Robert Houston Thompson

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.

Percutaneous Cryoablation of Stage T1b Renal Cell Carcinoma: Technique Considerations, Safety, and Local Tumor Control

PURPOSE To describe the technical methods, safety, and local tumor control rate associated with percutaneous cryoablation of stage T1b renal cell carcinoma (RCC). MATERIALS AND METHODS A retrospective review of a percutaneous renal ablation registry was used to identify 46 patients with a total of 46 biopsy-proven RCC lesions measuring 4.1-7.0 cm treated with cryoablation between 2003 and 2011. The main outcome parameters investigated were adjunctive maneuvers, complications, and local tumor progression, and cancer-specific survival rates. Complication rates were categorized and recorded using the Clavien-Dindo classification system. Progression-free and cancer-specific survival rates were estimated using the Kaplan-Meier method. RESULTS The mean treated RCC size was 4.8 cm (range, 4.1-6.4 cm). Prophylactic tumor embolization was performed in 7 patients (15%), ipsilateral ureteral stents were placed in 7 patients (15%), and hydrodisplacement of bowel was performed in the treatment of 16 tumors (35%). A single technical failure (2.2%) was observed at the time of ablation. Thirty-six tumors (78%) had follow-up imaging at 3 months or later following ablation, including a single recurrence at 9 months after ablation. The mean duration of follow-up for the 35 RCC tumors that did not recur was 2.0 years (range, 0.3-6.1 y). Estimated local progression-free survival rate at 3 years was 96.4%. Of the 46 cryoablation procedures, there were 7 complications (15.2%) of grade II or worse. CONCLUSIONS The results suggest that cryoablation represents a valid treatment alternative for select patients with clinical stage T1b RCC. Complications are frequent enough that multidisciplinary patient management should be considered.

Preoperative neutrophil-lymphocyte ratio predicts death among patients with localized clear cell renal carcinoma undergoing nephrectomy.

OBJECTIVES The neutrophil-lymphocyte ratio (NLR) is an indicator of the systemic inflammatory response. An increased pretreatment NLR has been associated with adverse outcomes in other malignancies, but its role in localized (M0) clear cell renal cell carcinoma (ccRCC) remains unclear. As such, we evaluated the ability of preoperative NLR to predict oncologic outcomes in patients with M0 ccRCC undergoing radical nephrectomy (RN). METHODS AND MATERIALS From 1995 to 2008, 952 patients underwent RN for M0 ccRCC. Of these, 827 (87%) had pretreatment NLR collected within 90 days before RN. Metastasis-free, cancer-specific, and overall survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate models were used to analyze the association of NLR with clinicopathologic outcomes. RESULTS At a median follow-up of 9.3 years, 302, 233, and 436 patients had distant metastasis, death from ccRCC, and all-cause mortality, respectively. Higher NLR was associated with larger tumor size, higher nuclear grade, histologic tumor necrosis, and sarcomatoid differentiation (all, P < 0.001). A NLR ≥ 4.0 was significantly associated with worse 5-year cancer-specific (66% vs. 85%) and overall survival (66% vs. 85%). Finally, after controlling for clinicopathologic features, NLR remained independently associated with risks of death from ccRCC and all-cause mortality (hazard ratio for 1-unit increase: 1.02, P < 0.01). CONCLUSIONS Our results suggest that NLR is independently associated with increased risks of cancer-specific and all-cause mortality among patients with M0 ccRCC undergoing RN. Accordingly, NLR, an easily obtained marker of biologically aggressive ccRCC, may be useful in preoperative patient risk stratification.

The association of tumor volume with mortality following radical prostatectomy.

Background:Data regarding the prognostic significance of tumor volume (TV) in prostate cancer are conflicting. Herein, we evaluated the association of TV with prostate cancer mortality following radical prostatectomy (RP), and assessed the additive prognostic value of TV to an established predictive model.Methods:We identified 13 687 patients who underwent RP without preoperative therapy between 1987 and 2009. TV was estimated using the prolate ellipsoid formula. Survival was estimated using the Kaplan–Meier method and compared with the log-rank test. Cox proportional hazard regression models were used to evaluate the association of TV with mortality. The ability of TV to enhance the performance of an established prognostic model (Mayo Clinic GPSM (Gleason, PSA, seminal vesicle and margin status) score) was assessed using the c-index.Results:Median TV was 1.57 cm3 (interquartile range (IQR) 0.48–4.19). Increasing TV was associated with significantly higher risks of seminal vesicle invasion (hazard ratio (HR) 1.58; P<0.0001), positive surgical margins (HR 1.28; P<0.0001) and lymph node involvement (HR 1.26; P<0.0001). Median postoperative follow-up was 9.4 years (IQR 5.0–14.5). Patient grouping into quartiles according to TV resulted in a significant stratification of outcome, as the 15-year cancer-specific survival by TV quartile was 99%, 98%, 95% and 88%, respectively (P<0.0001). Moreover, on multivariate analysis, greater TV remained associated with significantly increased risks of systemic progression (HR 1.27; P<0.0001), death from prostate cancer (HR 1.29; P<0.0001) and all-cause mortality (HR 1.05; P<0.0001). Meanwhile, addition of TV to the GPSM score increased the c-index for the model’s prediction of prostate cancer mortality from 0.803 to 0.822.Conclusions:TV is associated with survival following RP, and enhances, although modestly, the performance of an established prediction model. As such, TV warrants continued assessment in risk stratification tools.

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.

Radiographic size of retroperitoneal lymph nodes predicts pathological nodal involvement for patients with renal cell carcinoma: development of a risk prediction model.

To evaluate the ability of clinical and radiographic features to predict lymph node (pN1) disease among patients with renal cell carcinoma undergoing radical nephrectomy (RN), and to develop a preoperative risk prediction model.

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.

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.