BACKGROUNDSunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. METHODSIn this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety. RESULTSThe median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P = 0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects. CONCLUSIONSAmong patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. n engl j med nejm.org 2T h e ne w e ngl a nd jou r na l o f m e dicine E ach year, approximately 300,000 persons worldwide are diagnosed with renalcell carcinoma, resulting in 129,000 deaths.

ClinicalTrials.gov NCT00375674.

Purpose We investigated the relationship between the tertiary Gleason component in radical prostatectomy specimens and biochemical recurrence in what is to our knowledge the largest single institution cohort to date. Materials and Methods We evaluated data on 3,230 men who underwent radical prostatectomy at our institution from 2000 to 2005. Tertiary Gleason component was defined as Gleason grade pattern 4 or greater for Gleason score 6 and Gleason grade pattern 5 for Gleason score 7 or 8. Results Biochemical recurrence curves for cancer with tertiary Gleason component were intermediate between those of cancer without a tertiary Gleason component in the same Gleason score category and cancer in the next higher Gleason score category. The only exception was that Gleason score 4 + 3 = 7 with a tertiary Gleason component behaved like Gleason score 8. The tertiary Gleason component independently predicted recurrence when factoring in radical prostatectomy Gleason score, radical prostatectomy stage and prostate specific antigen (HR 1.45, p = 0.029). Furthermore, the magnitude of the tertiary Gleason component effect on recurrence did not differ by Gleason score category (p = 0.593). Conclusions Although the tertiary Gleason component is frequently included in pathology reports, it is routinely omitted in other situations, such as predictive nomograms, research studies and patient counseling. The current study adds to a growing body of evidence highlighting the importance of the tertiary Gleason component in radical prostatectomy specimens. Accordingly consideration should be given to a modified radical prostatectomy Gleason scoring system that incorporates tertiary Gleason component in intuitive fashion, including Gleason score 6, 6.5 (Gleason score 6 with tertiary Gleason component), 7 (Gleason score 3 + 4 = 7), 7.25 (Gleason score 3 + 4 = 7 with tertiary Gleason component), 7.5 (Gleason score 4 + 3), 8 (Gleason score 4 + 3 with tertiary Gleason component or Gleason score 8), 8.5 (Gleason score 8 with tertiary Gleason component), 9 (Gleason score 4 + 5 or 5 + 4) and 10.

. There were no statistically significant differences in positive margin rates between the three surgical techniques for pT2 disease ( P = 0.264).• In multivariate logistic regression analysis, surgical technique ( P = 0.016), biopsy Gleason score ( P < 0.001) and preoperative PSA ( P < 0.001) were predictors of positive surgical margins.• Kaplan-Meier analysis did not show any statistically significant differences with respect to biochemical recurrence for the three surgical groups. CONCLUSIONS• RRP, LRP and RARP represent effective surgical approaches for the treatment for clinically localized prostate cancer. A higher overall positive SM rate was observed for the RARP group compared to RRP and LRP; however, there was no difference with respect to biochemical recurrence-free survival between groups.• Further prospective studies are warranted to determine whether any particular technique is superior with regard to longterm clinical outcomes. KEYWORDSprostate cancer, biochemical recurrence, radical prostatectomy, robotic prostatectomy, laparoscopic prostatectomy Study Type -Therapy (case series) Level of Evidence 4 OBJECTIVE• To investigate a single institution experience with radical retropubic prostatectomy (RRP), laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP) with respect to pathological and biochemical outcomes. PATIENTS AND METHODS• A group of 522 consecutive patients who underwent RARP between 2003 and 2008 were matched by propensity scoring on the basis of patient age, race, preoperative prostate-specific antigen (PSA), biopsy Gleason score and clinical stage with an equal number of patients who underwent LRP and RRP at our institution.• Pathological and biochemical outcomes of the three cohorts were examined. RESULTS• Overall positive surgical margin rates were lower among patients who underwent RRP (14.4%) and LRP (13.0%) compared to patients who underwent RARP (19.5%) ( P = BJUI B J U I N T E R N A T I O N A LWhat's known on the subject? and What does the study add? Thus far, no institution has investigated the impact of the most commonly used surgical techniques -open, laparoscopic and robotic radical prostatectomy -on biochemical outcome. However, recent data from large meta-analysis suggest that the impact of the chosen surgical technique on biochemical outcome is minimal and statistically not relevant.We are the first to apply the method of propensity score matching in the urology literature to compare three different surgical techniques. This method is intended to simulate a randomized trial which is unlikely to be undertaken for radical prostatectomies. We confirmed previous data that the surgical technique does not seem to have an impact on biochemical outcome following radical prostatectomy.

Radical prostatectomy (RP) remains the standard treatment for men with clinically localized prostate cancer, despite the range of alternative treatment modalities. Even with significant advances in surgical technique and superb results for cancer control and preservation of urinary function, erectile dysfunction (ED) following RP is a common complication. This is mainly attributed to temporary cavernous nerve damage (neuropraxia) resulting in penile hypoxia, smooth muscle apoptosis, fibrosis and veno-occlusive dysfunction. One of the most promising new approaches is the concept of early penile rehabilitation, which is thought to prevent ED after RP by countering post-RP pathophysiological changes during the period of neural recovery. Various treatments, such as vacuum constriction devices, intraurethral and intracorporal alprostadil, and phosphodiesterase type 5 (PDE5) inhibitors, might serve to facilitate recovery of erectile function. PDE5 inhibitors are considered as the first-line treatment for early penile rehabilitation, with superior erectile function outcomes compared to placebo. Definitive conclusions regarding the success of penile rehabilitation cannot be drawn at this time because of differences in study design, data acquisition, and definitions of potency. Continued prospective, rigorous study is needed to develop and bring forward this important field and to establish the best evidence basis for counseling and treating patients suffering from ED after RP.