Nephrectomy improves overall survival in patients with metastatic renal cell carcinoma in cases of favorable MSKCC or ECOG prognostic features.

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.

Are warm ischemia and ischemia time still predictive factors of poor renal function after partial nephrectomy in the setting of elective indication?

PURPOSE: To evaluate renal function and to identify factors associated with renal dysfunction in the elective indications setting of nephron-sparing surgery (NSS). METHODS: We retrospectively reviewed operative data and glomerular filtration rate (GFR) of 519 patients treated by NSS in an elective indications setting between 1984 and 2006 in eight academic institutions. A GFR decrease under the thresholds of 60 or 45 ml/min at last follow-up was considered a significant renal dysfunction. Univariate and multivariate regression models were used to assess multiple factors of renal function. RESULTS: Median age, tumor size, preoperative, and final GFR were 59.5 years (27-84), 2.7 cm (0.9-11), 79 (45-137), and 69 ml/min (p < 0.0001), respectively, with a median follow-up of 23 months (1-416). Hilar clamping was performed in 375 procedures (72.3 %). Significant GFR decrease was observed in 89 patients (17.1 %). Median operating time, hilar clamping duration, and blood loss were 137 min (55-350), 22 min (0-90), and 150 ml (0-4150), respectively. At univariate analysis, age (p = 0.002), preoperative GFR (p = 0.001), pedicular clamping (p = 0.01), and ischemia time (p = 0.0001) were associated with renal dysfunction. Age (p = 0.004; HR 1.2), pedicular clamping (p = 0.04; HR 1.3), and ischemia time (p = 0.0001; HR 1.8) remained independent risk factors for renal function deterioration in multivariate analysis. CONCLUSION: Non- or time-limited clamping techniques are associated with preservation of renal function in the elective indications setting of NSS.

National prospective study on the use of local haemostatic agents during partial nephrectomy.

OBJECTIVE: To assess the use of local haemostatic agents (HAs) in a prospective multicentre large series of partial nephrectomies (PNs). PATIENTS AND METHODS: Prospective National Observational Registry on the Practices of Haemostasis in Partial Nephrectomy (NEPHRON): the study was conducted in 54 French urological centres from 1 June to 31 December 2010. In all, 570 consecutive patients undergoing a PN were enrolled in this study in a prospective manner. The data was collected prospectively via an electronic case-report form: five different sheets were included for preoperative, perioperative, postoperative and follow-up data respectively. Information related to haemostasis was analysed. RESULTS: The median patient age was 60 years and the mean (range) tumour size was 3.68 (0.19-15) cm. An HA was primarily used in 71.4% of patients, with a statistically significant difference among surgical approaches (P = 0.024). In 91.8% of cases, a single use of a HA was sufficient for achieving haemostasis. The HA was used either alone (13.9%) or in association with sutures (80.3%). One or more additional haemostatic action(s) was needed in 12.3% of the cases. When comparing patients who received a HA with those who did not receive a HA, there was no statistical difference between the groups for tumour size (P = 0.542), collecting system drainage (P = 0.538), hospital stay (P = 0.508), operation time (P = 0.169), blood loss (P = 0.387) or transfusion rate (P = 0.713). CONCLUSION: HAs are widely used by urologists during PN. Progress is needed for standardising HA application, especially for the timing of application. For the time being, the role of the HA in nephron-sparing surgery is still to be evaluated.

Cardiopulmonary bypass and renal cell carcinoma with level IV tumour thrombus: can deep hypothermic circulatory arrest limit perioperative mortality?

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.

A population-based comparison of cancer-control rates between radical and partial nephrectomy for T1A renal cell carcinoma.

OBJECTIVES: To complement existing data with population-based cancer control outcomes that account for the effect of other-cause mortality (OCM). Cancer control rates are virtually equivalent between partial (PN) and radical nephrectomy (RN) for patients with T1aN0M0 renal cell carcinoma (RCC). To date, only 6 studies from centers of excellence examined cancer control rates after PN vs RN for T1aN0M0 RCC. OCM was unaccounted for in those studies, which may introduce a bias. We relied on the surveillance, epidemiology, and end results (SEER) database and assessed cancer-specific mortality (CSM) after either PN or RN for T1aN0M0 RCC, in competing-risks models. METHODS: Between 1988 and 2004, the SEER-9 database identified 1622 PN (22.3%) and 5658 RN (77.7%) T1aN0M0 RCC. Competing-risks regression models, controlling for OCM and matched for age, year of surgery, tumor size, and Fuhrman grade, addressed the effect of nephrectomy type (PN vs RN) on CSM. RESULTS: At 5 years, in a PN and RN matched-population controlling for OCM, CSM after PN and RN was respectively 1.8% vs 2.5% (P = .5). The CSM rates in this cohort for patients aged ≥ 70 years were respectively 1.0% and 3.4% (P = .7). CONCLUSIONS: This competing-risks population-based analysis confirmed the CSM equivalence between PN and RN for T1aN0M0 RCC and showed virtually perfect CSM-free rates (97.5% or better) even in older patients.

The prognostic value of erythrocyte polyamines in the preoperative evaluation of patients with renal cell carcinoma.

INTRODUCTION: Polyamines, spermine and spermidine, are ubiquitous polycationic structures, which are essential for cell proliferation and differentiation. We tested whether spermine and spermidine could improve the prognostic ability of six established preoperative predictors of cancer-specific mortality (CSM) after partial or radical nephrectomy for renal cell carcinoma (RCC). MATERIALS AND METHODS: Overall, 385 patients with clinical stages T(1-3), M(0-1) RCC were treated with radical or partial nephrectomy at a single institution between 1990 and 2007. Kaplan-Meier plots depicted CSM after stratification according to spermine and spermidine levels (dichotomised to above and below the median value). Univariable and multivariable Cox regression models tested the prognostic ability of continuously coded spermine and spermidine levels in preoperative CSM predictions. Covariates consisted of pre-treatment T stage, M stage, age, gender and symptom classification. RESULTS: The 5-year CSM-free survival of patients with spermine levels < or =4.5 and >4.5 nmol/8x10(9) erythrocytes were, respectively, 79.5% and 65.0%. Similarly, the 5-year CSM-free survival of patients with spermidine levels < or =9.0 and >9.0 nmol/8x10(9) erythrocytes were, respectively, 81.1% and 63.7%. In multivariable analyses addressing CSM after surgery, both spermine (p< or =0.002) and spermidine (p< or =0.001) achieved independent predictor status and improved the accuracy of established preoperative CSM predictors by 2.1% (p<0.001). CONCLUSIONS: Circulating polyamine levels may significantly improve the prognostic value of established determinants of CSM in patients with RCC of all stages prior to nephrectomy. External validation of our findings is required prior to implementation in clinical practice.

Predictive factors for ipsilateral recurrence after nephron-sparing surgery in renal cell carcinoma.

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.

A comparative population-based analysis of the rate of partial vs radical nephrectomy for clinically localized renal cell carcinoma.

STUDY TYPE: Prevalence (prospective cohort with good follow up). LEVEL OF EVIDENCE: 1a. OBJECTIVE: To examine contemporary (1989-2004) trends in partial nephrectomy (PN) within the Surveillance, Epidemiology and End Results (SEER) database, as among other considerations, a survival benefit due to avoidance of surgically induced renal insufficiency distinguishes PN from radical nephrectomy (RN). PATIENTS AND METHODS: Diagnostic, stage and surgical codes of patients with T1-2N0M0 renal cell carcinoma treated with either PN or RN were assessed. Proportions, trends and multivariable logistic regression models tested the predictors of the use of PN. RESULTS: Of 19 733 assessable patients, 2614 (13.2%) and 17 119 (86.8%), respectively, had PN or RN. The use of PN decreased with increasing tumour size, was more frequent in younger patients and increased with more contemporary years of surgery (all P < 0.001). Intriguingly, there was important geographical variability (P < 0.001), e.g. in the San Francisco-Oakland Metropolitan Area the absolute PN rate was 16.4%, vs 7.6% in New Mexico (P < 0.001). In multivariable analyses, tumour size, age, year of surgery, gender and SEER registries were independent predictors of PN use. CONCLUSION: Although as expected the rate of PN use increased over time, unexplained variability remained. For example, gender and SEER registries affected the likelihood of PN. These variables warrant further analyses to reduce unnecessary variability and to maximize PN use and its benefit.

Nephron-sparing surgery is equally effective to radical nephrectomy for T1BN0M0 renal cell carcinoma: a population-based assessment.

OBJECTIVES: To test the effect of nephron-sparing surgery (NSS) vs radical nephrectomy (RN) on cancer-specific mortality (CSM) in patients with T1bN0M0 renal cell carcinoma (RCC) in a population-based cohort. To date, only few series from tertiary care centers supported the use of NSS for T1bN0M0 (range 4-7 cm) RCC. METHODS: The Surveillance, Epidemiology, and End Results database allowed us to identify 275 NSS (5.3%) and 4866 RN (94.7%) patients treated for T1bN0M0 RCC between 1988 and 2004. Analyses matched for age, year of surgery, tumor size, and Fuhrman grade addressed the effect of nephrectomy type (NSS vs RN) on CSM. RESULTS: Five years after surgery, the surviving proportions of NSS and RN patients matched for age, tumor size, and year of surgery were respectively 91.4 and 95.3% and 90.1 and 93.8% in the cohort, where additional matching for Fuhrman grade was performed. Neither of the matched analyses resulted in statistically significant CSM difference (P = .1 and .4) between NSS and RN. Similarly, competing-risks regression analyses based on both matching schemes also failed to reveal statistically significant CSM differences (P = .3 and .3). CONCLUSIONS: Our study represents the largest and the only population-based analysis of cancer control efficacy of NSS vs RN in T1bN0M0 RCC. It indicates that NSS does provide equivalent cancer control relative to RN. In consequence, based on cancer control equivalence, NSS should be given equal consideration to RN in patients with T1bN0M0 lesions.

Limited prognostic value of tumor necrosis in patients with renal cell carcinoma.

OBJECTIVES: To test whether tumor necrosis (TN) could improve the prognostic ability of the predictors of 2 established prognostic renal cell carcinoma (RCC) models. Presence of TN within the nephrectomy specimen is considered an important prognostic marker in patients with RCC. However, its added prognostic value along with established cancer-specific mortality (CSM) predictors has never been formally tested. METHODS: We retrospectively analyzed data of 1526 patients with all stages of RCC, who were treated with radical or partial nephrectomy at 6 institutions between 1988 and 2004. Univariate and multivariate Cox-regression models tested the statistical significance of TN in CSM predictions. Covariates consisted of TNM stage, Fuhrman grade, tumor size, and symptom classification. The analyses first addressed the entire patient population (n=1526) and then repeated in patients with exclusive clear-cell histology (n=1320). RESULTS: TN was present in 476 patients (31.2%). TN was a statistically significant predictor of CSM (hazard ratio: 2.73; P<.001) but not an independent predictor of CSM (adjusted hazard ratio: 0.88; P=.4). Accuracy of TN ranked sixth among 7 examined predictors and TN failed to improve the accuracy of other variables. The same results were recorded in patients with exclusive clear-cell histology. CONCLUSIONS: TN does not improve the accuracy of established predictors of CSM that are used in 2 prognostic RCC models for patients with RCC of all stages.

Positive surgical margin appears to have negligible impact on survival of renal cell carcinomas treated by nephron-sparing surgery.

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.

Does histologic subtype affect oncologic outcomes after nephron-sparing surgery?

OBJECTIVES: To test whether renal cell carcinoma (RCC) histologic subtypes (HSs) affect cancer-specific mortality after nephron-sparing surgery (NSS). HSs are considered of prognostic value in RCC. For example, the papillary HS might confer a worse prognosis, and, at some centers, only radical nephrectomy is performed for the papillary HS. METHODS: We used univariate and multivariate Cox regression models to study patients with Stage T1N0M0 RCC treated with NSS (n = 1205) from 1988 to 2004. The data were taken from 9 Surveillance, Epidemiology, and End Results registries. RESULTS: At 36 months after NSS, the cancer-specific mortality rate was 97.8%, 100%, and 97.4% for a clear cell, chromophobe, and papillary RCC HS, respectively. On univariate and multivariate analyses, no statistically significant differences were recorded with regard to the HS. CONCLUSIONS: Despite the suggested more aggressive phenotype of the papillary HS, we found no difference among the papillary, chromophobe, and clear cell variants. Thus, the diagnosis of one HS vs another HS should not deter from the use of NSS when cancer-specific mortality is considered as an endpoint.

Survival of patients with nonmetastatic pT3 renal tumours: a matched comparison of laparoscopic vs open radical nephrectomy.

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.

Population-based study of perioperative mortality after retroperitoneal lymphadenectomy for nonseminomatous testicular germ cell tumors.

OBJECTIVES: To determine whether retroperitoneal lymphadenectomy (RPLND) perioperative mortality (PM) rates reported from a center of excellence (Indiana University: 0% for primary and 0.8% for postchemotherapy RPLND) are applicable to institutions at large. METHODS: We used the data from 882 assessable patients with nonseminomatous testicular germ cell tumor treated with RPLND from 1988 to 1997 accessed from the Surveillance, Epidemiology, and End Results (SEER) database. These data did not include data from Indiana University. The observed PM rates were stratified according to age and SEER stage. RESULTS: The median age at RPLND was 29 years. Of the 882 cases, 435 (49.3%) were performed for localized (Stage I), 380 (43.1%) for regional (Stage II), and 67 (7.6%) for metastatic (Stage III) SEER stage. Of the 882 patients, 7 patients died during the initial 90 days after RPLND, for a 0.8% PM rate. PM increased with increasing age: < or =29 years, 0.0%; 30-39 years, 1.3%; and > or =40 years, 2.7% (chi(2) trend test, P = .002). PM also increased with increasing stage: 0.0% for localized, 0.8% for regional, and 6.0% for metastatic disease (chi(2) trend test, P < .001). CONCLUSIONS: RPLND is associated with virtually no or low PM in patients with localized and regional disease. The PM rates for these 2 groups replicated those of Indiana University. In contrast, the PM rate of 6% for patients with distant metastases implies that RPLND for these higher risk patients should ideally be performed at centers of excellence, with the intent of reducing the PM rate.

Partial versus radical nephrectomy in patients with adverse clinical or pathologic characteristics.

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.

Cancer-specific and non-cancer-related mortality rates in European patients with T1a and T1b renal cell carcinoma.

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.

Prognostic variables to predict cancer-related death in incidental renal tumours.

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.

Metachronous bilateral renal cell carcinoma: risk assessment, prognosis and relevance of the primary-free interval.

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.

Clinicopathological features and prognosis of synchronous bilateral renal cell carcinoma: an international multicentre experience.

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.