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Objectives: The role of cytoreductive nephrectomy (CN) in the treatment of patients harboring metastatic renal cell carcinoma (mRCC) has become controversial since the emergence of effective targeted therapies. The aim of our study was to compare the overall survival (OS) between CN and non-CN groups of patients presenting with mRCC in the era of targeted drugs and to assess these outcomes among the different Memorial Sloan-Kettering Cancer Center (MSKCC) and The Eastern Cooperative Oncology Group (ECOG) performance status subgroups., Methods and Materials: A total of 351 patients with mRCC at diagnosis recruited from 18 tertiary care centers who had been treated with systemic treatment were included in this retrospective study. OS was assessed by the Kaplan-Meier method according to the completion of a CN. The population was subsequently stratified according to MSKCC and ECOG prognostic groups., Results: Median OS in the entire cohort was 37.1 months. Median OS was significantly improved for patients who underwent CN (16.4 vs. 38.1 months, P<0.001). However, subgroup analysis demonstrated that OS improvement after CN was only significant among the patients with an ECOG score of 0 to 1 (16.7 vs. 43.3 months, P = 0.03) and the group of patients with good and intermediate MSKCC score (16.8 vs. 42.4 months, P = 0.02). On the contrary, this benefit was not significant for the patients with an ECOG score of 2 to 3 (8.0 vs. 12.6 months, P = 0.8) or the group with poor MSKCC score (5.2 vs. 5.2, P = 0.9)., Conclusions: CN improves OS in patients with mRCC. However, this effect does not seem to be significant for the patients in ECOG performance status groups of 2 to 3 or poor MSKCC prognostic group., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: • To review experience with nephrectomy/thrombectomy for a renal cell carcimoma (RCC) with a level IV tumour thrombus and to evaluate the benefit of deep hypothermic circulatory arrest (DHCA) with cardiopulmonary bypass (CPBP)., Patients and Methods: • A multi-institutional retrospective database was created to assess the outcomes of surgery for RCC and associated level IV tumour thrombus from 1983 to 2007. Patients were identified based on radiographic records/operative findings. • Only cases using CPBP were analysed. Clinicopathological and operative characteristics including use of DHCA were recorded. • Overall survival (OS) for all patients and by use of DHCA was assessed. Comparisons of clinical and operative characteristics by use of DHCA were performed. • A Cox regression model determined predictors of perioperative/in-hospital mortality., Results: • In all, 63 patients underwent resection with CPBP; overall perioperative mortality was 22.2%. • There were no significant differences in clinicopathological characteristics, operative duration, estimated blood loss, transfusions, and hospital stay by use of DHCA. • Perioperative mortality rate was lower in patients undergoing DHCA (8.3% vs 37.5%, P = 0.006). • The median OS was longer for the patients undergoing DHCA (15.8 vs 7.7 months); however, this failed to reach statistical significance (P = 0.357). • On multivariate analysis, age of > 60 years (hazard ratio [HR] 6.7, 95% confidence interval [CI] 1.5-31.1, P = 0.015) and the use of DHCA (HR 0.13, 95% CI 0.036-0.51, P = 0.003) were independent predictors of perioperative mortality., Conclusions: • Radical nephrectomy and level IV tumour thrombectomy is associated with significant mortality. • The use of DHCA does not appear to adversely affect operative characteristics and may limit perioperative mortality. • Further prospective studies should be performed to confirm the benefit of DHCA., (© 2010 BJU INTERNATIONAL. NO CLAIM TO ORIGINAL US GOVERNMENT WORKS.)

Background: Ipsilateral recurrence after nephron-sparing surgery (NSS) is rare, and little is known about its specific determinants., Objective: To determine clinical or pathologic features associated with ipsilateral recurrence after NSS performed for renal cell carcinoma (RCC)., Design, Setting, and Participants: We analysed 809 NSS procedures performed at eight academic institutions for sporadic RCCs retrospectively., Measurements: Age, gender, indication, tumour bilaterality, tumour size, tumour location, TNM stage, Fuhrman grade, histologic subtype, and presence of positive surgical margins (PSMs) were assessed as predictors for recurrence in univariate and multivariate analysis by using a Cox proportional hazards regression model., Results and Limitations: Among 809 NSS procedures with a median follow-up of 27 (1-252) mo, 26 ipsilateral recurrences (3.2%) occurred at a median time of 27 (14.5-38.2) mo. In univariate analysis, the following variables were significantly associated with recurrence: pT3a stage (p=0.0489), imperative indication (p<0.01), tumour bilaterality (p<0.01), tumour size >4cm (p<0.01), Fuhrman grade III or IV (p=0.0185), and PSM (p<0.01). In multivariate analysis, tumour bilaterality, tumour size >4cm, and presence of PSM remained independent predictive factors for RCC ipsilateral recurrence. Hazard ratios (HR) were 6.31, 4.57, and 11.5 for tumour bilaterality, tumour size >4cm, and PSM status, respectively. The main limitations of this study included its retrospective nature and a short follow-up., Conclusions: RCC ipsilateral recurrence risk after NSS is significantly associated with tumour size >4cm, tumour bilaterality (synchronous or asynchronous), and PSM. Careful follow-up should be advised in patients presenting with such characteristics., (Copyright © 2010 European Association of Urology. All rights reserved.)

Background: The occurrence of positive surgical margins (PSMs) after partial nephrectomy (PN) is rare, and little is known about their natural history., Objective: To identify predictive factors of cancer recurrence and related death in patients having a PSM following PN., Design, Setting, and Participants: Some 111 patients with a PSM were identified from a multicentre retrospective survey and were compared with 664 negative surgical margin (NSM) patients. A second cohort of NSM patients was created by matching NSM to PSM for indication, tumour size, and tumour grade., Measurements: PSM and NSM patients were compared using student t tests and chi-square tests on independent samples. A Cox proportional hazards regression model was used to test the independent effects of clinical and pathologic variables on survival., Results and Limitations: Mean age at diagnosis was 61+/-12.5 yr. Mean tumour size was 3.5+/-2 cm. Imperative indications accounted for 39% (43 of 111) of the cases. Some 18 patients (16%) underwent a second surgery (partial or total nephrectomy). With a mean follow-up of 37 mo, 11 patients (10%) had recurrences and 12 patients (11%) died, including 6 patients (5.4%) who died of cancer progression. Some 91% (10 of 11) of the patients who had recurrences and 83% of the patients (10 of 12) who died belonged to the group with imperative surgical indications. Rates of recurrence-free survival, of cancer-specific survival, and of overall survival were the same among NSM patients and PSM patients. The multivariable Cox model showed that the two variables that could predict recurrence were the indication (p=0.017) and tumour location (p=0.02). No other variable, including PSM status, had any effect on recurrence. None of the studied parameters had any effect on the rate of cancer-specific survival., Conclusions: PSM status occurs more frequently in cases in which surgery is imperative and is associated with an increased risk of recurrence, but PSM status does not appear to influence cancer-specific survival. Additional follow-up is needed., (2009 European Association of Urology. All rights reserved.)

Objectives: To compare the oncological outcome of patients with pT3 renal tumours treated either by laparoscopic radical nephrectomy (LRN) or open RN (ORN)., Patients and Methods: In a retrospective review of a multi-institutional database, we identified 1003 patients with a T3N0M0 renal tumour and with no vena caval invasion. Sixty-five patients treated by LRN were matched with up to four patients treated by ORN. Exact matches were made for age, gender, tumour size, perirenal fat invasion, renal vein invasion, and histological subtype. Following the matching process there were 44 patients treated by LRN and 135 by ORN. Qualitative and continuous variables were compared using chi-square and independent-sample t-tests, respectively. Differences in survival were compared using the Kaplan-Meier method. A Cox regression model was used to test the effect of variables on survival., Results: The two groups were comparable for age (P = 0.4), gender, tumour size (P = 0.4), tumour grade (P = 0.25) and histological subtype (P = 0.45). The mean follow-up was longer in the ORN group (55 vs 28 months, P < 0.001). There was no difference in survival between the ORN and LRN groups in the whole T3 population (P = 0.7), in those with perirenal fat invasion (P = 0.9), or in the subset with renal vein invasion (P = 0.31). In univariate analysis, the only predictor for death from cancer was tumour grade (P = 0.05). In multivariate analysis, no variable was significantly associated with cancer survival., Conclusions: LRN has no adverse effect on cancer survival compared to ORN in patients with microscopic T3 renal cancer. Additional prospective evaluation is warranted.

Objectives: To assess cancer-specific survival of partial nephrectomy (PN) patients with >or= 7-cm lesions or unfavorable pathology (stage T3a or Fuhrman grades III-IV)., Material and Methods: At 13 participation centers, 4072 partial or radical nephrectomies (RN) were performed for RCC between 1984 and 2001. Of all procedures, 925 (22.7%) were for tumors > 7 cm, 973 (23.9%) had Fuhrman grades III or IV, and 861 (21.1%) had stage pT3a. None had nodal or distant metastases. Matched (age, gender, tumor size, T stage, histologic subtype, and Fuhrman grade [FG]) survival analyses addressed the effect of nephrectomy type (partial vs radical) on cancer-specific mortality., Results: Partial nephrectomy for tumors > 7 cm was associated with higher mortality than RN (HR = 5.3; P = .025). No significant cancer-specific survival differences were recorded after PN for FG III-IV (HR = 0.7, P = .5) or for pT3a lesions (HR = 2.5, P = .9)., Conclusions: Partial nephrectomy may undermine cancer control in patients with tumors > 7 cm. Conversely, after PN, the same cancer control rates as after RN may be expected in patients with Fuhrman grades III-IV or with pT3a histology.

Objective: To examine cancer-specific and non-cancer-related mortality rates in 451 patients with T1a-bN0M0 renal cell carcinoma (RCC) treated with either radical or partial nephrectomy (RN or PN) in Europe., Patients and Methods: Between 1987 and 2007, 451 patients with T1a-bN0M0 RCC were treated for histologically confirmed RCC with RN or PN at one of seven participating European institutions. The preoperative American Society of Anesthesiology (ASA) score was available for all patients and was used to control for baseline comorbidities. The preoperative glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease study group equation. We used univariate and multivariate competing-risks regression analyses to test the effect of the ASA score, GFR, T stage (T1a vs T1b) and nephrectomy type (RN or PN) on RCC-specific mortality and non-RCC-related mortality., Results: In patients with T1a-b RCC cancer- specific mortality was unaffected by stage, nephrectomy type or GFR. Conversely, non-RCC-related mortality was strongly affected by the ASA score and GFR. Unlike in a previous report, nephrectomy type did not affect non-RCC-related mortality. This lack of significance relative to RN may stem from the relatively high rate of PN use in the present series., Conclusion: PN or RN virtually eliminate the risk of cancer-specific mortality in patients with T1a-b RCC. Poor preoperative ASA score and impaired renal function appear to represent relative contra-indications to surgical management of T1a-b lesions.

Objective: To identify, in a large multicentre series of incidental renal tumours, the key factors that could predict cancer-related deaths, as such tumours have a better outcome than symptomatic tumours and selected patients are increasingly being included in watchful-waiting protocols., Patients and Methods: Data from 3912 patients were extracted from three international kidney-cancer databases. Age, gender, Eastern Cooperative Oncology Group (ECOG) performance status (PS), Tumour-Node-Metastasis (TNM) stage, tumour size, Fuhrman grade, and final pathology were recorded. Benign tumours and malignant lesions with incomplete information were excluded from final analysis., Results: The mean (SD) age of the patients was 60.6 (12.2) years and the mean tumour size 5.5 (3.5) cm. Most tumours were malignant (90.2%) and of low stage (T1-T2, 71.7%) and low grade (G1-G2, 72.4%). There were nodal and distant metastases in 5.7% and 13% of the patients. In all, 525 (14.4%) patients died from cancer; in this group, tumours were >4 cm in 88.2% and had nodal or distant metastases in 20.2% and 49.3%, respectively. Multivariable analysis showed that tumour size >4 cm, ECOG PS >or=1, TNM stage and Fuhrman grade were independent predictors of cancer-related death., Conclusion: A significant proportion of incidental renal tumours can lead to the death of the patient. Standard prognostic variables for renal cell carcinoma appear to remain valid for this subset of patients. A watchful-waiting strategy should not be recommended if the tumour diameter is >4 cm, if biopsy confirms high-grade tumours, or if there is an impaired ECOG PS, or computed tomography findings suggest the presence of advanced T stage.

Objective: To present a multicentre experience and the largest cohort to date of nonmetastatic (N0M0) synchronous bilateral renal cell carcinoma (RCC), as because it is rare the single-institutional experience is limited., Patients and Methods: We retrospectively studied 10 337 patients from 12 urological centres to identify patients with N0M0 synchronous bilateral RCC; the clinicopathological features and cancer-specific survival were compared to a cohort treated for N0M0 unilateral RCC., Results: In all, 153 patients had synchronous bilateral solid renal tumours, of whom 135 (88%) had synchronous bilateral RCC, 118 with nonmetastatic disease; 91% had nonfamilial bilateral RCC. Bilateral clear cell RCC was the major histological subtype (76%), and papillary RCC was the next most frequent (19%). Multifocality was found in 54% of bilateral RCCs. Compared with unilateral RCC, patients did not differ in Eastern Cooperative Oncology Group performance status (ECOG PS) and T classification, but bilateral RCCs were more frequently multifocal (54% vs 16%, P < 0.001) and of the papillary subtype (19% vs 12%), and less frequently clear cell RCC (76% vs 83%, P = 0.005). For the outcome, patients with nonmetastatic synchronous bilateral RCC and unilateral RCC had a similar prognosis (P = 0.63); multifocality did not affect survival (P = 0.60). Multivariate analysis identified ECOG PS, T classification, and Fuhrman grade, but not laterality, as independent prognostic factors for cancer-specific survival., Conclusions: Patients with N0M0 synchronous bilateral RCC and N0M0 unilateral RCC have a similar prognosis. The frequency of a familial history for RCC (von Hippel-Lindau disease or familial RCC) was significantly greater in bilateral synchronous than in unilateral RCC. The significant pathological findings in synchronous bilateral RCC are papillary subtype and multifocality.

Objective: To analyse through a large multicentre series, morbidity of nephron-sparing surgery (NSS) in relation to tumour size and surgical indication., Methods: The study included patients from eight international academic centres. Age, sex, TNM stage, tumour size, Fuhrman grade, Eastern Cooperative Oncology Group performance status (ECOG-PS), surgical margins, local and distant recurrences, and overall and cancer-specific survival rates were collected and analysed. Indication for elective or mandatory NSS, medical and surgical complication rates, mean blood loss, blood transfusion, and length of hospital stay were specifically recorded for the purpose of this study. Groups were compared for qualitative and quantitative variables by using chi(2) (Fischer exact test) and Student t tests, respectively., Results: A total of 1048 NSS procedures were included in this study. Mean tumour size was 3.4+/-2.1cm. In 730 elective procedures mean operative time (p=0.002), mean blood loss (p=0.01), the need for blood transfusion (p=0.001), and urinary fistula rate (p=0.01) were significantly increased for tumours >4 cm. However, these differences did not result in significantly increased medical (p=0.4), surgical complication rates (p=0.6), or length of hospital stay (p=0.9). Finally, in elective procedures for malignant tumours, positive surgical margins, local or distant recurrence rates, and cancer-specific survival were not significantly different in tumours < or =4 cm and >4 cm., Conclusion: Excellent cancer control and outcomes can be achieved with NSS in carefully selected patients with tumours >4 cm. Expanding the size indication of elective NSS results in an increased but acceptable morbidity.

Purpose: We evaluated the prognosis, risk factors and relevance of the primary-free interval in a large cohort with metachronous bilateral renal cell carcinoma., Materials and Methods: We studied 120 patients with metachronous, bilateral renal cell carcinoma who were treated at 12 international academic centers. Logistic regression was performed to evaluate risk factors for contralateral metachronous renal cell carcinoma during followup. Disease specific survival was evaluated with univariate and multivariate analysis., Results: Median age at diagnosis of the first and second renal cell carcinomas was 54 and 62 years, respectively. The most common histological subtype was bilateral clear cell renal cell carcinoma (89% of cases). Familial renal cell carcinoma was found in 14% of patients, von Hippel-Lindau disease was found in 4% and nonfamilial renal cell carcinoma was found in 81%. The 15-year disease specific survival rates for the first and second renal cell carcinomas were 66% and 44%, respectively. Logistic regression revealed von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age as independent risk factors for contralateral renal cell carcinoma after surgery for unilateral renal cell carcinoma. A longer primary-free interval was associated with a better prognosis. When calculating disease specific survival from the diagnosis of the first renal cell carcinoma, the primary-free interval was an independent prognostic factor., Conclusions: Long-term survival rates of metachronous, bilateral renal cell carcinoma are moderate. von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age are independent risk factors for contralateral renal cell carcinoma. These risk factors support close and extended abdominal surveillance following nephrectomy for unilateral renal cell carcinoma. Patients with a longer primary-free interval have a more favorable prognosis.