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Background: The ipsilateral renal parenchymal volume (RPV) experiences a sharp decrease shortly after partial nephrectomy (PN), mainly due to surgical remove or devascularization of kidney tissue. However, the subsequent change of RPV and its association with glomerular filtration rate (GFR) fast decline remains unknown. Our objective was to investigate the change of ipsilateral RPV and renal function status from new baseline (1-12 months after PN) to latest follow-up (≥1 year) after PN, and to explore factors associated with ipsilateral RPV decrease rate and correlation between RPV decrease and GFR fast decline., Materials and Methods: A retrospective review of 367 patients with PN was conducted. Three-dimensional reconstruction of computed tomography (CT)/MRI images was performed for RPV calculation. Spectrum score was used to assess the degree of acute kidney injury (AKI) in the operated kidney after PN. GFR decline greater than 3 ml/min/1.73 m 2 /year was defined as GFR fast decline. One hundred fourteen patients underwent abdominal surgery was used as control. Predictive factors for subsequent decrease of RPV rate and GFR fast decline were evaluated by linear and logistic regression, respectively., Results: With a median interval time of 21.1 (interquartile range:13.8-35.5) months, median ipsilateral RPV significantly decreased from 118.7 (interquartile range:100.7-137.1) ml at new baseline to 111.8 (IQR: 92.3-131.3) ml at latest follow-up. The interval time [β: 1.36(0.71-2.01), P <0.001] and spectrum score [β: 5.83 (2.92-8.74), P <0.001] were identified as independent predictors of ipsilateral RPV decrease rate. GFR fast decline was observed in 101 (27.5%) patients. Annual ipsilateral RPV decrease rate [odds ratio:1.67 (1.05-2.67), P =0.03] and overweight [odds ratio:1.63 (1.02-2.60), P =0.04] were independent predictors of GFR fast decline., Conclusions: Ipsilateral RPV experienced a moderate but significant decrease during follow-up after PN, especially in those with severer acute kidney injury. The presence of GFR fast decline was found to be associated with reduction of ipsilateral RPV, particularly in overweight individuals., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: There are undetectable levels of fat in fat-poor angiomyolipoma. Thus, it is often misdiagnosed as renal cell carcinoma. We aimed to develop and evaluate a multichannel deep learning model for differentiating fat-poor angiomyolipoma (fp-AML) from renal cell carcinoma (RCC)., Methods: This two-center retrospective study included 320 patients from the First Affiliated Hospital of Sun Yat-Sen University (FAHSYSU) and 132 patients from the Sun Yat-Sen University Cancer Center (SYSUCC). Data from patients at FAHSYSU were divided into a development dataset (n = 267) and a hold-out dataset (n = 53). The development dataset was used to obtain the optimal combination of CT modality and input channel. The hold-out dataset and SYSUCC dataset were used for independent internal and external validation, respectively., Results: In the development phase, models trained on unenhanced CT images performed significantly better than those trained on enhanced CT images based on the fivefold cross-validation. The best patient-level performance, with an average area under the receiver operating characteristic curve (AUC) of 0.951 ± 0.026 (mean ± SD), was achieved using the "unenhanced CT and 7-channel" model, which was finally selected as the optimal model. In the independent internal and external validation, AUCs of 0.966 (95% CI 0.919-1.000) and 0.898 (95% CI 0.824-0.972), respectively, were obtained using the optimal model. In addition, the performance of this model was better on large tumors (≥ 40 mm) in both internal and external validation., Conclusion: The promising results suggest that our multichannel deep learning classifier based on unenhanced whole-tumor CT images is a highly useful tool for differentiating fp-AML from RCC., (© 2023. The Author(s).)

Background: Although sex bias has been reported in the development and progression of renal cell carcinoma (RCC), the underlying mechanisms remain enigmatic. Here, we investigated the sex differences in the tumor microenvironment (TME) of RCC and explored a promising combination drug regimen to enhance the efficacy of immunotherapy., Methods: Single-cell RNA sequencing (scRNA-seq) data from four published datasets were analyzed to investigate the sex differences in RCC patients, and tumor tissues were collected to validate the sex differences using multiplex immunofluorescence (MxIF) and flow cytometry (FCM). The function of the androgen-androgen receptor axis in sex differences was explored in vivo and in vitro experiments., Results: Our analysis of scRNA-seq data from 220,156 cells, as well as MxIF and FCM assays, revealed that CD8 + T-cells infiltrated highly in the TME of male RCC, but were mostly in an exhausted and dysfunctional state. In vitro and in vivo experiments indicated that the dysfunction and exhaustion of CD8 + T-cells in male TME were induced by androgen. Clinically, higher serum androgen was significantly associated with a worse prognosis in male RCC patients receiving immunotherapy. Androgen receptor inhibitors could activate tumor-infiltrating CD8 + T-cells and enhance the efficacy of immunotherapy of RCC in vivo., Conclusions: Our study delineated the difference in TME between male and female patients with RCC, and demonstrated that the androgen-androgen receptor axis plays an important role in immunosuppression in male RCC. Our findings suggest that androgen receptor inhibitors in combination with immunotherapy may be a promising treatment option for male RCC patients., (© 2023. Society for Women's Health Research and BioMed Central Ltd.)

Objectives: To investigate the association of computed tomography-assessed body composition with survival outcomes of metastatic renal cell carcinoma (mRCC) received immunotherapy., Methods: In this multicenter, retrospective study, we reviewed 251 mRCC patients who received anti-PD1 from five centers. We analyzed the relationship between BMI, skeletal muscle area (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and subcutaneous adipose percentage (SAT%) with progression-free survival (PFS) and overall survival (OS). The spatial localization T cells was investigated by multiplex immunofluorescence., Results: Among 224 evaluable patients, 23 (10.3%) patients were underweight, 118 (52.7%) had normal weight, 65 (29%) were overweight, and 18 patients (8%) were obese. The median age was 55 years and most patients were male (71%). No significant improvement in PFS (HR, 0.61; 95% CI, 0.27-1.42) or OS (HR, 1.09; 95% CI, 0.38-3.13) was observed for the obese patients. Besides, SM, VAT, and SAT were not associated with survival outcomes (all p > 0.05). Interestingly, SAT% independently predicted PFS (as continuous variable, HR: 0.02; 95% CI, 0.01-0.11) and OS (HR:0.05; 95% CI, 0.01-0.39), which remained significant in multivariate modeling (as continuous variable, adjusted HR for PFS, 0.01; 95% CI, 0.00-0.04; adjusted HR for OS, 0.08; 95% CI, 0.01-0.72). These associations were consistent in subgroup analysis of different gender, BMI, PD-L1 positive, and sarcopenia group. Tumor of high SAT% patients had a higher intratumoral PD1 + CD8 + T cell density and ratio., Conclusion: High SAT% predicts better outcomes in mRCC patients treated with anti-PD1 and T cell location may account for the better response., Key Points: • CT-based subcutaneous adipose percentage independently predicted progression-free survival and overall survival. • Patients with a higher subcutaneous adipose percentage had a higher intratumoral PD1 + CD8 + T cell density and ratio., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Conventional imaging examinations are not sensitive enough for the early detection of recurrent or metastatic lesions in renal cell carcinoma (RCC) patients. We aimed to explore the role of 68 Ga-prostate specific membrane antigen (PSMA)-11 positron emission tomography (PET)/computed tomography (CT) in the detection of primary and metastatic lesions in such patients. We retrospectively analyzed 50 RCC patients who underwent 68 Ga-PSMA-11 PET/CT from November 2017 to December 2020. We observed a higher median accuracy and tumor-to-background maximum standard uptake value (SUV max ) ratio (TBR) of 68 Ga-PSMA-11 PET/CT in clear cell RCC (ccRCC; 96.57% and 6.00, respectively) than in non-clear cell RCC (ncRCC; 82.05% and 2.99, respectively). The accuracies in detecting lesions in the renal region, bone, lymph nodes and lungs in ccRCC were 100.00%, 95.00%, 98.08% and 75.00%, respectively, and those in the renal region, bone and lymph nodes in ncRCC were 100.00%, 86.67% and 36.36%, respectively. The median TBRs of the lesions from the above locations were 0.38, 10.96, 6.69 and 13.71, respectively, in ccRCC and 0.13, 4.02 and 0.73, respectively, in ncRCC. The PSMA score evaluated with immunohistochemistry was correlated with the SUV max (P = .046) in RCC. Higher PSMA scores were observed in ccRCC than in ncRCC (P = .031). 68 Ga-PSMA-11 PET/CT resulted in changes in clinical management in 12.9% (4/31) of cases because of the discovery of new metastases not detected with conventional imaging. These results indicate that 68 Ga-PSMA-11 PET/CT is a promising method for the detection of metastatic lesions in ccRCC, especially for those in the bone and lymph nodes., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Locoregional recurrence after nephrectomy for localized renal cell carcinoma (RCC) is rare with diverse manifestations. The selection criteria and efficacy of different treatments are unanswered. The objective was to compare different treatment modalities and present data on stereotactic body radiotherapy (SBRT) for recurrent RCC., Materials and Methods: Patients with locoregional recurrence after nephrectomy without distant metastasis were identified from institutional big data intelligence platform between 2001 and 2020. Patients receiving local therapy (surgery or SBRT) or systemic therapy alone (targeted therapy or PD-1 inhibitors) were divided into two groups. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method, Cox regression model. Patients were matched with propensity score matching., Results: Among 106 patients, 33 (31.1%) received systemic therapy alone and 73 (68.9%) received local therapy. Local therapy was surgery in 34 patients (32.1%) and SBRT in 39 (36.8%) patients. Patients treated with systemic therapy alone had more non-clear cell type (p = 0.044), more advanced T stage (p = 0.006), higher number (p = 0.043) but smaller size of lesions (p = 0.042). Patients receiving local therapy had significantly longer PFS than systemic therapy (19.7 vs. 7.5 months, p = 0.001). After matching, the PFS in the local therapy group remained higher (23.9 vs. 7.5 months, p = 0.001). The 2-year OS of the local therapy group and systemic therapy group was 91.6% and 71.8%, respectively (p = 0.084). Local therapy was associated with better PFS (HR 0.37; p = 0.0003) and OS (HR 0.23; p = 0.002) in multivariate analysis. Grade 2 or higher toxicities related to local therapy occurred in nine patients., Conclusions: Local therapy could delay disease progression compared with systemic therapy alone. SBRT is safe and effective for locally recurrent RCC., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Fumarate hydratase-deficient renal cell carcinoma (FHRCC) is highly malignant, but the urgent need for effective treatment remains unmet. We aimed to analyze the genomic characteristics and microenvironment of FHRCC and the cause of heterogeneous response to immune checkpoint inhibitor (ICI)-based treatment at single-cell level., Experimental Design: Whole-exome sequencing and IHC staining analyses were performed in 30 advanced FHRCC patients. Single-cell RNA sequencing following ICI-based treatment was conducted in 4 patients. The clinical characteristics, therapeutic effect, and follow-up data were analyzed., Results: The median tumor mutation burden was only 0.14 mutations per megabase. IHC staining showed an immune-active tumor microenvironment characterized by extensive CD8+ T-cell infiltration. ATM expression was inversely correlated with percentage of tumor-infiltrating CD8+ T cells. Trajectory analysis indicated gradually upregulated exhausted markers and an increased apoptotic trend of CD8+ T cells despite continuous exposure to ICI-based treatment. ICI-based treatment was associated with improved overall response rate (17.6% vs. 0%, P = 0.046) and disease control rate (DCR; 64.7% vs. 12.5%, P = 0.004) compared with tyrosine kinase inhibitor. Among patients with germline mutation, the ORR (16.7% vs. 0%, P = 0.086) and the DCR (66.7% vs. 14.3%, P = 0.011) were higher after ICI-based treatment., Conclusions: Immune infiltration is frequent in FHRCC. ICI-based treatment is a promising regimen, and treatment response depends on the functional status of tumor-infiltrating lymphocytes. ICI-based treatment cannot reverse the exhaustion of CD8+ T cells in patients with progressive disease, highlighting the need for additional therapeutic strategies., (©2022 American Association for Cancer Research.)

Sunitinib is one of the first-line targeted drugs for metastatic renal cell carcinoma (RCC) with dual effects of antiangiogensis and proapoptosis. Sam68 (Src-associated in mitosis, 68 KDa), is found being involved in cell apoptosis. This article reveals that Sam68 impacts the sensitivity to sunitinib by mediating the apoptosis of RCC cells. Immunohistochemical staining indicated that the Sam68 expression levels in sunitinib sensitive tumor tissues were markedly higher than those in sunitinib resistant tumor tissues. Sunitinib induced RCC cell apoptosis in a concentration-dependent manner and inhibited the expression of total and phosphorylated Sam68 (p-Sam68). Downregulation of Sam68 expression inhibited RCC cell apoptosis induced by sunitinib. While upregulation of Sam68 expression could enhance apoptosis induced by sunitinib. Xenograft models showed that tumors in the Sam68-knockdown group did not shrink as much as those in the control group after treatment with sunitinib for 4 weeks. Together, our results suggest that Sam68 expression is associated with the sensitivity of ccRCC patients to sunitinib. Sam68 may promote cell apoptosis induced by sunitinib, and the Sam68 expression level may be a biomarker for predicting sunitinib sensitivity in ccRCC patients., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Although high body mass index (BMI) was reported to associate with a better prognosis for metastatic renal cell cancer (mRCC) patients receiving anti-vascular endothelial growth factor (anti-VEGF) therapy, it is an imperfect proxy for the body composition, especially in Asian patients with a lower BMI. The role of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and perirenal fat thickness (PRFT) in mRCC patients was still unknown. Therefore, a multicenter retrospective study of 358 Chinese mRCC patients receiving anti-VEGF therapy was conducted and their body composition was measured via computed tomography. We parameterized VAT, SAT and PRFT according to their median value and BMI according to Chinese criteria (overweight: BMI ≥ 24). We found VAT, SAT, and PRFT (all p < 0.05) but not BMI, significantly associated with overall survival (OS) and progression-free survival (PFS). Multivariate Cox analysis identified PRFT was the independent predictor of OS and PFS, and IMDC expanded with PRFT showed the highest C-index in predicting OS (OS:0.71) compared with VAT, SAT, and BMI. PRFT could increase the area under the curve of the traditional International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in OS (70.54% increase to 74.71%) and PFS (72.22% increase to 75.03%). PRFT was introduced to improve the IMDC model and PRFT-modified IMDC demonstrated higher AIC in predicting OS and PFS compared with the traditional IMDC model. Gene sequencing analysis (n = 6) revealed that patients with high PRFT had increased angiogenesis gene signatures (NES = 1.46, p = 0.04) which might explain why better drug response to anti-VEGF therapy in mRCC patients with high PRFT. The main limitation is retrospective design. This study suggests body composition, especially PRFT, is significantly associated with prognosis in Chinese mRCC patients receiving anti-VEGF therapy. PRFT-modified IMDC model proposed in this study has better clinical predictive value.

Background: Most partial nephrectomies (PNs) are performed with hilar occlusion to reduce blood loss and optimize visualization. However, the histologic status of the preserved renal parenchyma years after PN is unknown., Objective: To compare the histologic chronic kidney disease (CKD) score of renal parenchyma before and years after PN, and to explore factors associated with CKD-score increase and glomerular filtration rate (GFR) decline., Design, Setting, and Participants: A retrospective review of 147 renal cell carcinoma patients who underwent PN and subsequent radical nephrectomy (RN) due to tumor recurrence was performed in 19 Chinese centers and Cleveland Clinic. Macroscopic normal renal parenchyma was evaluated at least 5 mm away from the tumor in PN specimens and at remote sites in RN specimens., Intervention: PN/RN and ischemia., Outcome Measurements and Statistical Analysis: Histologic CKD score (0-12) represents a summary of glomerular/tubular/interstitial/vascular status. Predictive factors for a substantial increase of CKD score (≥3) were evaluated by logistic regression., Results and Limitations: Sixty-five patients with all necessary data were analyzed. The median interval between PN and RN was 2.4 yr. Median durations of warm ischemia (n = 42) and hypothermia (n = 23) were both 23 min. The histologic CKD score was increased after RN in 47 (72%) patients, with 29 (45%) experiencing more substantial increase (≥3). There was no significant difference in the change of CKD score related to the type and duration of ischemia (p = 0.7 and p = 0.4, respectively) or interval from PN to RN (p > 0.9). However, patients with comorbidities of hypertension, diabetes, and/or pre-existing CKD (hypertension [HTN]/diabetes mellitus [DM]/CKD) demonstrated increased rate and extent of CKD-score increase. On univariate analysis, HTN/DM/CKD was the only predictor of a substantial CKD-score increase (odds ratio: 3.53 [1.12-11.1]). Decline of GFR was modest and similar between patients with/without a substantial CKD-score increase., Conclusions: Within the context of conventional, limited durations of ischemia, histologic deterioration of preserved parenchyma after PN appears to be primarily due to pre-existing medical comorbidities rather than ischemia. A subsequent decline in renal function was mild and independent of histologic changes., Patient Summary: After clamped PN, the preserved renal parenchyma demonstrated histologic deterioration in many cases, which correlated with the presence of comorbidities such as hypertension, diabetes mellitus, or chronic kidney disease. In contrast, the type and duration of ischemia did not correlate with histologic changes after PN, suggesting that ischemia insult had only limited impact on parenchyma deterioration., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Radiotherapy may work synergistically with immunotherapy and targeted agents. We aimed to assess the safety and outcomes of stereotactic body radiotherapy (SBRT) plus non-first-line programmed death-1 (PD-1) inhibitors and targeted agents (TA) in metastatic renal cell carcinoma (mRCC)., Methods: We retrospectively reviewed 74 patients treated with non-first-line PD-1 inhibitors plus TA in non-first-line setting. Survival outcomes were calculated from the anti-PD-1 treatment using the Kaplan-Meier method. Univariate and multivariate analyses were performed by Cox proportional hazards models., Results: Thirty-two (43.2%) patients received anti-PD-1/TA therapy alone (anti-PD-1/TA alone group), and 42 (56.8%) received SBRT in addition (anti-PD-1/TA + SBRT group). The median duration of first-line therapy was 8.6 months. Patients in the anti-PD-1/TA + SBRT group had significantly longer overall survival (OS) (38.5 vs 15.4 months; P = 0.022). On multivariate analysis, oligometastasis, ECOG performance status 0-1, anti-PD-1/TA + SBRT, and duration of first-line therapy ≥ 8.6 months were predictors for OS. The addition of SBRT was associated with improved OS in patients with clear-cell type (HR 0.19; 95% CI 0.07-0.55; P = 0.002) and duration of first-line therapy ≥ 8.6 months (HR 0.22; 95% CI 0.06-0.88; P = 0.032). Grade ≥ 3 toxicities occurred in 23 patients (54.8%) in the anti-PD-1/TA + SBRT group, and in 21 patients (65.6%) in the anti-PD-1/TA alone group., Conclusions: Incorporating SBRT into anti-PD-1/TA therapy is safe and tolerable. Further investigation is needed, particularly in patients with clear-cell histology and a longer duration of response to first-line antiangiogenic therapy., (© 2021. The Author(s).)

Purpose: We aimed to explore whether complete eradication of tumor burden with stereotactic body radiotherapy (SBRT) would affect the outcomes of oligometastatic renal cell carcinoma (RCC)., Materials and Methods: Patients diagnosed with extracranial oligometastatic RCC (no more than five metastases) between 2007 and 2019 were reviewed. Those without nephrectomy were excluded. SBRT to all, some and no lesions were defined as complete, incomplete, and no SBRT. Progression-free survival (PFS) and cancer-specific survival (CSS) were analyzed using Kaplan-Meier method, Cox regression model and the Fine and Gray method., Result: A total of 101 patients were included, 51.5% of whom had < 3 metastases. Forty (39.6%) patients received complete SBRT, and 61 (60.4%) received no or incomplete SBRT. The 1-year LC rate was 97.3%. The complete SBRT group had significantly longer PFS (26.0 vs 18.8 months; p = 0.043) and CSS (not reached vs. 55.3 months; p = 0.012) compared with the no or incomplete SBRT group. In multivariate analysis, ECOG 0-1 (HR 0.389, 95% CI 0.167-0.906, p = 0.029) and complete SBRT were prognostic factors for CSS (HR 0.307, 95% CI 0.108-0.876, p = 0.027). Complete SBRT was associated with improved CSS in the subgroups of patients with age < 55 years, ECOG 0-1, clear-cell histology, IMDC intermediate/poor risk, metachronous metastasis, and < 3 lesions., Conclusion: Complete eradication of tumor burden with SBRT was associated with better survival in patients with oligometastatic RCC. The recommendation of SBRT to all lesions should be individualized., (© 2021. The Author(s).)

Objective: Long-lasting control is rarely achieved with tyrosine kinase inhibitors (TKI) alone in metastatic renal cell carcinoma (mRCC). Our study aimed to investigate the survival outcomes of adding stereotactic body radiotherapy (SBRT) to TKI in mRCC., Materials and Methods: From September 2015 to September 2018, 56 patients treated with TKI received SBRT for 103 unresectable lesions. A total of 24 and 32 patients were irradiated before and after TKI failure, respectively. Overall survival (OS) was calculated from metastases. Progression-free survival (PFS) was calculated from SBRT., Results: Overall, 10, 32, and 12 patients had International Metastatic Renal Cell Carcinoma Database Consortium favorable, intermediate, and poor risk. Median follow-up was 21.7 months (range, 5.1 to 110.6 mo). Median OS was 61.2 months. The median PFS was 11.5 months, while the 2-year LC rate was 94%. Sixteen (34%) lesions achieved complete response (CR) in patients irradiated before TKI failure, whereas only 4 (7%) lesions yielded CR in those irradiated after TKI failure (P=0.001). The median PFS in CR group was significantly longer than that of non-CR group (18.9 vs. 7.1 mo; P=0.003). The 5-year OS in CR group was 86%, compared with 48% in non-CR group (P=0.010). Four (7%) patients experienced Grade 3 toxicity., Conclusions: Adding SBRT to TKI is safe and seems to improve survival in mRCC. Patients irradiated before TKI failure have higher CR rate, and the favorable local response might turn into survival benefit.

Background: Percentage parenchymal mass preserved (PPMP) is a key determinant of functional outcomes after partial nephrectomy (PN); however, predictors of PPMP have not been defined., Objective: To provide a comprehensive analysis of the functional impact of and potential predictive factors for PPMP., Design, Setting, and Participants: We analyzed data for 464 patients managed with PN at our center with necessary studies to determine vascularized parenchymal mass and function preserved within the operated kidney. PPMP was measured from computed tomography scans <2 mo before and 3-12 mo after PN., Intervention: PN., Outcome Measurements/statistical Analysis: Recovery from ischemia was defined as percentage ipsilateral glomerular filtration rate (GFR) preserved normalized by PPMP. We used Pearson correlation to evaluate the relationships between GFR preserved and PPMP. Multivariable logistic regression was used to assess predictors of PPMP., Result and Limitations: Ninety-six patients (21%) had a solitary kidney. The median tumor size and RENAL score were 3.5cm and 8, respectively. Cold/warm ischemia were utilized in 183/281 patients for which the median ischemia time were 28/20min. The median preoperative and postoperative vascularized parenchymal mass in the operated kidney were 194 and 157cm 3 , respectively, resulting in median PPMP of 84%. GFR preservation correlated strongly with PPMP (r=0.64; p<0.001). Recovery from ischemia was suboptimal (<80%) in 71 patients (15%), while suboptimal PPMP (<80%) was a more common adverse event, occurring in 160 patients (34%; p<0.001). Multivariable analysis demonstrated that greater tumor size and complexity were associated with lower PPMP (p≤0.04), while solitary kidney and hypothermia were associated with higher PPMP (p<0.001). Longer ischemia time was also associated with lower PPMP (p=0.003), probably reflecting the complexity of the surgery. Limitations include the retrospective design., Conclusion: PPMP correlates strongly with functional outcomes after PN, and lower PPMP is the most common and important source of functional decline after PN. Larger tumors, greater tumor complexity, and prolonged ischemia time were associated with lower PPMP, while PPMP tended to be greater for solitary kidneys, confirming that PPMP is a modifiable factor., Patient Summary: Kidney function after partial nephrectomy primarily depends on the amount of vascularized kidney preserved by the procedure. Lower recovery of function is seen when operating on larger tumors in unfavorable locations, but preservation of the parenchymal mass can be improved when truly necessary, such as when operating on a tumor in a solitary kidney., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma, can easily invade local tissues and metastasize, and is resistant to currently available treatments. Recent studies profiling microRNA expression in ccRCC have suggested miR-30a-5p may be deregulated in these cancer cells. To determine its role and mechanism of action in ccRCC, miR-30-5p expression levels were quantified and functions were analyzed using in vitro and in vivo experiments and bioinformatics. A decrease in miR-30a-5p expression was frequently noted in ccRCC cells and tissues. Importantly, low miR-30a-5p levels were significantly associated with a poor ccRCC patient prognosis. Stable overexpression of miR-30a-5p in 769-P cells was sufficient to prevent cellular proliferation and invasion in vitro and in vivo. Upon further examination, it was found that miR-30a-5p directly targeted the 3'-UTR of ZEB2 and suppressed ccRCC cell epithelial-mesenchymal transition. In addition, miR-30a-5p may be downregulated by the long non-coding RNA DLEU2. Taken together, these data reveal an important role for miR-30a-5p in the regulation of ccRCC proliferation and invasion, and indicate the potential for miR-30a-5p in applications furthering ccRCC prognostics and therapeutics.

Objective: To evaluate whether excised parenchymal mass (EPM) during partial nephrectomy (PN) correlates with functional decline and can serve as a surrogate for functional outcomes., Materials and Methods: All 215 patients managed with PN for unifocal renal mass with necessary studies to determine EPM and percent glomerular filtration rate (GFR) and parenchymal mass preserved (both global and specific to the operated kidney) were analyzed. EPM was estimated from the pathologic specimen by subtracting the tumor mass from the specimen mass, with both calculated using the elliptical formula. Vascularized parenchymal mass preserved was measured from computed tomography scans obtained <2 months prior and 3-12 months after surgery. All functional analyses were required to be within the same time frames, and patients with a contralateral kidney were also required to have nuclear renal scans., Results: The median tumor size was 3.5 cm and the median R.E.N.A.L. was 7. Warm and cold ischemia were utilized in 123 and 92 patients, respectively (median ischemia time = 23 minutes). The median global GFR preserved was 89%, the median total parenchymal mass preserved was 93%, and the median estimated EPM was 16 cm 3 . Whereas percent parenchymal mass preserved correlated strongly with global and ipsilateral GFR preserved (both P < .001), EPM failed to correlate with functional outcomes on both univariable and multivariable analyses., Conclusion: Our data suggest that parenchymal mass preserved with standard PN by experienced surgeons associates strongly with function preserved, whereas EPM fails to correlate with functional outcomes. Further study of the functional impact of EPM in other circumstances will be required, such as enucleation or PN performed by less-experienced surgeons., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To compare the surgical precision for optimizing nephron-mass preservation of tumor enucleation (TE) vs standard partial nephrectomy (SPN), with primary focus on functional outcomes. TE is presumed to optimize preservation of parenchymal mass and function but this has not yet been rigorously studied and quantified., Materials and Methods: Robotic partial nephrectomy patients who had appropriate pre- and postoperative studies for analysis of parenchymal mass preservation specific to the operated kidney were included. Computed tomography or magnetic resonance imaging and estimated glomerular filtration rate were required to be <2 months prior and 4-12 months after surgery. Parenchymal mass preservation and surgical precision were estimated for each technique, with precision defined as actual postoperative parenchymal volume or predicted postoperative parenchymal volume, presuming loss of a 5 mm rim of parenchyma associated with tumor excision and reconstruction., Results: Analysis included 57 TE and 53 SPN. Median age, body mass index, and tumor size were comparable. Percent parenchymal mass preserved in the operated kidney with TE was 96% (interquartile range [IQR] = 90-100) vs 89% (IQR = 83-96) for SPN (P = .003). Precision of excision or reconstruction was 101% (IQR = 96-105) for TE vs 94% (IQR = 88-100) for SPN (P < .001). On multivariable analysis, only TE correlated with improved surgical precision (coefficient = 6.7, 95% confidence interval = 1.6-11.8, P = .01). Although preservation of global renal function also favored TE, the differences were marginal (96% vs 93%), and statistical significance was not observed (P = .2)., Conclusion: Our analysis, which specifically focuses on the functional implications of TE, demonstrates that TE maximally spares normal parenchyma compared to SPN. Thus far, functional differences remain marginal and not statistically significant. Clinical significance of these findings in various clinical settings will require further investigation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Acute ischemic injury in the operated kidney after partial nephrectomy (PN) is often masked by a functional contralateral kidney; however, there is no practical method to assess this and its prognostic significance has not been defined., Objective: We propose a spectrum score to reflect the degree of ischemic insult in the ipsilateral kidney and study its relationship to subsequent functional recovery., Design, Setting, and Participants: From 2007 to 2014, 243 patients with a functional contralateral kidney underwent PN with necessary studies for detailed analysis of function and parenchymal mass before and after surgery in the ipsilateral kidney. Based on split function and percent parenchymal mass preserved in the ipsilateral kidney, we determined: serum creatinine (SCr) ideal-peak : expected peak SCr presuming no ischemic injury; and SCr worstcase-peak : expected peak SCr presuming temporary complete nonfunction of the ipsilateral kidney. The acute ipsilateral renal dysfunction spectrum score was defined: (observed peak SCr - SCr ideal-peak )/(SCr worstcase-peak - SCr ideal-peak ). Subsequent functional recovery was defined: (percent function preserved)/(percent mass saved)., Intervention: PN., Outcome Measurements and Statistical Analysis: Factors associated with spectrum score and relationship between spectrum score and subsequent functional recovery were evaluated by linear regression., Results and Limitations: Median duration of warm ischemia (n=152) was 21min (interquartile range [IQR] = 15-27) and hypothermia (n=91) 26min (IQR=23-30). Median parenchymal mass preservation was 83% (IQR=74-91%). Warm ischemia and longer ischemia duration associated with higher spectrum score (both p<0.05). Increased spectrum score (<25%, 25-50%, 50-75%, and >75% quartiles) had decreased functional recovery (98%, 94%, 90%, and 89%, respectively, p<0.001). However, this trend was not observed in the hypothermia cohort. On multivariable analysis spectrum score and ischemia type significantly associated with functional recovery (both p<0.01), while age and comorbidities failed to associate (p=0.3-0.7)., Conclusions: Acute ipsilateral renal dysfunction spectrum score unmasks the degree of ischemic insult in the operated kidney after PN and associates with functional recovery. While increased spectrum score associates with suboptimal recovery, even patients with a high spectrum score reached 89-90% recovery., Patient Summary: Acute functional decline after partial nephrectomy is difficult to evaluate in patients with two kidneys, but a proposed spectrum score can be used to evaluate this. Increased spectrum score reflects increased ischemia and may impact the functional recovery of the kidney., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate whether surgeons can predict the percent parenchymal mass that will be preserved by partial nephrectomy (PN) based on preoperative imaging, which could have potential utility for preoperative surgical planning and patient counseling. The proportion of preserved viable parenchyma following PN is the primary determinant of functional recovery. However, direct measurement of parenchymal volume preservation (VP) can be complex and time consuming., Materials and Methods: For patients managed with PN at our institution (2007-2014), we randomly selected 45 with a third in each of low, intermediate, or high R.E.N.A.L. complexity groups. All patients had recorded postoperative surgeon assessment of volume preservation (SAVP) and measured VP based on preoperative or postoperative computed tomography. Nine clinical providers predicted VP based solely on review of preoperative imaging while blinded to SAVP and measured VP. Clinical experience of the providers ranged from medical students to experienced urologic surgeons., Results: Median age was 66 years, median tumor size was 4.0 cm, and median R.E.N.A.L. was 8. Median measured VP was 81% (interquartile range of 74-89%). Preoperative prediction of VP correlated poorly with measured VP among the different surgeons (mean correlation coefficient, R = 0.34, range = 0.24-0.40). Surgeon experience provided minimal incremental improvement. Correlation between R.E.N.A.L. and measured VP was also marginal (R = 0.43). In contrast, correlation between postoperative SAVP and measured VP was much more robust (R = 0.75, P <.001)., Conclusion: Preoperative prediction of VP and R.E.N.A.L. score correlated poorly with measured VP for patients managed with PN. In contrast, postoperative SAVP provided a relatively reliable estimate of VP, and should be considered an acceptable substitute in most clinical circumstances., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The prognostic value of serum lipid-profile in renal cell cancer (RCC) remains unknown. The purpose of the study is to explore the association between the serum lipid-profile and RCC patients.The levels of preoperative serum lipid-profile (including cholesterol, triglycerides, high-density lipoprotein-cholesterol [HDL-C], low-density lipoprotein-cholesterol [LDL-C], apolipoprotein A-I [ApoA-I], and apolipoprotein B [ApoB]) were retrospectively performed in 786 patients with RCC. The cutoff values of the lipids were determined by the receiver-operating characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic value of serum lipids in RCC.Combined ROC analysis and univariate and multivariate Cox regression analyses, for overall survival (OS), revealed patients with low ApoA-I (<1.04) had significantly lower OS than the high ApoA-I (≥1.04) group (multivariate Cox regression analyses, hazard ratio [HR], 0.57; P = 0.003). Not only in the whole RCC cohort but also in the subgroups stratified according to the pT1-2 (P = 0.002), pN0 (P < 0.001), and pM0 (P = 0.001) status, respectively. Moreover, in the 755 patients with nonmetastasis, the low ApoA-I group was also associated with shortened disease-free survival (DFS) time compared to the high ApoA-I group (multivariate Cox regression analyses, HR, 0.65; P = 0.033). However, the other lipids were not independent prognostic factors for surgical RCC.An elevated level of preoperative ApoA-I was demonstrated to be related with better survival in patients with surgical RCC. Measuring the preoperative ApoA-I might be a simple way for finding the poor prognostic patients who should enrolled in further clinical trials and management., Competing Interests: The authors have no conflicts of interest to disclose.

Purpose: Cryoablation and radio frequency ablation are attractive modalities for small renal masses in patients with substantial comorbidities. However, salvage extirpative therapy for local recurrence after thermal ablation can be challenging due to associated perinephric fibrosis., Materials and Methods: Patients with thermal ablation refractory tumors requiring surgical salvage from 1997 to 2013 were identified and retrospectively reviewed., Results: A total of 27 patients were treated surgically after cryoablation (18) or radio frequency ablation (9) failed. Subjective assessment indicated moderate/severe fibrosis in 22 cases (81%). Partial nephrectomy was preferred in all patients but was not possible in 12, primarily due to unfavorable tumor size/location. In the intended partial nephrectomy group (15) open surgery was performed in all patients and completed in 14, with the procedure aborted in 1 due to extensive perinephric fibrosis. Radical nephrectomy was planned in 12 patients, of whom 8 were treated laparoscopically with 1 requiring conversion to open. Median estimated blood loss was 225 ml. Overall 17 patients experienced no complications and 4 had minor complications. However, 6 patients experienced more significant complications (Clavien III-IVb). Since January 2008 partial nephrectomy was performed more frequently (12 of 17, or 71% vs 2 of 10, or 20% for previous cases, p=0.02)., Conclusions: Surgical salvage after failed thermal ablation is feasible in most instances, and partial nephrectomy is often possible but can be challenging due to associated perinephric fibrosis. The difficulty of surgical salvage should be recognized as a potential limitation of the thermal ablation treatment strategy. Prospective studies of thermal ablation vs partial nephrectomy should be prioritized to provide higher quality data about the merits and limitations of each approach., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: In the current Tumour-Node-Metastasis (TNM) classification system for renal cell carcinoma (RCC), both renal sinus fat invasion (SFI) and perinephric fat invasion (PFI) are defined as T3a, suggesting that the prognosis should be similar for the two pathologic findings. Several studies, however, have reported a worse prognosis for SFI in patients with a T3a tumor. In order to compare the prognosis of these two pathologic findings (SFI versus. PFI) in a more comprehensive way, this meta-analysis was performed., Methods: To identify relevant studies, Medline, Embase, Cochrane Library, and Scopus database were searched from the inception until October 2014. A meta-analysis was performed using Review Manager 5.2 and STATA 11. Pooled Odds ratio (OR) and/or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard association., Results: A total of 6 studies including 1031 patients qualified for analysis. T3a RCC patients with SFI were significantly associated with poor cancer specific survival(CSS) (HR: 1.47, 95% CI: 1.19-1.83; P<0.001) compared to those with PFI. In T3aNx/N0M0 subgroup, SFI patients also showed a worse prognosis than those with PFI (CSS, HR: 1.94, 95% CI: 1.21-3.12; P = 0.006). T3a RCC patients with SFI had higher Furhman grade, greater possibility of lymph node metastasis, sarcomatoid differentiation and tumour necrosis. Main limitation is the relatively small number of included studies., Conclusion: The present meta-analysis suggested that SFI is associated with worse CSS in patients with pT3a RCC. However, due to the small number of included studies, future studies with a large sample size are required to further verify our findings.

Objective: To evaluate the impact of extended warm ischemia on incidence of acute kidney injury (AKI) and ultimate functional recovery after partial nephrectomy (PN), incorporating rigorous control for loss of parenchymal mass, and embedded within comparison to cohorts of patients managed with hypothermia or limited warm ischemia., Materials and Methods: From 2007 to 2014, 277 patients managed with PN had appropriate studies to evaluate changes in function/mass specifically within the operated kidney. Recovery from ischemia was defined as %function saved/%parenchymal mass saved. AKI was based on global renal function and defined as a ≥1.5-fold increase in serum creatinine above the preoperative level., Results: Hypothermia was utilized in 112 patients (median = 27 minutes) and warm ischemia in 165 (median = 21 minutes). AKI strongly correlated with solitary kidney (P < .001) and duration (P < .001) but not type (P = .49) of ischemia. Median recovery from ischemia in the operated kidney was 100% (interquartile range [IQR] = 88%-109%) for cold ischemia, with 6 (5%) noted to have <80% recovery from ischemia. For the warm ischemia group, median recovery from ischemia was 91% (IQR = 82%-101%, P < .001 compared with hypothermia), and 34 (21%) had recovery from ischemia <80% (P < .001). For warm ischemia subgrouped by duration <25 minutes (n = 114), 25-35 minutes (n = 35), and >35 minutes (n = 16), median recovery from ischemia was 92% (IQR = 86%-100%), 90% (IQR = 78%-104%), and 91% (IQR = 80%-96%), respectively (P = .77)., Conclusion: Our results suggest that AKI after PN correlates with duration but not with type of ischemia. However, subsequent recovery, which ultimately defines the new baseline glomerular filtration rate, is most reliable with hypothermia. However, most patients undergoing PN with warm ischemia still recover relatively strongly from ischemia, even if extended to 35-45 minutes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Chronic kidney disease (CKD) can be associated with a higher risk of progression to end-stage renal disease and mortality, but the etiology of nephron loss may modify this. Previous studies suggested that CKD primarily due to surgical removal of nephrons (CKD-S) may be more stable and associated with better survival than CKD due to medical causes (CKD-M)., Objective: We addressed limitations of our previous work with comprehensive control for confounding factors, differentiation of non-renal cancer-related mortality, and longer follow-up for more discriminatory assessment of the impact of CKD-S., Design, Setting, and Participants: From 1999 to 2008, 4299 patients underwent surgery for renal cancer at a single institution. The median follow-up was 9.4 yr (7.3-11.0). The new baseline glomerular filtration rate (GFR) was defined as the highest GFR between the nadir and 42 d after surgery. Three cohorts were retrospectively evaluated: no CKD (new baseline GFR >60 ml/min/1.73 m(2)); CKD-S (new baseline GFR<60 but preoperative >60 ml/min/1.73 m(2)); and CKD-M/S (new baseline and preoperative GFR both <60 ml/min/1.73 m(2)). Cohort status was permanently set at 42 d after surgery., Intervention: Renal surgery., Outcome Measurements and Statistical Analysis: Decline in renal function (50% reduction in GFR or dialysis), all-cause mortality, and non-renal cancer mortality were examined using a multivariable Cox proportional hazards model., Results and Limitations: CKD-M/S had a higher incidence of relevant comorbidities and the new baseline GFR was lower. On multivariable analysis (controlling for age, gender, race, diabetes, hypertension, and cardiac disease), CKD-M/S had higher rates of progressive decline in renal function, all-cause mortality, and non-renal cancer mortality when compared to CKD-S and no CKD (hazard ratio [HR] 1.69-2.33, all p<0.05). All-cause mortality was modestly higher for CKD-S than for no CKD (HR 1.19, p=0.030), but renal stability and non-renal cancer mortality were similar for these groups. New baseline GFR of <45 ml/min/1.73 m(2) significantly predicted adverse outcomes. The main limitation is the retrospective design., Conclusions: CKD-S is more stable than CKD-M/S and has better survival, approximating that for no CKD. However, if the new baseline GFR is <45 ml/min/1.73 m(2), the risks of functional decline and mortality increase. These findings may influence counseling for patients with localized renal cell carcinoma and higher oncologic potential when a normal contralateral kidney is present., Patient Summary: Survival is better for surgically induced chronic kidney disease (CKD) than for medically induced CKD, particularly if the postoperative glomerular filtration rate is ≥45 ml/min/1.73 m(2). Patients with preexisting CKD are at risk of a significant decline in kidney function after surgery, and kidney-preserving treatment should be strongly considered in such cases., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Preservation of renal function is prioritized during surgical management of localized renal cell carcinoma. VEGF targeted agents can downsize tumors in metastatic renal cell carcinoma and may do the same in localized renal cell carcinoma, allowing for optimal preservation of renal parenchyma associated with partial nephrectomy., Materials and Methods: Localized clear cell renal cell carcinoma patients meeting 1 or both of the following criteria were enrolled in a prospective phase II trial, including radical or partial nephrectomy likely to yield a glomerular filtration rate of less than 30 ml/minute/1.73 m(2), or partial nephrectomy high risk due to high complexity (R.E.N.A.L. 10 to 12) or tumor adjacent to hilar vessels. Pazopanib (800 mg once daily) was administered for 8 to 16 weeks with repeat imaging at completion of therapy, followed by surgery., Results: A total of 25 patients enrolled with a median tumor size of 7.3 cm and a median R.E.N.A.L. score of 11. Of index lesions 80% were high complexity and 56% of patients had a solitary kidney. Patients received a median of 8 weeks of pazopanib. The median interval from treatment start to surgery was 10.6 weeks. R.E.N.A.L. score decreased in 71% of tumors and 92% of patients experienced a reduction in tumor volume. Six of 13 patients for whom partial nephrectomy was not possible at baseline were able to undergo partial nephrectomy after treatment. The mean parenchymal volume that could be saved with surgery increased from an estimated 107 to 173 cc (p = 0.0015). In 5 patients a urine leak developed, which was managed conservatively, and 7 received a transfusion, of whom 1 required embolization., Conclusions: Neoadjuvant pazopanib resulted in downsizing localized renal cell carcinoma, allowing for improved preservation of renal parenchyma and enabling partial nephrectomy in a select subset of patients who would otherwise require radical nephrectomy., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Age at diagnosis has been shown to be an independent prognostic factor of localized renal cell carcinoma (RCC) in several studies. We used contemporary statistical methods to reevaluate the effect of age on the cancer-specific survival (CSS) of localized RCC., Methods and Findings: 1,147 patients with localized RCC who underwent radical nephrectomy between 1993 and 2009 were identified in our four institutions. The association between age and CSS was estimated, and the potential threshold was identified by a univariate Cox model and by martingale residual analysis. Competing risks regression was used to identify the independent impact of age on CSS. The median age was 52 years (range, 19-84 years). The median follow-up was 61 months (range, 6-144 months) for survivors. A steep increasing smoothed martingale residual plot indicated an adverse prognostic effect of age on CSS. The age cut-off of 45 years was most predictive of CSS on univariate Cox analysis and martingale residual analysis (p = 0.005). Age ≤45 years was independently associated with a higher CSS rate in the multivariate Cox regression model (HR = 1.59, 95% CI = 1.05-2.40, p = 0.027) as well as in competing risks regression (HR = 3.60, 95% CI = 1.93-6.71, p = 0.001)., Conclusions: Increasing age was associated with a higher incidence of cancer-specific mortality of localized RCC. Age dichotomized at 45 years would maximize the predictive value of age on CSS, and independently predict the CSS of patients with localized RCC.

Background: The molecular mechanisms involved in the development and progression of clear cell renal cell carcinomas (ccRCCs) are poorly understood. The objective of this study was to analyze the expression of dual-specificity phosphatase 9 (DUSP-9) and determine its clinical significance in human ccRCCs., Methods: The expression of DUSP-9 mRNA was determined in 46 paired samples of ccRCCs and adjacent normal tissues by using real-time qPCR. The expression of the DUSP-9 was determined in 211 samples of ccRCCs and 107 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between the expression of DUSP-9 and the clinical features of ccRCC., Results: The mRNA level of DUSP-9, which was determined by real-time RT-PCR, was found to be significantly lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). An immunohistochemical analysis of 107 paired tissue specimens showed that the DUSP-9 expression was lower in tumorous tissues than in the adjacent non-tumorous tissues (p < 0.001). Moreover, there was a significant correlation between the DUSP-9 expression in ccRCCs and gender (p = 0.031), tumor size (p = 0.001), pathologic stage (p = 0.001), Fuhrman grade (p = 0.002), T stage (p = 0.001), N classification (p = 0.012), metastasis (p = 0.005), and recurrence (p < 0.001). Patients with lower DUSP-9 expression had shorter overall survival time than those with higher DUSP-9 expression (p < 0.001). Multivariate analysis indicated that low expression of the DUSP-9 was an independent predictor for poor survival of ccRCC patients., Conclusion: To our knowledge, this is the first study that determines the relationship between DUSP-9 expression and prognosis in ccRCC. We found that decreased expression of DUSP-9 is associated with poor prognosis in ccRCC. DUSP-9 may represent a novel and useful prognostic marker for ccRCC.

Purpose: This retrospective study aimed to examine the expression and localization of SAM68 (Src-associated in mitosis, 68 kDa) in a larger cohort of surgical specimens of renal cell carcinoma and their correlation with the progression of human renal cell carcinoma., Experimental Design: The protein and mRNA expression levels of SAM68 in normal renal tubular epithelial cells, renal cell carcinoma cell lines, as well as nine pairs of renal cell carcinoma and matched tumor-adjacent renal tissues were examined using reverse transcription-PCR and Western blot. Moreover, SAM68 protein expression and localization in 241 clinicopathologically characterized renal cell carcinoma samples were examined by immunohistochemistry. Prognostic and diagnostic associations were examined by statistical analyses., Results: SAM68 was markedly overexpressed in renal cell carcinoma cell lines and renal cell carcinoma tissues at both the transcriptional and translational levels. Immunohistochemical analysis revealed high SAM68 protein expression in 129 of the 241 (53.5%) paraffin-embedded archival renal cell carcinoma specimens. Moreover, there was a significant correlation between SAM68 expression and pathologic stage (P < 0.001), T classification (P = 0.003), N classification (P = 0.001), M classification (P = 0.006), and Fuhrman grade (P < 0.001). Patients with higher SAM68 expression had shorter overall survival time than patients with lower SAM68 expression, and the cytoplasmic localization of SAM68 significantly correlated with clinicopathologic grade and outcome. Multivariate analysis indicated that SAM68 protein overexpression and cytoplasmic localization were independent predictors for poor survival of renal cell carcinoma patients., Conclusions: Our results suggest that SAM68 could represent a novel and useful prognostic marker for renal cell carcinoma. High SAM68 expression and cytoplasmic localization are associated with poor overall survival in renal cell carcinoma patients.