Safety and Efficacy of Retrograde Pyeloperfusion for Ureteral Protection during Renal Tumor Cryoablation.

PURPOSE: To determine safety and efficacy of retrograde pyeloperfusion for ureteral protection during cryoablation of adjacent renal tumors. MATERIALS AND METHODS: Retrospective review of 155 patients treated with renal cryoablation, including adjunctive retrograde pyeloperfusion, from 2005 to 2019 was performed. Ice contacted the ureter in 67 of the 155 patients who represented the study cohort. Median patient age was 68 years old (interquartile range [61, 74]), 52 patients (78%) were male, and 37 tumors (55%) were clear cell histology. Mean tumor size was 3.4 ± 1.3 cm, and 42 tumors (63%) were located at the lower pole. Treatment-related complication and oncologic outcomes were recorded based on a review of post-procedural images and chart review. RESULTS: Technical success of cryoablation was attained in 67 cases (100%), and technical success of pyeloperfusion was attained in 66 cases (99%). A total of 13 patients (19.4%) experienced SIR major C or D complications related to the procedure, including hemorrhage (n = 4), urine leak (n = 3), transient urinary obstruction (n = 2), pulmonary embolism (n = 1), hypertensive urgency (n = 1), acute respiratory failure (n = 1), and ureteropelvic junction (UPJ) stricture (n = 1). No complications were attributable to pyeloperfusion. Three of 45 patients with biopsy-proven renal cell carcinoma experienced local recurrence resulting in local recurrence-free survival of 92% (95% confidence interval, 81.5%-100%) 3 years after ablation. CONCLUSIONS: Retrograde pyeloperfusion of the renal collecting system is a relatively safe and efficacious option for ureteral protection during renal tumor cryoablation. This adjunctive procedure should be considered for patients in whom cryoablation of a renal mass could potentially involve the ureter.

Comprehensive assessment of renal tumour complexity in a large percutaneous cryoablation cohort.

OBJECTIVE: To evaluate the association between renal tumour complexity and outcomes in a large cohort of patients undergoing percutaneous cryoablation (PCA). PATIENTS AND METHODS: Patients with renal tumours treated with PCA were identified using our prospectively maintained ablation registry (2003-2015). Salvage procedures and inherited tumour syndromes were excluded. The associations between R.E.N.A.L. nephrometry score (NS) and risk of complications, renal function impairment, local failure and cancer-specific mortality (CSM) were evaluated using univariate and multivariable logistic, linear and Cox regression models. RESULTS: The cohort included 618 tumours treated during 580 procedures in 565 patients. The median (interquartile range [IQR]) follow-up was 34 (14.66) months. Complications (any grade) during a procedure (n[total] = 87, 15%) were more frequent with higher NS (NS 4-6: 10%; NS 7-9: 14%; NS 10-12: 36%; P < 0.001). Higher NS was independently associated with risk of complications (odds ratio [OR; per 1 point] = 1.3; 95% confidence interval [CI] 1.2-1.5; P < 0.001). Of all the NS components, tumour size was the most strongly associated with complication risk (OR 3.4; 95% CI 2.2-5.2; P < 0.001). The median (IQR) decline in glomerular filtration rate (GFR) from baseline was 9% (0, 22) at last follow-up. Each additional point in NS was associated with a 1.3% (95% CI 0.4-2.1; P = 0.005) greater GFR decline from baseline. NS was not significantly associated with local failure (n [total] = 14, 2%; NS 4-6: 2%; NS 7-9: 3%; NS 10-12: 5%; P = 0.32) or CSM (n [total] = 8, 2%; NS 4-6: 2%; NS 7-9: 3%; NS 10-12: 2%; P = 0.88). CONCLUSION: In high-complexity tumours PCA was associated with a tumour size-driven increased risk of post-procedural complications. Higher NS was associated with a small, clinically minor additional decline in renal function. Risks for local failure and CSM were low, regardless of tumour complexity.

Malignant ureteroenteric anastomotic stricture following radical cystectomy with urinary diversion: Patterns, risk factors, and outcomes.

OBJECTIVE: The development of a ureteroenteric anastomotic (UEA) stricture has been reported in up to 15% of patients undergoing radical cystectomy (RC) with urinary diversion. Although benign strictures are thought to be the result of ischemia, the incidence, risk factors, and outcomes of patients with malignant UEA strictures have not been well described. MATERIAL AND METHODS: We reviewed 2,523 patients treated with RC for bladder cancer from 1980 to 2012 at Mayo Clinic. Patients diagnosed with a UEA stricture following the surgery were identified, and a subset with malignant UEA was then analyzed. Cox proportional hazard regression models were performed to evaluate factors associated with the diagnosis of malignant UEA. Survival was assessed using the Kaplan-Meier method. RESULTS: At a median of 10.5 years of follow-up, 232 (9.2%) patients were diagnosed with UEA stricture, of which 38 (16.4%) had malignant strictures (MS). Median time from RC to the diagnosis of a malignant vs. benign UEA stricture was 32.4 months and 7.2 months, respectively (P = 0.004). Pathologic non-muscle-invasive disease stage at RC was more common among patients diagnosed with a MS compared with patients who did not develop a MS (71.1% vs. 45.9%; P = 0.002). The presence of carcinoma in situ on initial ureteral margin at RC was associated with a significantly increased risk of subsequent diagnosis (hazard ratio = 4.1; P<0.001). Following malignant stricture diagnosis, 2- and 5-year cancer-specific survival was 50% and 30%, respectively, whereas overall survival was 44% and 23%, respectively. CONCLUSIONS: MS are uncommon after RC, and present later than benign strictures. Ureteral margin involvement with carcinoma in situ was associated with a significantly increased risk of MS diagnosis.

Paraneoplastic syndromes are associated with adverse prognosis among patients with renal cell carcinoma undergoing nephrectomy.

OBJECTIVES: To analyze the association of paraneoplastic syndromes (PNS) with progression-free (PFS) and cancer-specific survival (CSS) among patients with renal cell carcinoma (RCC) undergoing nephrectomy. METHODS: We performed a retrospective analysis of 2865 patients undergoing nephrectomy for localized RCC at Mayo Clinic from 1990 to 2010. PNS analyzed were anemia, polycythemia, hypercalcemia, recent-onset hypertension, and liver dysfunction. PFS and CSS were estimated using Kaplan-Meier method and compared with Cox proportional hazard models, unadjusted and adjusted for clinicopathologic features. RESULTS: A total of 661 (23 %) patients had anemia, 37 (1 %) had polycythemia, 177 (9 %) had hypercalcemia, 51 (2 %) had recent-onset hypertension, and 224 (10 %) had liver dysfunction at time of nephrectomy. Patients with PNS were more likely to have high-grade tumors and advanced disease stages. A total of 675 (24 %) patients developed progression and 1171 (41 %) died of RCC, over a median follow-up of 8.2 years. On univariable analysis, the presence of any PNS was associated with inferior CSS [hazard ratio (HR) = 1.86, p = 0.007] and a trend toward shorter PFS (HR = 1.33, p = 0.07) compared with patients without PNS. Specifically, anemia, polycythemia, hypercalcemia, and liver dysfunction were each associated with inferior CSS and PFS (all p < 0.05). However, on multivariable analysis PNS (overall or each individual syndrome) did not remain independently associated with CSS or PFS. CONCLUSIONS: Patients with RCC undergoing nephrectomy presenting with PNS have worse oncologic outcome than those with incidentally found tumors. However, the adverse outcome among PNS patients seems to be largely explained by adverse pathologic features of these tumors.

The association of ABO blood type with disease recurrence and mortality among patients with urothelial carcinoma of the bladder undergoing radical cystectomy.

OBJECTIVES: To evaluate the association of ABO blood type with clinicopathologic outcomes and mortality among patients with urothelial carcinoma of the bladder treated with radical cystectomy (RC). PATIENTS AND METHODS: We identified 2,086 consecutive patients who underwent RC between 1980 and 2008. Postoperative recurrence-free survival (RFS) and cancer-specific survival (CSS) were estimated using the Kaplan Meier method and compared with the log-rank test. Cox proportional hazards regression models were used to evaluate the association of ABO blood type with outcomes. RESULTS: A total of 913 (44%), 881 (42%), 216 (10%), and 76 (4%) patients had blood type O, A, B, and AB, respectively. Median postoperative follow-up among survivors was 11.0 years (interquartile range: 7.7-15.9y). Overall, 1,561 patients died, with 770 deaths attributable to bladder cancer. Non-O blood type was associated with significantly worse 5-year RFS (65% vs. 69%; P = 0.04) and/or CSS (64% vs. 70%; P = 0.02). In particular, among patients with≤pT2N0 disease, the 5-year RFS for those with non-O vs. O blood type was 75% vs. 82%, respectively (P = 0.002), whereas the 5-year CSS was 77% vs. 85%, respectively (P = 0.001). Moreover, on multivariable analysis, blood type A remained independently associated with an increased risk of cancer-specific mortality (hazard ratio = 1.22; P = 0.01). CONCLUSIONS: Non-O blood type, particularly blood type A, is associated with a significantly increased risk of death from bladder cancer among patients undergoing RC. If validated, the utility of a multimodal therapy approach, including perioperative chemotherapy, or more frequent postoperative surveillance in this cohort warrants further study.

Evaluation of pT0 prostate cancer in patients undergoing radical prostatectomy.

OBJECTIVE: To evaluate the incidence, predictors and oncological outcomes of pT0 prostate cancer (PCa). METHODS: We conducted a retrospective analysis of 20 222 patients undergoing radical prostatectomy (RP) for PCa at the Mayo Clinic between 1987 and 2012. Disease recurrence was defined as follow-up PSA >0.4 ng/mL or biopsy-proven local recurrence. Systemic progression was defined as development of metastatic disease on imaging. Comparisons of baseline characteristics between pT0 and non-pT0 groups were carried out using chi-squared tests. Recurrence-free survival was estimated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 62 patients (0.3%) had pT0 disease according to the RP specimen. In univariable analysis, pT0 disease was significantly associated with older age (P = 0.045), lower prostate-specific antigen (PSA; P = 0.002), lower clinical stage (P < 0.001), lower biopsy Gleason score (P = 0.042), and receipt of preoperative transurethral resection, hormonal and radiation therapies (all P < 0.001). In multivariable analysis, lower PSA levels, lower Gleason score, and receipt of preoperative treatment were independently associated with pT0 (all P < 0.05). Seven patients (11%) with pT0 PCa developed disease recurrence over a median follow-up of 10.9 years. All seven patients had preoperative treatment(s) and three had recurrence with a PSA doubling time of <9 months. Compared with non-pT0 disease, pT0 disease was associated with longer recurrence-free survival (P < 0.05). Only one (1.6%) patient with pT0 disease developed systemic progression. CONCLUSIONS: pT0 stage PCa is a rare phenomenon and is associated with receipt of preoperative treatment and features of low-risk PCa. Although pT0 has a very favourable prognosis, some men, especially those who received preoperative treatment, experience a small but non-negligible risk of disease recurrence and systemic progression.

Oncological control associated with surgical resection of isolated retroperitoneal lymph node recurrence of renal cell carcinoma.

OBJECTIVE: To evaluate the outcome of patients after surgical resection of isolated retroperitoneal lymph node (RPLN) recurrence of renal cell carcinoma (RCC) using a multicentre international cohort. PATIENTS AND METHODS: In all, 50 patients were identified who underwent resection of isolated RPLN recurrence of RCC at four institutions after nephrectomy for pTany Nany M0 disease. Progression-free (PFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess the association of clinicopathological characteristics with disease progression. RESULTS: The median (interquartile range, IQR) age at resection was 57.0 (50.0-62.5) years. The median (IQR) time to RPLN recurrence after nephrectomy was 12.6 (6.9-39.5) months, with no significant difference in median time to RPLN recurrence between patients with N+ disease at nephrectomy (10.7 [6.5-24.6] months) and those with Nx/pN0 disease at nephrectomy (13.7 [8.7-44.2] months) (P = 0.66). The median (IQR) size of the RPLN recurrence before resection was 2.6 (1.9-5) cm. The most common site for RPLN recurrence was within the interaortocaval region (34%). The median (IQR) follow-up after RPLN resection for patients alive at last follow-up was 28.0 (13.7-51.2) months. During follow-up, 26 patients developed RCC recurrence, at a median (IQR) of 9.9 (4.0-18.5) months after RPLN resection. Of those who developed a secondary recurrence, disease was again isolated to the retroperitoneum in seven patients. In all, 11 patients subsequently died, including 10 who died from disease. The median PFS after RPLN resection was 19.5 months, with a 3- and 5-year PFS of 40.5% and 35.4%, respectively. We also found that RPLN recurrence at ≤12 months after nephrectomy was associated with a significantly inferior median PFS (12.3 months) compared with RPLN recurrence at >12 months after nephrectomy (47.6 months; P = 0.003). Moreover, on multivariate analysis, a shorter time to recurrence remained associated with a significantly increased risk for subsequent disease progression (hazard ratio 3.51; P = 0.005). CONCLUSION: Surgical resection of isolated RPLN recurrence from RCC may result in durable cancer control in appropriately selected patients. Recurrence at ≤12 months after nephrectomy was associated with a significantly increased risk of progression after resection, underscoring the importance of this variable for risk stratification. Thus, we recommend that, in the setting of isolated RPLN recurrence of RCC (in patients without precluding comorbidities), careful consideration with the patients and medical oncology colleagues be undertaken about the relative and individualised benefits of surgical resection, systemic therapy, and surveillance.

Validation of Gene Expression Signatures to Identify Low-risk Clear-cell Renal Cell Carcinoma Patients at Higher Risk for Disease-related Death.

BACKGROUND: Approximately 5-10% of patients with "low-risk" clear cell renal cell carcinoma (ccRCC), as stratified by externally validated clinicopathologic prognostic algorithms, eventually have disease relapse and die. Improving prognostic algorithms for these low-risk patients could help to provide improved individualized surveillance recommendations. OBJECTIVE: To identify genes that are differentially expressed in patients with low-risk ccRCC who did and did not die of their disease. DESIGN, SETTING, AND PARTICIPANTS: Using the Mayo Clinic Renal Registry, we identified formalin-fixed paraffin-embedded samples from patients with low-risk ccRCC, as defined by Mayo Clinic stage, size, grade, and necrosis score of 0-3. We conducted a nested case-control study between patients who did (cases) and did not (controls) have ccRCC relapse and death, using two independent sets (discovery and validation). We performed RNA sequencing of all samples in the discovery set to identify differentially expressed genes. In the independent validation set, we assessed the top 50 expressed genes using the nCounter Analysis System (NanoString Technologies, Seattle, WA, USA). RESULTS AND LIMITATIONS: In the discovery set of 24 cases and 24 controls, 92 genes were differentially expressed with p<0.001. The top 50 genes were validated in an independent set of 22 cases and 22 controls using linear mixed models. In the validation set, 10 genes remained differentially expressed between the groups. CONCLUSIONS: RNA signatures from formalin-fixed paraffin-embedded blocks can identify patients with low-risk ccRCC who die of their disease. This finding provides an opportunity to help guide improved surveillance in patients with low-risk ccRCC. PATIENT SUMMARY: In the current study we identified RNA signatures from low-risk clear cell renal cell carcinoma patients who died from this disease. Improving prognostic algorithms for these low-risk patients could help to provide improved individualized surveillance recommendations.

Clinicopathologic characteristics and survival for adult renal sarcoma: A population-based study.

INTRODUCTION: To analyze the association of clinicopathologic characteristics and treatment modality with survival among adult patients with renal sarcoma. METHODS: We identified 489 adults diagnosed with renal sarcoma from the Surveillance, Epidemiology and End Results registry between 1973 and 2011. Cancer-specific survival was estimated using the Kaplan-Meier method and was compared between groups with log rank and Cox models. RESULTS: Median age at diagnosis was 61 years, while median tumor size was 11 cm. Tumor histology was leiomyosarcoma in 175, liposarcoma in 100, other subtypes in 129, and unknown in 85 cases. Tumor stage at diagnosis was nonmetastatic in 322 (67%) and metastatic in 167 (33%) cases. Treatment of nonmetastatic disease was surgical resection in 171 patients, radiation in 24, both in 35, neither in 18, and unknown in 74 cases. Treatment of metastatic disease was surgery in 39 patients, radiation in 27, both in 11, neither in 42, and unknown in 48. For nonmetastatic and metastatic disease, 5-year cancer-specific survival rates were 58% and 16%, respectively. On multivariable analysis, surgery was associated with decreased cancer-specific mortality among both patients with nonmetastatic disease (hazard ratio = 0.34; 95% CI: 0.14-0.85) and those with metastatic disease (hazard ratio = 0.38; 95% CI: 0.18-0.77). Age, race, tumor size, and tumor grade were independently associated with cancer death in nonmetastatic disease, whereas race and tumor histology remained associated with mortality in metastatic disease (all P < 0.05). CONCLUSION: Although metastatic renal sarcoma has an ominous prognosis, durable survival may be achieved for localized tumors. Although we recognize the potential for selection bias, our results suggest an association between surgical resection and decreased mortality for both nonmetastatic and metastatic renal sarcoma.

Evaluation of current surveillance guidelines following radical cystectomy and proposal of a novel risk-based approach.

BACKGROUND: Evidence supporting surveillance guidelines after radical cystectomy (RC) are lacking. Herein, we evaluate the ability of the National Comprehensive Cancer Network (NCCN) guidelines and the European Association of Urology (EAU) guidelines to capture recurrences and provide an alternative approach that balances risks of recurrence with non-bladder cancer death. METHODS: We identified 1,797 patients who had M0 urothelial carcinoma who underwent RC at our institution between 1980 and 2007. The success of current guidelines to capture recurrences was assessed by calculating the percentage of recurrences detected during the recommended follow-up time: the NCCN--2 years and the EAU--5 years. An alternative protocol was created using Weibull distributions, which estimate when a patient׳s risk of non-bladder cancer death exceeds their risk of recurrence. RESULTS: At a median follow-up of 10.6 years (interquartile range : 6.8-15.2), a total of 714 patients recurred. Of these, 491 (68.7%) would have been detected by the NCCN guidelines and 642 (89.8%) by the EAU guidelines. Using a risk-adapted approach, vastly different surveillance durations were appreciated. For example, for patients older than 80 years with pT0Nx-0 or pTa/CIS/1Nx-0 disease, recurrence risk to any location never exceeded their risk of non-bladder cancer death, whereas for patients aged 60 years and younger with pT3/4Nx-0 or pTanyN+disease, risk of abdominal/pelvis recurrence remained greater than their risk of non-bladder cancer death for>20 years. CONCLUSIONS: The duration of post-RC follow-up recommended by the NCCN and the EAU does not comprehensively capture recurrences. A surveillance algorithm based on the interaction between recurrence risk and competing health factors individualizes recommendations and may improve capture of recurrences and resource allocation.

Preoperative multivariable prognostic models for prediction of survival and major complications following surgical resection of renal cell carcinoma with suprahepatic caval tumor thrombus.

OBJECTIVE: Surgical resection for renal cell carcinoma (RCC) with suprahepatic inferior vena cava tumor thrombus is associated with significant morbidity, yet there are currently no tools for preoperative prognostic evaluation. Our goal was to develop a preoperative multivariable model for prediction of survival and risk of major complications in patients with suprahepatic thrombi. METHODS: We identified patients who underwent surgery for RCC with suprahepatic tumor thrombus extension from 2000 to 2013 at 4 tertiary centers. A Cox proportional hazard model was used for analysis of overall survival (OS) and logistic regression was used for major complications within 90 days of surgery (Clavien ≥ 3A). Nomograms were internally calibrated by bootstrap resampling method. RESULTS: A total of 49 patients with level III thrombus and 83 patients with level IV thrombus were identified. During median follow-up of 24.5 months, 80 patients (60.6%) died and 46 patients (34.8%) experienced major complication. Independent prognostic factors for OS included distant metastases at presentation (hazard ratio = 2.52, P = 0.002) and Eastern Cooperative Oncology Group (ECOG) performance status (hazard ratio = 1.84, P<0.0001). Variables associated with increased risk of major complications on univariate analysis included preoperative systemic symptoms, level IV thrombus, and elevated preoperative alkaline phosphatase and aspartate transaminase levels; however, only systemic symptoms (odds ratio = 8.45, P<0.0001) was an independent prognostic factor. Preoperative nomograms achieved a concordance index of 0.72 for OS and 0.83 for major complications. CONCLUSIONS: We have developed and internally validated multivariable preoperative models for the prediction of survival and major complications in patients with RCC who have a suprahepatic inferior vena cava thrombus. If externally validated, these tools may aid in patient selection for surgical intervention.

A novel grading system for clear cell renal cell carcinoma incorporating tumor necrosis.

Grading of renal cell carcinoma (RCC) has prognostic significance, and there is recent consensus by the International Society of Urological Pathology (ISUP) that for clear cell and papillary RCC, grading should primarily be based on nucleolar prominence. Microscopic tumor necrosis also predicts outcome independent of tumor grading. This study was undertaken to assess whether the incorporation of microscopic tumor necrosis into the ISUP grading system provides survival information superior to ISUP grading alone. Data on 3017 patients treated surgically for clear cell RCC, 556 for papillary RCC, and 180 for chromophobe RCC were retrieved from the Mayo Clinic Registry. Median follow-up periods were 8.9, 9.7, and 8.5 years, respectively. Four proposed grades were defined: grade 1: ISUP grade 1+ISUP grade 2 without necrosis; grade 2: ISUP grade 2 with necrosis+ISUP grade 3 without necrosis; grade 3: ISUP grade 3 with necrosis+ISUP grade 4 without necrosis; grade 4: ISUP grade 4 with necrosis or sarcomatoid/rhabdoid tumors. There was a significant difference in survival between each of the grades for clear cell RCC, and the concordance index was superior to that of ISUP grading. The proposed grading system also outperformed the ISUP grading system when cases were stratified according to the TNM stage. Similar results were not obtained for papillary RCC or chromophobe RCC. We conclude that grading for clear cell RCC should be based on nucleolar prominence and necrosis, that ISUP grading should be used for papillary RCC, and that chromophobe RCC should not be graded.

Chromophobe renal cell carcinoma: the impact of tumor grade on outcome.

It has been reported that Fuhrman grading is not appropriate for chromophobe renal cell carcinoma (RCC). The objective of this study was to determine whether nucleolar grading and the recently described chromophobe RCC grading system by Paner and colleagues provide prognostic information. Pathologic features of 185 patients with chromophobe RCC treated surgically between 1970 and 2006 were reviewed, including nucleolar grade, chromophobe RCC grade, the 2010 TNM groupings, sarcomatoid differentiation, and coagulative tumor necrosis. Cancer-specific (CS) survival was estimated using the Kaplan-Meier method, and associations with CS survival were evaluated using Cox proportional hazard regression models. Twenty-three patients died from RCC at a mean of 3.0 years after surgery (median 1.3; range 0 to 16) with estimated CS rates (95% confidence interval) of 89% (84 to 94), 86% (81 to 92), and 85% (78 to 91) at 5, 10, and 15 years after surgery. Univariate associations with CS survival included the 2010 TNM stage groupings, sarcomatoid differentiation, coagulative tumor necrosis, chromophobe RCC grade, and nucleolar grade (all P<0.001). These last 4 features remained significantly associated with CS survival after adjusting for the 2010 TNM stage groupings. When the analysis was restricted to the 155 patients with nonsarcomatoid TNM stage groupings I and II chromophobe RCC, only stage grouping (I vs. II) was significantly associated with CS survival (P=0.03). Although the chromophobe RCC grading system described by Paner and colleagues and nucleolar grade are associated with CS survival in chromophobe RCC, they add no additional prognostic information once TNM stage and sarcomatoid differentiation are assessed.

Patients with pT1 renal cell carcinoma who die from disease after nephrectomy may have unrecognized renal sinus fat invasion.

Prior studies suggest that the renal sinus permits early tumor spread in otherwise localized renal cell carcinoma (RCC) tumors. We hypothesized that renal sinus fat invasion may be unrecognized in pT1 patients who subsequently die from RCC. Between 1985 and 2002, we identified 577 patients who underwent radical nephrectomy for localized pT1 clear cell RCC as reviewed by a single urologic pathologist (J.C.C.). Among these patients, 49 died from RCC including 33 who had their original nephrectomy specimen stored in formalin. These specimens were then resectioned with thin cuts of the renal sinus and reviewed by the same pathologist. For comparison, 33 patients who did not die from RCC (controls) also had their original nephrectomy specimen resectioned. Among the 33 patients who died from seemingly localized RCC, 14 (42%) had previously unrecognized renal sinus fat invasion compared with 2 (6%) of the controls (P<0.001). In addition, 19 (58%) patients who died from RCC had renal sinus small vein (microscopic venous) invasion, a pathologic feature not currently incorporated into the TNM staging system for RCC. This feature was present in 7 (21%) of the controls (P=0.003). In total, 22 (67%) patients who died from RCC had unrecognized renal sinus fat or small vein invasion compared with 7 (21%) of the controls (P<0.001). We conclude that renal sinus fat invasion is an important adverse pathologic feature that is clearly underreported in the literature. Appropriate assessment of nephrectomy specimens should include proper sampling of the renal sinus even for seemingly localized tumors.