Gain of Chromosome 5q Predicts a Favorable Prognosis in Localized Renal Cell Carcinoma.

Approximately 65% of renal cell carcinomas (RCC) are diagnosed at a localized stage. We investigated the chromosome 5q gain impact on disease-free survival (DFS) in RCC patients. Overall, 676 patients with stages 1-2 RCC and having cytogenetic analysis were included.

CD70 is Consistently Expressed in Primary and Metastatic Clear Cell Renal Cell Carcinoma.

Background: CD70 is commonly overexpressed in renal cell carcinoma and is minimally expressed in normal human tissue, making it a potential therapeutic target for patients with advanced renal cell carcinoma. The expression frequency of CD70 in metastatic renal cell carcinoma is not well established.

Materials And Methods: We assessed CD70 immunohistochemistry in 391 primary renal tumors and 72 metastatic renal cell carcinomas on a tissue microarray including 26 sets of paired primary and metastatic tumors.

Pathological and genetic markers improve recurrence prognostication with the University of California Los Angeles Integrated Staging System for patients with clear cell renal cell carcinoma.

Purpose: To elucidate which patients with clear cell renal cell carcinoma have the highest risk for disease relapse after curative nephrectomy is challenging but is acutely relevant in the era of approved adjuvant therapies. Pathological and genetic markers were used to improve the University of California Los Angeles Integrated Staging System (UISS) for the risk stratification and prognostication of recurrence free survival (RFS).

Patients And Methods: Necrosis, sarcomatoid features, Rhabdoid features, chromosomal loss 9p, combined chromosomal loss 3p14q and microvascular invasion (MVI) were tested in univariable and multivariable analyses for their ability to improve the discriminatory ability of the UISS.

Thioredoxin 1 (Trx1) is associated with poor prognosis in clear cell renal cell carcinoma (ccRCC): an example for the crucial role of redox signaling in ccRCC.

Purpose: Thioredoxins are major regulatory proteins of oxidative signaling. Trx1 is the most prominent thioredoxin and, therefore, the current study sought to evaluate the prognostic role of Trx1 in ccRCC.

Methods And Patients: A tissue micro-array (TMA) study was carried out to evaluate the association of Trx1 with clinicopathological features and survival outcome.

p53 is functionally inhibited in clear cell renal cell carcinoma (ccRCC): a mechanistic and correlative investigation into genetic and molecular characteristics.

Purpose: Although p53 is rarely mutated in ccRCC, its overexpression has been linked to poor prognosis. The current study sought to elucidate the unique role of p53 in ccRCC with genomic, proteomic, and functional analyses.

Materials And Methods: Data from the Cancer Genome Atlas (TCGA) were evaluated for genomic and proteomic characteristics of p53; a tissue micro array (TMA) study was carried out to evaluate the association of p53 and phosphorylated p53 (pp53) with clinical outcome.

Prognostic Impact of Membranous/Nuclear Epidermal Growth Factor Receptor Localization in Clear Cell Renal Cell Carcinoma.

EGFR is overexpressed in the majority of clear cell renal cell carcinomas (CCRCCs). Although EGFR deregulation was found to be of great significance in CCRCC biology, the EGFR overexpression is not associated with EGFR-targeted therapy responsiveness. Moreover, the prognostic role of EGFR expression remains controversial.

Evaluation of Clear Cell, Papillary, and Chromophobe Renal Cell Carcinoma Metastasis Sites and Association With Survival.

Importance: There exists considerable biological and clinical variability between histologic variants of metastatic renal cell carcinoma (mRCC). Data reporting on patterns of metastasis in histologic variants of mRCC are sparse.

Objective: To characterize sites of metastasis and their association with survival across the 3 most common histologic variants of mRCC: clear cell (ccRCC), papillary (pRCC), and chromophobe (chrRCC).

Systemic treatment of advanced/metastatic renal cell carcinoma in the context of SARS-CoV-2 pandemic: recommendations from the interdisciplinary working group for renal tumors (IAG-N).

This letter summarizes recommendations from the interdisciplinary working group of renal tumors (IAGN) of the German Cancer Society for the systemic treatment of advanced/metastatic renal cell carcinoma in the context of the current SARS-CoV-2 pandemic.

The cytosolic isoform of glutaredoxin 2 promotes cell migration and invasion.

Backround: Cytosolic glutaredoxin 2 (Grx2c) controls axonal outgrowth and is specifically induced in many cancer cell lines. We thus hypothesized that Grx2c promotes cell motility and invasiveness.

Methods: We characterized the impact of Grx2c expression in cell culture models.

The VENUSS prognostic model to predict disease recurrence following surgery for non-metastatic papillary renal cell carcinoma: development and evaluation using the ASSURE prospective clinical trial cohort.

Background: The current World Health Organization classification recognises 12 major subtypes of renal cell carcinoma (RCC). Although these subtypes differ on molecular and clinical levels, they are generally managed as the same disease, simply because they occur in the same organ. Specifically, there is a paucity of tools to risk-stratify patients with papillary RCC (PRCC).

Evaluation of the prognostic role of co-morbidities on disease outcome in renal cell carcinoma patients.

Background: Co-morbidities may induce local and systemic tumor progression of renal cell carcinoma (RCC); however, the prognostic impact of co-morbidities has not yet been well characterized.

Patients And Methods: RCC patients (n = 2206) surgically treated at three academic institutions in the US and Europe were included in the analysis. Presence of diabetes mellitus, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, coronary heart disease, and hypothyroidism were investigated for their association with clinicopathological features and cancer-specific survival.

Active Smoking Is Associated With Worse Prognosis in Metastatic Renal Cell Carcinoma Patients Treated With Targeted Therapies.

Background: Smoking increases the risk of developing renal cell carcinoma (RCC) but the effect of tobacco consumption on survival outcome of patients with metastatic RCC (mRCC) treated with targeted therapies has not been well characterized.

Patients And Methods: The primary outcome was overall survival (OS) and secondary outcome was progression-free survival (PFS). Patients with mRCC were categorized as current, former, and nonsmokers at the time of starting targeted therapy.

Receptor activator of NF-κB (RANK)-mediated induction of metastatic spread and association with poor prognosis in renal cell carcinoma.

Background: Inhibition of the receptor activator of NF-κB ligand (RANKL) has become a standard of care supportive treatment to prevent skeletal related events in cancer patients. Moreover, RANKL inhibition has been implicated with better survival outcome in lung cancer, while RANKL expression induces tumor progression and metastatic spread in vivo in breast cancer. Whether RANK/RANKL may have an impact on the pathogenesis of clear cell renal cell carcinoma (ccRCC) is currently unknown.

Microvascular and lymphovascular tumour invasion are associated with poor prognosis and metastatic spread in renal cell carcinoma: a validation study in clinical practice.

Objective: To validate microvascular (MVI) and lymphovascular (LVI) invasion as prognostic factors in patients with renal cell carcinoma (RCC).

Patients And Methods: Data of patients with RCC who underwent radical or nephron-sparing surgery were prospectively collected from three academic centres. The occurrence of MVI and LVI was determined with standard staining protocols by experienced pathologists at the time of diagnosis.

Partial nephrectomy versus radical nephrectomy for clinical localised renal masses.

Background: Partial nephrectomy and radical nephrectomy are the relevant surgical therapy options for localised renal cell carcinoma. However, debate regarding the effects of these surgical approaches continues and it is important to identify and summarise high-quality studies to make surgical treatment recommendations.

Objectives: To assess the effects of partial nephrectomy compared with radical nephrectomy for clinically localised renal cell carcinoma.

Adjuvant Treatment of High-risk Renal Cell Carcinoma: Leaving the Desert?

In a recent trial, adjuvant treatment with sunitinib significantly prolonged disease-free survival compared to placebo. This positive result is muted by the rate of side effects and overtreatment, raising the question of proper patient and agent selection in the adjuvant setting.

Risk factors and model for predicting toxicity-related treatment discontinuation in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted therapy: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Background: Vascular endothelial growth factor (VEGF)-targeted therapies are standard treatment for metastatic renal cell carcinoma (mRCC); however, toxicities can lead to drug discontinuation, which can affect patient outcomes. This study was aimed at identifying risk factors for toxicity and constructing the first model to predict toxicity-related treatment discontinuation (TrTD) in mRCC patients treated with VEGF-targeted therapies.

Methods: The baseline characteristics, treatment outcomes, and toxicity data were collected for 936 mRCC patients receiving first-line VEGF-targeted therapy from the International Metastatic Renal Cell Carcinoma Database Consortium.

PI3K/AKT/mTOR pathway plays a major pathogenetic role in glycogen accumulation and tumor development in renal distal tubules of rats and men.

Activation of the PI3K/AKT/mTOR pathway is a crucial molecular event in human clear cell renal cell carcinoma (ccRCC), and is also upregulated in diabetic nephropathy. In diabetic rats metabolic changes affect the renal distal tubular epithelium and lead to glycogen-storing Armanni-Ebstein lesions (AEL), precursor lesions of RCC in the diabetes induced nephrocarcinogenesis model. These lesions resemble human sporadic clear cell tubules (CCT) and tumor cells of human ccRCC.

The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study.

Background: Previous prognostic models for second-line systemic therapy in patients with metastatic renal cell carcinoma have not been studied in the setting of targeted therapy. We sought to validate the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in patients with metastatic renal cell carcinoma receiving next-line targeted therapy after progression on first-line targeted therapy.

Methods: In this population-based study, we analysed patients who received second-line targeted therapy for metastatic renal cell carcinoma at 19 centres in Canada, USA, Greece, Japan, Singapore, South Korea, and Denmark.

Characterizing the impact of lymph node metastases on the survival outcome for metastatic renal cell carcinoma patients treated with targeted therapies.

Background: It is unknown whether lymph node metastases (LNM) and their localization negatively affect clinical outcome in metastatic renal cell carcinoma (mRCC) patients.

Objective: To evaluate the clinicopathological features, survival outcome, and treatment response in mRCC patients with LNM versus those without LNM after treatment with targeted therapies (TT).

Design, Setting, And Participants: Patients (n=2996) were first analyzed without consideration of lymph node (LN) localization or histologic subtype.

Outcome of patients with metastatic sarcomatoid renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium.

Background: Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking.

Patients And Methods: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed.

First-line Mammalian target of rapamycin inhibition in metastatic renal cell carcinoma: an analysis of practice patterns from the International Metastatic Renal Cell Carcinoma Database Consortium.

Introduction/background: Approval of the mTOR inhibitors for the treatment of mRCC was based on efficacy in poor-risk patients in the first-line setting for temsirolimus and in vascular endothelial growth factor inhibitor-refractory patients for everolimus. We strove to characterize temsirolimus and everolimus use and effectiveness in the first-line setting.

Patients And Methods: We performed a retrospective database analysis of mRCC patients who received mTOR inhibitors as first-line targeted therapy.