Non-metastatic Renal Cell Carcinoma Research Articles

The critical role of lymph node dissection in selecting high-risk nonmetastatic renal cancer candidates for adjuvant therapy after nephrectomy

BackgroundThe role of lymph node dissection (LND) during nephrectomy for renal cell carcinoma (RCC) is controversial. We looked at the clinical usefulness of performing LND to stratify the risk of patients with RCC and select candidates for systemic treatment after nephrectomy. Materials and MethodsWe identified 730 patients with nonmetastatic RCC treated with nephrectomy and LND at a single center. We compared the accuracy and clinical usefulness of a base model including factors defining high-risk patients according to the S-TRAC trial [(pT3 and Grade≥2 and performance status score ≥1) or pT4] relative to the base model plus pN stage for the prediction of early progression after surgery. ResultsLN invasion resulted the most informative predictor of early progression (odds ratio: 6.39; 95% confidence interval [CI]: 3.26, 12.54; P < 0.0001). The accuracy was higher (P = 0.008) for the model implemented with pN (area under the curve: 0.76; 95% CI: 0.71, 0.80) as compared to the base model (area under the curve: 0.72; 95% CI: 0.68, 0.76). Performing LND to select patients for postoperative systemic treatment, resulted in a slightly higher net benefit as compared to a strategy defining risk on the base of factors other than pN. Patients with high-risk disease showed a large difference in the risk of progression according to pN-status (1-year risk: 58% [95% CI: 45, 72] for pN1; 31% [95% CI: 25, 38] for pN0; P < 0.001). ConclusionsPerforming LND at the time of nephrectomy improves risk stratification, resulting into a small but nonnegligible clinical advantage for selecting high-risk patients for further treatment after surgery. Further trials should investigate whether high-risk pN1 patients would benefit from a different postoperative management.

DNA methylation associates with survival in non-metastatic clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cancer and is associated with poor prognosis if metastasized. Up to one third of patients with local disease at diagnosis will develop metastasis after nephrectomy, and there is a need for new molecular markers to identify patients with high risk of tumor progression. In the present study, we performed genome-wide promoter DNA methylation analysis at diagnosis to identify DNA methylation profiles associated with risk for progress.MethodDiagnostic tissue samples from 115 ccRCC patients were analysed by Illumina HumanMethylation450K arrays and methylation status of 155,931 promoter associated CpGs were related to genetic aberrations, gene expression and clinicopathological parameters.ResultsThe ccRCC samples separated into two clusters (cluster A/B) based on genome-wide promoter methylation status. The samples in these clusters differed in tumor diameter (p < 0.001), TNM stage (p < 0.001), morphological grade (p < 0.001), and patients outcome (5 year cancer specific survival (pCSS5yr) p < 0.001 and cumulative incidence of progress (pCIP5yr) p < 0.001. An integrated genomic and epigenomic analysis in the ccRCCs, revealed significant correlations between the total number of genetic aberrations and total number of hypermethylated CpGs (R = 0.435, p < 0.001), and predicted mitotic age (R = 0.407, p < 0.001). We identified a promoter methylation classifier (PMC) panel consisting of 172 differently methylated CpGs accompanying progress of disease. Classifying non-metastatic patients using the PMC panel showed that PMC high tumors had a worse prognosis compared with the PMC low tumors (pCIP5yr 38% vs. 8%, p = 0.001), which was confirmed in non-metastatic ccRCCs in the publically available TCGA-KIRC dataset (pCIP5yr 39% vs. 16%, p < 0.001).ConclusionDNA methylation analysis at diagnosis in ccRCC has the potential to improve outcome-prediction in non-metastatic patients at diagnosis.

Prognostic value of the albumin-to-alkaline phosphatase ratio on urologic outcomes in patients with non-metastatic renal cell carcinoma following curative nephrectomy.

Background: Few studies focused on the relationship between the albumin-to-alkaline phosphatase ratio (AAPR) and the urologic outcomes in patients with non-metastatic renal cell carcinoma (RCC) following curative surgery. The aim of this study was to evaluate the prognostic value of preoperative AAPR in non-metastatic RCC patients.Methods: The prognostic value of AAPR was evaluated in a primary cohort with 419 non-metastatic RCC patients following curative radical or partial nephrectomy and then further validated in an independent cohort consisting of 204 patients. A nomogram was developed based on the independent predictors, and its predictive value was assessed.Results: Kaplan-Meier survival analysis demonstrated that patients with low AAPR levels were significantly associated with worse overall survival (OS) and cancer-specific survival (CSS) compared with patients with high AAPR levels both in two cohorts. Univariate and multivariate analyses revealed that low AAPR was an independent risk factor for OS (HR = 2.745; 95%CI, 1.266-5.953; P = 0.011) and CSS (HR = 3.042; 95%CI, 1.278-7.243; P = 0.012). Moreover, subgroup analysis (Fuhrman grade G1+G2 and Fuhrman grade G3+G4; T1+T2 stage and T3+T4 stage) revealed that low AAPR was also related to worse urological outcomes. Although no significant differences between patients with low AAPR and patients with high AAPR can be observed with regard to CSS under Fuhrman grade G1+G2 (P=0.058) and T1+T2 stage (P=0.318), there was a worse CSS trend in low AAPR patients. The established nomograms for OS and CSS were well calibrated and had moderate discriminative ability (concordance index: 0.821 and 0.839, respectively)Conclusions: Preoperative AAPR might be an independent prognostic factor in patients with non-metastatic RCC. The ratio should be applied in RCC patients for risk stratification and clinical decision-making.

Nachsorge beim Nierenzellkarzinom im nicht fernmetastasierten Stadium

Postoperative follow-up care after curative surgery or ablative treatment is the standard of care in patients with nonmetastatic renal cell carcinoma. The goal is to identify and treat postoperative complications and local recurrences early on. Follow-up investigations and their relevance are widely acknowledged and validated and patients undergoing follow-up seem to benefit from alonger survival in nonmetastatic renal cell carcinoma. Hence there is no consensus on a standardized follow-up strategy. The most disputed question is around the frequency of the investigations and the duration of the follow-up. Without an evidence-based follow-up protocol, urologists should carry out an individualized, potentially lifelong follow-up regimen, which also includes the patients' needs and perspectives.

The author's reply: Prognostic significance of preoperative and follow-up neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with non-metastatic clear cell renal cell carcinoma

The author's reply: Prognostic significance of preoperative and follow-up neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with non-metastatic clear cell renal cell carcinoma

Neutrophil-to-Lymphocyte Ratio Predicts Pathological Renal Sinus Fat Invasion in Renal Cell Carcinomas of ≤7 cm with Presumed Renal Sinus Fat Invasion.

PurposeComputed tomography (CT) is the most useful diagnostic modality for staging renal cell carcinoma (RCC). However, CT is limited in its ability to predict renal sinus fat invasion (SFI). Here, we aimed to evaluate whether preoperative neutrophil-to-lymphocyte ratio (NLR) could predict pathological SFI in patients with RCC of ≤7 cm for whom preoperative imaging reveals potential renal SFI.Materials and MethodsWe reviewed the medical records of 1311 patients who underwent extirpative renal surgery for non-metastatic RCC of ≤7 cm between November 2005 and December 2014. After excluding patients with no SFI in preoperative imaging, unavailable preoperative data, and morbidity affecting inflammatory markers, a total of 476 patients were included in this study. Multivariate logistic regression analysis was used to evaluate predictors of pathological SFI.ResultsWe implemented a cut-off value of 1.98, which was calculated by ROC analysis to obtain high (≥1.98) and low (<1.98) NLR groups. A total of 93 patients with pathological SFI had larger clinical tumor size, higher preoperative NLR, larger pathological tumor size, more frequent renal vein involvement, and higher Fuhrman nuclear grade. Multivariate analysis indicated that high NLR [odds ratio (OR) 2.032, p=0.004], clinical tumor size (OR 1.586, p<0.001), and collecting system involvement on preoperative imaging (OR 3.957, p=0.011) were significantly associated with pathological SFI in these tumors.ConclusionPreoperative high NLR was associated with pathological SFI in patients with RCC of ≤7 cm and presumed SFI on preoperative imaging. Greater surgical attention is needed to obtain negative margins during partial nephrectomy in these patients.

Trends and outcomes of lymphadenectomy for nonmetastatic renal cell carcinoma: A propensity score-weighted analysis of the National Cancer Database

PurposeLymph node (LN) involvement in renal cell carcinoma (RCC) is associated with a poor prognosis. While lymph node dissection (LND) may provide diagnostic information, its therapeutic benefit remains controversial. Thus, the aim of our study is to analyze survival outcomes after LND for nonmetastatic RCC and to characterize contemporary practice patterns. Materials and methodsThe National Cancer Database was queried for patients with nonmetastatic RCC who underwent either partial or radical nephrectomy from 2010 to 2014. A total of 11,867 underwent surgery and LND. Chi-square tests were used to examine differences in patient demographics. To minimize selection bias, propensity score matching (PSM) was used to select one control for each LND case (n = 19,500). Cox regression analyses were conducted to examine overall survival (OS) in patients who received LND compared to those who did not. ResultsOf all patients undergoing LND for RCC (n = 11,867), 5%, 23%, 31%, 47% were performed for tumors of clinical T stage 1, 2, 3, and 4, respectively. Proportions of LND have not significantly changed from 2010 to 2014. No significant improvement in median OS for patients undergoing LND compared to no LND was shown (34.7 vs. 34.9 months, respectively; P = 0.98). Similarly, no significant improvement in median OS was found for clinically LN positive patients undergoing LND compared to no LND (P = 0.90). On Cox regression analysis, LND dissection was not associated with an OS benefit (hazard ratio: 1.00; 95% confidence interval 0.97 to 1.04). ConclusionsAmong all RCC patients, LNDs are often performed for low stage disease, suggesting a potential overutilization of LND. No OS benefit was seen in any subgroup of patients undergoing LND. Further investigation is needed to determine which patient populations may benefit most from LND.

Outcome of sentinel lymph node biopsy in patients with clinically non-metastatic renal cell carcinoma

Objective: To investigate the rate of occult SN metastases, oncological outcome, and association of recurrence with the pattern of lymphatic tumour drainage in RCC.Materials and methods: A pooled RCC sub-group analysis was conducted of secondary endpoints from a published feasibility and a phase II prospective single-arm SN study to investigate oncological outcome. Patients with cT1-3 (<10 cm) cN0M0 RCC of any sub-type were enrolled. After intratumoural injection of Tc99m nanocolloid, pre-operative imaging of SNs with SPECT/CT was followed by (partial) nephrectomy with SN and regional lymph node dissection using a γ-probe. The patients were followed with a risk-adapted surveillance programme. Endpoints of the studies were analysed using Cox proportional hazard models.Results: Sixty-six RCC patients were included. Two patients (3%, 95% CI =0.5–11%) had occult SN metastases and remained free of disease at 57 and 72 months. Ten patients (15%, 95% CI =7–26%) developed recurrences, and four (6%, 95% CI =2.3–14.5%) had died of disease at a median follow-up of 57 months (IQR =18–72 months). Occurrence of distant metachronous metastases were associated with tumour size (HR =1.39, p = 0.02), pT stage (HR =6.83, p < 0.01 for comparison T1 vs T3/4), Grade 3/4 (HR =8.38, p = 0.05 for comparison 1/2 vs 3/4) and interaortocaval sentinel lymph node location (HR =10.52, p = 0.03 for comparison yes vs no).Conclusions: The rate of occult metastatic SN is low, but long disease-free survival (DFS) was observed in two patients with occult SN metastases. We hypothesize an interaortocaval lymphatic route in thoracic recurrences. Evaluation of the prognostic and therapeutic role of sentinel lymph node biopsy (SLNB) requires a clinical trial in high-risk RCC.

Predictive value of preoperative monocyte-lymphocyte ratio among patients with localized clear renal cell carcinoma of ≤7 cm on preoperative imaging.

We investigated the prognostic ability of preoperative monocyte–lymphocyte ratio for oncologic outcomes in non-metastatic clear cell renal cell carcinoma of ≤7 cm on preoperative computed tomography (CT).We retrospectively reviewed 1637 patients who underwent radical or partial nephrectomy for solid renal masses ≤7 cm (2005–2014). We included 1137 patients after exclusion of benign pathology, non-clear cell, morbidity affecting inflammatory markers, metastasis, regional lymphadenopathy, positive margin, and follow up <12 months. According to cutoff values of 0.21, we had high ≥0.21 and low <0.21 preoperative monocyte–lymphocyte ratio groups. Mann–Whitney U and chi-squared tests were used for continuous and Dichotomous variables. Univariate and multivariate Cox regression analysis were used to predict factors affecting recurrence and survival. Kaplan–Meier curve was used for survival analysis.At a median age of 56 years with a median follow up of 65 months, 51 patients had a recurrence (4.5%). There were no statistical differences between the high and low monocyte–lymphocyte ratio groups as regard the pathological characters (P > .005). Monocyte–lymphocyte ratio was a predictor for recurrence-free and cancer-specific survivals (hazard risk [HR] 2.17, P = .012 and HR 4.06, P = .004, respectively). A higher monocyte–lymphocyte ratio was significantly associated with worse, both 10-year recurrence-free (90.2% vs 94.9%) and cancer-specific survival (89.5% vs 98.8%) (Log-rank, P = .002 and P < .001, respectively).The preoperative monocyte–lymphocyte ratio is an independent prognostic marker for recurrence-free and cancer-specific survivals after curative surgery for non-metastatic clear cell renal cell carcinoma of ≤7 cm on preoperative CT.

Intensive Imaging-based Follow-up of Surgically Treated Localised Renal Cell Carcinoma Does Not Improve Post-recurrence Survival: Results from a European Multicentre Database (RECUR)

The optimal follow-up (FU) strategy for patients treated for localised renal cell carcinoma (RCC) remains unclear. Using the RECUR database, we studied imaging intensity utilised in contemporary FU to evaluate its association with outcome after detection of disease recurrence. Consecutive patients with nonmetastatic RCC (n=1612) treated with curative intent at 12 institutes across eight European countries between 2006 and 2011 were included. Recurrence occurred in 336 patients. Cross-sectional (computed tomography, magnetic resonance imaging) and conventional (chest X-ray, ultrasound) methods were used in 47% and 53%, respectively. More intensive FU imaging (more than twofold) than recommended by the European Association of Urology (EAU) was not associated with improved overall survival (OS) after recurrence. Overall, per patient treated for recurrence remaining alive with no evidence of disease, the number of FU images needed was 542, and 697 for high-risk patients. The study results suggest that use of more imaging during FU than that recommended in the 2017 EAU guidelines is unlikely to improve OS after recurrence. Prospective studies are needed to design optimal FU strategies for the future. Patient summaryAfter curative treatment for localised kidney cancer, follow-up is necessary to detect any recurrence. This study illustrates that increasing the imaging frequency during follow-up, even to double the number of follow-up imaging procedures recommended by the European Association of Urology guidelines, does not translate into improved survival for those with recurrence.

Gender- and cholesterol-specific predictive value of body mass index in renal cell carcinoma: A multicenter study.

Recently, there have been some reports on preoperative body mass index (BMI) and total cholesterol (TC) as a prognostic predictor for patients with renal cell carcinoma (RCC) but the topic is controversial and still poorly understood. So we analyzed the effects of BMI and TC on the prognosis of RCC. Retrospective data from 1988 to 2015 were collected from eight centers with a total of 7,271 patients surgically treated for nonmetastatic RCC. Receiver operating characteristic curve analysis was analyzed and the highest Youden index was shown at 163.5 mg/dL. According to the Asian BMI criteria, patients were divided into normal BMI<25kg/m2 and high BMI≥25kg/m2 . Kaplan-Meier analysis, multivariate Cox regression model were performed to identify the overall survival (OS) and the recurrence-free survival (RFS). Normal BMI and low TC group was associated with the shortest OS and RFS as compared to the other groups significantly. In the male patients, the results showed similar to the whole sample. But in the female, BMI had no effect on both OS and RFS. On multivariate Cox regression analysis, low TC was an independent predictor for OS in both genders. However, normal BMI was a significant prognostic factor in the males only. Preoperative BMI and TC are good predictive factors for both OS and RFS significantly in RCC patients. Also, TC was an independent predictor for OS in all RCC patients; however, BMI was a significant predictor in males only.

Abstract B64: Characterizing the tumor immune microenvironment of metastatic and nonmetastatic renal clear cell carcinomas and colorectal carcinomas using computational methods

Abstract Cancer is a leading cause of mortality worldwide with most cancer-related deaths attributed to metastatic disease progression. Engaging the immune system to fight cancer has several advantageous features, particularly given the unique role the immune system plays in initiating, maintaining, and fighting tumor metastasis. Here, we examine the tumor immune microenvironment in metastatic (primary stage IV -M1) and non-metastatic (primary stage I/II- M0) tumors in renal clear cell carcinoma (RCCC) and colorectal carcinoma (CRC) through the application of deconvolution algorithms and pathway analyses. Preliminary data suggests the tumor microenvironment varies based on cancer type as well as metastatic disease status, and these differences in immune infiltration significantly affect survival outcomes. The prevailing belief of the association of CD8+ T cells with a positive survival outcome did not hold true for renal clear cell carcinoma in our analysis. We further characterized the heterogeneity of the microenvironments in CRC and RCCC. Specific immune cell types consistently and differentially infiltrate tumors (NK and CD4+ T cells in particular), albeit their cellular status and influences on survival vastly differ based on the tumor type, suggesting each tumor type uniquely evades the immune system to promote metastasis. Citation Format: Yasmin Kamal, Frederick S. Varn, Jr., Chao Chen, Hildreth Robert Frost, Christopher I. Amos. Characterizing the tumor immune microenvironment of metastatic and nonmetastatic renal clear cell carcinomas and colorectal carcinomas using computational methods [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B64.

Correction: Serum soluble B7-H4 is a prognostic marker for patients with non-metastatic clear cell renal cell carcinoma.

[This corrects the article DOI: 10.1371/journal.pone.0199719.].

Pathologically examining a minimum of three lymph nodes could better determine node negativity in patients with non-metastatic chromophobe renal cell carcinoma.

To evaluate the prognostic value of lymph node (LN) involvement for patients with chromophobe renal cell carcinoma (chRCC) and ascertain the minimum number of LNs that need to be pathologically examined to reliably diagnose a patient with node negative chRCC. From 2004 to 2014, non-metastatic chRCC patients receiving radical nephrectomy together with lymphadenectomy were identified from the Surveillance, Epidemiology and End Results (SEER) database. The primary outcome was overall survival (OS). Two hundred and forty-six patients received lymph node dissection during the surgery. Of the patients, 24 (10%) had pathologically confirmed positive LN. Multivariate Cox regression model showed that positive LN was an independent unfavorable predictor for OS (HR = 2.83, 95%CI = 1.14-6.98, P = 0.024). More importantly, LN(-) patients with at least three LNs dissected had significantly better OS compared with when 1-2 LNs were examined (P = 0.048). Multivariate analysis confirmed that in LN(-) patients, the examination of three or more LNs could independently predict better OS compared with patients with only 1-2 LNs dissected (HR≥3LNs = 0.362, 95% CI = 0.135-0.972, P = 0.044). Additionally, the likelihood of finding at least one positive LN was significantly higher on dissection of ≥3 LNs compared with examination of 1-2 LNs (15% vs 5%, P = 0.018). Decision curve analysis found a better clinical validity of the '3 LNs examined'-based classification compared with the traditional LN(-)/LN(+) classification. The proportion of positive LNs in chRCC was far from neglectable and LN metastasis could independently predict unfavorable OS. We recommended a minimum of three LNs should be pathologically examined in order to reliably determine node negative.

Serum soluble B7-H4 is a prognostic marker for patients with non-metastatic clear cell renal cell carcinoma.

BackgroundB7-H4 is a member of the B7 family of immune-regulatory ligands and is considered to be a negative regulator of the immune response. We investigated the clinical significance of serum soluble B7-H4 in patients with non-metastatic clear cell renal cell carcinoma.MethodsWe analyzed 108 patients in whom non-metastatic clear cell renal cancer was diagnosed at Tokyo Metropolitan Tama Medical Center between 2008 and 2013. We measured the serum soluble B7-H4 level using the Enzyme-Linked ImmunoSorbent Assay (ELISA) and evaluated the association between the peripheral blood neutrophil count and sB7-H4 as well as the utility of soluble B7-H4 as a prognostic biomarker for clear cell renal cancer. The Cox proportional hazards regression model was used to assess the PFS and OS with the soluble B7-H4 level.ResultsWe detected high levels of soluble B7-H4 in the sera of 56% of patients with non-metastatic clear cell renal cell carcinoma versus only 10% of healthy donors. Elevated soluble B7-H4 levels were associated with changes in an elevated peripheral blood neutrophil count. The increase of soluble B7-H4 also was significantly associated with poor PFS and OS. Multivariate analysis showed that the elevation of the soluble B7-H4 level was an independent prognostic factor for PFS and OS.ConclusionsOur data suggest that the association between serum soluble B7-H4 and peripheral blood neutrophil count, as well as the evaluation of serum soluble B7-H4 expression is a useful tool for predicting the prognosis of patients with non-metastatic clear cell renal cell carcinoma.

Clinical utility of the S3-score for molecular prediction of outcome in non-metastatic and metastatic clear cell renal cell carcinoma

BackgroundStratification of cancer patients to identify those with worse prognosis is increasingly important. Through in silico analyses, we recently developed a gene expression-based prognostic score (S3-score) for clear cell renal cell carcinoma (ccRCC), using the cell type-specific expression of 97 genes within the human nephron. Herein, we verified the score using whole-transcriptome data of independent cohorts and extend its application for patients with metastatic disease receiving tyrosine kinase inhibitor treatment. Finally, we sought to improve the signature for clinical application using qRT-PCR.MethodsA 97 gene-based S3-score (S397) was evaluated in a set of 52 primary non-metastatic and metastatic ccRCC patients as well as in 53 primary metastatic tumors of sunitinib-treated patients. Gene expression data of The Cancer Genome Atlas (n = 463) was used for platform transfer and development of a simplified qRT-PCR-based 15-gene S3-score (S315). This S315-score was validated in 108 metastatic and non-metastatic ccRCC patients and ccRCC-derived metastases including in part several regions from one metastasis. Univariate and multivariate Cox regression stratified by T, N, M, and G were performed with cancer-specific and progression-free survival as primary endpoints.ResultsThe S397-score was significantly associated with cancer-specific survival (CSS) in 52 ccRCC patients (HR 2.9, 95% Cl 1.0–8.0, PLog-rank = 3.3 × 10–2) as well as progression-free survival in sunitinib-treated patients (2.1, 1.1–4.2, PLog-rank = 2.2 × 10–2). The qRT-PCR based S315-score performed similarly to the S397-score, and was significantly associated with CSS in our extended cohort of 108 patients (5.0, 2.1–11.7, PLog-rank = 5.1 × 10–5) including metastatic (9.3, 1.8–50.0, PLog-rank = 2.3 × 10–3) and non-metastatic patients (4.4, 1.2–16.3, PLog-rank = 1.6 × 10–2), even in multivariate Cox regression, including clinicopathological parameters (7.3, 2.5–21.5, PWald = 3.3 × 10–4). Matched primary tumors and metastases revealed similar S315-scores, thus allowing prediction of outcome from metastatic tissue. The molecular-based qRT-PCR S315-score significantly improved prediction of CSS by the established clinicopathological-based SSIGN score (P = 1.6 × 10–3).ConclusionThe S3-score offers a new clinical avenue for ccRCC risk stratification in the non-metastatic, metastatic, and sunitinib-treated setting.

Age-dependent prognostic value of body mass index for non-metastatic clear cell renal cell carcinoma: A large multicenter retrospective analysis.

The prognostic value of obesity is unestablished for renal cell carcinoma. We assessed the age-dependent prognostic value of body mass index (BMI) in a large multicenter cohort of patients with non-metastatic clear cell renal cell carcinoma (nm-cRCC). This study evaluated 2092 patients with nm-cRCC who underwent surgery with curative intent at five Korean institutions between 2001 and 2014. There was no significant difference in BMI between the young (<45 years) and older patients (≥45 years) (P = 0.398). Among older patients, high BMI (≥25 kg/m2 ) was associated with better 5-year rates of recurrence-free survival (RFS) and cancer-specific survival (CSS) (P = 0.003 and 0.004, respectively), and multivariate analysis confirmed that high BMI was independently associated with better RFS and CSS (RFS hazard ratio [HR]: 0.617, P = 0.005; CSS HR: 0.588, P = 0.024). However, among young patients, there were no significant BMI-related differences in the 5-year RFS and CSS rates (P = 0.457 and 0.420, respectively), and high BMI was not independently associated with RFS or CSS (P = 0.822 and 0.749, respectively). Among patients with nm-cRCC, high BMI was associated with a favorable prognosis among older patients but not among young patients. Therefore, the relationship between obesity and nm-cRCC prognosis might vary according to age.

Canadian Urological Association guideline for followup of patients after treatment of non-metastatic renal cell carcinoma

Canadian Urological Association guideline for followup of patients after treatment of non-metastatic renal cell carcinoma

The loss of BAP1 protein expression predicts poor prognosis in patients with nonmetastatic clear cell renal cell carcinoma with inferior vena cava tumor thrombosis

ObjectivesRenal cell carcinoma (RCC) is characterized by a propensity for extension into the renal vein and inferior vena cava (IVC) and is associated with poor prognosis. BAP1 mutation, which occurs in about 15% of patients with clear cell RCC (ccRCC), also predicts poor prognosis. The aim of this study was to elucidate the association between BAP1 protein expression and clinicopathological outcomes in patients with nonmetastatic ccRCC with an IVC tumor thrombus (IVCTT). Material and methodsThirty-five patients with nonmetastatic ccRCC with an IVCTT who underwent radical nephrectomy and tumor thrombectomy at our institution from 1999 to 2010 were retrospectively evaluated. Immunohistochemical (IHC) analyses were performed for the expression of BAP1 protein, and the associations between the expression of BAP1 and clinical outcomes were assessed. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Multivariate analyses of the associations between disease-free survival (DFS) and clinical variables including BAP1 protein expression, tumor size, Karnofsky performance status (KPS) score, and the extension level of the tumor thrombus were performed using a Cox proportional hazard model. ResultsThe median follow-up time was 58.8 months (range: 2–130 months). The median age was 68 years (range: 37–80 years). The median size of the primary tumor was 9.6cm (range: 3.0–15.0cm). The IVCTT extended above and below the diaphragm in 10 (28.6%) and 25 (71.4%) patients, respectively. The KPS score was>80 in 23 patients (65.7%). BAP1 protein expression on IHC was positive in 24 cases (68.8%) and negative in 11 cases (31.2%). The median overall survival in cases with BAP1-negative and -positive tumor on IHC staining were 44.7 and 81.5 months, respectively (P = 0.052). BAP1-negative tumor on IHC staining was associated with a significantly shorter DFS than BAP1-positive tumor (median DFS = 10.0 vs. 26.0 months, respectively; P = 0.011). Multivariate analysis showed that only BAP1-negative tumor on IHC staining was significantly associated with shorter DFS (P = 0.004). ConclusionsPatients whose tumors had loss of BAP1 protein expression were significantly associated with poor prognosis in patients with ccRCC with an IVCTT who underwent radical nephrectomy and tumor thrombectomy.

A phase 2, single-arm trial of neoadjuvant axitinb plus avelumab in patients (pts) with localized renal cell carcinoma (RCC) who are at high risk of relapse after nephrectomy (NeoAvAx).

TPS4604Background: Surgery is the standard treatment for non-metastatic RCC. Despite curative intent, pts with a high risk of relapse have a 5-year metastasis-free survival rate of only 30 % and pr...