Prognostic value of B7-H1, B7-H3 and the stage, size, grade and necrosis (SSIGN) score in metastatic clear cell renal cell carcinoma.

INTRODUCTION: We compared the potential prognostic impact of B7-H1 and B7-H3 glycoprotein expressions with the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score in metastatic clear cell renal cell carcinoma (mccRCC) during a long term follow-up. MATERIAL AND METHODS: We investigated 44 mccRCC patients, who underwent radical nephrectomy between 1995 and 2006 at a single tertiary academic center and received interferon therapy (IFNT) for at least three months. The SSIGN score was applied as a validated prediction outcome model. Representative tumor sections were immunostained with anti-B7-H3 and anti-B7-H1 antibodies. Hereafter, positive antigen-antibody reactions were measured using the Positive-Pixel-Count Algorithm of the Aperio-Technology Image Scope software. RESULTS: In total, 48% of patients were treated with cytoreductive nephrectomy and postoperative IFNT due to synchronous mccRCC, whereas 52% received IFNT after developing metachronous mccRCC. The SSIGN score was independently associated with a higher mortality risk. Patients with a SSIGN score ≤9 showed an extended 'nephrectomy to start of INFT'-interval (p = 0.02), less synchronous clinical metastases (p = 0.0002), as well as an increased median overall - (OS) or cancer-specific survival (CSS) (p = 0.01), respectively. Furthermore, B7-H3 expression levels of ≤16% were associated with an improved OS or CSS and correlated with a more frequent pathologic grade 1-2, as well as a longer 'nephrectomy to start of IFNT'-interval, respectively. B7-H1 expression patterns did not correlate with survival. CONCLUSIONS: The SSIGN score demonstrated the best prognostic performance. In contrast, B7-H3 expression patterns showed a low association with histopathological parameters, but predicted the cut-off-dependent impaired survival and in the future may define a cut-off to indicate checkpoint-inhibitor treatment.

Renal cell carcinoma with inferior vena cava involvement: Prognostic effect of tumor thrombus consistency on cancer specific survival.

BACKGROUND: Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort. METHODS: The records of 413 patients collected by the International Renal Cell Carcinoma-Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan-Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors. RESULTS: VTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasion, and higher Fuhrman grade. Survival analysis and Cox regression rejected TC as prognostic marker for CSS. CONCLUSIONS: In the largest cohort published so far, TC seems not to be independently associated with survival in RCC patients and should therefore not be included in risk stratification models. J. Surg. Oncol. 2016;114:764-768. © 2016 Wiley Periodicals, Inc.

The Adoption of Nephron-Sparing Surgery in Europe - A Trend Analysis in Two Referral Centers from Austria and Germany.

OBJECTIVE: To compare the trends of partial nephrectomy (PN) and radical nephrectomy (RN) in 2 European tertiary referral centers with regards to guideline changes. MATERIALS AND METHODS: A total of 1,573 patients who underwent RN or PN for localized (≤T2) renal cell carcinoma (RCC) were included. Logistic regression analyses assessed the predictors of PN and laparoscopy over time. RESULTS: Out of the total, 1,013 patients (65.6%) were treated with RN and 560 patients (34.4%) with PN. Also, 1,233 patients (80%) had open surgery whereas 340 patients (22%) were treated with a laparoscopic approach. Laparoscopic RN and PN were performed in 216 (13.7%) and 124 (7.8%) patients, respectively. T1b tumors were 73% less likely (p < 0.001) to be treated with PN compared to T1a tumors. The odds of undergoing PN or laparoscopy in 2008-2010 relative to 2000-2001 were 6.5-fold (p < 0.001) and 36-fold higher (p < 0.001), respectively. CONCLUSIONS: Tumor size and year of surgery are independent predictors of PN in our cohort. Our data exemplify the adoption of PN for RCC in tertiary care centers in Austria and Germany in line with implemented guideline changes. The utilization of PN has increased over time regardless of surgical approach. Further studies need to address the use of robot-assisted surgery and care in community hospitals.

Cardiopulmonary Bypass has No Significant Impact on Survival in Patients Undergoing Nephrectomy and Level III-IV Inferior Vena Cava Thrombectomy: Multi-Institutional Analysis.

PURPOSE: The impact of cardiopulmonary bypass in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We determine the impact of cardiopulmonary bypass on overall and cancer specific survival, as well as surgical complication rates and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without cardiopulmonary bypass. MATERIALS AND METHODS: We retrospectively analyzed 362 patients with renal cell cancer and with level III or IV tumor thrombus from 1992 to 2012 at 22 U.S. and European centers. Cox proportional hazards models were used to compare overall and cancer specific survival between patients with and without cardiopulmonary bypass. Perioperative mortality and complication rates were assessed using logistic regression analyses. RESULTS: Median overall survival was 24.6 months in noncardiopulmonary bypass cases and 26.6 months in cardiopulmonary bypass cases. Overall survival and cancer specific survival did not differ significantly in both groups on univariate analysis or when adjusting for known risk factors. On multivariate analysis no significant differences were seen in hospital length of stay, Clavien 1-4 complication rate, intraoperative or 30-day mortality and cancer specific survival. Limitations include the retrospective nature of the study. CONCLUSIONS: In our multi-institutional analysis the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality on multivariate analysis. Greater surgical complications were not independently associated with the use of cardiopulmonary bypass.

Impact of synchronous metastasis distribution on cancer specific survival in renal cell carcinoma after radical nephrectomy with tumor thrombectomy.

PURPOSE: Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival. MATERIALS AND METHODS: The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates. RESULTS: Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival. CONCLUSIONS: In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease.

Lessons learned from the International Renal Cell Carcinoma-Venous Thrombus Consortium (IRCC-VTC).

Renal cell carcinoma (RCC) extension into the renal vein or the inferior vena cava occurs in 4%-10% of all kidney cancer cases. This entity shows a wide range of different clinical and surgical scenarios, making natural history and oncological outcomes variable and poorly characterized. Infrequency and variability make it necessary to share the experience from different institutions to properly analyze surgical outcomes in this setting. The International Renal Cell Carcinoma-Venous Tumor Thrombus Consortium was created to answer the questions generated by competing results from different retrospective studies in RCC with venous extension on current controversial topics. The aim of this article is to summarize the experience gained from the analysis of the world's largest cohort of patients in this unique setting to date.

Do young patients with renal cell carcinoma feature a distinct outcome after surgery? A comparative analysis of patient age based on the multinational CORONA database.

PURPOSE: We analyzed the distinct clinicopathological features and prognosis of patients with renal cell carcinoma age 40 years or less compared to a reference group of patients 60 to 70 years old. MATERIALS AND METHODS: Overall 2,572 patients retrieved from a multicenter international database comprised of 6,234 patients with surgically treated renal cell carcinoma were included in this retrospective study. Clinical and histopathological features of 297 patients 40 years old or younger (4.8%) were compared to those of 2,275 patients (36.5%) 60 to 70 years old, who served as the reference group. Median followup was 59 months. The impact of young age and further parameters on disease specific mortality and all cause mortality was evaluated by multivariate Cox proportional hazards regression analyses. RESULTS: Young patients more frequently underwent nephron sparing surgery (27% vs 20%, p = 0.008) and regional lymph node dissection compared to older patients (38% vs 32%, p = 0.025). Organ confined tumor stage (81% vs 70%, p <0.001), smaller tumor diameter (4.5 vs 4.7 cm, p = 0.014) and chromophobe subtype (10% vs 4%, p <0.001) were significantly more frequent in young patients. On multivariate analysis older patients had a higher disease specific (HR 2.21, p <0.001) and all cause mortality (HR 3.05, p <0.001). The c indices for the Cox models were 0.87 and 0.78, respectively. However, integration of the variable age group did not significantly increase the predictive accuracy of the disease specific and all cause mortality models. CONCLUSIONS: Young patients with renal cell carcinoma (40 years old or younger) have significantly different frequencies of clinical and histopathological features, and a significantly lower all cause and disease specific mortality compared to patients 60 to 70 years old.

Impact of histologic subtype on cancer-specific survival in patients with renal cell carcinoma and tumor thrombus.

BACKGROUND: Although different prognostic factors for patients with renal cell carcinoma (RCC) and vena cava tumor thrombus (TT) have been studied, the prognostic value of histologic subtype in these patients remains unclear. OBJECTIVE: We analyzed the impact of histologic subtype on cancer-specific survival (CSS). DESIGN, SETTINGS, AND PARTICIPANTS: We retrospectively analyzed the records of 1774 patients with RCC and TT who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 US and European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable ordered logistic and Cox regression models were used to quantify the impact of tumor histology on CSS. RESULTS AND LIMITATIONS: Overall 5-yr CSS was 53.4% (confidence interval [CI], 50.5-56.2) in the entire group. TT level (according to the Mayo classification of macroscopic venous invasion in RCC) was I in 38.5% of patients, II in 30.6%, III in 17.3%, and IV in 13.5%. Histologic subtypes were clear cell renal cell carcinoma (cRCC) in 89.9% of patients, papillary renal cell carcinoma (pRCC) in 8.5%, and chromophobe RCC in 1.6%. In univariable analysis, pRCC was associated with a significantly worse CSS (p<0.001) compared with cRCC. In multivariable analysis, the presence of pRCC was independently associated with CSS (hazard ratio: 1.62; CI, 1.01-2.61; p<0.05). Higher TT level, positive lymph node status, distant metastasis, and fat invasion were also independently associated with CSS. CONCLUSIONS: In our multi-institutional series, we found that patients with pRCC and vena cava TT who underwent radical nephrectomy and tumor thrombectomy had significantly worse cancer-specific outcomes when compared with patients with other histologic subtypes of RCC. We confirmed that higher TT level and fat invasion were independently associated with reduced CSS.

Prognostic effect of sarcomatoid dedifferentiation in patients with surgically treated renal cell carcinoma: a matched-pair analysis.

BACKGROUND: The aim of this study was to assess the prognostic relevance of SD in patients with RCC. PATIENTS AND METHODS: Among 8126 RCC patients surgically treated at 12 academic centers (members of the Collaborative Research on Renal Neoplasms Association [CORONA] project), 316 patients (3.9%) had SD with sarcomatoid areas comprising at least 10% of the tumor tissue. After propensity score-based matched-pair analysis, 281 with and 281 matched RCC patients without SD remained available for direct comparison of cancer-specific survival (CSS). Median follow-up was 36.5 months (interquartile range, 15-82). Uni- and multivariable Cox proportional hazards regression analyses were performed to assess the prognostic value of parameters. RESULTS: In univariable analysis, there was no difference in CSS between patients with or without SD (1 and 5 years CSS, 79% vs. 83% and 59% vs. 64%, respectively; hazard ratio, 1.21; P = .16). Multivariable analysis in patients with SD identified metastatic dissemination at the time of surgery, pT-stage, nodal status, and tumor size as independent predictors of CSS. This study was limited by its retrospective multicenter design and lack of central histopathological review. CONCLUSION: Sarcomatoid dedifferentiation was not an independent predictor of CSS in surgically treated RCC patients in the present matched-pair series. Because pathology reports form the basis on which study specimens are selected for further studies, which are clearly needed to advance our understanding of the prognostic value of SD in RCC, it is imperative that pathologists reliably report on absence or presence and the estimated percentage of a coexisting sarcomatoid component.

Tumour-associated macrophages might represent a favourable prognostic indicator in patients with papillary renal cell carcinoma.

AIMS: Tumour-associated macrophages (TAM) have been reported to be regulators of progression in various human cancers. We evaluated the prognostic relevance of TAM in a large series of patients with papillary renal cell carcinoma (PRCC). METHODS AND RESULTS: The impact of TAM on cancer-specific survival (CSS) in 177 patients with PRCC was assessed using the Kaplan-Meier method and log-rank test. A multivariate Cox regression analysis was performed with respect to CSS. The presence of TAM was noted in 112 of 177 (63%) tumours and was associated statistically significantly with favourable pathological parameters, including low pathological T stage, node-negative tumours, low tumour grade, absence of vascular invasion and papillary subtype (all P < 0.05), respectively. Five-year CSS probabilities for patients with TAM-positive tumours were 93.5%, compared with 72.5% in patients with TAM-negative tumours, respectively (P < 0.001). Multivariate analysis revealed node-positive tumours, distant metastases and UICC stage (I versus II-IV) as independent predictors of death from PRCC, whereas the presence of TAM was associated independently with favourable outcome (hazard ratio = 0.45, 95% confidence interval 0.24-0.84, P = 0.012). CONCLUSIONS: The presence of TAM was shown independently to reduce the risk of death from cancer by 55%. The presence of TAM should therefore become part of routine pathology reporting in PRCC.

Gender differences in clinicopathological features and survival in surgically treated patients with renal cell carcinoma: an analysis of the multicenter CORONA database.

PURPOSE: To investigate gender differences in clinicopathological features and to analyze the prognostic impact of gender in renal cell carcinoma (RCC) patients undergoing surgery. METHODS: A total of 6,234 patients (eleven centers; Europe and USA) treated by radical or partial nephrectomy were included in this retrospective study (median follow-up 59 months; IQR 30-106). Gender differences in clinicopathological parameters were assessed. Multivariable Cox regression models were applied to determine the influence of parameters on disease-specific survival (DSS) and overall survival (OS). RESULTS: A total of 3,751 patients of the study group were male patients (60.2 %), who were significantly younger at diagnosis and received more frequently NSS than women. Significantly, more often high-grade tumors and simultaneous metastasis were present in men. Whereas tumor size and pTN stages did not differ between genders, clear-cell and chromophobe RCC was diagnosed less frequently, but papillary RCC more often in men. Gender also independently influenced DSS (HR 0.75, p < 0.001) and OS (HR 0.80, p < 0.001) with a benefit for women. However, inclusion of gender in multivariable models did not significantly gain predictive accuracies (PA) for DSS (0.868-0.870, p = 0.628) and OS (0.775-0.777, p = 0.522). Furthermore, no significantly different DSS and OS rates were found in patients undergoing NSS. CONCLUSIONS: This study demonstrates important gender differences in clinicopathological features and outcome of RCC patients with improved DSS and OS for women compared to men, even if solely patients with clear-cell RCC or M0-stage are taken into evaluation. However, inclusion of gender in multivariable models does not significantly gain PA of multivariable models.

Assessing the accuracy and generalizability of the preoperative and postoperative Karakiewicz nomograms for renal cell carcinoma: results from a multicentre European and US study.

OBJECTIVE: To assess the accuracy and generalizability of the pre- and postoperative Karakiewicz nomograms for predicting cancer-specific survival (CSS) in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS: This retrospective study included 3231 patients from European and US centres, who were treated by radical or partial nephrectomy for RCC between 1992 and 2010. Prognostic scores for each patient were calculated and the primary endpoint was CSS. Discriminating ability was assessed by Harrell's c-index for censored data. The 'validation by calibration' method proposed by Van Houwelingen was used for checking the calibration of covariate effects. Calibration was graphically explored. RESULTS: Local and systemic symptoms were present in 23.2% and 9.1% of the patients, respectively. The median follow-up (FU) was 49 months. At the last FU, 408 cancer-related deaths were recorded, Kaplan-Meier estimates of CSS (with 95% confidence intervals [CIs]) at 5 and 10 years were 0.86 (0.84-0.87) and 0.77 (0.75-0.80), respectively. Both nomograms discriminated well. Stratified c-indices for CSS were 0.784 (95% CI 0.753-0.814) for the preoperative nomogram, and 0.842 (95% CI 0.816-0.867) for the postoperative one, with a significant difference between the two values (P < 0.001). The covariate-based predictions on our data for both nomograms were valid. The calibration plots showed no relevant departures from ideal predictions. CONCLUSIONS: The results suggest that the postoperative Karakiewicz nomogram discriminates substantially better than the preoperative one. These nomogram-based predictions may be used as benchmark data for pretreatment and postoperative decision-making in patients at various stages of RCC.

Impact of clinical and histopathological parameters on disease specific survival in patients with collecting duct renal cell carcinoma: development of a disease specific risk model.

PURPOSE: Collecting duct renal cell carcinoma is a rare, aggressive histological subtype of renal cell carcinoma. Since few groups have evaluated the oncological prognosis in these patients based on clinical and pathological parameters, we assessed parameters prognostic for disease specific mortality. MATERIALS AND METHODS: From a cohort of 14,047 patients with renal cell carcinoma we retrieved the records of 95 with collecting duct renal cell carcinoma at a total of 16 European and American centers of the CORONA (Collaborative Research on Renal Neoplasms Association) and SATURN (Surveillance and Treatment Update Renal Neoplasms) projects, and another 2 centers. Multivariable Cox regression analysis was applied to determine the influence of parameters on disease specific mortality. Median followup was 48.1 months (IQR 24-103). RESULTS: The disease specific survival rate at 1, 2, 5 and 10 years was 60.4%, 47.3%, 40.3% and 32.8%, respectively. American Society of Anesthesiologists (ASA) score 3-4, tumor size greater than 7 cm, stage M1, Fuhrman grade 3-4 and lymphovascular invasion independently predicted disease specific mortality. Based on these parameters, patients were divided into 26 (27%) at low, 13 (14%) at intermediate and 56 (59%) at high risk with a 5-year disease specific survival rate of 96%, 62% and 8%, respectively (bootstrap corrected c-index 0.894, 95% CI 0.820-0.967, p <0.001). CONCLUSIONS: While patients with collecting duct renal cell carcinoma are commonly diagnosed at advanced stage and have poor prognosis after surgery, a subset has excellent survival. Histopathological features can help risk stratify patients based on the described, highly accurate risk model to predict disease specific mortality, facilitating patient counseling and risk based clinical decision making for adjuvant therapy and clinical trial inclusion.

Does preoperative platelet count and thrombocytosis play a prognostic role in patients undergoing nephrectomy for renal cell carcinoma? Results of a comprehensive retrospective series.

PURPOSE: To evaluate the still controversially discussed prognostic role of preoperative platelet level (PPL) and thrombocytosis (TC) in patients who undergo surgery for renal cell carcinoma (RCC) based on the largest patient series reported to date. METHODS: A total of 3,139 patients, who underwent radical or nephron-sparing nephrectomy at four centres, were subdivided based on a threshold for preoperative platelets of 400 × 10(9) cells/L. Univariate and multivariable Cox regression analyses were applied to determine the prognostic influence of PPL and TC on cancer-specific survival (CSS) for patients with localized and metastatic disease at presentation. RESULTS: Group 1 (PPL ≤ 400/nl) and Group 2 (PPL > 400/nl) included 2,862 (91 %) and 277 patients (9 %), respectively. With a median follow-up (FU) of 69.5 months (IQR: 35-105), CSS of all patients after 5 years was 84.6 % in Group 1 versus 53.4 % in Group 2 (p < 0.001). At multivariable analysis, TC (HR:1.337; p = 0.007) and continuous PPL (HR:1.001; p = 0.002) independently predicted a decreased survival. However, integration of these parameters into multivariable models for the entire study group and for patients with localized tumours did only result in marginal improvement of the model quality (0.66 and 1.04 %, respectively). Interestingly, neither TC (p = 0.257) nor PPL (p = 0.132) significantly influenced survival in M1 patients. CONCLUSIONS: Preoperative TC turned out an independent predictor for decreased CSS in patients undergoing surgery for localized RCC. However, significant improvement of multivariable models comprising standard clinical and pathological parameters by the inclusion of TC is not achieved. In metastatic disease, TC did not reveal an independent influence on CSS.

Presence and extent of histological tumour necrosis is an adverse prognostic factor in papillary type 1 but not in papillary type 2 renal cell carcinoma.

AIMS: To date, only limited information is available on the prognostic significance of the presence and extent of histological tumour necrosis with regard to papillary renal cell carcinoma (RCC) types 1 and 2 subclassification. Thus, the aim of this study was to evaluate the prognostic impact of these pathological features on the clinical outcome in papillary subtypes. METHODS AND RESULTS: The influence of histological tumour necrosis on the clinical outcome in 177 patients with papillary RCC was evaluated. For papillary subtype 1, the presence of histological tumour necrosis was an independent negative prognostic factor for disease-free survival (P = 0.039), and a greater extent of necrosis (>20%) was significantly associated with both poor disease-free and overall survival (P = 0.033 and P = 0.041, respectively). Regarding papillary subtype 2, neither the presence nor extent of histological tumour necrosis was a statistically significant negative prognostic factor. CONCLUSION: Our findings suggest that the presence and extent of histological tumour necrosis are independent prognosticators in papillary RCC subtype 1, but not in papillary subtype 2. Thus, previously reported conflicting data regarding the prognostic impact of tumour necrosis in papillary RCC might be explained, in part, by heterogeneous subtypes.

Obesity is associated with worse oncological outcomes in patients treated with radical cystectomy.

OBJECTIVE: To investigate the association between body mass index (BMI) and oncological outcomes in patients after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) in a large multi-institutional series. PATIENTS AND METHODS: Data were collected from 4118 patients treated with RC and pelvic lymphadenectomy for UCB. Patients receiving preoperative chemotherapy or radiotherapy were excluded. Univariable and multivariable models tested the effect of BMI on disease recurrence, cancer-specific mortality and overall mortality. BMI was analysed as a continuous and categorical variable (<25 vs 25-29 vs ≥30 kg/m(2)). RESULTS: Median BMI was 28.8 kg/m(2) (interquartile range 7.9); 25.3% had a BMI <25 kg/m(2), 32.5% had a BMI between 25 and 29.9 kg/m(2), and 42.2% had a BMI ≥30 kg/m(2). Patients with a higher BMI were older (P < 0.001), had higher tumour grade (P < 0.001), and were more likely to have positive soft tissue surgical margins (P = 0.006) compared with patients with lower BMI. In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI >30 was associated with higher risk of disease recurrence (hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.46-1.91, P < 0.001), cancer-specific mortality (HR 1.43, 95% CI 1.24-1.66, P < 0.001), and overall mortality (HR 1.81, CI 1.60-2.05, P < 0.001). Themain limitation is the retrospective design of the study. CONCLUSIONS: Obesity is associated with worse cancer-specific outcomes in patients treated with RC for UCB. Focusing on patient-modifiable factors such as BMI may have significant individual and public health implications in patients with invasive UCB.

Extranodal extension is a powerful prognostic factor in bladder cancer patients with lymph node metastasis.

BACKGROUND: Lymph node metastasis (LNM) is the most powerful pathologic predictor of disease recurrence after radical cystectomy (RC). However, the outcomes of patients with LNM are highly variable. OBJECTIVE: To assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 748 patients with urothelial carcinoma of the bladder and LNM treated with RC and lymphadenectomy without neoadjuvant therapy at 10 European and North American centers (median follow-up: 27 mo). INTERVENTION: All subjects underwent RC and bilateral pelvic lymphadenectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Each LNM was microscopically evaluated for the presence of ENE. The number of LNs removed, number of positive LNs, and LN density were recorded and calculated. Univariable and multivariable analyses addressed time to disease recurrence and cancer-specific mortality after RC. RESULTS AND LIMITATIONS: A total of 375 patients (50.1%) had ENE. The median number of LNs removed, number of positive LNs, and LN density were 15, 2, and 15, respectively. The rate of ENE increased with advancing pT stage (p<0.001). In multivariable Cox regression analyses that adjusted for the effects of established clinicopathologic features and LN parameters, ENE was associated with disease recurrence (hazard ratio [HR]: 1.89; 95% confidence interval [CI], 1.55-2.31; p<0.001) and cancer-specific mortality (HR: 1.90; 95% CI, 1.52-2.37; p<0.001). The addition of ENE to a multivariable model that included pT stage, tumor grade, age, gender, lymphovascular invasion, surgical margin status, LN density, number of LNs removed, number of positive LNs, and adjuvant chemotherapy improved predictive accuracy for disease recurrence and cancer-specific mortality from 70.3% to 77.8% (p<0.001) and from 71.8% to 77.8% (p=0.007), respectively. The main limitation of the study is its retrospective nature. CONCLUSIONS: ENE is an independent predictor of both cancer recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of ENE status could help with patient counseling, clinical decision making regarding inclusion in clinical trials of adjuvant therapy, and tailored follow-up scheduling after RC.

Features associated with recurrence beyond 5 years after nephrectomy and nephron-sparing surgery for renal cell carcinoma: development and internal validation of a risk model (PRELANE score) to predict late recurrence based on a large multicenter database (CORONA/SATURN Project).

BACKGROUND: Approximately 10-20% of recurrences in patients treated with nephrectomy for renal cell carcinoma (RCC) develop beyond 5 yr after surgery (late recurrence). OBJECTIVE: To determine features associated with late recurrence. DESIGN, SETTING, AND PARTICIPANTS: A total of 5009 patients from a multicenter database comprising 13 107 RCC patients treated surgically had a minimum recurrence-free survival of 60 mo (median follow-up [FU]: 105 mo [range: 78-135]); at last FU, 4699 were disease free (median FU: 103 mo [range: 78-134]), and 310 patients (6.2%) experienced disease recurrence (median FU: 120 mo [range: 93-149]). INTERVENTIONS: Patients underwent radical nephrectomy or nephron-sparing surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable regression analyses identified features associated with late recurrence. Cox regression analyses evaluated the association of features with cancer-specific mortality (CSM). RESULTS AND LIMITATIONS: Lymphovascular invasion (LVI) (odds ratio [OR]: 3.07; p<0.001), Fuhrman grade 3-4 (OR: 1.60; p=0.001), and pT stage >pT1 (OR: 2.28; p<0.001) were significantly associated with late recurrence. Based on accordant regression coefficients, these parameters were weighted with point values (LVI: 2 points; Fuhrman grade 3-4: 1 point, pT stage >1: 2 points), and a risk score was developed for the prediction of late recurrences. The calculated values (0 points: late recurrence risk 3.1%; 1-3 points: 8.4%; 4-5 points: 22.1%) resulted in a good-, intermediate- and poor-prognosis group (area under the curve value for the model: 70%; 95% confidence interval, 67-73). Multivariable Cox regression analysis showed LVI (HR: 2.75; p<0.001), pT stage (HR: 1.24; p<0.001), Fuhrman grade (HR: 2.40; p<0.001), age (HR: 1.01; p<0.001), and gender (HR: 0.71; p=0.027) to influence CSM significantly. Limitations are based on the multicenter and retrospective study design. CONCLUSIONS: LVI, Fuhrman grade 3/4, and a tumor stage >pT1 are independent predictors of late recurrence after at least 5 yr from surgery in patients with RCC. We developed a risk score that allows for prognostic stratification and individualized aftercare of patients with regard to counseling, follow-up scheduling, and clinical trial design.

Predictive ability of the 2002 and 2010 versions of the Tumour-Node-Metastasis classification system regarding metastasis-free, cancer-specific and overall survival in a European renal cell carcinoma single-centre series.

OBJECTIVE: To compare the predictive ability of the Tumour-Node-Metastasis (TNM) classification systems for renal cell carcinoma (RCC) using three different endpoints: metastasis-free (MFS); overall (OS); and cancer-specific survival (CSS). PATIENTS AND METHODS: Data from 2739 consecutive patients with RCC, who underwent surgery at a single academic centre, were evaluated using multivariate Cox proportional models, Harrell's concordance (c)-index and by applying decision curve analysis (DCA) with regard to MFS, OS and CSS. RESULTS: According to TNM 2010, significant differences for MFS were observed for pT1a vs pT1b, pT1b vs pT2a, pT3a vs pT3b and pT3b vs pT3c stages, respectively (all P < 0.05). With regard to OS, significant differences could be observed in pT1a vs pT1b and pT3a vs pT3b stages, respectively (all P < 0.05). The c-index for CSS, OS and MFS was slightly higher for the 2002 than for the 2010 version of the TNM classification system. Non-inferiority of the 2002 TNM system is supported by the results of the DCA. CONCLUSION: According to our data, the predictive ability of the 2010 version of the TNM classification system regarding three different clinical endpoints is not superior to the 2002 version of this staging system.

Comparison of the 2002 and 2010 TNM classification systems regarding outcome prediction in clear cell and papillary renal cell carcinoma.

AIMS: A novel version of the tumour-node-metastasis (TNM) classification system for renal cell carcinoma (RCC) was introduced in 2010, although the prognostic significance with regard to different histological subtypes has not been explored. Therefore, the aim of our study was to compare the predictive ability of the 2002 and 2010 versions of the TNM classification system for clear cell and papillary RCC. METHODS AND RESULTS: Data from 2263 consecutive clear cell and 309 papillary RCC patients, operated at a single tertiary academic centre, were evaluated. According to TNM 2010, statistically significant differences for cancer-specific survival (CSS) were observed for pT1a versus pT1b (P < 0.001) and pT3a versus pT3b (P < 0.004) in clear cell RCC; and pT1b versus pT2a (P = 0.002) and pT3b versus pT3c (P = 0.046) in papillary RCC. The c-index for CSS in clear cell RCC was 0.74 and 0.73, and in papillary RCC 0.79 and 0.78, for the 2002 and 2010 versions of the TNM classification system, respectively. CONCLUSIONS: According to our data, the predictive ability of the 2010 version of the TNM classification system regarding CSS is not superior to the 2002 version, either in clear cell or in papillary RCC.