A Call for a Neoadjuvant Kidney Cancer Consortium: Lessons Learned from Other Cancer Types.

Neoadjuvant systemic treatment strategies have improved outcomes in several solid tumour types. This success has not yet been replicated in renal cell carcinoma (RCC). A consensus and international collaboration are urgently needed for the development of adaptive perioperative immunotherapy strategies for patients with RCC at high risk of recurrence.

Prediction of checkpoint inhibitor immunotherapy efficacy for cancer using routine blood tests and clinical data.

Predicting whether a patient with cancer will benefit from immune checkpoint inhibitors (ICIs) without resorting to advanced genomic or immunologic assays is an important clinical need. To address this, we developed and evaluated SCORPIO, a machine learning system that utilizes routine blood tests (complete blood count and comprehensive metabolic profile) alongside clinical characteristics from 9,745 ICI-treated patients across 21 cancer types. SCORPIO was trained on data from 1,628 patients across 17 cancer types from Memorial Sloan Kettering Cancer Center.

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.

Obesity-dependent selection of driver mutations in cancer.

Obesity is a risk factor for cancer, but whether obesity is linked to specific genomic subtypes of cancer is unknown. We examined the relationship between obesity and tumor genotype in two clinicogenomic corpora. Obesity was associated with specific driver mutations in lung adenocarcinoma, endometrial carcinoma and cancers of unknown primaries, independent of clinical covariates, demographic factors and genetic ancestry.

Sample Site Impacts RNA Biomarkers for Renal Cell Carcinoma.

Immunotherapy (ICIs) remains a mainstay for treatment of advanced clear-cell renal cell carcinoma (ccRCC). Biomarker analyses have demonstrated that gene expression profiles are associated with regimen-specific outcomes. These transcriptomic analyses used mixed sample cohorts (primary and metastatic tumor specimens) and it is unknown whether the clinical relevance of transcriptomic signatures is impacted by tissue site.

Clinical Outcomes and Targeted Genomic Analysis of Renal Cell Carcinoma Brain Metastases Treated with Stereotactic Radiosurgery.

Background: Molecular profiles of renal cell carcinoma (RCC) brain metastases (BMs) are not well characterized. Effective management with locoregional therapies, including stereotactic radiosurgery (SRS), is critical as systemic therapy advancements have improved overall survival (OS).

Objective: To identify clinicogenomic features of RCC BMs treated with SRS in a large patient cohort.

Radiodensities of Skeletal Muscle and Visceral Adipose Tissues Are Prognostic Factors in Clear-Cell Renal Cell Carcinoma.

Background: Body composition may be related to survival in patients with clear-cell renal cell carcinoma (ccRCC), but studies have not simultaneously considered adipose and muscle tissue quantity and radiodensity.

Methods: We analyzed data from 1,022 patients with ccRCC who underwent nephrectomy between 2000 and 2020 at Memorial Sloan Kettering Cancer Center. Skeletal muscle, visceral adipose tissue, and subcutaneous adipose tissue indexes (cm2/m2) and radiodensities [Hounsfield units (HU)] were assessed from noncontrast presurgical CT scans; clinical and demographic characteristics were available from the time of surgery.

Surgical Outcomes and Genomic Insights of Nonclear Cell Renal Cell Carcinoma With Synchronous and Metachronous Nodal Disease.

Introduction: Oncological outcomes in patients with nonclear cell renal cell carcinoma (non-ccRCC) treated with surgery for locoregional nodal disease (ND) remain incompletely characterized. The objective was to investigate the characteristics and outcomes of non-ccRCC patients treated with lymph node dissection (LND) and salvage-LND (S-LND).

Methods: A total of 1627 patients underwent nephrectomy for nonmetastatic non-ccRCC at Memorial Sloan Kettering Cancer Center between 2007 and 2023.

Skeletal muscle and visceral adipose radiodensities are pre-surgical, non-invasive markers of aggressive kidney cancer.

Introduction: Most studies on body composition in kidney cancer have been conducted among patients with metastatic disease. Given that aggressive tumours can adversely impact body composition and even non-metastatic tumours can be aggressive, we evaluated associations between pre-surgical body composition features and tumour pathological features in patients with non-metastatic clear cell renal cell cancer (ccRCC).

Methods: The Resolve Cohort consists of 1239 patients with non-metastatic ccRCC who underwent nephrectomy at Memorial Sloan Kettering Cancer Center between 2000 and 2020.

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.

Chromophobe renal cell carcinoma.

Chromophobe renal cell carcinoma (ChRCC) is the second most common variant histology (non-clear cell) RCC. ChRCC is distinct from clear cell RCC (ccRCC) in terms of genetics, genomics, metabolism, cell of origin, and response to targeted and immune therapies. The pathogenesis of ChRCC remains unclear, but current data suggest two potential mechanisms: mTORC1 hyperactivation through PTEN pathway mutations and mitochondrial dysfunction leading to oxidative stress.

Adverse pathologic features impact survival outcomes for small renal masses following nephrectomy.

Purpose: While most small renal masses (SRM) < 4 cm have an excellent prognosis following resection, the impact of adverse T3a pathologic features on oncologic outcomes of SRMs remains unclear. We sought to compare clinical outcomes for surgically resected pT3a versus pT1a SRMs at our institution.

Materials And Methods: We retrospectively reviewed records of patients who underwent radical or partial nephrectomy (RN, PN) for renal tumors <4 cm at our institution between 2010 and 2020.

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.

Prognostic Factors for Survival in Patients Undergoing Surveillance After Cytoreductive Nephrectomy.

Purpose: The clinical course of patients being placed on surveillance in a cohort of systemic therapy-naïve patients who undergo cytoreductive nephrectomy is not well documented. Thus, we evaluated the clinical course of patients placed on surveillance following cytoreductive nephrectomy and identified predictors of survival.

Materials And Methods: In this large single-institution study, we retrospectively analyzed metastatic renal cell carcinoma patients who underwent cytoreductive nephrectomy followed by surveillance.

Current Landscape of Genomic Biomarkers in Clear Cell Renal Cell Carcinoma.

Context: Dramatic gains in our understanding of the molecular biology of clear cell renal cell carcinoma (ccRCC) have created a foundation for clinical translation to improve patient care.

Objective: To review and contextualize clinically impactful data surrounding genomic biomarkers in ccRCC.

Evidence Acquisition: A systematic literature search was conducted focusing on genomic-based biomarkers with an emphasis on studies assessing clinical outcomes.

Cytoreductive Nephrectomy for Patients with Metastatic Sarcomatoid and/or Rhabdoid Renal Cell Carcinoma Treated with Immune Checkpoint Therapy.

Background: Renal cell carcinoma (RCC) with sarcomatoid and/or rhabdoid (S/R) dedifferentiation is a highly aggressive tumor with a poor prognosis. Immune checkpoint therapy (ICT) has shown significant treatment efficacy in this subtype. There remains uncertainly regarding the role of cytoreductive nephrectomy (CN) for patients with metastatic RCC (mRCC) with S/R who received ICT.