Localised non-metastatic sarcomatoid renal cell carcinoma: a 31-year externally verified study.

Objective: To evaluate post-nephrectomy outcomes and predictors of cancer-specific survival (CSS) between patients with localised sarcomatoid renal cell carcinoma (sRCC) and those with Grade 4 RCC (non-sRCC), as most sRCC research focuses on advanced or metastatic disease with limited studies analysing outcomes of patients with localised non-metastatic sRCC.

Patients And Methods: A total of 564 patients with localised RCC underwent partial or radical nephrectomy between June 1988 to March 2019 for sRCC (n = 204) or World Health Organization/International Society of Urological Pathology Grade 4 non-sRCC (n = 360). The CSS at every stage between groups was assessed.

Immunometabolic coevolution defines unique microenvironmental niches in ccRCC.

Tumor cell phenotypes and anti-tumor immune responses are shaped by local metabolite availability, but intratumoral metabolite heterogeneity (IMH) and its phenotypic consequences remain poorly understood. To study IMH, we profiled tumor/normal regions from clear cell renal cell carcinoma (ccRCC) patients. A common pattern of IMH transcended all patients, characterized by correlated fluctuations in the abundance of metabolites and processes associated with ferroptosis.

Interferon signaling promotes tolerance to chromosomal instability during metastatic evolution in renal cancer.

Molecular routes to metastatic dissemination are critical determinants of aggressive cancers. Through in vivo CRISPR-Cas9 genome editing, we generated somatic mosaic genetically engineered models that faithfully recapitulate metastatic renal tumors. Disruption of 9p21 locus is an evolutionary driver to systemic disease through the rapid acquisition of complex karyotypes in cancer cells.

Are high-risk prostate cancer patients being treated equally? The impact of PSA.

Background: Patients with high-risk (HR) prostate cancer (PCa) represent a heterogeneous group, however, current treatment guidelines do not consider their specific features. The objective of this study was to evaluate treatment trends and outcomes in HR patients defined by PSA alone and otherwise low-risk features.

Methods: Using the National Cancer Database, we identified patients diagnosed with HR PCa between 2010 and 2016.

Spatiotemporal evolution of the clear cell renal cell carcinoma microenvironment links intra-tumoral heterogeneity to immune escape.

Background: Intratumoral heterogeneity (ITH) is a hallmark of clear cell renal cell carcinoma (ccRCC) that reflects the trajectory of evolution and influences clinical prognosis. Here, we seek to elucidate how ITH and tumor evolution during immune checkpoint inhibitor (ICI) treatment can lead to therapy resistance.

Methods: Here, we completed a single-arm pilot study to examine the safety and feasibility of neoadjuvant nivolumab in patients with localized RCC.

Urethral Melanoma - Clinical, Pathological and Molecular Characteristics.

Background: Mucosal melanoma involving the urethra is a rare disease with distinct clinical and molecular characteristics and poor outcomes. Our current knowledge is limited by the small number of reports regarding this disease.

Objective: To describe the clinical, pathological, and molecular characteristics of urethral melanoma.

The role of multiparametric ultrasound in the detection of clinically significant prostate cancer.

Purpose: Transrectal ultrasound (US) imaging is paramount to the successful completion of prostate biopsies. Certain US features have been associated with prostate cancer (PCa), but their utility remains controversial. We explored the role of multiparametric US (mpUS) in the detection of clinically significant PCa.

Effect of COVID-19 on Graduating Urology Resident Case Logs: Analysis of the Accreditation Council of Graduate Medical Education National Data Reports.

Objective: To assess the national case logs of the first graduating urologic resident cohorts to have trained during the COVID-19 pandemic for effects on surgical volumes.

Methods: The nationally aggregated Accreditation Council for Graduate Medical Education urology resident case logs were obtained for graduates of academic years (AYs) 2015-2016 through 2020-2021. Case volume differences for tracked index categories were compared between AYs with a 1-way analysis of variance.

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.

Systemic Immunological Determinants of Oncological Outcomes After Surgery for Localized Renal Cell Carcinoma.

Introduction & Objectives: In systemic therapy trials, a decreasing neutrophil-to-lymphocyte ratio (NLR) after treatment for metastatic renal cell carcinoma (RCC) has been associated with improved oncologic outcomes. Paradoxically, for patients with localized RCC treated with upfront surgery the opposite effect has been reported. We thus aimed to evaluate NLR dynamics on localized RCC recurrence.

Somatic mutations as preoperative predictors of metastases in patients with localized clear cell renal cell carcinoma - An exploratory analysis.

Objective: Recurrent genomic alterations in clear cell renal cell carcinoma (ccRCC) have been associated with treatment outcomes; however, current preoperative predictive models do not include known genetic predictors. We aimed to explore the value of common somatic mutations in the preoperative prediction of metastatic disease among patients treated for localized ccRCC.

Materials And Methods: After obtaining institutional review board approval, data of 254 patients with localized ccRCC treated between 2005 and 2015 who underwent genetic sequencing was collected.

Resource-efficient pooled sequencing expands translational impact in solid tumors.

Intratumoral genetic heterogeneity (ITH) poses a significant challenge to utilizing sequencing for decision making in the management of cancer. Although sequencing of multiple tumor regions can address the pitfalls of ITH, it does so at a significant increase in cost and resource utilization. We propose a pooled multiregional sequencing strategy, whereby DNA aliquots from multiple tumor regions are mixed prior to sequencing, as a cost-effective strategy to boost translational value by addressing ITH while preserving valuable residual tissue for secondary analysis.

Evolving biological associations of upfront cytoreductive nephrectomy in metastatic renal cell carcinoma.

Background: Systemic responses to cytoreductive nephrectomy (CN) in the management of metastatic renal cell carcinoma (mRCC) are variable and difficult to anticipate. The authors aimed to determine the association of CN with modifiable International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors and oncological outcomes.

Methods: Consecutive patients with mRCC referred for potential CN (2009-2019) were reviewed.

High Response Rate and Durability Driven by HLA Genetic Diversity in Patients with Kidney Cancer Treated with Lenvatinib and Pembrolizumab.

Immune checkpoint blockade (ICB) therapy has substantially improved the outcomes of patients with many types of cancers, including renal cell carcinoma (RCC). Initially studied as monotherapy, immunotherapy-based combination regimens have improved the clinical benefit achieved by ICB monotherapy and have revolutionized RCC treatment. While biomarkers like PD-L1 and tumor mutational burden (TMB) are FDA approved as biomarkers for ICB monotherapy, there are no known biomarkers for combination immunotherapies.

Single-cell sequencing links multiregional immune landscapes and tissue-resident T cells in ccRCC to tumor topology and therapy efficacy.

Clear cell renal cell carcinomas (ccRCCs) are highly immune infiltrated, but the effect of immune heterogeneity on clinical outcome in ccRCC has not been fully characterized. Here we perform paired single-cell RNA (scRNA) and T cell receptor (TCR) sequencing of 167,283 cells from multiple tumor regions, lymph node, normal kidney, and peripheral blood of two immune checkpoint blockade (ICB)-naïve and four ICB-treated patients to map the ccRCC immune landscape. We detect extensive heterogeneity within and between patients, with enrichment of CD8A tissue-resident T cells in a patient responsive to ICB and tumor-associated macrophages (TAMs) in a resistant patient.

Identifying Clear Cell Renal Cell Carcinoma Coexpression Networks Associated with Opioid Signaling and Survival.

While opioids constitute the major component of perioperative analgesic regimens for surgery in general, a variety of evidence points to an association between perioperative opioid exposure and longer term oncologic outcomes. The mechanistic details underlying these effects are not well understood. In this study, we focused on clear cell renal cell carcinoma (ccRCC) and utilized RNA sequencing and outcome data from both The Cancer Genome Atlas, as well as a local patient cohort to identify survival-associated gene coexpression networks.

The Clinicopathologic and Molecular Landscape of Clear Cell Papillary Renal Cell Carcinoma: Implications in Diagnosis and Management.

Background: Clear cell papillary renal cell carcinoma (CCPRCC) is a recently described tumor entity. Several questions remain about its epidemiology, molecular features, and clinical behavior.

Objective: To comprehensively evaluate clinicopathologic and molecular features of CCPRCC, and compare it with more common kidney cancer subtypes.

Genomics-based immuno-oncology: bridging the gap between immunology and tumor biology.

The first hypotheses about how the immune system affects cancers were proposed in the early 20th century. These early concepts about cancer immunosurveillance were further developed in the decades that followed, but a detailed understanding of cancer immunity remained elusive. It was only recently, through the advent of high-throughput technologies, that scientists gained the ability to profile tumors with a resolution that allowed for granular assessment of both tumor cells and the tumor microenvironment.

Preoperative nomogram predicting 12-year probability of metastatic renal cancer - evaluation in a contemporary cohort.

Objectives: Preoperative models, based on patient and tumor characteristics, predict risk for adverse outcomes after nephrectomy. Changes in renal tumor characteristics over the last decades, warrant further evaluation using contemporary cohorts. We aimed to validate a previously published preoperative nomogram predicting 12-year metastasis-free probability after nephrectomy for localized renal tumors in a contemporary cohort.

A pan-cancer analysis of PBAF complex mutations and their association with immunotherapy response.

There is conflicting data regarding the role of PBAF complex mutations and response to immune checkpoint blockade (ICB) therapy in clear cell renal cell carcinoma (ccRCC) and other solid tumors. We assess the prevalence of PBAF complex mutations from two large cohorts including the pan-cancer TCGA project (n = 10,359) and the MSK-IMPACT pan-cancer immunotherapy cohort (n = 3700). Across both cohorts, PBAF complex mutations, predominantly PBRM1 mutations, are most common in ccRCC.

DNA damage repair pathway alterations in metastatic clear cell renal cell carcinoma and implications on systemic therapy.

Background: Loss-of-function alterations in DNA damage repair (DDR) genes are associated with human tumorigenesis and may determine benefit from immune-oncology (I/O) agents as shown in colon cancer. However, biologic significance and relevance to I/O in metastatic clear cell RCC (ccRCC) are unknown.

Methods: Genomic data and treatment outcomes were retrospectively collected for patients with metastatic ccRCC.