A novel tumor grading scheme for chromophobe renal cell carcinoma: prognostic utility and comparison with Fuhrman nuclear grade.

Chromophobe renal cell carcinoma (RCC) is a histologic subtype of RCC that portends a favorable prognosis. It is controversial whether the Fuhrman nuclear grade of chromophobe RCC has prognostic utility. Irregular nuclei, prominent nucleoli, and nuclear pleomorphism are inherently present in chromophobe RCC. Hence, the Fuhrman nuclear grade is higher even though the majority of these tumors have a favorable outcome. In this study, the prognostic utility of a novel 3-tiered tumor grading system in which the innate nuclear atypia of chromophobe RCC was discounted, herein referred to as chromophobe tumor grade from a series of 124 chromophobe RCC, was compared with Fuhrman nuclear grade. Chromophobe tumor grade is based on the assessment of geographic nuclear crowding and anaplasia. The Fuhrman nuclear grade distribution between the tumors was grade 1 (1%), grade 2 (19%), grade 3 (74%), and grade 4 (6%), whereas the chromophobe tumor grade distribution was grade 1 (74%), grade 2 (16%), and grade 3 (10%). Neither Fuhrman nuclear grade nor chromophobe tumor grade was significantly associated with patient's age or sex and chromophobe RCC cell types, but both showed a significant association with tumor size. Both Fuhrman nuclear grade and chromophobe tumor grade showed statistically significant positive associations with broad alveolar growth, necrosis, vascular invasion, and with pathologic stage; however, all these associations tended to be dictated by tumors with sarcomatoid change. When tumors with sarcomatoid change were excluded, a strong positive association persisted between chromophobe tumor grade and pathologic stage. In contrast, there was no such association between Fuhrman nuclear grade and stage in nonsarcomatoid chromophobe RCCs. Characterizing aggressive chromophobe RCC with aggressive behavior with the time from surgery to first occurrence of metastasis, local recurrence, or death owing to disease, we found that both Fuhrman nuclear grade and chromophobe tumor grade were highly associated with adverse outcome. However, as with the pathologic stage, only a significant association between chromophobe tumor grade and outcome was retained among nonsarcomatoid chromophobe RCCs. Multivariable Cox regression analysis also tended to support chromophobe tumor grade rather than Fuhrman nuclear grade as an independent predictor of adverse outcome, controlling for other univariably significant risk factors [estimated relative hazard=3.68 (P=0.026) vs. 1.86 (P=0.42)]. In conclusion, the novel chromophobe tumor grading system proposed herewith provides superior prognostic value to that of the Fuhrman nuclear grade in chromophobe RCC and will potentially help stratify patients of chromophobe RCC who are at a greater risk of disease progression.

Early oncological outcomes of robot-assisted radical prostatectomy for high-grade prostate cancer.

OBJECTIVE: To evaluate the oncological outcomes of patients with specimen Gleason 8 and 9 prostate cancers and to determine factors that predict biochemical recurrence-free survival (BCRFS) after robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: Of 4156 patients who underwent RARP from January 2001 to 2009, we identified 368 men with Gleason 8 or 9 tumours who met the inclusion criteria. BCR was defined as a PSA level of ≥0.2 ng/mL with a second rising value. The Kaplan-Meier method and log-rank test were used to compare BCRFS while factors that predict BCRFS were determined by Cox proportional hazards modelling. RESULTS: The median age and PSA level were 62 years and 6.4 ng/mL for men with Gleason 8, and 63 years and 6.7 ng/mL for Gleason 9 cancers. The median (interquartile range, IQR) overall follow-up was 23 (10-46) months and 19 (7-37) months for Gleason 8 and 9 tumours, respectively. At 60 months the mean (se) overall BCRFS was 36 (5)% and for Gleason 8 it was 47 (6)% and for Gleason 9 it was 21 (7)% (P < 0.001). At 5 years, extraprostatic extension (pT3a) resulted in BCRFS of 52 (9)% for Gleason 8 tumours and 21 (11)% for Gleason 9 (P= 0.012). On multivariable analysis, lymph node invasion, specimen Gleason score, pathological stage and tumour volume predicted BCRFS. CONCLUSIONS: Early results suggest RARP monotherapy performs comparably to RP for BCRFS in men with high-grade prostate cancer. There are significant oncological differences between Gleason 8 and 9 tumours.

Men presenting for radical prostatectomy on preoperative statin therapy have reduced serum prostate specific antigen.

PURPOSE: Studies have suggested that statin (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors) medication use may decrease prostate specific antigen in healthy men. We determined the effect of preoperative statin use on total preoperative prostate specific antigen and the risk of biochemical recurrence in patients with prostate cancer presenting for radical prostatectomy. MATERIALS AND METHODS: A retrospective review of 3,828 patients undergoing radical prostatectomy from January 2001 to July 2008 at our institution identified 1,031 on statin medications. We compared these 1,031 patients to the remaining 2,797 not on statins preoperatively. We evaluated differences in prostate specific antigen overall, and when patients were stratified by age specific groups, body mass index and Gleason grades on final pathology. We also investigated differences in biochemical recurrence rates. RESULTS: Overall median serum prostate specific antigen was lower in patients on preoperative statins (5.0 vs 5.2 ng/ml, p = 0.002). Median prostate specific antigen was lower in men on statins with Gleason grades 7 or 8/9 disease (p <0.05). Using a multivariate logistic regression model statin therapy was associated with a 4.7% decrease in prostate specific antigen (p <0.001). Statin therapy was not associated with an overall decreased risk of biochemical recurrence (p = 0.73) at a mean followup of 26 months. CONCLUSIONS: In this cohort of men presenting for radical prostatectomy serum prostate specific antigen is significantly lower in patients with prostate cancer on preoperative statins compared to those not taking these medications. Prospective studies are required to evaluate if this decrease in prostate specific antigen leads to later detection of prostate cancer or variations in oncological outcomes.

Posterior support for urethrovesical anastomosis in robotic radical prostatectomy: single surgeon analysis.

INTRODUCTION: Posterior urethrovesical anastomotic support has been reported to improve early return of urinary continence following radical prostatectomy. We adapted this technique to evaluate enhancement of early urinary control in patients undergoing robotic radical prostatectomy. MATERIALS AND METHODS: Forty-two consecutive men undergoing radical prostatectomy by a single surgeon between September and December 2007 received a posterior urethrovesical supporting stitch prior to the standard urethrovesical anastomosis (group 1). Operative data, postoperative complications, and follow up data were compared with those of the 42 consecutive men who underwent robotic radical prostatectomy by the same surgeon between March and August 2007 with a standard urethrovesical anastomosis (group 2). Continence was assessed at routine follow up visit 6 to 8 weeks following catheter removal. Continence was defined as zero pads or small security liner for infrequent urinary leakage in 24 hours. RESULTS: Thirty-four (81%) and 37 (88%) men in groups 1 and 2 respectively had follow up available between 45 and 75 days following prostatectomy. Preoperative demographics were similar between the two groups. At a mean follow up of 60 and 53 days following surgery, 29/34 (85%) of men in group 1 and 32/37 (86%) of men in group 2 were continent. On multivariate logistic regression analysis, no factors were associated with improved continence between the two groups. CONCLUSIONS: Posterior urethrovesical anastomotic support did not result in improved early urinary control following radical prostatectomy. Excellent urinary control can be achieved in the patients undergoing robotic radical prostatectomy without posterior urethrovesical anastomotic support.

Chromophobe renal cell carcinoma: histomorphologic characteristics and evaluation of conventional pathologic prognostic parameters in 145 cases.

The aggregate literature suggests that chromophobe renal cell carcinoma (RCC) is biologically a tumor of low malignant potential with reported 5-year and 10-year survival rates of 78% to 100% and 80% to 90%, respectively. The conventional prognostic parameters that determine the outcome of the tumors that progress remain to be fully characterized. Clinicopathologic features of 145 cases were correlated with outcome. The mean age of the patients was 59 years (range, 27 to 82) and the male to female ratio was 1.1:1. Most tumors were well circumscribed and averaged 8.0 cm (range, 1.0 to 30.0 cm); multifocality and bilaterality were present in 8% and 3% of patients. Sixty (41%) were eosinophilic variant (greater than 80% eosinophilic cells), 18 (12%) were classic type (greater than 80% pale cells), and 67 (46%) were mixed (containing variable admixture of pale and eosinophilic cells). A subset of eosinophilic chromophobe RCC contained or had areas similar to renal oncocytomas. These tumors tended to be more commonly bilateral (11%) and multifocal (22%) and were not associated with necrosis or sarcomatoid change. Sarcomatoid change was present in 12/145 (8%) tumors. By histologic grade, 1%, 19%, 74%, 6% were Fuhrman nuclear grade 1, 2, 3, and 4. Nineteen percent, 21%, 28%, 13%, 4%, 1%, and 3% were pT (2002) stage pT1a, pT1b, pT2, pT3a, pT3b, pT3c, and pT4 tumors. Two percent tumors were pN1 at presentation and 2.8% tumors were M1 at presentation. Follow-up (1 to 182 mo, mean 48 mo, median 37 mo) was available in 123 cases. Disease progression (local recurrence 4, metastasis 15, and/or death 10) was seen in 20 patients. In univariable analysis, tumor size (P=0.025), pT stage (P<0.001), broad alveolar architecture (P=0.012), Fuhrman nuclear grade (P<0.001), microscopic tumor necrosis (P=0.001), vascular invasion (P=0.020), and sarcomatoid change (P< or =0.001) were associated with progression. A multivariable Cox regression model revealed sarcomatoid change (P=0.013, estimated relative hazard 4.7), microscopic necrosis (P=0.020, relative hazard=3.5), and pT stage (P=0.025, relative hazard 3.4) as independent predictors of aggressive chromophobe RCC. Although the large majority of chromophobe RCCs have a favorable prognosis, a distinct subset of patients progress. The pT stage of tumor, tumor necrosis, and sarcomatoid change all predict aggressive phenotype of chromophobe RCC. The adverse presence of these features in a nephrectomy specimen with chromophobe RCC warrants active surveillance, and these patients may be candidates for adjuvant therapies as they become available.

Radical prostatectomy: a single surgeon comparison of retropubic, perineal, and robotic approaches.

OBJECTIVE: To compare perioperative, functional and oncological outcomes of a single surgeon's experience with retropubic (RRP), perineal (RPP), and robotic assisted (RARP) radical prostatectomy. METHODS: Results from 150 radical prostatectomies performed by a single surgeon were compared. The groups consisted of the last 50 consecutive RRP (group 1) and RPP patients (group 2) and his first 50 RARP patients (group 3). He had significant experience in RRP and RPP and extensive training prior to performing RARP. The data was obtained from record review and patient survey. Patient demographics, operative parameters, pathological characteristics, complications, and functional outcomes were compared between groups. RESULTS: The groups were comparable with respect to patient demographics. Hospital stay, blood loss, and transfusion requirements were significantly better in the robotic group. Complications were least in the robotic group. Urinary continence (one pad or less) at 12 months was 96% in RRP, 96% in RPP, and 96% in RARP group. Positive surgical margins in organ confined disease were significantly lower for RARP although overall positive margins were similar. Potency data was still maturing and was not included in this analysis. CONCLUSIONS: There were no major differences in outcomes between the RRP and RPP groups. The RARP group had equal or better perioperative outcomes in all analyzed categories with the least complications. Urinary function outcomes were excellent in all groups. Prior open experience and extensive training facilitate encouraging outcomes for robotic prostatectomy even in a surgeon's initial series of patients.

Design considerations for incorporating sodium iodide symporter reporter gene imaging into prostate cancer gene therapy trials.

This study was done to aid in the design of a phase I gene therapy trial in patients with prostate cancer. We determined the dosimetric characteristics of our reporter gene system when coupled with intravenous administration of radioactive sodium pertechnetate (Na(99m) TcO(4)) and determined the feasibility of using human sodium iodide symporter (hNIS) as a reporter gene to study the dynamics of adenoviral transgene expression in a large animal tumor. A replication-competent Ad5-yCD/mutTK(SR39) rep-hNIS adenovirus was injected into the prostate gland of dogs for dosimetry purposes, and into a canine soft tissue sarcoma (STS) for imaging purposes. After resection of the prostate, the amount of (99m)TcO(4)() sequestered in the prostate was determined, the radiation dose absorbed by the prostate and nontarget critical organs was calculated, and hNIS reporter gene expression was imaged in the STS by single-photon emission computed tomography (SPECT). On the basis of the findings from 25 dogs, the amount of (99m)TcO (4)() sequestered in the prostate ranged from 13 to 276 muCi. Using the highest value observed, absorbed radiation dose to critical organs was calculated and found to be below U.S. Food and Drug Administration limits for diagnostic imaging. Also, (99m)TcO (4)() uptake was readily detected by SPECT and found to persist in vivo for at least 4 days. On the basis of our dosimetry calculations, up to five imaging procedures can be safely performed in humans after intraprostatic injection of the Ad5-yCD/mutTK(SR39)rep-hNIS adenovirus and the hNIS reporter gene system can be used to study the dynamics of adenoviral gene therapy vectors in large animal tumors.