Perioperative dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin in muscle-invasive bladder cancer (VESPER): survival endpoints at 5 years in an open-label, randomised, phase 3 study.

BACKGROUND: The optimal perioperative chemotherapy for patients with muscle-invasive bladder cancer is not defined. The VESPER (French Genito-Urinary Tumor Group and French Association of Urology V05) trial reported improved 3-year progression-free survival with dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) versus gemcitabine and cisplatin (GC) in patients who received neoadjuvant therapy, but not in the overall perioperative setting. In this Article, we report on the secondary endpoints of overall survival and time to death due to bladder cancer at 5-year follow-up. METHODS: VESPER was an open-label, randomised, phase 3 trial done at 28 university hospitals or comprehensive cancer centres in France, in which adults (age ≤18 years and ≤80 years) with primary bladder cancer and histologically confirmed muscle-invasive urothelial carcinoma were randomly allocated (1:1; block size four) to treatment with dd-MVAC (every 2 weeks for a total of six cycles) or GC (every 3 weeks for a total of four cycles). Overall survival and time to death due to bladder cancer (presented as 5-year cumulative incidence of death due to bladder cancer) was analysed by intention to treat (ITT) in all randomly assigned patients. Overall survival was assessed by the Kaplan-Meier method with the treatment groups compared with log-rank test stratified for mode of administration of chemotherapy (neoadjuvant or adjuvant) and lymph node involvement. Time to death due to bladder cancer was analysed with an Aalen model for competing risks and a Fine and Gray regression model stratified for the same two covariates. Results were presented for the total perioperative population and for the neoadjuvant and adjuvant subgroups. The trial is registered with ClinicalTrials.gov, NCT01812369, and is complete. FINDINGS: From Feb 25, 2013, to March 1, 2018, 500 patients were randomly assigned, of whom 493 were included in the final ITT population (245 [50%] in the GC group and 248 [50%] in the dd-MVAC group; 408 [83%] male and 85 [17%] female). 437 (89%) patients received neoadjuvant chemotherapy. Median follow-up was 5·3 years (IQR 5·1-5·4); 190 deaths at the 5-year cutoff were reported. In the perioperative setting (total ITT population), we found no evidence of association of overall survival at 5 years with dd-MVAC treatment versus GC treatment (64% [95% CI 58-70] vs 56% [50-63], stratified hazard ratio [HRstrat] 0·79 [95% CI 0·59-1·05]). Time to death due to bladder cancer was increased in the dd-MVAC group compared with in the GC group (5-year cumulative incidence of death: 27% [95% CI 21-32] vs 40% [34-46], HRstrat 0·61 [95% CI 0·45-0·84]). In the neoadjuvant subgroup, overall survival at 5 years was improved in the dd-MVAC group versus the GC group (66% [95% CI 60-73] vs 57% [50-64], HR 0·71 [95% CI 0·52-0·97]), as was time to death due to bladder cancer (5-year cumulative incidence: 24% [18-30] vs 38% [32-45], HR 0·55 [0·39-0·78]). In the adjuvant subgroup, the results were not conclusive due to the small sample size. Bladder cancer progression was the cause of death for 157 (83%) of the 190 deaths; other causes of death included cardiovascular events (eight [4%] deaths), deaths related to chemotherapy toxicity (four [2%]), and secondary cancers (four [2%]). INTERPRETATION: Our results on overall survival at 5 years were in accordance with the primary endpoint analysis (3-year progression-free survival). We found no evidence of improved overall survival with dd-MVAC over GC in the perioperative setting, but the data support the use of six cycles of dd-MVAC over four cycles of GC in the neoadjuvant setting. These results should impact practice and future trials of immunotherapy in bladder cancer. FUNDING: French National Cancer Institute.

Impact of Divergent Differentiation and/or Histological Subtype of Urothelial Carcinoma on Patient Outcomes in the GETUG-AFU V05 VESPER Trial.

PURPOSE: Variant histology or divergent differentiation (VH/DD) of urothelial carcinoma (UC) may impact outcomes after neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer. Our aim was to assess the pathological response and progression-free survival (PFS) of patients with VH/DD in the prospective VESPER clinical trial. MATERIALS AND METHODS: This post hoc study included 300 NAC-treated patients with available transurethral diagnostic slides. Presence and percentage of VH/DDs were reviewed. For pathological response, logistic regression models were computed to measure association with VH/DD. For PFS, the associations were estimated in Cox proportional hazard regression model. All models were adjusted for randomization arm. RESULTS: VH/DD was identified in 177/300 patients (59%) and was predominant (≥50%) in 85/177. Compared to pure UC, VH/DD (≥10% or ≥50%) was not associated with a difference in proportion of complete pathological response (ypT0N0; OR adjusted: 0.79, 95% CI 0.49-1.29), downstaging (≤ypT1N0; OR adjusted: 0.62, 95% CI 0.37-1.02), or with an increased hazard of PFS (HR adjusted: 1.24, 95% CI 0.83-1.85). However, comparing specific VH/DD to pure UC, nested subtype was associated with decreased odds of complete pathological response (OR adjusted: 0.33, 95% CI 0.12-0.88) and downstaging (OR adjusted: 0.30, 95% CI 0.13-0.74), and an increased hazard of PFS was observed for UC with ≥ 50% squamous differentiation (HR adjusted: 2.11, 95% CI 1.01-4.38) or micropapillary subtype (HR adjusted: 2.03, 95% CI 0.98-4.22). CONCLUSIONS: In the VESPER trial, we did not observe evidence for association of VH/DD with outcomes after NAC, but the specific presence of a predominant squamous differentiation or micropapillary subtype may be associated with shorter PFS.

Prognostic value of programmed death ligand-1 and programmed death-1 expression in patients with upper tract urothelial carcinoma.

OBJECTIVE: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). RESULTS: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%]). CONCLUSIONS: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.

Evaluation of the efficacy of sacral neuromodulation in the treatment of voiding dysfunction after endometriosis surgery.

Pelvic surgery for endometriosis is associated with a risk of bladder and digestive sequelae. Sacral neuromodulation (SNM) has been shown to be effective in the treatment of overactive bladder (OAB) and voiding dysfunction (VD). This study aimed to evaluate the efficacy of sacral neuromodulation (SNM) in treating voiding dysfunction (VD) following endometriosis surgery. A retrospective analysis was conducted on data from women who underwent SNM testing for persistent VD after endometriosis surgery. The study included 21 patients from a French tertiary referral center. Patient characteristics, lower urinary tract symptoms, urodynamic findings, SNM procedures, and outcomes were assessed. The primary outcome was the success of SNM treatment for VD. After a median follow-up of 55 months, 60% of patients achieved successful outcomes, with significant improvements of VD and quality of life. Moreover, more than half of patients who required clean intermittent self-catheterization (CISC) before SNM were able to wean off CISC. Complications such as infections and paraesthesia were observed, but overall, SNM was found to be effective and well tolerated. Age and the interval between endometriosis surgery and SNM testing were associated with treatment success. This study adds to the limited existing literature on SNM for VD after endometriosis surgery and suggests that SNM can be a valuable therapeutic option for these patients. Further research is needed to identify predictive factors and mechanisms underlying the effectiveness of SNM in this context. MRI-compatible and rechargeable devices, has improved the feasibility of SNM for these patients. In conclusion, SNM offers promise as a treatment option for persistent VD after endometriosis surgery, warranting further investigation. LEVEL OF EVIDENCE: 4.

Observation vs. early drainage for grade IV blunt renal trauma: a multicenter study.

INTRODUCTION: The aim of this study was to compare observation and early drainage by ureteral stenting in patients with blunt renal trauma and urinary extravasation. MATERIALS AND METHODS: A retrospective national multicenter study was performed including all patients admitted for renal trauma at 17 hospitals between 2005 and 2015. Patients presenting with a urinary extravasation on initial imaging were considered for inclusion. Patients were divided in two groups according to the initial approach: observation vs. early drainage by ureteral stent (within 48 h after admission). The primary endpoint was the persistence of urinary extravasation on follow-up imaging. RESULTS: Out of 1799 patients with renal trauma, 238 were included in the analysis (57 in the early drainage and 181 in the observation group). In the early drainage group, 29 patients had persistent urinary extravasation vs. 77 in the observation group (50.9% vs. 42.5%; p value = 0.27). The rates of secondary upper urinary tract drainage did not differ significantly between the early drainage group (26.4%) and the observation group (16%) (p = 0.14). There were no statistically significant differences between the two groups in terms of secondary nephrectomy (0% vs. 2.8%; p = 0.34), and death from trauma (0% vs. 1.8%; p = 0.99). In multivariate analysis, early drainage remained not statistically associated with persistence of urinary extravasation on follow-up imaging (OR = 1.35; p = 0.36) CONCLUSION: In this multicenter cohort, observation was not different from early drainage in terms of persistent urinary extravasation after grade IV blunt renal trauma. Further randomized controlled prospective trials are needed to confirm these findings.

Long survival of patients with metastatic clear cell renal cell carcinoma. Results of real life study of 344 patients.

The treatment landscape in metastatic renal cell carcinoma has changed fundamentally over the last decade by the development of antiangiogenic agents, mammalian target of rapamycin inhibitors and immunotherapy. Outside of the context of a clinical trial, the treatments are used sequentially. We describe results under real-life conditions of a sequential treatment strategy, before the era of immunotherapy. All patients were treated according to their prognostic score (either Memorial Sloan Kettering Cancer Center or International Metastatic Renal Cell Carcinoma Database Consortium) for advanced renal cell carcinoma. A treatment strategy involving 1 to 4 lines was determined including a rechallenge criterion for the repeat use of a treatment class. Three hundred forty-four patients were included over 3 years. Overall survival was 57 months in patients with good or intermediate prognosis and 19 months in patients with poor prognosis. In the former group, the proportions of patients treated with 2 to 4 treatment lines were 70%, 38% and 16%, respectively. The best objective response rates for lines 1 to 4 were 46%, 36%, 16% and 17%, respectively. Grade III/IV toxicity did not appear to be cumulative. The recommended strategy was followed in 68% of patients. A large proportion of patients with good or intermediate prognosis who progress after two lines of treatment still have a performance status good enough to receive a systemic treatment, which justifies such a strategy. Overall survival of patients with good and intermediate prognosis was long, suggesting a benefit from the applied approach. These results might be used as selection criterion for the treatment of patients in the era of immune checkpoint inhibitors.

Clinical interest of PD-L1 immuno-histochemistry expression as a predictive factor of Bacillus Calmette Guerin (BCG) efficacy in refractory high-risk non-muscle-invasive bladder cancer (NMIBC).

OBJECTIVE: To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC. MATERIALS AND METHODS: Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included. Early recurrence (ER) was defined as tumor recurrence after BCG induction course. The association between ER and immuno-histochemistry PD-L1 (E1L3N clone) expression by tumors cells (TC) and tumor infiltrating immune cells (IC) was investigated using an exact Fisher test variant. RESULTS: A total of 186 patients were included, of whom 38 (20.4%) were ER, 35 (18.8%) were positive for TC PD-L1 expression and 60 (32.3%) were positive for IC PD-L1. ER was not significantly (p = 0.97) more frequent in the TC PD-L1 ≥ 1% group (n = 7, 20.0%) than in the TC PD-L1-negative group (n = 31, 20.5%). Patients with IC PD-L1 negative had ER in 15 (19.2%) cases and patients with IC PD-L1 ≥ 1% had ER in 23 (21.3%) cases. PD-L1-positive expression for IC (threshold > 1%) was correlated with immune infiltrate density (95.2% dense immune infiltrate vs 47.2% low immune infiltrate, p < 0.05), with increased expression of PD-L1 by IC after BCG therapy (p = 0.006). CONCLUSION: No association was observed between immuno-histochemistry PD-L1 positivity and ER after BCG therapy. Nevertheless, the relationship between immune infiltrate and PD-L1 positivity confirmed the interest of assessing the immune infiltrate density to define tumor's profile.

Safety and efficacy of temsirolimus as second line treatment for patients with recurrent bladder cancer.

BACKGROUND: Bladder cancer is the 7th cause of death from cancer in men and 10th in women. Metastatic patients have a poor prognosis with a median overall survival of 14 months. Until recently, vinflunine was the only second-line chemotherapy available for patients who relapse. Deregulation of the PI3K/AKT/mTOR pathway was observed in more than 40% of bladder tumors and suggested the use of mTOR as a target for the treatment of urothelial cancers. METHODS: This trial assessed the efficacy of temsirolimus in a homogenous cohort of patients with recurrent or metastatic bladder cancer following first-line chemotherapy. Efficacy was measured in terms of non-progression at two months according to the RECIST v1.1 criteria. Based on a two-stage optimal Simon's design, 15 non-progressions out of 51 evaluable patients were required to claim efficacy. Patients were treated at a weekly dose of 25 mg IV until progression, unacceptable toxicities or withdrawal. RESULTS: Among the 54 patients enrolled in the study between November 2009 and July 2014, 45 were assessable for the primary efficacy endpoint. A total of 22 (48.9%) non-progressions were observed at 2 months with 3 partial responses and 19 stable diseases. Remarkably, 4 patients were treated for more than 30 weeks. Fifty patients experienced at least a related grade1/2 (94%) and twenty-eight patients (52.8%) a related grade 3/4 adverse event. Eleven patients had to stop treatment for toxicity. This led to recruitment being halted by an independent data monitoring committee with regard to the risk-benefit balance and the fact that the primary objective was already met. CONCLUSIONS: While the positivity of this trial indicates a potential benefit of temsirolimus for a subset of bladder cancer patients who are refractory to first line platinum-based chemotherapy, the risk of adverse events associated with the use of this mTOR inhibitor would need to be considered when such an option is envisaged in this frail population of patients. It also remains to identify patients who will benefit the most from this targeted therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01827943 (trial registration date: October 29, 2012); Retrospectively registered.

The maximum detrusor pressure as a predictive factor of success after sphincterotomy in detrusor-sphincter dyssynergia.

AIMS: To evaluate the impact of the pre-operative maximum detrusor pressure (MDP) on efficacy outcomes after incontinentation by sphincterotomy or urethral stent placement in male patients with neurogenic detrusor-sphincter dyssynergia (DSD). METHODS: A retrospective study was performed in 41 male patients treated between 2006 and 2013 in a tertiary reference center. All patients had a neurogenic DSD confirmed by baseline urodynamic studies, and were unable or secondary failed to practice CISC. Success was defined as a post-void residual volume <150 mL. Influence of MDP on treatment efficacy was evaluated through a Mann-Whitney U-Test. RESULTS: Median (range) age was 39 years (20-69). Spinal cord injury was the main underlying condition. Twenty-six patients had a sphincteric stent placement (Memocath®, Bard, Covington) and 15 had surgical sphincterotomy. Treatment was successful in 31 patients (76%). Patients with immediate successful outcomes had a significantly higher mean preoperative MDP (59.6 vs 29.7 cmH2 O; P = 0.002). Patients with MDP over the threshold of 40 cmH2 O had a 90% success rate. These differences were maintained at 6 months, MDP being higher in the success group than in the failure group (59.5 vs 39.8 cmH2 O, respectively, P = 0.008). The technique used (stent placement or incision) had no impact on immediate or 6-month success rates. CONCLUSIONS: Our results suggested that MDP is associated with treatment success rate after surgical management of DSD of neurogenic origin by sphincteric stent placement or surgical sphincterotomy. A threshold of 40 mH2 O is associated with higher success rates.

Final results of the phase III URO-BCG 4 multicenter study: efficacy and tolerance of one-third dose BCG maintenance in nonmuscle invasive bladder cancer.

The objective of this study was to assess at 3 years bacillus Calmette-Guerin (BCG) maintenance treatment for NMIBC using one-third dose schedule and fewer instillations every 3 or 6 months. This was a phase III randomized study including patients with intermediate-risk or high-risk NMIBC, who received, after a full-dose induction schedule, three-weekly instillations of one-third dose BCG every 6 months (group I) and two-weekly instillations every 3 months (group II) during 3 years. We assessed oncological efficacy, BCG side effects, leukocyturia, and prostate-specific antigen. No tumor recurrence was reported at 36 months for 55 (82.09%) patients in group I versus 64 (90.14%) patients in group II (P=0.241). Muscle invasion was observed in six patients at 36 months (P=0.942). In terms of BCG toxicity, grade II and III local or systemic side effects were, respectively, reported in 8.7 and 23.9% of patients during the first year. Nevertheless, the adverse events (AEs) score at 36 months underlined a lower median value of 0.8 in group I versus 1.1 in group II (P=0.037). Furthermore, 9.9% major AEs occurred in group II versus 3% in group I (P=0.031). Leukocyturia and prostate-specific antigen level were not associated significantly with either tumor recurrence or muscle progression. We observed a significant difference in the AEs score at 36 months, suggesting less toxicity in patients who were treated with one-third dose of BCG for 3 consecutive weeks every 6 months.

Diagnostic performance of contrast-enhanced ultrasonography and magnetic resonance imaging for the assessment of complex renal cysts: A prospective study.

OBJECTIVES: To compare the diagnostic performance of computed tomography, magnetic resonance imaging and contrast enhanced ultrasonography for the assessment of complex renal cysts. METHODS: We carried out a prospective single-center study from January 2012 to December 2013. We included patients with Bosniak category 2F or 3 renal cysts found on computed tomography and reviewed by two expert radiologists. Magnetic resonance imaging and contrast-enhanced ultrasonography were then carried out. Patients with a Bosniak ≥3 cyst on magnetic resonance imaging, as well as those upgraded as appearing malignant on contrast-enhanced ultrasonography, were surgically managed. Imaging results were compared with histological data. For patients without surgery, imaging examinations were compared with follow-up data. For each imaging examination, diagnostic performance and Cohen's kappa coefficient were assessed. RESULTS: A total of 47 patients were included. The median follow up was 36 months (range 17-48 months). At initial computed tomography, cysts were classified as Bosniak 2F and Bosniak ≥3 in 34 and 13 patients, respectively. Magnetic resonance imaging found 13 Bosniak ≥3 cysts, and contrast-enhanced ultrasonography upgraded six more patients with cysts that appeared malignant. A total of 19 patients had surgery. Histological analysis reported 14 malignant tumors. No tumor progression was found in followed-up patients. Computed tomography showed poor sensitivity (36%) and specificity (76%; κ = 0.11). Magnetic resonance imaging showed 71% sensitivity and 91% specificity (κ = 0.64). Contrast-enhanced ultrasonography showed high sensitivity (100%) and specificity (97%), and a negative predictive value at 100% (κ = 0.95). CONCLUSIONS: The present results suggested that contrast-enhanced ultrasonography could be useful in improving the assessment of complex renal cysts. Indeed, computed tomography accuracy might be limited in this indication requiring further investigations to determine the best treatment strategy.

The subclassification of papillary renal cell carcinoma does not affect oncological outcomes after nephron sparing surgery.

OBJECTIVES: To evaluate the oncological outcomes of papillary renal cell carcinoma (pRCC) following nephron sparing surgery (NSS) and to determine whether the subclassification type of pRCC could be a prognostic factor for recurrence, progression, and specific death. MATERIALS AND METHODS: An international multicentre retrospective study involving 19 institutions and the French network for research on kidney cancer was conducted after IRB approval. We analyzed data of all patients with pRCC who were treated by NSS between 2004 and 2014. RESULTS: We included 486 patients. Tumors were type 1 pRCC in 369 (76 %) cases and type 2 pRCC in 117 (24 %) cases. After a mean follow-up of 35 (1-120) months, 8 (1.6 %) patients experienced a local recurrence, 12 (1.5 %) had a metastatic progression, 24 (4.9 %) died, and 7 (1.4 %) died from cancer. Patients with type I pRCC had more grade II (66.3 vs. 46.1 %; p < 0.001) and less grade III (20 vs. 41 %; p < 0.001) tumors. Three-year estimated cancer-free survival (CFS) rate for type 1 pRCC was 96.5 % and for type 2 pRCC was 95.1 % (p = 0.894), respectively. Three-year estimated cancer-specific survival rate for type 1 pRCC was 98.4 % and for type 2 pRCC was 97.3 % (p = 0.947), respectively. Tumor stage superior to pT1 was the only prognostic factor for CFS (HR 3.5; p = 0.03). CONCLUSION: Histological subtyping of pRCC has no impact on oncologic outcomes after nephron sparing surgery. In this selected population of pRCC tumors, we found that tumor stage is the only prognostic factor for cancer-free survival.

Post-chemotherapy retroperitoneal teratoma in nonseminomatous germ cell tumors: Do predictive factors exist? Results from a national multicenter study.

BACKGROUND AND OBJECTIVES: To identify predictive preoperative factors of the presence of teratoma in retroperitoneal lymph node dissection specimens. METHODS: We performed a 20 years multicenter retrospective analysis of all patients who underwent retroperitoneal lymph node dissection for residual masses after chemotherapy (PC-RPLND). Patients had undergone PC-RPLND after chemotherapy for advanced testicular cancer. The histologic components of the primary tumor were compared with those of the residual masses using logistic regression. RESULTS: A total of 469 NSGCT patients underwent PC-RPLND (complete data available for 211). By PC-RPLND, necrosis was found in 84 cases, teratoma in 102 cases, and viable tumor in 25 cases. The univariate and multivariate analyses showed that teratoma (P = 0.001 and P = 0.002, respectively) and yolk sac tumor (P = 0.009 and P = 0.035, respectively) in orchiectomy specimens were statistically significant predictors of the presence of teratoma in retroperitoneal lymph nodes. CONCLUSIONS: PC-RPLND is the standard treatment for any supracentimetric residual lesion. This procedure is associated with a high morbidity, and almost half patients are overtreated. The presence of teratoma and yolk sac tumor in the orchiectomy specimen were independent significant predictors of teratoma in retroperitoneal masses. J. Surg. Oncol. 2016;114:992-996. © 2016 Wiley Periodicals, Inc.

Morbidity-mortality conference for adverse events associated with totally implanted venous access for cancer chemotherapy.

PURPOSE: Although considered safer than central venous catheters for administration of cancer chemotherapy, totally implanted venous access (TIVA) is associated with adverse events that may impair prognosis and quality of life of patients receiving chemotherapy. Our aim was to assess the feasibility and interest of surveillance of cancer chemotherapy TIVA-adverse events (AE), associated with morbidity-mortality conferences (MMCs) on TIVA-AE. METHODS: We performed a prospective interventional study in two hospitals (a university hospital and a comprehensive care center). For each cancer chemotherapy care pathway within each hospital, we set up surveillance of TIVA-AE and MMC on these events. Patients included in surveillance were those with a TIVA either placed or used for chemotherapy cycles in one of the participating wards. Feasibility of MMC was assessed by the number of MMC meetings that actually took place and the number of participants at each meeting. The interest of MMC was assessed by the number of TIVA-AE identified and analyzed, and the number and type of improvement actions selected and actually implemented. RESULTS: We recorded 0.41 adverse events per 1000 TIVA-day. MMCs were implemented in all care pathways, with sustained pluriprofessional attendance throughout the survey; 39 improvement actions were identified during meetings, and 18 were actually implemented. CONCLUSIONS: Surveillance of TIVA-AE associated with MMC is feasible and helps change practices. It could be useful for improving care of patients undergoing cancer chemotherapy.

Baseline chronic kidney disease is associated with toxicity and survival in patients treated with targeted therapies for metastatic renal cell carcinoma.

To assess the impact of baseline chronic kidney disease on targeted therapy (TT)-induced toxicities and survival in patients treated for metastatic renal cell carcinoma (mRCC). Data from patients receiving first-line TT from January 2006 to June 2012 were collected retrospectively. TT side effects, time to treatment failure (TTF), and overall survival (OS) were analyzed according to the baseline glomerular filtration rate (GFR) calculated using the modification diet in renal disease formula. Hundred and two patients treated with sunitinib (N=67), sorafenib (N=24), or temsirolimus (N=11) were included. Forty-two patients (41%) had baseline chronic kidney disease with GFR less than 60 ml/min/1.73 m. Patients with GFR less than 60 were more likely to encounter severe (grade 3-4) TT-induced toxicities (79 vs. 32%, P<0.0001). Moreover, renal function impairment was significantly associated with higher median TTF and OS (respectively, 12 vs. 6 months for TTF, P=0.003; and 33 vs. 13 months for OS, P=0.001). On multivariate analysis, GFR less than 60 was identified as the only factor associated with a higher rate of severe toxicity: odds ratio=4.74 (1.67-13.41), P=0.003. Severe toxicity (P=0.05) was identified as an independent prognostic factor for OS and TTF. Baseline chronic kidney disease was associated with higher TT-induced toxicities, which were identified as a prognostic factor of higher survival in mRCC treatment. These results suggest that GFR measurement could be used to optimize the efficacy of TT in patients treated for an mRCC.

Prostate cancer incidence on cystoprostatectomy specimens is directly linked to age: results from a multicentre study.

OBJECTIVE: To assess the incidence and age-related histopathological characteristics of incidentally diagnosed prostate cancer from specimens obtained via radical cystoprostatectomy (RCP) for muscle-invasive bladder cancer. PATIENTS AND METHODS: A retrospective review of the histopathological features of 2424 male patients who underwent a RCP for bladder cancer was done at eight centres between January 1996 and June 2012. No patient had preoperative suspicion of prostate cancer. Statistical analyses were performed in different age-related groups. RESULTS: Overall, prostate cancer was diagnosed in 518 men (21.4%). Incidences varied significantly according to age (5.2% in those aged <50 years to 30.5% in those aged >75 years, P < 0.001). Most of the prostate cancers were considered as 'non-aggressive', that is to say organ-confined (≤pT2) and well-differentiated (Gleason score <7). Tumour-Node-Metastasis (TNM) stage and proportion with a Gleason score of ≥7 were significantly greater in older patients (P < 0.001). Apart from age, there were no preoperative predictive factors for 'non-aggressive' prostate-cancer status. At the end of the follow-up, only nine patients (1.7%) had biochemical recurrence of prostate cancer, and no preoperative predictive factors were identified. CONCLUSION: The rate of incidentally diagnosed prostate cancer from RCP specimens is ≈20%, most of them being organ-confined and well-differentiated. The probability of having a 'non-aggressive' prostate cancer decreases in older men.

Are warm ischemia and ischemia time still predictive factors of poor renal function after partial nephrectomy in the setting of elective indication?

PURPOSE: To evaluate renal function and to identify factors associated with renal dysfunction in the elective indications setting of nephron-sparing surgery (NSS). METHODS: We retrospectively reviewed operative data and glomerular filtration rate (GFR) of 519 patients treated by NSS in an elective indications setting between 1984 and 2006 in eight academic institutions. A GFR decrease under the thresholds of 60 or 45 ml/min at last follow-up was considered a significant renal dysfunction. Univariate and multivariate regression models were used to assess multiple factors of renal function. RESULTS: Median age, tumor size, preoperative, and final GFR were 59.5 years (27-84), 2.7 cm (0.9-11), 79 (45-137), and 69 ml/min (p < 0.0001), respectively, with a median follow-up of 23 months (1-416). Hilar clamping was performed in 375 procedures (72.3 %). Significant GFR decrease was observed in 89 patients (17.1 %). Median operating time, hilar clamping duration, and blood loss were 137 min (55-350), 22 min (0-90), and 150 ml (0-4150), respectively. At univariate analysis, age (p = 0.002), preoperative GFR (p = 0.001), pedicular clamping (p = 0.01), and ischemia time (p = 0.0001) were associated with renal dysfunction. Age (p = 0.004; HR 1.2), pedicular clamping (p = 0.04; HR 1.3), and ischemia time (p = 0.0001; HR 1.8) remained independent risk factors for renal function deterioration in multivariate analysis. CONCLUSION: Non- or time-limited clamping techniques are associated with preservation of renal function in the elective indications setting of NSS.

Efficacy and tolerance of one-third full dose bacillus Calmette-Guérin maintenance therapy every 3 months or 6 months: two-year results of URO-BCG-4 multicenter study.

OBJECTIVES: To assess bacillus Calmette-Guérin maintenance treatment schedule for non-muscle invasive bladder cancer at 2 years, using one-third of the full dose and fewer instillations every 3 months or 6 months. METHODS: This was a prospective, randomized, multicenter study. All patients had an intermediate- or high-risk non-muscle invasive bladder cancer. They received three weekly instillations of one-third dose bacillus Calmette-Guérin every 6 months (group I) and two weekly instillations every 3 months (group II) during 3 years. In the two schedules we assessed efficacy, tolerance, leukocyturia and prostate-specific antigen. RESULTS: No significant difference was observed between the two groups for recurrence at 6, 12 or 18 months. At 2 years, tumor recurrence was observed in 10.9% and muscle invasion in 2.9% of cases. Bacillus Calmette-Guérin tolerance was comparable - the adverse events score was 0.8 in group I and 1 in group II (P = 0.242). No statistical correlation was observed between the adverse events score over 2 years, either for leukocyturia (P = 0.8891) or prostate-specific antigen level (P = 0.7155). Leukocyturia level was not significantly associated with tumor recurrence or progression. CONCLUSION: One-third dose maintenance bacillus Calmette-Guérin is effective with no impact on tumor recurrence or muscle invasion. Furthermore, there seems to be no difference in tumor response or side-effects between patients receiving two or three maintenance instillations every 3 months or 6 months. In clinical practice, the use of leukocyturia or total prostate-specific antigen levels do not appear to be useful in predicting bacillus Calmette-Guérin toxicity.

Clinicopathological characteristics of incidental prostate cancer discovered from radical cystoprostatectomy specimen: a multicenter French study.

PURPOSE: The present study assessed the incidence and histopathological features of incidentally diagnosed prostate cancer (PCa) in specimens from radical cystoprostatectomy (RCP) for bladder cancer. The patient outcomes also were evaluated. METHODS: We retrospectively reviewed the histopathological features and survival data of 4,299 male patients who underwent a RCP for bladder cancer at 25 French centers between January 1996 and June 2012. No patients had preoperative clinical or biological suspicion of PCa. RESULTS: Among the 4,299 RCP specimens, PCa was diagnosed in 931 patients (21.7%). Most tumors (90.1%) were organ-confined (pT2), whereas 9.9% of them were diagnosed at a locally advanced stage (≥pT3). Gleason score was <6 in 129 cases (13.9%), 6 in 575 cases (61.7%), 7 (3 + 4) in 149 cases (16.0%), 7 (4 + 3) in 38 cases (4.1%), and >7 in 40 cases (4.3%). After a median follow-up of 25.5 months (interquartile range 14.2-47.4), 35.4% of patients had bladder cancer recurrence and 23.8% died of bladder cancer. Only 16 patients (1.9%) experienced PCa biochemical recurrence during follow-up, and no preoperative predictive factor was identified. No patients died from PCa. CONCLUSIONS: The rate of incidentally diagnosed PCa in RCP specimens was 21.7%. The majority of these PCas were organ-confined. PCa recurrence occurred in only 1.9% of cases during follow-up.