Renal Cell Carcinoma Death Research Articles

Obesity in Relation to Renal Cell Carcinoma Incidence and Survival in Three Prospective Studies

To disentangle the “obesity paradox” in renal cell carcinoma (RCC), we examined associations of body mass index (BMI) and weight change with RCC risk and survival in the Health Professionals Follow-up Study (HPFS) and Nurses’ Health Study (NHS) 1 and 2. We estimated cohort-specific and summary covariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for RCC incidence, as well as RCC-specific survival among cases in the pooled HPFS and NHS data. Cumulative average BMI was associated with a higher risk of total RCC (summary HR 2.16, 95% CI 1.77–2.63 for BMI ≥30 vs 18–<25 kg/m2; p trend <0.001) and fatal RCC (HR 2.03, 95% CI 1.37–3.01; p trend <0.001). Prediagnosis BMI was not associated with RCC death. However, first postdiagnosis BMI (HR 0.51, 95% CI 0.29–0.89; p trend 0.006) and prediagnosis to postdiagnosis weight change (HR 0.52, 95% CI 0.29–0.91; p trend 0.001) were significantly inversely associated with RCC death. These results support obesity as a risk factor for total and fatal RCC. They undermine the obesity paradox by suggesting that weight loss around diagnosis, and not low BMI itself, is associated with worse prognosis. Patient summaryWe studied obesity in kidney cancer and found that obesity is associated with getting and dying from the disease. Body mass index at diagnosis is not an ideal factor for predicting prognosis, as patients who have lost weight are likely to have more aggressive cancer.

Transperitoneal Robot-assisted Partial Nephrectomy with Minimum Follow-up of 5 Years: Oncological and Functional Outcomes from a Single Institution

BackgroundRobot-assisted partial nephrectomy (RAPN) is an established, minimally invasive nephron-sparing technique with excellent perioperative and intermediate oncological outcomes. However, long-term oncological outcomes have not been reported to date. ObjectiveTo report oncological and functional outcomes of RAPN among patients with minimum follow-up of 5 yr. Design, setting, and participantsData for consecutive patients undergoing RAPN since October 2006 were extracted from a prospectively-maintained institutional PN database. Patients with benign tumors, genetic mutations, prior radical or ipsilateral PN, and those with follow-up of <5 yr were excluded. InterventionTransperitoneal RAPN for renal cell carcinoma (RCC). Outcomes measurements and statistical analysisDemographic, perioperative, postoperative, functional, and oncological data were evaluated. A linear random-effects model was used to estimate the effect of follow-up duration on the estimated glomerular filtration rate (eGFR) after adjustment for potential confounders. Univariable competing-risks regression analyses were performed to evaluate the hazard ratio (HR) for cancer-related events for the variables of interest. Results and limitationsA total of 278 RAPNs for RCC were included. eGFR was significantly lower at follow-up time points than at baseline. At last follow-up (median 46 mo, interquartile range 30–58) the mean eGFR difference was −10.6ml/min (95% confidence interval −12.56 to −8.66; p < 0.0001). There were 28 deaths (10.1%) in the cohort during the follow-up period, of which five (1.8%) were related to metastatic RCC. The 5-yr and 7-yr cumulative incidence of RCC deaths was 1.80% at both 5 and 7 yr, while the cumulative incidence of local recurrence was 3.61% and 4.16%, and that of metastasis was 3.24% and 4.57% at 5 and 7 yr, respectively. Univariable competing-risks regression revealed that higher Fuhrman grade (HR 8.76; p = 0.051), larger tumor size (HR 1.67; p < 0.0001), and tumor necrosis (HR 16.73; p = 0.0019) were independent predictors of RCC death. The retrospective design and potential selection bias due to patient selection in the early RAPN experience may limit the generalizability of the findings. ConclusionsThis is the first study reporting minimum oncological follow-up of 5 yr after RAPN. The results demonstrate excellent long-term oncological outcomes after RAPN in a selected cohort of patients. Our data confirm that the renal functional deterioration after RAPN remains stable over time after the early postoperative decrease. Patient summaryRobot-assisted partial nephrectomy is being more widely used as a standard treatment for small localized renal cell carcinomas. This study reveals excellent long-term cancer control for both local recurrences and distant metastases. Renal function is stable after an initial postoperative deterioration.

Are We Using the Best Tumor Size Cut-points for Renal Cell Carcinoma Staging?

To compare the predictive ability for oncologic outcomes among current tumor size cut-points and clinically relevant alternatives to determine which are optimal. Patients who underwent radical or partial nephrectomy between 1970 and 2010 for T1-2Nx/N0M0 renal cell carcinoma (RCC) were identified. Associations between tumor size and progression-free survival (PFS) and cancer-specific survival (CSS) were evaluated using Kaplan-Meier analyses and Cox models. Predictive ability was assessed using c-indexes. The cohort included 3304 patients with a median age of 63 years (interquartile range 53, 70). Median follow-up among survivors was 9.9 years (interquartile range 6.9, 14.3). There were 536 patients who progressed and 354 who died from RCC. For RCC tumors ≤3.0 cm, 10-year PFS and CSS rates were 93%-95% and 97%-99%, respectively. For tumors >3.0-4.0 cm, PFS and CSS began to decline (91% and 95%, respectively), with further gradual declines in PFS and CSS with increasing tumor size. Plots of hazard ratios for progression and RCC death as a function of tumor size did not reveal major inflection points. Differences in discrimination based on various combinations of tumor-size cut-points for progression or RCC death were small, with c-indexes ranging between 0.691-0.704 and 0.734-0.750, respectively. RCC tumors ≤3.0 cm in size are associated with favorable outcomes. Thereafter, risks of progression and RCC death increase gradually with tumor size, with no compelling biological reason to endorse a given cut-point over another.

Tumor Growth Kinetics and Oncologic Outcomes of Patients Undergoing Active Surveillance for Residual Renal Tumor following Percutaneous Thermal Ablation

PurposeTo evaluate growth kinetics and oncologic outcomes of patients with renal tumors undergoing active surveillance (AS) for residual viable tumor following percutaneous ablation. Materials and MethodsFollowing percutaneous thermal ablation, residual tumor was detected in 21/133 (16%) patients on initial follow-up imaging, and AS was undertaken in 17/21 (81%) patients. Initial tumor volumes and volumes after ablation were assessed from cross-sectional imaging to calculate volumetric growth rate (VGR) and volume doubling time (VDT) of residual tumor. The rate of metastasis, overall survival, and renal cell carcinoma (RCC)–specific survival were compared between patients in the AS group and in the routine follow up group of patients who did not have residual tumor. ResultsMedian tumor volume prior to ablation, after first ablation, and at final follow-up were 25 cm3, 6 cm3, and 6 cm3, respectively, in patients with residual tumor. Stable, mild, and moderate VGR occurred in 8/17 (47%), 4/17 (24%), and 5/17 (29%) cases, respectively. The 4 cases with fastest VDT underwent delayed intervention with ablation (n = 1) and nephrectomy (n = 3) without subsequent residual, recurrence, or metastasis. There was no significant difference in the rates of RCC metastasis, overall survival, or RCC-specific survival between AS and routine follow-up groups. Metastatic RCC and subsequent death occurred in 1 patient in the AS group, after the patient had refused offers for retreatment for local progression over 60.7 months of follow-up. ConclusionsIn cases when patients are not amenable to further intervention, AS of residual tumor may be an acceptable alternative and allows for successful delayed intervention when needed.

MP78-11 DO SARCOMATOID AND RHABDOID DIFFERENTIATION HAVE SIMILAR PROGNOSTIC EFFECTS FOR PATIENTS WITH GRADE 4 RENAL CELL CARCINOMA?

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging II1 Apr 2016MP78-11 DO SARCOMATOID AND RHABDOID DIFFERENTIATION HAVE SIMILAR PROGNOSTIC EFFECTS FOR PATIENTS WITH GRADE 4 RENAL CELL CARCINOMA? Onder Kara, Homayoun Zargar, Matthew Maurice, Hiury Andrade, Oktay Akca, Peter Caputo, Daniel Ramirez, Ercan Malkoc, Brian Rini, and Jihad Kaouk Onder KaraOnder Kara More articles by this author , Homayoun ZargarHomayoun Zargar More articles by this author , Matthew MauriceMatthew Maurice More articles by this author , Hiury AndradeHiury Andrade More articles by this author , Oktay AkcaOktay Akca More articles by this author , Peter CaputoPeter Caputo More articles by this author , Daniel RamirezDaniel Ramirez More articles by this author , Ercan MalkocErcan Malkoc More articles by this author , Brian RiniBrian Rini More articles by this author , and Jihad KaoukJihad Kaouk More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1967AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The presence of sarcomatoid or rhabdoid elements within RCC has been reported to be associated with clinically poor outcomes. We aim to examine the impact of rhabdoid and sarcomatoid differentiation on cancer-specific survival (CSS) in patients with grade 4 renal cell carcinoma (RCC) undergoing extirpative surgery. METHODS We retrospectively analyzed our IRB-approved database of 1176 consecutive patients who underwent radical or partial nephrectomy for RCC between 2005 and 2013. We identified patients with Fuhrman grade IV RCC. The study cohort was divided into four groups: Grade IV without differentiation, Grade IV with rhabdoid features, Grade IV with sarcomatoid features, and Grade IV sarcomatoid and rhabdoid (mixed) features. The primary outcome was CSS, which was plotted by the Kaplan-Meier method and analyzed using the log-rank test and Cox proportional hazards modeling. RESULTS Of 264 patients with grade IV RCC, 159 (60.2%) had tumor differentiation, including 45 (28.3%) with rhabdoid only, 87 (54.7%) with sarcomatoid only, and 27 (16.9%) with both rhabdoid and sarcomatoid features (Table 1). Median CSS for the Grade IV group without tumor differentiation was 3.3 years (3.2-4.5) vs. 3.8 years (0.7-6.9) for the Grade IV-rhabdoid group (p=0.55). Median CSS for the Grade IV-sarcomatoid group and for the Grade IV-mixed group was 1.1 years (0.7-1.4) and 0.9 years (0.6-1.2), respectively, vs. 3.8 years (0.7-6.9) for the Grade IV-rhabdoid group (p=0.01 and p<0.01, respectively)(Figure 1). On multivariable analysis, there was a significant association between sarcomatoid differentiation and RCC death (HR 1.94; 95% CI 1.4-2.69; p<0.01); however, rhabdoid differentiation was no longer significant (HR 1.16; 95% CI 0.73-1.61; p=0.45). CONCLUSIONS Grade IV RCC with sarcomatoid differentiation is associated with worse CSS than grade IV RCC alone. Alternatively, rhabdoid differentiation does not appear to confer additional mortality risk for patients with grade 4 RCC. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1029-e1030 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Onder Kara More articles by this author Homayoun Zargar More articles by this author Matthew Maurice More articles by this author Hiury Andrade More articles by this author Oktay Akca More articles by this author Peter Caputo More articles by this author Daniel Ramirez More articles by this author Ercan Malkoc More articles by this author Brian Rini More articles by this author Jihad Kaouk More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Kidney Size and Cancer-specific Survival for Patients Undergoing Nephrectomy for pT1 Clear Cell Renal Cell Carcinoma

To examine the association between kidney size and renal cell carcinoma (RCC) death among patients with Stage pT1 clear cell RCC undergoing surgery. We used a case-cohort design and evaluated 191 patients from our Nephrectomy Registry who had undergone open radical nephrectomy for unilateral, sporadic, Stage pT1N0/NxM0, noncystic clear cell RCC from 1989 to 2004. Of these, 47 patients died of RCC ("cases") and 144 patients were alive at the last follow-up visit or had died of other causes ("cohort"). Univariate and multivariate associations with RCC death were evaluated using weighted Cox regression analysis and summarized with hazard ratios and 95% confidence intervals. The median kidney size was 12 cm. We observed a positive association between increasing kidney size and the risk of RCC death. A 1-cm increase in kidney size was associated with an 18% increased risk of RCC death, even after adjusting for tumor size, nuclear grade, and the presence of necrosis. After multivariate adjustment, those patients with a kidney size greater than the median were 95% more likely to die of RCC than those with a kidney size less than the median (hazard ratio 1.95, 95% confidence interval 1.00-3.81; P = .05). The limitations of our study included a lack of data on the 3-dimensional kidney volume and an inability to generalize to patients with larger tumors (ie, Stage pT2) or other RCC subtypes. Our data suggest that kidney size is an independent predictor of survival for patients with Stage pT1 clear cell RCC. Future investigations are needed to confirm this finding and investigate this issue in larger, organ-confined tumors and other RCC subtypes.

Does left side renal cell carcinoma (RCC) with renal vein/vena cava thrombus predict worse prognosis than equivalent right side RCC tumor thrombus?

To determine whether renal cell carcinoma (RCC) thrombi that reach the vena cava from the left kidney are associated with a greater risk of RCC death than equivalent thrombi from the right kidney. Two hundred and fifty-nine patients treated with radical nephrectomy (1970-2006) for unilateral, sporadic RCC with level 1-4 RCC tumor thrombus were identified. Clinicopathologic features between patients with right-sided (N = 183) and left-sided (N = 76) thrombus were compared utilizing Wilcoxon rank sum and Fisher's exact tests. Associations with RCC-specific death using hazard ratios (HR) and 95 % confidence intervals (CIs) from Cox proportional hazards models were evaluated. Left-sided RCC patients with thrombus are less likely to be clear cell subtype (85 % vs. 93 %; p = 0.013) and more likely to have nodal involvement (28 % vs. 16 %; p = 0.018) compared to right side RCC patients with thrombus. Overall, there is little evidence that the risk of RCC death is higher for left versus right-sided RCC thrombus (HR = 1.11; 95 % CI 0.81-1.53; p = 0.52). However, among those patients with a thrombus that has reached the vena cava (level III/IV), we observe evidence after multivariate adjustment that the risk of RCC death is higher for left versus right side patients (HR = 2.02; 95 % CI 0.91-4.47; p = 0.08). Left side RCC with tumor thrombus is not associated with worse prognosis than right-sided tumors (all tumor thrombi levels). Our data suggest that among RCC patients with advanced tumor thrombi (level III/IV), a left side thrombus may be associated with worse prognosis compared to a right side thrombus.

Three‐dimensional tumour volume and cancer‐specific survival for patients undergoing nephrectomy to treat pT1 clear‐cell renal cell carcinoma

Study Type - Prognosis (case series) Level of Evidence 4. What's known on the subject? and What does the study add? The positive association of tumour size (largest tumour dimension on pathology review) and risk of RCC progression and survival following nephrectomy is well documented. Moreover, several clinicopathological scoring systems (i.e. nomograms and algorithms) have been developed to predict outcomes for surgically treated RCC patients and each of these includes tumour size as an independent predictor of RCC outcome. There is still the question of whether information on three-dimensional tumour volume (cm(3) ) can provide additional prognostic information, particularly among patients with small pT1 tumours where the range of tumour size is more limited. Our study demonstrates that increasing tumour volume is associated with a greater risk of RCC-specific death in patients with pT1 ccRCC, with a more pronounced association in pT1a tumours specifically. In addition, we observed evidence that tumour volume may provide more accurate prognostic information than tumour size alone in pT1a patients. Tumour volume may add prognostic information specifically in pT1a RCC. To address whether information on three-dimensional tumour volume can provide additional prognostic information for patients with small, localized renal cell carcinoma (RCC) superior to tumour size alone. We identified 955 patients treated with radical nephrectomy or nephron-sparing surgery for unilateral, sporadic, pT1, pN0/NX, M0, non-cystic clear-cell RCC (ccRCC) between 1980 and 2004, including 515 pT1a patients and 440 pT1b patients. • We estimated tumour volume using three tumour dimensions recorded on pathological analysis and the equation for the volume of an ellipsoid [π/6 (length × width × height)]. For tumour size alone, we used the maximum tumour diameter recorded on pathological analysis. • Univariate and multivariable associations with RCC-specific death were evaluated using Cox proportional hazards regression models summarized with hazard ratios (HRs) and 95% confidence intervals (CIs). Among pT1a patients, the risk of RCC death associated with having a tumour volume above the median (HR = 4.55; 95% CI, 1.30-15.83; P= 0.018) was markedly higher than having a tumour size above the median (HR = 2.55; 95% CI 0.83-7.85; P= 0.10). Comparison of concordance (c) index values further supported the idea that additional prognostic information was provided by tumour volume (c= 0.659) compared with tumour size (c= 0.600) for pT1a patients. • Among pT1b patients, we noted that associations of tumour volume and tumour size with RCC-specific death were similar. • Multivariable adjustment did not alter our findings. Tumour volume could provide valuable prognostic information for patients with pT1a ccRCC but not pT1b ccRCC. • Future investigations are needed to confirm this finding, explore other RCC subtypes and evaluate accuracy of tumour volume determination on radiographic imaging for potential patient management before surgery.

Evaluation of the association of current cigarette smoking and outcome for patients with clear cell renal cell carcinoma

Cigarette smoking is a well known risk factor for the development of renal cell carcinoma (RCC); however, its association with tumor aggressiveness and patient outcome remains in question. Herein, we test the hypothesis that cigarette smoking is associated with a more aggressive phenotype and poorer outcome among patients with RCC. We examined data on 2242 patients treated with radical nephrectomy or nephron-sparing surgery for unilateral, sporadic, clear cell RCC at Mayo Clinic Rochester between 1970 and 2002. Associations of self-reported smoking status with death from RCC were assessed using Cox proportional hazards regression models summarized with hazard ratios (HR) and 95% confidence intervals (CI). While former cigarette smoking was not associated with an increased risk of RCC death, current cigarette smokers were 31% more likely to die from RCC compared with non-smokers on a hazard ratio scale (HR 1.31; 95% CI 1.09-1.58; P = 0.004). Interestingly, current smokers were more likely to present with advanced disease (i.e. later TNM stage) compared with both former and never smokers. After adjustment for TNM stage group and tumor grade, there was no longer a statistically significant increase in the risk of death from RCC for current cigarette smokers (HR 0.99; 95% CI 0.82-1.19; P = 0.875). Patients who report current smoking at time of surgery are at increased risk of RCC death; however, this association is attenuated after adjustment for standard pathological indices and is therefore of little prognostic value. Nevertheless, the association of current smoking with more advanced disease at presentation (e.g. metastatic spread) warrants further investigation.

Questionable Relevance of γδ T Lymphocytes in Renal Cell Carcinoma

Adoptive gammadelta T cell immunotherapy has moved briskly into clinical trials prompted by several small studies suggesting abundant accumulation of gammadelta T cells within renal cell carcinoma (RCC). In this study, we re-examined levels of gammadelta T cells within RCC tumors and correlated levels of these cells with pathologic features and outcome associated with this form of cancer. Tissues from 248 consecutive clear cell RCC tumors obtained from 2000 to 2003 were stained and quantified for total CD3+ and gammadelta T cells per mm2. Wilcoxon rank sum and Kruskal-Wallis tests were used to evaluate associations between T cell amounts and prognostic factors (age, gender, tumor size, stage, grade, tumor necrosis). Cox models were used to assess associations with RCC-specific death. Median numbers of total CD3+ and gammadelta T cells were 281/mm2 (interquartile range (IQR): 149-536) and 2.6/mm2 (IQR: 1.3-4.6), respectively. The median percentage of CD3+ T cells that were gammadelta T cells was 1.0% (IQR: 0.4-1.9). This low percentage of intratumoral gammadelta T cells was diluted even further with rising CD3+ T cell infiltration. Percentages of gammadelta T cells were not associated with even one single clinicopathologic feature examined. Median follow-up for this study was 3.1 years (48 patients died of RCC) and Cox analysis failed to demonstrate that gammadelta T cells (hazard ratio=1.02, p=0.25) were predictive of RCC-specific death. gammadelta T cells are rare and not recruited nor expanded within RCC tumors. Percentages of gammadelta T cells fail to correlate with any prognostic features of RCC nor specific death. As such, the role of gammadelta T cells in RCC immunobiology remains questionable.

Tumor-Infiltrating Foxp3−CD4+CD25+ T Cells Predict Poor Survival in Renal Cell Carcinoma

Regulatory T cells (Tregs) have been implicated as inhibitors of antitumoral immunity, and evidence suggests that elimination of Tregs may augment natural and pharmacologic immunity. We tested for the presence of putative Tregs within renal cell carcinoma (RCC) tumors. We identified 170 patients who underwent radical or partial nephrectomy for clear cell RCC between 2000 and 2002. Specimens were stained with anti-CD4, anti-CD25, and anti-Foxp3 antibodies and examined using confocal microscopy. Associations of CD4(+)CD25(+)Foxp3(-) and CD4(+)CD25(+)Foxp3(+) T cells with death from RCC were evaluated using Cox proportional hazards regression models. At last follow-up, 46 of 170 patients had died; of these, 37 died from RCC at a median of 1.4 years following nephrectomy (range, 0-4.4). Among the 124 remaining patients, median follow-up was 3.7 years (range, 0-5.7). Forty-three (25.3%) tumors harbored CD4(+)CD25(+)Foxp3(+) T cells. The presence of Foxp3(+) T cells was not significantly associated with RCC death univariately. One hundred forty-three (84.1%) tumors harbored CD4(+)CD25(+)Foxp3(-) T cells. The indicator for >or=10% CD4(+)CD25(+)Foxp3(-) T cells was significantly associated with RCC death univariately [risk ratio (RR), 2.60; 95% confidence interval (95% CI), 1.35-4.98; P = 0.004], after adjusting for tumor B7-H1 expression (RR, 2.53; 95% CI, 1.32-4.85; P = 0.005) and lymphocytic infiltration (RR, 2.53; 95% CI, 1.32-4.87; P = 0.005). Increased presence of CD4(+)CD25(+)Foxp3(+) T cells was not significantly associated with RCC death. In contrast, CD4(+)CD25(+)Foxp3(-) T cells, which may represent a unique set of Tregs or activated helper T cells, was significantly associated with outcome.

Greater body mass index is associated with better pathologic features and improved outcome among patients treated surgically for clear cell renal cell carcinoma

Objectives Obesity increases the risk of developing renal cell carcinoma (RCC); however, it remains unclear whether obesity is associated with RCC aggressiveness and survival. We used data from a large cohort of patients treated surgically for clear cell RCC to evaluate the association of obesity with the pathologic features of tumor aggressiveness and cancer-specific outcomes. Methods From 1988 to 2002, 970 patients underwent nephrectomy at Mayo Clinic Rochester for clear cell RCC and had body mass index (BMI) data available. To evaluate the association of BMI at surgery with the tumor pathologic features, we used the chi-square and Fisher’s exact tests. We then analyzed the association of BMI with cancer-specific survival using Kaplan-Meier curves and Cox regression models. Results Overweight (BMI 25 to less than 30 kg/m 2) and obese (BMI 30 kg/m 2 or more) patients were more likely to present with less-aggressive tumors compared with normal-weight patients (BMI less than 25 kg/m 2). The 5-year cancer-specific survival rate was 62.3%, 76.9%, and 81.7% for the normal, overweight, and obese patients, respectively. The overweight (hazard ratio 0.64, 95% confidence interval 0.49 to 0.84) and obese (hazard ratio 0.48, 95% confidence interval 0.36 to 0.66) patients were at a reduced risk of RCC death compared with patients with a BMI in the normal range. The inverse association of BMI with survival was attenuated after adjustment for well-known pathologic predictors of tumor aggressiveness. Conclusions BMI offers little additional prognostic information beyond the accepted prognostic features; however, the association of an increased BMI with a less-aggressive disease profile at presentation warrants further exploration.