Association Between Epidural Analgesia and Cancer Recurrence or Survival After Surgery for Renal Cell Carcinoma: A Propensity Weighted Analysis

Whether epidural anesthesia and analgesia (EA) is beneficial for postoperative cancer outcomes remains controversial and we conducted this historical cohort study to evaluate the association between EA and long-term outcomes following surgery for renal cell carcinoma (RCC). We collected patients receiving RCC surgery from 2011 to 2017 and followed up them until February 2020. Patient attributes, surgical factors and pathological features were gathered through electronic medical chart review. The association between EA and recurrence-free and overall survival after surgery was evaluated using Cox regression models with inverse probability of treatment weighting (IPTW) to balance the observed covariates. The median follow-up time for the 725 included patients was 50 months (interquartile range: 25.3–66.5) and 145 of them (20%) received perioperative EA. We demonstrated EA use was associated with better recurrence-free survival [IPTW adjusted hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.49–0.83, p < 0.001] and overall survival [IPTW adjusted HR: 0.66, 95% CI: 0.49–0.89, p = 0.006] in patients receiving surgical resection for RCC. More prospective studies are needed to verify this connection between EA and superior cancer outcomes after RCC surgery.

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Association Between Epidural Analgesia and Cancer Recurrence or Survival After Surgery for Renal Cell Carcinoma: a Propensity Weighted Analysis

10.21203/rs.3.rs-453037/v1 ◽

2021 ◽

Author(s):

Fang-Yu Yen ◽

Shih-Pin Lin ◽

Tzu-Ping Lin ◽

Wen-Kuei Chang ◽

Mei-Yung Tsou ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Cox Regression ◽

Cancer Recurrence ◽

Cancer Outcomes ◽

Historical Cohort ◽

Medical Chart Review ◽

Weighted Analysis

Abstract Whether epidural anesthesia and analgesia (EA) is beneficial for postoperative cancer outcomes remains controversial and we conducted this historical cohort study to evaluate the association between EA and long-term outcomes following surgery for renal cell carcinoma (RCC). We collected patients receiving RCC surgery from 2011 to 2017 and followed up them until February 2020. Patient attributes, surgical factors and pathological features were gathered through electronic medical chart review. The association between EA and recurrence-free and overall survival after surgery was evaluated using Cox regression models with inverse probability of treatment weighting (IPTW) to balance the observed covariates. The median follow-up time for the 725 included patients was 50 months (interquartile range: 25.3–66.5) and 145 of them (20%) received perioperative EA. We demonstrated EA use was associated with better recurrence-free survival (IPTW adjusted hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.49–0.83, p < 0.001) and overall survival (IPTW adjusted HR: 0.66, 95% CI: 0.49–0.89, p = 0.006) in patients receiving surgical resection for RCC. More prospective studies are needed to verify this connection between EA and superior cancer outcomes after RCC surgery.

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A novel 10 glycolysis-related genes signature could predict overall survival for clear cell renal cell carcinoma

BMC Cancer ◽

10.1186/s12885-021-08111-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qianwei Xing ◽

Tengyue Zeng ◽

Shouyong Liu ◽

Hong Cheng ◽

Limin Ma ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Cox Regression ◽

Clear Cell ◽

Low Risk ◽

The Cancer Genome Atlas ◽

Regression Analyses ◽

Cell Renal Cell Carcinoma

Abstract Background The role of glycolysis in tumorigenesis has received increasing attention and multiple glycolysis-related genes (GRGs) have been proven to be associated with tumor metastasis. Hence, we aimed to construct a prognostic signature based on GRGs for clear cell renal cell carcinoma (ccRCC) and to explore its relationships with immune infiltration. Methods Clinical information and RNA-sequencing data of ccRCC were obtained from The Cancer Genome Atlas (TCGA) and ArrayExpress datasets. Key GRGs were finally selected through univariate COX, LASSO and multivariate COX regression analyses. External and internal verifications were further carried out to verify our established signature. Results Finally, 10 GRGs including ANKZF1, CD44, CHST6, HS6ST2, IDUA, KIF20A, NDST3, PLOD2, VCAN, FBP1 were selected out and utilized to establish a novel signature. Compared with the low-risk group, ccRCC patients in high-risk groups showed a lower overall survival (OS) rate (P = 5.548Ee-13) and its AUCs based on our established signature were all above 0.70. Univariate/multivariate Cox regression analyses further proved that this signature could serve as an independent prognostic factor (all P < 0.05). Moreover, prognostic nomograms were also created to find out the associations between the established signature, clinical factors and OS for ccRCC in both the TCGA and ArrayExpress cohorts. All results remained consistent after external and internal verification. Besides, nine out of 21 tumor-infiltrating immune cells (TIICs) were highly related to high- and low- risk ccRCC patients stratified by our established signature. Conclusions A novel signature based on 10 prognostic GRGs was successfully established and verified externally and internally for predicting OS of ccRCC, helping clinicians better and more intuitively predict patients’ survival.

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Profiles of overall survival-related gene expression-based risk signature and their prognostic implications in clear cell renal cell carcinoma

Bioscience Reports ◽

10.1042/bsr20200492 ◽

2020 ◽

Vol 40 (9) ◽

Author(s):

Zihao He ◽

Tuo Deng ◽

Xiaolu Duan ◽

Guohua Zeng

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Family Member ◽

Renal Cell ◽

Cox Regression ◽

Clear Cell ◽

Training Set ◽

Cell Renal Cell Carcinoma ◽

Validation Set

Abstract The present work aimed to evaluate the prognostic value of overall survival (OS)-related genes in clear cell renal cell carcinoma (ccRCC) and to develop a nomogram for clinical use. Transcriptome data from The Cancer Genome Atlas (TCGA) were collected to screen differentially expressed genes (DEGs) between ccRCC patients with OS > 5 years (149 patients) and those with <1 year (52 patients). In TCGA training set (265 patients), seven DEGs (cytochrome P450 family 3 subfamily A member 7 (CYP3A7), contactin-associated protein family member 5 (CNTNAP5), adenylate cyclase 2 (ADCY2), TOX high mobility group box family member 3 (TOX3), plasminogen (PLG), enamelin (ENAM), and collagen type VII α 1 chain (COL7A1)) were further selected to build a prognostic risk signature by the least absolute shrinkage and selection operator (LASSO) Cox regression model. Survival analysis confirmed that the OS in the high-risk group was dramatically shorter than their low-risk counterparts. Next, univariate and multivariate Cox regression revealed the seven genes-based risk score, age, and Tumor, lymph Node, and Metastasis staging system (TNM) stage were independent prognostic factors to OS, based on which a novel nomogram was constructed and validated in both TCGA validation set (265 patients) and the International Cancer Genome Consortium cohort (ICGC, 84 patients). A decent predictive performance of the nomogram was observed, the C-indices and corresponding 95% confidence intervals of TCGA training set, validation set, and ICGC cohort were 0.78 (0.74–0.82), 0.75 (0.70–0.80), and 0.70 (0.60–0.80), respectively. Moreover, the calibration plots of 3- and 5 years survival probability indicated favorable curve-fitting performance in the above three groups. In conclusion, the proposed seven genes signature-based nomogram is a promising and robust tool for predicting the OS of ccRCC, which may help tailor individualized therapeutic strategies.

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The role of cytoreductive nephrectomy in renal cell carcinoma patients with liver metastasis

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2020.4896 ◽

2020 ◽

Author(s):

Boda Guo ◽

Shengjing Liu ◽

Miao Wang ◽

Huimin Hou ◽

Ming Liu

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Liver Metastasis ◽

Propensity Score ◽

Cell Carcinoma ◽

Propensity Score Matching ◽

Renal Cell ◽

Cox Regression ◽

Cytoreductive Nephrectomy ◽

Dismal Prognosis

It is widely accepted that renal cell carcinoma with liver metastasis carries a dismal prognosis. We aimed to explore the value of cytoreductive nephrectomy among these patients. Patients were extracted from the SEER database between 2010 and 2017. The univariate and multivariate Cox proportional hazards models were conducted to select the prognostic predictors of survival. Patients were divided into nephrectomy and non-nephrectomy groups. Propensity score-matching analyses were applied to reduce the above factors’ differences between the groups. Overall survival was compared by Kaplan-Meier (K-M) analyses. Data from 683 patients was extracted from the database. The univariate Cox regression and multivariate Cox regression revealed that factors including age, histologic type, T and N stages, lung metastasis, brain metastasis, and nephrectomy were significant predictors of survival in the patients. After the propensity score-matching analyses, we found that nephrectomy prolonged overall survival. Nephrectomy can prolong overall survival in eligible renal cell carcinoma patients with liver metastasis.

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FDG-PET avidity as a prognostic biomarker for overall survival in renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16564 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16564-e16564

Author(s):

Justin Ferdinandus ◽

Ines Maríc ◽

Christopher Darr ◽

Claudia Kesch ◽

Thomas Hilser ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Pet Imaging ◽

Fdg Pet ◽

Renal Cell ◽

Rating Scale ◽

Cox Regression ◽

Multivariable Analysis ◽

Histologic Grade

e16564 Background: Positron emission tomography with (18F)-fluorodeoxyglucose (FDG-PET) is not considered a standard of care (SOC) in renal cell carcinoma (RCC) because of its variability in metabolic activity. We investigated the rate of PET-positivity in our institutional cohort and tested whether PET-positivity had prognostic value in metastatic (m)RCC. Methods: Patients with FDG-PET imaging at any time during the course of disease were identified from medical records. PET-positivity was defined according to PERCIST criteria and a five-point rating scale analogue to Deauville Scoring was used to stratify PET-avidity. Tracer uptake of the hottest lesion was measured as SUVmax. Clinical parameters and PET-positivitywere correlated with overall survival (OS). Kaplan-Meier plots, log-rank analyses, kendall rank correlation, univariate and multivariable cox regression models were employed, where appropriate. Results: A totalof 90 patients was analyzed. The median age was 64.0 (34.0-83.0) and 56 (62.2%) patients had clear cell RCC. Metastatic disease was present in 64 (71.1%) and 22 (24.4%) patients received ongoing medical treatment. 72 (80.0%) patients had prior nephrectomy. PET-positivity occurred in 57 (63.3%) patients, with similar rates among metastatic (41/64; 64%) and non-metastatic patients (16/26; 62%). PET-positive patients had shorter median OS compared to PET-negative patients (38.5 months (CI95:24.5-NR) vs. not reached (CI95: 69.6-NR), P= 0.0013). A weak correlation was found between PET-Uptake and histologic grade (Kendall’s tau 0.22; P= 0.03). Prior nephrectomy, presence of primary lesions, presence of distant metastases, histologic grade and PET-positivity were significant predictors of OS in univariate regression. In multivariable analysis, only PET-positivity remained significant (HR 4.1 (CI95: 1.1-15.4), P= 0.04). Conclusions: RCC is a metabolically active cancer, which in the majority of patients is suitable for FDG-PET diagnostic procedures. PET-positivity was an independent prognostic factor for OS in RCC, indicating its putative clinical use. Further studies to define the role of FDG-PET imaging in RCC are ongoing.

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Epigenetic signature predicts overall survival clear cell renal cell carcinoma

Cancer Cell International ◽

10.1186/s12935-020-01640-x ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Yejinpeng Wang ◽

Liang Chen ◽

Lingao Ju ◽

Kaiyu Qian ◽

Xinghuan Wang ◽

...

Keyword(s):

Dna Methylation ◽

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Cox Regression ◽

Clear Cell ◽

The Cancer Genome Atlas ◽

Cell Renal Cell Carcinoma ◽

Cox Regression Analysis

Abstract Background Recently, increasing study have found that DNA methylation plays an important role in tumor, including clear cell renal cell carcinoma (ccRCC). Methods We used the DNA methylation dataset of The Cancer Genome Atlas (TCGA) database to construct a 31-CpG-based signature which could accurately predict the overall survival of ccRCC. Meanwhile, we constructed a nomogram to predict the prognosis of patients with ccRCC. Result Through LASSO Cox regression analysis, we obtained the 31-CpG-based epigenetic signature which were significantly related to the prognosis of ccRCC. According to the epigenetic signature, patients were divided into two groups with high and low risk, and the predictive value of the epigenetic signature was verified by other two sets. In the training set, hazard ratio (HR) = 13.0, 95% confidence interval (CI) 8.0–21.2, P < 0.0001; testing set: HR = 4.1, CI 2.2–7.7, P < 0.0001; entire set: HR = 7.2, CI 4.9–10.6, P < 0.0001, Moreover, combined with clinical indicators, the prediction of 5-year survival of ccRCC reached an AUC of 0.871. Conclusions Our study constructed a 31-CpG-based epigenetic signature that could accurately predicted overall survival of ccRCC and staging progression of ccRCC. At the same time, we constructed a nomogram, which may facilitate the prediction of prognosis for patients with ccRCC.

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Relationship of aberrant glycosylation of n-glycan on immunoglobulins with survival of patients with renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.438 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 438-438

Author(s):

Shingo Hatakeyama ◽

Maho Amano ◽

Takuya Koie ◽

Yuki Tobisawa ◽

Tohru Yoneyama ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Cox Regression ◽

Patient Survival ◽

Characteristic Curve ◽

Carrier Protein ◽

Aberrant Glycosylation ◽

Flight Mass Spectrometry

438 Background: Biomarkers for early detection and prediction of patient survival for renal cell carcinoma (RCC) have not yet been established. We have developed a novel glycoblotting method that allows high-throughput, comprehensive, and quantitative glycan analysis of whole human serum. We examined the relationship between serum N-glycan profiling and survival of the patient with RCC. Furthermore, we attempted to identify carrier protein to which the responsible N-glycan attached. Methods: We performed a comprehensive N-glycan structural analysis of sera from 64 patients with RCC using the glycoblotting methods and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The intensity of the N-glycans was then analyzed with the help of the logistic regression analysis and a receiver operating characteristic curve to select N-glycans which associated with patient survival in RCC. The candidate N-glycans which had statistically significant relationship in overall survival were evaluated their independency using Cox-regression model to elucidate its superiority comparing to other conventional biomarkers of RCC. Then, we recovered the responsible N-glycan together with its carrier protein by sialobloting method to identify the carrier protein. Results: We identified 56 kinds of N-glycans in sera from RCC patients. The intensity of peak 19 was significantly higher, and the intensity of peak 49 was significantly lower in the patients who survived longer. Multivariate analysis revealed that peaks 19 and 49 were independent predictors of overall survival as well as conventional risk factors. Protein analysis for the carrier protein revealed that the aberrant N-glycan was harbored by IgA1 or IgG4. Conclusions: Aberrant glycosylation of N-glycan on IgA1 or IgG4 may serve as novel biomarkers for RCC. Further validation study is warranted.

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Potential impact of prior high-dose IL-2 on the outcomes of sunitinib (Su) treatment (tx) in patients (pts) with metastatic renal cell carcinoma (mRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.494 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 494-494

Author(s):

Eli Rosenbaum ◽

Maya Gottfried ◽

Hans J. Hammers ◽

Mario A. Eisenberger ◽

Michael Anthony Carducci ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Cox Regression ◽

Objective Response ◽

Progression Free Survival ◽

High Dose ◽

Free Survival

494 Background: Targeted txs are the tx of choice in most mRCC pts. However, HDIL2 which may produce durable responses in a small percentage of cases, is still an option in carefully selected pts. While the effect of prior HDIL2 on the outcome of targeted txs in mRCC pts is poorly defined, a recent single center report (Birkhäuser FD, Cancer J 2013) revealed an improved disease-specific survival in pts treated with prior HDIL2. We aimed to study the effect of prior HDIL2 tx on outcome of mRCC pts treated with sunitinib. Methods: Records from 302 mRCC pts treated with Su from 2004 to 2013 in 9 centers across 2 countries were retrospectively reviewed. We compared the response rate, progression free survival (PFS), and overall survival (OS), between post HDIL2 pts (n=27) and individually matched tx naïve pts (n=27). Progression free survival and overall survival were determined by Cox regression. Results: All pts had prior nephrectomy and clear cell histology. The groups were matched by age (median 61), gender (male 74%), Heng risk (favorable 37%, intermediate 59%, poor 4%), sunitinib induced hypertension (67%), sunitinib dose reduction/treatment interruption (41%), smoking status (active 7%), use of angiotensin system inhibitors (41%), the presence of more than one metastases site (96%), and pre-tx neutrophil to lymphocyte ratio (> 3 in 22%). Furthermore, they were balanced regarding the presence of lung (68%), liver (31%), and bone (43%) metastases, and the use of bisphosphonates (32%). In prior HDIL2 versus tx naïve pts, objective response was partial response/stable disease 89% (n=24) versus 74% (n=20), and progressive disease at first imaging evaluation within the first 3 months (mos) 11% (n=3) versus 26% (n=7) (p=0.29, OR 2.4). Median progression free survival was 21 versus 12 mos (HR 2.3, p=0.005), and median overall survival 25 versus 20 mos (HR 2.2, p=0.013). Conclusions: In metastatic renal cell carcinoma patients treated with sunitinib, prior high dose IL-2 therapy may improve the outcome.

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SBRT versus nephrectomy in the treatment of renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.5059 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 5059-5059

Author(s):

Mausam Patel ◽

Thomas Kim ◽

Chenghui Li ◽

Ahmed Safar ◽

Sanjay Maraboyina

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Survival Analysis ◽

Propensity Score ◽

Cell Carcinoma ◽

Renal Cell ◽

Cox Regression ◽

Rank Test ◽

Risk Of Death ◽

Increased Risk

5059 Background: Stereotactic body radiotherapy (SBRT) is being increasingly used for renal cell carcinoma (RCC) treatment in non-surgical candidates. However, no studies have compared survival between nephrectomy and SBRT. The National Cancer Database (NCDB) database was used to assess overall survival in patients undergoing SBRT vs nephrectomy. Methods: All cases of T1-T4, N0, M0 RCC diagnosed between 2004 and 2016 were extracted from the NCDB. Only patients undergoing either nephrectomy or SBRT, but not both, were included in the final analysis. Primary outcome was overall survival, defined as time in months from diagnosis to death due to any cause. Descriptive statistics were calculated for all variables. Univariate survival analysis was performed using the Kaplan Meier method and log rank test. Multivariate Cox proportional hazards regression models were performed to determine the predictive performance of covariates with respect to overall survival, reported as hazard ratio [HR] with 95% CIs. Nephrectomy patients were propensity score matched to SBRT patients for sub-cohort survival analysis. Comparisons were considered statistically significant at P < 0.05. Results: There were 243,754 patients meeting inclusion criteria with 243,488 undergoing nephrectomy and 266 undergoing SBRT. Five year OS rates were 53% and 80% for SBRT and nephrectomy, respectively (P < 0.001). On multivariate Cox regression, SBRT was associated with an increased risk of death as compared to nephrectomy (HR, 2.05; 95% CI, 1.72 – 2.44; P < 0.001). Sex, race, insurance coverage, comorbidity index, tumor grade, lymphovascular invasion status, T-stage, tumor size, and academic status of treatment facility were also independent predictors of survival. After propensity score matching of 266 SBRT patients to 266 nephrectomy patients, there were no significant differences in baseline characteristics between the groups. However, SBRT continued to demonstrate worse survival and an increased risk of death as compared to nephrectomy (HR, 1.85; 95% CI, 1.41 – 2.44; P < 0.001). Conclusions: Among node-negative, non-metastatic RCC patients, SBRT is associated with inferior survival outcomes as compared to nephrectomy, even after correcting for underlying differences in demographics, tumor characteristics, socioeconomic status, and comorbidities. These results indicate that nephrectomy should remain the standard of care for RCC patients, with SBRT reserved for non-surgical candidates.

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Coffee consumption and risk of renal cell carcinoma in the NIH-AARP Diet and Health Study

International Journal of Epidemiology ◽

10.1093/ije/dyab011 ◽

2021 ◽

Author(s):

Jongeun Rhee ◽

Erikka Loftfield ◽

Neal D Freedman ◽

Linda M Liao ◽

Rashmi Sinha ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Cox Regression ◽

Coffee Consumption ◽

Health Study ◽

Coffee Intake ◽

Decaffeinated Coffee ◽

Incident Cases ◽

Reduced Risk

Abstract Background Coffee consumption has been associated with a reduced risk of some cancers, but the evidence for renal cell carcinoma (RCC) is inconclusive. We investigated the relationship between coffee and RCC within a large cohort. Methods Coffee intake was assessed at baseline in the National Institutes of Health–American Association of Retired Persons Diet and Health Study. Among 420 118 participants eligible for analysis, 2674 incident cases were identified. We fitted Cox-regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for coffee consumption vs non-drinkers. Results We observed HRs of 0.94 (95% CI 0.81, 1.09), 0.94 (0.81, 1.09), 0.80 (0.70, 0.92) and 0.77 (0.66, 0.90) for usual coffee intake of <1, 1, 2–3 and ≥4 cups/day, respectively (Ptrend = 0.00003). This relationship was observed among never-smokers (≥4 cups/day: HR 0.62, 95% CI 0.46, 0.83; Ptrend = 0.000003) but not ever-smokers (HR 0.85, 95% CI 0.70, 1.05; Ptrend = 0.35; Pinteraction = 0.0009) and remained in analyses restricted to cases diagnosed >10 years after baseline (HR 0.65, 95% CI 0.51, 0.82; Ptrend = 0.0005). Associations were similar between subgroups who drank predominately caffeinated or decaffeinated coffee (Pinteraction = 0.74). Conclusion In this investigation of coffee and RCC, to our knowledge the largest to date, we observed a 20% reduced risk for intake of ≥2 cups/day vs not drinking. Our findings add RCC to the growing list of cancers for which coffee consumption may be protective.

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