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A large proportion of patients with non-muscle-invasive bladder cancer (NMIBC) fall in the gap between bacillus Calmette-Guérin (BCG)-naïve and BCG-unresponsive disease. As multiple therapeutic agents move into this gray area, there is a critical need to define the disease state and establish recommendations for optimal trial design.To develop a consensus on optimal trial design for patients with BCG-exposed NMIBC, defined as high-grade recurrence after BCG treatment that does not meet the criteria for BCG-unresponsive disease.We conducted a literature review using the Cochrane Library, Medline, and Embase and a review of clinical trials in ClinicalTrials.gov as a basis to generate consensus recommendations for clinical trial design in BCG-exposed NMIBC.BCG-exposed NMIBC encompasses BCG resistance (presence of high-grade Ta or carcinoma in situ [CIS] at 3-mo evaluation after induction BCG) and delayed relapse. Randomized controlled trials are required to compare experimental therapies to a control arm receiving additional BCG, although ongoing BCG shortages may impact our ability to follow an optimal trial design. A placebo should be used in combination with BCG if the treatment arm includes BCG plus a study drug. Trials will either need to separate patients with and without CIS into two cohorts, or stratify by the presence of CIS at the time of randomization. If two cohorts are used, the primary endpoint for CIS patients should be complete response within a predetermined time. The primary endpoint in a cohort with Ta/T1 only, or if a single combined cohort is used, should be the duration of event-free survival. Suggested efficacy thresholds and corresponding sample sizes are provided.The International Bladder Cancer Group has developed recommendations regarding definitions, endpoints, and clinical trial design for BCG-exposed NMIBC to encourage uniformity among studies in this disease state.Our consensus provides a precise definition of the disease state for bladder cancer not invading the bladder muscle and exposed to bacillus Calmette-Guérin (BCG) treatment. Clear guidance for conducting optimal clinical trials in this disease setting was established and we believe that this will promote further progress in this field.

BACKGROUND: Alterations in fibroblast growth factor receptor 3 (FGFR3) occur in ~15% of muscle-invasive bladder cancers (MIBCs) and metastatic urothelial carcinomas (mUCs). OBJECTIVE: To determine the association between FGFR3 status and response to platinum-based chemotherapy in patients with MIBC or mUC. DESIGN, SETTING, AND PARTICIPANTS: The authors conducted a retrospective review and comparison of patients having (1) MIBC treated with neoadjuvant chemotherapy (NAC), (2) mUC treated with first-line platinum-based chemotherapy (M1 cohort), and (3) MIBC who were from The Cancer Genome Atlas (TCGA). INTERVENTION: Platinum-based chemotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Pathologic response, recurrence-free (RFS) or progression-free (PFS) survival, and overall survival (OS) were compared between patients with FGFR3 alteration (FGFR3alt) and those without it (FGFR3 wild type [FGFR3wt]) in the three cohorts. RESULTS AND LIMITATIONS: Nine of 72 NAC patients (13%) had FGFR3alt, of whom none had pathologic complete response and three had residual non-MIBC (carcinoma in situ, n = 1; pT1, n = 2). FGFR3alt was associated with shorter RFS (hazard ratio, 2.74; p = 0.044) but not OS. Among TCGA patients who underwent adjuvant chemotherapy (n = 74), FGFR3alt patients had shorter RFS as well. Conversely, among chemotherapy-naive TCGA patients, FGFR3alt was associated with longer RFS and OS. In the M1 cohort (FGFR3alt, n = 27; FGFR3wt, n = 81), FGFR3alt was associated with higher rates of pulmonary metastases and nonregional lymphadenopathy. Despite lower response rates among FGFR3alt patients (37% vs 49%; p = 0.056), PFS and OS were not significantly different from FGFR3wt patients. CONCLUSIONS: FGFR3 status is associated with lower responses to platinum-based chemotherapy, which may prompt exploration of nonchemotherapeutic approaches for perioperative management of FGFR3alt urothelial cancers. PATIENT SUMMARY: Approximately 15% of bladder cancers harbor mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Our findings suggest that FGFR3 mutations might be associated with lower responses and shorter time to recurrence among patients with muscle-invasive bladder cancer who received perioperative platinum-based chemotherapy. FGFR3 status does not significantly impact response to chemotherapy among those with metastatic urothelial cancers.

Robotic partial nephrectomy (RPN) has a significant morbidity. Nephrometry scores have been described to predict the occurrence of complications. Their usefulness is debated.To evaluate the clinical utility of three nephrometry scores (radius, exophytic/endophytic, nearness, anterior/posterior, location [RENAL], preoperative aspects and dimensions used for an anatomical [PADUA], and simplified PADUA Renal [SPARE]) to predict perioperative outcomes and compare their performance to the simple measurement of tumor size in a large cohort of patients who underwent RPN.We analyzed 1581 consecutive patients who underwent RPN for small renal masses.Tumor size, RENAL, PADUA, and SPARE scores were calculated based on preoperative imaging. Correlation between scores, estimated blood loss (EBL), operative time (OT), and warm ischemia time (WIT) were calculated. Logistic regression analyses were performed to identify predictors of overall and major complications. The area under the curve was used to identify models with the highest discrimination. Decision curve analyses determined the net benefit associated with their use.The median age was 62 yr (interquartile range [IQR]: 52-70) and the median tumor size was 35 mm (IQR: 25-47). Postoperative complications were observed in 346 patients (21.9%), including 5.6% of major complications. All scores were significantly correlated with EBL, OT, and WIT. However, correlation coefficients were all0.3, suggesting a weak association. Nephrometry scores and tumor size were significant predictors of overall complications in univariate and adjusted multivariable logistic regression model analysis. However, decision curve analysis demonstrated net benefit of tumor size comparable with all nephrometry scores. Finally, neither nephrometry scores nor tumor size was found to be associated with the risk of major complications.Tumor size has the same ability as nephrometry scores to predict perioperative outcomes of RPN.We evaluated the association between tumor size, nephrometry scores, and perioperative outcomes of robotic partial nephrectomy (RPN). We found that tumor size could predict perioperative outcomes of RPN as well as nephrometry scores.

It is not known whether the primary tumour location of upper urinary tract urothelial carcinoma (UUT-UC) is associated with prognosis.To evaluate the impact of initial primary tumour location on survival in patients who had undergone radical nephroureterectomy (RNU).Using a multi-institutional, retrospective database, we identified 609 patients with UUT-UC who had undergone RNU between 1995 and 2010. Tumour location was categorised as renal pelvis, ureter, or multifocal.All patients had undergone RNU.Tumour location was tested as a prognostic factor for survival through univariate and multivariable Cox regression analysis.Tumour location was renal pelvis in 317 cases (52%), ureter in 185 cases (30%), and multifocal in 107 cases (18%). Compared to renal pelvic and ureteral tumours, multifocal tumours were more likely to be associated with advanced stages (pT3/pT4; 39%, 30%, and 54%, respectively; p0.001) and high-grade disease (53%, 56%, and 76%, respectively; p0.001). On multivariable analysis, tumour location was an independent prognostic factor for cancer-specific death, disease recurrence, and metastasis (p0.05). The 5-yr cancer-specific death-free survival probability was 86.8% for renal pelvic tumours, 68.9% for ureteral tumours, and 56.8% for multifocal tumours (p0.001). The retrospective design of this study was its main limitation.Ureteral and multifocal tumours had a worse prognosis than renal pelvic tumours. These findings are not in line with recently published data and should be investigated in a prospective assessment to obtain a definitive statement regarding this matter.

We report the first totally robotic procedure for kidney transplantation with transvaginal insertion. The initial results suggested reduced pain and improved cosmesis and the absence of lymphocele formation without compromising graft function or patient outcome. The patient was a 50-yr-old woman who received a living donor transplant for end-stage chronic kidney disease. We used a 4-arm Si HD da Vinci robot (Intuitive Surgical Inc., Sunnyvale, CA, USA) with standard port placement. The following procedural steps were performed sequentially: transperitoneal dissection of the external vessels, uterine mobilisation with transparietal stitching to allow full visualisation of the posterior vaginal wall to be used for graft insertion (through an Alexis retractor [Applied Medical