Does presence of bone metastases portend worsened prognosis in metastatic renal cell carcinoma? Analysis of the REMARCC (Registry of MetAstatic RCC) database.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 655-655
Author(s):  
Aaron Bradshaw ◽  
Maria Carmen Mir ◽  
Ricardo Autorino ◽  
Andrea Minervini ◽  
Maximilian Kriegmair ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Bone Metastases ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Secondary Outcome ◽  
Risk Category ◽  
Metastatic Rcc

655 Background: The presence of brain metastases and bone metastases are generally understood to herald worsened prognosis following nephrectomy in patients with renal cell carcinoma (RCC). However, we sought to determine the effect of bone metastases on outcomes when already present at the time of cytoreductive radical nephrectomy (RN). Methods: Multicenter retrospective analysis of mRCC patients from the REgistry of MetAstatic RCC) REMARCC. Demographics, clinical variables, and outcomes were collected. Patients were stratified into low, medium, and high-risk groups based on Motzer Criteria, and analysis of impact of bone metastases was conducted within each group utilizing Kaplan-Meier analysis (KMA). Multivariable analysis (MVA) was utilized to identify predictors for outcomes. Primary outcome was progression-free survival (PFS) and secondary outcome was overall survival (OS). Results: A total of 447 patients (low- n=30, intermediate- n=208, and high-risk mRCC n=123, median follow-up 14.3 months) were included in the analysis. 124 patients had bone metastases and 323 had mRCC but no bone metastases. No significant demographic differences were noted between groups. KMA (Figure) showed no difference in median PFS for bone metastases vs. non bone metastases groups (6.1 vs. 6.4 months, p=0.973). KMA showed no difference in median OS (25.5 vs. 26.5 months, p=0.958). Similarly, stratification of patients into different Motzer risk categories did not demonstrate difference between bone vs. none bone mRCC for PFS and OS. MVA for PFS demonstrated increasing Motzer risk category (low risk referent vs. intermediate OR 1.89, p=0.006, high risk OR 3.24, p<0.001) as independent predictors. MVA for OS revealed increasing Motzer risk category (low ref, vs. intermediate OR 1.88, p=0.033, high risk 5.17, p<0.001) as being predictive. In neither analysis was presence of bone metastases significant (PFS p=0.690, OS p=0.268). Conclusions: Presence of bone metastases does not independently predict survival or oncologic outcomes in mRCC. While further validation is needed, the prognostic significance of bone metastases may be less than previously thought.

scholarly journals A Mitochondrial Dysfunction and Oxidative Stress Pathway-Based Prognostic Signature for Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-32
Author(s):  
Yue Wu ◽  
Xi Zhang ◽  
Xian Wei ◽  
Huan Feng ◽  
Bintao Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Risk Group ◽  
Prognostic Significance ◽  
Individual Risk ◽  
Cell Renal Cell Carcinoma

Mitochondria not only are the main source of ATP synthesis but also regulate cellular redox balance and calcium homeostasis. Its dysfunction can lead to a variety of diseases and promote cancer and metastasis. In this study, we aimed to explore the molecular characteristics and prognostic significance of mitochondrial genes (MTGs) related to oxidative stress in clear cell renal cell carcinoma (ccRCC). A total of 75 differentially expressed MTGs were analyzed from The Cancer Genome Atlas (TCGA) database, including 46 upregulated and 29 downregulated MTGs. Further analysis screened 6 prognostic-related MTGs (ACAD11, ACADSB, BID, PYCR1, SLC25A27, and STAR) and was used to develop a signature. Kaplan-Meier survival and receiver operating characteristic (ROC) curve analyses showed that the signature could accurately distinguish patients with poor prognosis and had good individual risk stratification and prognostic potential. Stratified analysis based on different clinical variables indicated that the signature could be used to evaluate tumor progression in ccRCC. Moreover, we found that there were significant differences in immune cell infiltration between the low- and high-risk groups based on the signature and that ccRCC patients in the low-risk group responded better to immunotherapy than those in the high-risk group (46.59% vs 35.34%, P = 0.008 ). We also found that the expression levels of these prognostic MTGs were significantly associated with drug sensitivity in multiple ccRCC cell lines. Our study for the first time elucidates the biological function and prognostic significance of mitochondrial molecules associated with oxidative stress and provides a new protocol for evaluating treatment strategies targeting mitochondria in ccRCC patients.

Interleukin-4 Promoter Polymorphisms: A Genetic Prognostic Factor for Survival in Metastatic Renal Cell Carcinoma

2007 ◽  
Vol 25 (7) ◽  
pp. 845-851 ◽  
Author(s):  
Thomas Kleinrath ◽  
Christoph Gassner ◽  
Peter Lackner ◽  
Martin Thurnher ◽  
Reinhold Ramoner
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clinical Course ◽  
Prognostic Significance ◽  
Interleukin 4 ◽  
Promoter Polymorphisms ◽  
Cox Regression Analysis ◽  
Metastatic Rcc

Purpose Renal cell carcinoma (RCC) is considered a cytokine-responsive tumor. The clinical course of a patient may thus be influenced by the patient's capacity to produce distinct cytokines. Therefore, cytokine gene polymorphisms in RCC patients were analyzed to determine haplotype combinations with prognostic significance. Patients and Methods A selection of 21 single nucleotide polymorphisms within the promoter regions of 13 cytokine genes were analyzed in a cross-sectional single-center study of 80 metastatic RCC patients. Univariate and multivariate analyses and the Cox forward-stepwise regression model were chosen to assess genetic risk factors. Results Multivariate Cox regression analysis confirmed by a bootstrap technique identified the heterozygous IL4 genotype −589T−33T/−589C−33C as an independent prognostic risk factor (risk ratio, 3.1; P < .01; 95% CI, 1.4 to 6.9; adjusted for age, sex, and nuclear grading) in metastatic RCC patients. IL4 haplotype −589T−33T and −589C−33C were found with a frequency of 0.069 and 0.925, respectively, which represents a two-fold decrease of IL4 haplotype −589T−33T (P < .01) and an increase of IL4 haplotype −589C−33C frequency (P < .05) in metastatic RCC compared with other white reference study populations. The median overall survival was decreased 3.5-fold (P < .05) in heterozygote patients carrying IL4 haplotype −589T−33T and −589C−33C (3.78 months) compared with patients homozygote for IL4 haplotype −589C−33C (13.44 months). In addition, a linkage disequilibrium between the IL4 gene and the KIF3A gene was detected. Conclusion Our findings indicate that IL4 promoter variants influence prognosis in patients with metastatic RCC and suggest that genetically determined interleukin-4 (IL-4) production affects the clinical course of the disease possibly through regulation of immune surveillance.

Understanding the adverse event experience in the S-TRAC adjuvant trial of sunitinib for high-risk renal cell carcinoma

2020 ◽  
Vol 16 (4) ◽  
pp. 39-47
Author(s):  
Sarah Yenser Wood ◽  
Joanne C Ryan ◽  
Andrew G Clair ◽  
Daniel J George
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Event ◽  
High Risk ◽  
Cell Carcinoma ◽  
Adjuvant Treatment ◽  
Renal Cell ◽  
Disease Recurrence ◽  
Event Management ◽  
The Usa ◽  
Metastatic Rcc

Until recently, the sole treatment for patients with nonmetastatic renal cell carcinoma (RCC) was nephrectomy followed by observation. As metastatic RCC (mRCC) remains largely incurable (5-year survival rate ∼12%), adjuvant treatment, with potential to prevent/delay disease recurrence, is needed. In November 2017, sunitinib was approved in the USA as the first adjuvant therapy for patients at high risk for recurrent RCC postnephrectomy based on results from the S-TRAC trial. Patients eligible for adjuvant treatment have no evidence of disease and may be less willing to tolerate side effects. Therefore, proactive adverse event management is critical for keeping patients on adjuvant treatment and requires understanding the subtle differences in the adverse event profile of sunitinib in the adjuvant versus metastatic RCC setting.

scholarly journals Prognostic Significance of Bone Metastases and Bisphosphonate Therapy in Patients with Renal Cell Carcinoma

2014 ◽  
Vol 66 (3) ◽  
pp. 502-509 ◽  
Author(s):  
Rana R. McKay ◽  
Xun Lin ◽  
Julia J. Perkins ◽  
Daniel Y.C. Heng ◽  
Ronit Simantov ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Bone Metastases ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Significance ◽  
Bisphosphonate Therapy

scholarly journals Prognostic significance of pathologic nodal positivity in non-metastatic patients with renal cell carcinoma who underwent radical or partial nephrectomy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sung Han Kim ◽  
Boram Park ◽  
Eu Chang Hwang ◽  
Sung-Hoo Hong ◽  
Chang Wook Jeong ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Partial Nephrectomy ◽  
Renal Cell ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Survival Outcomes ◽  
Prognostic Impact ◽  
Cox Regression Analysis

AbstractThis retrospective, five-multicenter study was aimed to evaluate the prognostic impact of pathologic nodal positivity on recurrence-free (RFS), metastasis-free (MFS), overall (OS), and cancer-specific (CSS) survivals in patients with non-metastatic renal cell carcinoma (nmRCC) who underwent either radical or partial nephrectomy with/without LN dissection. A total of 4236 nmRCC patients was enrolled between 2000 and 2012, and followed up through the end of 2017. Survival measures were compared between 52 (1.2%) stage pT1-4N1 (LN+) patients and 4184 (98.8%) stage pT1-4N0 (LN−) patients using Kaplan–Meier analysis with the log-rank test and Cox regression analysis to determine the prognostic risk factors for each survival measure. During the median 43.8-month follow-up, 410 (9.7%) recurrences, 141 (3.3%) metastases, and 351 (8.3%) deaths, including 212 (5.0%) cancer-specific deaths, were reported. The risk factor analyses showed that predictive factors for RFS, CSS, and OS were similar, whereas those of MFS were not. After adjusting for significant clinical factors affecting survival outcomes considering the hazard ratios (HR) of each group, the LN+ group, even those with low pT stage, had similar to or worse survival outcomes than the pT3N0 (LN−) group in multivariable analysis and had significantly more relationship with RFS than MFS. All survival measures were significantly worse in pT1-2N1 patients (MFS/RFS/OS/CSS; HR 4.12/HR 3.19/HR 4.41/HR 7.22) than in pT3-4N0 patients (HR 3.08/HR 2.92/HR 2.09/HR 3.73). Therefore, LN+ had an impact on survival outcomes worse than pT3-4N0 and significantly affected local recurrence rather than distant metastasis compared to LN− in nmRCC after radical or partial nephrectomy.

scholarly journals The prognostic significance of NLR in non-metastatic renal cell carcinoma undergoing nephrectomy, A meta-analysis

2019 ◽  
Author(s):  
Li Na ◽  
Huimin Feng ◽  
Ligang Wu ◽  
Xuebo Han ◽  
Jia Cao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Cochrane Library ◽  
Term Survival ◽  
Metastatic Rcc

Abstract INTRODUCTION Neutrophil to Lymphocyte ratio (NLR) has been reported to correlate with poor survivals in many tumors. However, the association between preoperative NLR elevation and survival outcome in non-metastatic renal cell carcinoma (RCC) underdoing nephrectomy remains controversial. The aim of this meta-analysis was to investigate the prognostic significance of elevated NLR in non-metastatic RCC. EVIDENCE ACUISITION We systematically searched PubMed, EmBase, and the Cochrane Library databases in may 2018. Cancer specific survival (CSS), disease-free survival (DFS) and overall survival (OS) were pooled by hazard ratio (HR) with corresponding 95% confidence interval. EVIDENCE SYNTHESIS A total of 3,175 patients from 8 studies were analyzed. The results demonstrated that elevated pretreatment NLR was significantly related to poor CSS (HR 1.91, 95% CI=1.53-2.40), DFS (HR 1.38, 95% CI=1.09-1.74), and OS (HR 1.84, 95% CI=1.58-2.14) in patients with non-metastatic RCC. CONCLUSION Elevated NLR indicates a poor long-term survival (CSS, DFS and OS) in non-metastatic RCC. Patients with elevated NLR are more likely to have poor prognosis than those with lower NLR.

Population-based analysis of cancer control of partial nephrectomy for high-risk localized renal cell carcinoma.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 385-385 ◽  
Author(s):  
Rebecca Leigh O'Malley ◽  
Matthew H. Hayn ◽  
Greg Wilding ◽  
Thomas Schwaab
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Partial Nephrectomy ◽  
Renal Cell ◽  
Radical Nephrectomy ◽  
Multivariable Analysis ◽  
Cancer Control ◽  
High Risk Disease ◽  
Localized Renal Cell Carcinoma

385 Background: Partial nephrectomy (PN) has reported equivalent oncologic outcomes with superior renal function outcomes when compared to radical nephrectomy (RN) for treatment of localized renal cell carcinoma (RCC). Whether PN provides adequate cancer control in high risk disease is unclear. To clarify, survival outcomes were compared between those who underwent RN and PN for high risk RCC. Methods: Using the Surveillance, Epidemiology, and End Results database patients with RCC who underwent PN or RN for a localized tumor ≤ 7cm were identified. Cancer-specific (CSS) and overall survival (OS) were compared between those with high risk disease (defined as poorly or undifferentiated grade and/or pathologic stage T3) who underwent PN or RN. Results: Of 51,183 patients with localized RCC ≤ 7cm, 24.9% had high risk disease, 85.2% and 14.8% of which underwent RN and PN, respectively. Five-year CSS was superior in the PN group vs. the RN group (93.3% vs. 86.0%, p<0.001). On multivariable analysis undergoing RN was no longer predictive of CSS (HR 1.23, p=0.08). Similarly, 5-year OS was superior in the PN versus RN group (79.5% vs. 70.1%, p<0.001). RN remained independently associated with poor OS on multivariable analysis (HR 1.16, p=0.031). Propensity analysis accounting for factors affecting selection for type of nephrectomy produced similar results. RN did not influence CSS but portended a 20% increased risk of death from all causes (p=0.008). Conclusions: In patients with high risk RCC, partial nephrectomy is associated with improved OS and does not compromise cancer control as compared to radical nephrectomy.

Prognostic significance of perirenal fat invasion and tumor size in pT1 to pT3a renal cell carcinoma: Results of a comprehensive multicenter study of the CORONA project—Can we improve prognostic discrimination of patients with stage pT3a tumors?

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 416-416 ◽  
Author(s):  
Sabine Doris Brookman-May ◽  
Matthias May ◽  
Richard Zigeuner ◽  
Luca Cindolo ◽  
Shahrokh F. Shariat ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Size ◽  
Renal Cell ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Prognostic Impact ◽  
Fuhrman Grade ◽  
The Impact ◽  
Perirenal Fat

416 Background: The renal cell carcinoma (RCC) TNM system merges perirenal fat invasion (PFI) and renal vein invasion (RVI) as stage pT3a despite limited evidence concerning their prognostic equivalence. Additionally, the prognostic value of PFI compared to pT1-pT2 tumors remains controversial. Methods: Data of 7,595 pT1a-pT3a RCC patients undergoing radical nephrectomy or nephron-sparin surgery were pooled from 12 European and U.S. centers (1999-2010). Patients were grouped according to stages and presence of PFI/RVI, i.e., pT1-2N0M0 (n=6,137; 80.8%), pT3aN0M0+PFI (n=1,036; 13.6%), and pT3aN0M0 (RVI±PFI; n=422; 5.6%). Cancer-specific survival (CSS) was estimated by Kaplan-Meier method. Univariate and multivariable Cox proportional-hazards regression models, sensitivity and discrimination analyses were conducted to evaluate the impact of clinico-pathological parameters on cancer-specific mortality (CSM). Results: Compared to stage pT1-2, patients staged pT3a were significantly more frequently male (58.9 vs. 53.1%), older (65 vs. 62.1 yrs), more often had clear cell RCC (86.1 vs. 77.7%), Fuhrman grade 3-4 (30.5 vs. 13.4%), tumor size >7 cm (39.6% vs. 13%), and less often underwent NSS (7.1 vs. 36.6%; each p<0.001). On multivariable analysis, CSM of both patients with PFI and RVI±PFI was significantly enhanced compared to pT1-2 patients (HR 1.96 and 2.14, resp.; p<0.001), whereas patients featuring PFI only and RVI±PFI did not differ (HR 0.92; p=0.48). Tumor size instead significantly influenced CSM in stage pT3a (HR 1.07; p<0.001) with a 7 cm cut-off yielding the highest c-index. Conclusions: Since the prognostic impact of PFI and RVI on CSM seems to be comparable, merging both as stage pT3a might be justified. Enhanced prognostic discrimination of stage pT3a RCC patients appears to be possible by employing a 7 cm tumor size cut-off within an alternative staging system.

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