/CT), mpMRI, and PSMA PET/CT + mpMRI using 3 independent masked readers for each modality and with histopathology as the gold standard in the detection, intraprostatic localization, and determination of local extension of primary prostate cancer. Patients with intermediate- or high-risk prostate cancer who underwent PSMA PET/CT as part of a prospective trial (NCT03368547) and mpMRI before radical prostatectomy were included.

Sequencing of Renal Mass Biopsy and Ablation: Results from the National Cancer Database.

Introduction: We assessed current utilization and sequencing of renal mass biopsy (RMB) and thermal ablation for renal cell carcinoma (RCC) patients in the United States.

Methods: The 2004-2014 National Cancer Database was queried for adult patients with histopathologically diagnosed American Joint Committee on Cancer stage I RCC ≤5 cm undergoing RMB and thermal ablation. RMB sequencing was stratified into "staged RMB" (separate sessions for RMB/ablation) or "concomitant RMB" (same date RMB/ablation).

When is a Seminoma not a Seminoma? The Incidence, Risk Factors and Management of Patients With Testicular Seminoma With Discordant Elevated Serum Alpha-fetoprotein.

Objective: To describe the incidence, clinical and demographic factors, and treatment patterns associated with discordant elevated alpha-fetoprotein (AFP) findings in patients with pure seminomatous histology.

Methods: We queried the National Cancer Database to identify patients with testicular germ cell tumors (GCT) diagnosed in 2011-2015. Patients were grouped based on histologic diagnosis and pre-operative serum AFP level.

Molecular classification and diagnostics of upper urinary tract urothelial carcinoma.

Upper urinary tract urothelial carcinoma (UTUC) is one of the common urothelial cancers. Its molecular pathogenesis, however, is poorly understood, with no useful biomarkers available for accurate diagnosis and molecular classification. Through an integrated genetic study involving 199 UTUC samples, we delineate the landscape of genetic alterations in UTUC enabling genetic/molecular classification.

The role of neoadjuvant chemotherapy, lymph node dissection, and treatment delay in patients with muscle-invasive bladder cancer undergoing partial cystectomy.

Objectives: To investigate treatment patterns of partial cystectomy (PC), neoadjuvant chemotherapy (NAC), lymph node dissection (LND), and treatment delays, and the associations with overall survival (OS) among patients with muscle-invasive bladder cancer.

Patients And Methods: We identified patients with cT2-4cN0cM0 urothelial carcinoma of the bladder in the National Cancer Database who underwent PC from 2007 through 2015. We performed descriptive statistics and assessed temporal trends using the Cochrane-Armitage test.

Relationship Between Mobile Digital Sensor Monitoring and Perioperative Outcomes: Systematic Review.

Background: Monitoring surgical recovery has traditionally been confined to metrics measurable within the hospital and clinic setting. However, commercially available mobile sensors are now capable of extending measurements into a patient's home. As these sensors were developed for nonmedical applications, their clinical role has yet to be established.