Clinical implications of tumor laterality in renal cell carcinoma.

Introduction: It is unclear whether laterality has prognostic implications for patients with renal cell carcinoma (RCC). Some suggest that left sided tumors may have worse survival outcomes. The purpose of this study is to associate tumor characteristics and clinical outcomes with laterality in patients with RCC.

Clinical Impact of the CARMENA Trial on Cytoreductive Nephrectomy Practices in the USA: A Difference-in-differences Analysis.

Background And Objective: It is unclear whether cytoreductive nephrectomy (CN) practices have changed in the USA after the publication of the Cancer du Rein Métastatique Nephrectomie et Antiangiogéniques (CARMENA) trial in 2018. Our primary objective is to determine the effect of the CARMENA trial on CN rates in the USA.

Methods: Patients were identified in the National Cancer Database from 2004 to 2020.

Preoperative Oxybutynin Reduces Postoperative Opioid Use Following Common Pediatric Urology Surgeries.

Purpose: Urologic surgery involving placement of an indwelling ureteral and/or urethral drain can be associated with significant catheter-related bladder discomfort causing increased postoperative morbidity and opioid medication use. We sought to assess if a single dose of oxybutynin given preoperatively reduces immediate postoperative opioid use in common pediatric urology surgeries.

Materials And Methods: This single-institution retrospective study identified pediatric patients who underwent surgery on the urinary tract with concomitant placement of a urethral and/or ureteral drain.

Increased spatial coupling of integrin and collagen IV in the immunoresistant clear cell renal cell carcinoma tumor microenvironment.

Background: Immunotherapy (IO) has improved survival for patients with advanced clear cell renal cell carcinoma (ccRCC), but resistance to therapy develops in most patients. We use cellular-resolution spatial transcriptomics in patients with IO naïve and IO exposed primary ccRCC tumors to better understand IO resistance. Spatial molecular imaging (SMI) was obtained for tumor and adjacent stroma samples.

Predicting Limited Survival Following Inguinal Lymph Node Dissection in Penile Cancer: Should We Revisit the Goals of Care?

Objective: Patients with advanced penile squamous cell cancer have a poor prognosis and can benefit from early palliative care consultation. We built a model to identify those patients most likely to benefit.

Methods: Patients with penile squamous cell cancer undergoing inguinal lymph node dissection were identified from the National Cancer Database (NCDB) and a multi-institutional international dataset (INT).

Downstaging and Survival Associated with Neoadjuvant Immunotherapy Before Radical Cystectomy for Muscle-invasive Bladder Cancer.

Background: Neoadjuvant cisplatin-containing chemotherapy before radical cystectomy is the standard of care for patients with localized muscle-invasive bladder cancer (MIBC). However, a large proportion of patients are ineligible for cisplatin. Single-arm phase 2 neoadjuvant immunotherapy trials have reported promising tumor response rates, but interpretation is limited owing to lack of a comparator arm.

Geospatial characterization of immune cell distributions and dynamics across the microenvironment in clear cell renal cell carcinoma.

Introduction: In clear cell renal cell carcinoma (ccRCC), tumor-associated macrophage (TAM) induction of CD8+T cells into a terminally exhausted state has been implicated as a major mechanism of immunotherapy resistance, but a deeper biological understanding is necessary.

Methods: Primary ccRCC tumor samples were obtained from 97 patients between 2004 and 2018. Multiplex immunofluorescence using lymphoid and myeloid markers was performed in seven regions of interest per patient across three predefined zones, and geospatial analysis was performed using Ripley's K analysis, a methodology adapted from ecology.

Selecting patients for magnetic resonance imaging cognitive versus ultrasound fusion biopsy of the prostate: A within-patient comparison.

Objectives: To compare overall agreement between magnetic resonance imaging (MRI)-ultrasound (US) fusion biopsy (FB) and MRI cognitive fusion biopsy (CB) of the prostate and determine which factors affect agreement for prostate cancer (PCa) who underwent both modalities in a prospective within-patient protocol.

Patients And Methods: From August 2017 to January 2021, patients with at least one Prostate Imaging Reporting & Data System (PI-RADS) 3 or higher lesion on multiparametric MRI underwent transrectal FB and CB in a prospective within-patient protocol. CB was performed for each region of interest (ROI), followed by FB, followed by standard 12 core biopsy.

A Targetable Myeloid Inflammatory State Governs Disease Recurrence in Clear-Cell Renal Cell Carcinoma.

Unlabelled: It is poorly understood how the tumor immune microenvironment influences disease recurrence in localized clear-cell renal cell carcinoma (ccRCC). Here we performed whole-transcriptomic profiling of 236 tumors from patients assigned to the placebo-only arm of a randomized, adjuvant clinical trial for high-risk localized ccRCC. Unbiased pathway analysis identified myeloid-derived IL6 as a key mediator.

Proteogenomic, Epigenetic, and Clinical Implications of Recurrent Aberrant Splice Variants in Clear Cell Renal Cell Carcinoma.

Background: Alternative mRNA splicing can be dysregulated in cancer, resulting in the generation of aberrant splice variants (SVs). Given the paucity of actionable genomic mutations in clear cell renal cell carcinoma (ccRCC), aberrant SVs may be an avenue to novel mechanisms of pathogenesis.

Objective: To identify and characterize aberrant SVs enriched in ccRCC.

Calibrated Regression Models Based on the Risk of Clinical Nodal Metastasis Should be Used as Decision Aids for Prostate Cancer Staging to Reduce Unnecessary Imaging.

Introduction: Radionuclide imaging will change the role of computed tomography and magnetic resonance imaging (CT/MRI) for prostate cancer (CaP) staging. Current guidelines recommend abdominopelvic imaging for new cases of CaP categorized as unfavorable intermediate risk (UIR) or higher. We assessed the performance characteristics of CT/MRI based on the National Comprehensive Cancer Network (NCCN) guidelines and developed a model that predicts cN1 disease using conventional imaging.

Survival Outcomes Associated With Cytoreductive Nephrectomy in Patients With Metastatic Clear Cell Renal Cell Carcinoma.

Importance: Level I evidence has failed to demonstrate an overall survival (OS) advantage for cytoreductive nephrectomy in patients with metastatic clear cell renal cell carcinoma (ccRCC) in the modern era, which is at odds with observational studies reporting a marked OS benefit associated with these operations. These observational studies were not designed to adjust for unmeasured confounding.

Objective: To assess whether cytoreductive nephrectomy is associated with improved OS in patients with metastatic ccRCC.

Quantification of T- and B-cell Immune Receptor Distribution Diversity Characterizes Immune Cell Infiltration and Lymphocyte Heterogeneity in Clear Cell Renal Cell Carcinoma.

Unlabelled: Immune-modulating systemic therapies are often used to treat advanced cancer such as metastatic clear cell renal cell carcinoma (ccRCC). Used alone, sequence-based biomarkers neither accurately capture patient dynamics nor the tumor immune microenvironment. To better understand the tumor ecology of this immune microenvironment, we quantified tumor infiltration across three distinct ccRCC patient tumor cohorts using complementarity determining region-3 (CDR3) sequence recovery counts in tumor-infiltrating lymphocytes and a generalized diversity index (GDI) for CDR3 sequence distributions.

Evaluation of Patient-Reported Outcomes (PROs) Protocol Content and Reporting for Clinical Trials that Lead to the approval of frontline Immune Checkpoint Blockade Combination for Patients with Advanced Renal Cell Carcinoma - The Patients' Voice or a Missed Opportunity.

Introduction: Immune checkpoint blockade (ICB) is a rapidly emerging field of oncology that has revolutionized the metastatic renal cell carcinoma (mRCC) treatment. Four recent treatment regimens Nivolumab-Ipilimumab, Pembrolizumab-Axitinib, Nivolumab-Cabozantinib, and Pembrolizumab-Lenvatinib-have demonstrated improved clinical endpoints compared to standard of care and are endorsed by NCCN (2021). However, data on patient-reported outcomes (PROs) for patients receiving these regimens are limited.

spatialTIME and iTIME: R package and Shiny application for visualization and analysis of immunofluorescence data.

Summary: Multiplex immunofluorescence (mIF) staining combined with quantitative digital image analysis is a novel and increasingly used technique that allows for the characterization of the tumor immune microenvironment (TIME). Generally, mIF data is used to examine the abundance of immune cells in the TIME; however, this does not capture spatial patterns of immune cells throughout the TIME, a metric increasingly recognized as important for prognosis. To address this gap, we developed an R package spatialTIME that enables spatial analysis of mIF data, as well as the iTIME web application that provides a robust but simplified user interface for describing both abundance and spatial architecture of the TIME.

Risk factors and survival outcomes for upstaging after inguinal lymph node dissection for cN1 penile squamous cell carcinoma.

Objectives: To identify incidence and risk factors for upstaging from cN1 to pN2/N3 at inguinal lymphadenectomy (ILND) for penile cancer (pSCC). Our secondary objective is to assess survival outcomes and associations for cN1 patients undergoing ILND.

Subjects/patients And Methods: Patients with pT≥1cN1cM0 pSCC who underwent bilateral ILND and had complete data were identified in a multi-institutional international cohort from 8 referral centers in 7 countries diagnosed from 1980 to 2017.

Comparative effectiveness analysis of first-line immunotherapy versus chemotherapy in metastatic urothelial carcinoma of the bladder.

Background: Clinical trials have not shown a significant overall survival (OS) difference between chemotherapy and immunotherapy as first-line agents in metastatic urothelial carcinoma (UC). However, the generalizability of these findings in a real-world setting has not yet been evaluated in comparative effectiveness studies.

Objective: To assess the effectiveness of first-line immunotherapy compared with chemotherapy regimens on OS in patients with metastatic UC of the bladder.