Effet du carcinome in situ sur la survie de patients traités par chimiothérapie adjuvante après cystectomie

International audienceIntroduction: Factors predicting response to adjuvant chemotherapy (AC) are required to identify patients who will most benefit from it. The aim of this study was to evaluate the impact of carcinoma in situ (CIS) at radical cystectomy (RC) on recurrence free survival (RFS), cancer specific survival (CSS) and overall survival (OS) of patients treated by AC. Materials and methods: A single-center retrospective study was performed on patients who received AC after RC without pre-RC chemotherapy or trimodal therapy. Results: Among the 150 patients analyzed, 52,7% had CIS on the RC specimens. Baseline characteristics were not significantly different between the CIS negative and positive groups. Most patients received a cisplatin-based AC (74%). The median follow-up of the cohort was 36,4 months. The presence of CIS was not significantly associated to disease-recurrence (OR = 0.67; 95%CI = 0.35–1.29; P = 0.23), cancer related death (OR = 0.70; 95%CI = 0.36–1.33; P = 0.27) or death by any cause (OR = 0.80; 95%CI = 0.42–1.52; P = 0.50). The presence of CIS had no significant impact on RFS (HR = 0.86; 95%CI = 0.56–1.33; P = 0.49), CSS (HR = 0.85; 95%CI = 0.53–1.36; P = 0.50) or OS (HR = 0.93; 95%CI = 0.60–1.45; P = 0.74). Conclusion: The presence of CIS on RC specimens did not have an impact on survival of patients treated by AC. CIS could be evaluated as a prognostic factor of response to novel adjuvant regimens such as immunotherapy.Il est nécessaire d’identifier les facteurs prédictifs de réponse à la chimiothérapie adjuvante (CA) pour mieux cibler les patients pouvant en bénéficier. L’objectif de cette étude était d’évaluer l’effet du carcinome in situ (CIS) sur la survie sans récidive (SSR), survie spécifique (SS) et survie globale (SG) de patients traités par CA après cystectomie.Matériel et méthodesUne étude monocentrique et rétrospective a été réalisée sur des patients traités par CA après cystectomie sans chimiothérapie ou traitement trimodal au préalable.RésultatsSur les 150 patients inclus, 52,7 % présentaient du CIS sur la pièce de cystectomie. Les caractéristiques des patients sans et avec CIS n’étaient pas significativement différentes. La plupart ont reçu une CA à base de cisplatine (74 %). Le suivi médian était de 36,4 mois. La présence de CIS n’était pas significativement associée à un risque de récidive (OR = 0,67 ; IC95 % = 0,35–1,29 ; p = 0,23), de décès par cancer (OR = 0,70 ; IC95 % = 0,36–1,33 ; p = 0,27) ou de décès toute cause (OR = 0,80 ; IC95 % = 0,42–1,52 ; p = 0,50). Elle n’avait pas d’influence significative sur la SSR (HR = 0,86 ; IC95 % 0,56–1,33 ; p = 0,49), SS (HR = 0,85 ; IC95 % = 0,53–1,36 ; p = 0,50) ou SG (HR = 0,93 ; IC95 % = 0,60–1,45 ; p = 0,74).ConclusionLa présence de CIS sur les pièces de cystectomies n’a pas d’impact significatif sur la survie après CA. Elle pourrait être évaluée pour les nouveaux traitements adjuvants telle que l’immunothérapie

The impact of carcinoma in situ in ureteral margins during radical cystectomy: A case-controlled study

International audienceBackground and objective: The presence of carcinoma in situ (Cis) in association with bladder cancer is associated with a poor prognosis. However, the prognosis associated with the presence of Cis in ureteral margins (CUM) during radical cystectomy has been poorly defined. To assess the prognosis associated with the presence of Cis in ureteral margins in patients with pM0 bladder cancer who have not undergone neoadjuvant chemotherapy. Materials and Methods: A retrospective case-control study was conducted between 2001 and 2016 using data from one academic center in France. From 1,450 radical cystectomies, 122 patients (case) who had CUM were matched according to age, sex, pTNM stage and urinary diversion method with a population sample of 122 patients (controls) who did not have Cis in ureteral margins during radical cystectomy. The survival analysis was performed by Kaplan-Meier using a (95%) CI. Multivariate Cox regression analysis was used to test the effect of CUM on cancer-specific survival. Recurrence-free survival was defined as a recurrence of urothelial carcinoma in the upper urinary tract. Results and limitations: The mean follow-up period was 55.43 ± 39.6 months. The rate of Cis in the bladder in the CUM cases group was evaluated at 11.47%. The median overall and specific survival was inferior in the CUM cases group estimated at 43.3 [35.33-56.93] months, 52.43 [42.16-68.93] months respectively compared to the control group with a significant difference (P= 0.001, P= 0.0039). The cumulative probability of urothelial recurrence-free survival was decreased in the case group compared with the control group (63.9% vs. 92.6%, P = 0.0001). Multivariate analysis shown that urothelial recurrence was associated with CUM [(P <0.001), (HR adjusted =11.31), (95% CI): (3.38-37.77)] and the macroscopic appearance of the ureter (thickened, dilated) [(P= 0.003), (HR adjusted =4.62), (95% CI): (3.31-8.84)]. Conclusion: CUM is a poor prognostic factor that impacts cancer-specific survival and Recurrence-free survival. The presence of CUM has been independently associated with a significant increase in the risk of urothelial recurrence, and a decrease in both overall and specific survival. This supports the use of frozen section analysis to complete radical cystectomy without CUM

Measured glomerular filtration rate (GFR) significantly and rapidly decreases after radical cystectomy for bladder cancer

International audiencePrecise determination of glomerular filtration rate (GFR) is essential for the management of patients with muscle-invasive bladder cancer (MIBC). We aim to describe the early evolution of measured GFR (mGFR) after radical cystectomy and urinary diversion (RCUD) and to identify risk factors for GFR decline. GFR measurement using 51Cr-EDTA continuous infusion, estimated GFR (eGFR) from five published equations and renal scintigraphy with split renal function determination were performed before and 6 months after RCUD. Chronic Kidney Disease (mGFR &lt; 60 mL/min/1.73 m2) and GFR stages were defined according to the KDIGO guidelines using mGFR. Twenty-seven patients (men 85%, median age 65, IQR 59; 68 years) were included. A total of 20 (74%) patients experienced significant mGFR decline at 6 months postoperatively. Median mGFR decreased from 84.1 pre-operatively (IQR 65.3; 97.2) to 69.9 mL/min/1.73 m2 (IQR 55.0; 77.9) 6 months after surgery (p &lt; 0.001). Thirteen (48%) patients had a progression to a worse GFR stage. Of the 22 patients without pre-operative CKD, 5 (23%) developed post-operative CKD. Diabetes mellitus was more frequent in patients in the highest tertile of relative mGFR decline (44% vs. 11%, p = 0.02) and platinum-based adjuvant chemotherapy tended to be more frequently used in these patients (44% vs. 17%, p = 0.06). Importantly, pre-operative weight was independently and negatively associated with post-operative mGFR and with mGFR slope in multivariable analyses. In this prospective series, we demonstrated that early and significant mGFR decline occurred after RCUD and perioperative platinum-based chemotherapy, especially in patients with diabetes mellitus and overweight

Safety and feasibility of laparoscopic nephrectomy for big tumors (•10 cm): a retrospective multicentric study

International audienceObjectiveEvaluate the feasibility of laparoscopic nephrectomy (LN) for big tumors.Material & MethodsData from 116 patients were retrospectively collected from 16 tertiary centres. Clinical and operative parameters, tumor characteristics, per and post operative parameters and renal function before and after surgery were analyzed.ResultsMean age and BMI were 61 y.o and 27.8 kg/m2, respectively. Males represented 63.8% and 54.4% presented symptoms at diagnosis. Median tumor size was 11 cm and 75% of the cases were performed by expert surgeons. Median operative time and blood loss were 180 min and 200ml respectively. Conversion to open surgery was necessary in 20.7%. Intra operative complications related to massive haemorrhage occurred in 16.4%, resulting in open conversion in 62.5%. Major postoperative complications occurred in only 10 patients (8.6%). In univariate analysis, intra operative complications, age and blood loss were predictive factors of conversion to open surgery. Positive surgical margins occurred in 6 patients (5.2%). None of them presented a local recurrence. Predictive factors of recurrence or progression were lymph node invasion, metastases and Furhman grade.ConclusionLN for tumors>10 cm can be performed safely. Complication rate and positive surgical margins are similar to open surgery. In experienced hands, the benefit of a mini invasive surgery remains evident

Prognostic impact of variant histologies in urothelial bladder cancer treated with radical cystectomy

Objectives: To evaluate variant histologies (VHs) for disease-specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC). Materials and Methods: We analysed a multi-institutional cohort of 1082 patients treated with upfront RC for cT1-4aN0M0 urothelial BCa at eight centres. Univariable and multivariable Cox’ regression analyses were used to assess the effect of different VHs on DSS in overall cohort and three stage-based analyses. The stages were defined as ‘organ-confined’ (≤pT2N0), ‘locally advanced’ (pT3-4N0) and ‘node-positive’ (pTanyN1-3). Results: Overall, 784 patients (72.5%) had pure urothelial carcinoma (UC), while the remaining 298 (27.5%) harboured a VH. Squamous differentiation was the most common VH, observed in 166 patients (15.3%), followed by micropapillary (40 patients [3.7%]), sarcomatoid (29 patients [2.7%]), glandular (18 patients [1.7%]), lymphoepithelioma-like (14 patients [1.3%]), small-cell (13 patients [1.2%]), clear-cell (eight patients [0.7%]), nested (seven patients [0.6%]) and plasmacytoid VH (three patients [0.3%]). The median follow-up was 2.3 years. Overall, 534 (49.4%) disease-related deaths occurred. In uni- and multivariable analyses, plasmacytoid and small-cell VHs were associated with worse DSS in the overall cohort (both P = 0.04). In univariable analyses, sarcomatoid VH was significantly associated with worse DSS, while lymphoepithelioma-like VH had favourable DSS compared to pure UC. Clear-cell (P = 0.015) and small-cell (P = 0.011) VH were associated with worse DSS in the organ-confined and node-positive cohorts, respectively. Conclusions: More than 25% of patients harboured a VH at time of RC. Compared to pure UC, clear-cell, plasmacytoid, small-cell and sarcomatoid VHs were associated with worse DSS, while lymphoepithelioma-like VH was characterized by a DSS benefit. Accurate pathological diagnosis of VHs may ensure tailored counselling to identify patients who require more intensive management

FGFR3 Mutation Status and FGFR3 Expression in a Large Bladder Cancer Cohort Treated by Radical Cystectomy: Implications for Anti-FGFR3 Treatment?†

Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer (BC). FGFR3 mutations are common in noninvasive BC and associated with favorable BC prognosis. Overexpression was reported in up to 40% of FGFR3 wild-type muscle-invasive BC. We analyzed FGFR3 mutations, FGFR3, and p53 protein expression and assessed their prognostic value in a cohort of 1000 chemotherapy-naive radical cystectomy specimens. FGFR3 mutations were found in 11%, FGFR3 overexpression was found in 28%, and p53 overexpression was found in 69% of tumors. Among FGFR3 mutant tumors, 73% had FGFR3 overexpression versus 22% among FGFR3 wild-type tumors. FGFR3 mutations were significantly associated with lower pT stage, tumor grade, absence of carcinoma in situ, pN0, low-level p53, and longer disease-specific survival (DSS). FGFR3 overexpression was associated only with lower pT stage and tumor grade. Moreover, FGFR3 overexpression was not associated with DSS in patients with FGFR3 wild-type tumors. In conclusion, FGFR3 mutations identified patients with favorable BC at cystectomy. Our results suggest that FGFR3 mutations have a driver role and are functionally distinct from FGFR3 overexpression. Hence, patients with FGFR3 mutations would be more likely to benefit from anti-FGFR3 therapy. Ideally, further research is needed to test this hypothesis. Patient summary: Oncogenic fibroblast growth factor receptor 3 (FGFR3) mutations are very common in bladder cancer. In this report, we found that these FGFR3 mutations were associated with favorable features and prognosis of bladder cancer compared with patients with FGFR3 overexpressed tumors only. As a consequence, patients with FGFR3 mutant tumors would be more likely to benefit from anti-FGFR3 therapy than patients with FGFR3 protein overexpression only. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved

Prognostic markers in invasive bladder cancer: FGFR3 mutation status versus P53 and KI-67 expression: a multi-center, multi-laboratory analysis in 1058 radical cystectomy patients

Objectives: To determine the association between the FGFR3 mutation status and immuno-histochemistry (IHC) markers (p53 and Ki-67) in invasive bladder cancer (BC), and to analyze their prognostic value in a multicenter, multi-laboratory radical cystectomy (RC) cohort. Patients and methods: We included 1058 cN0M0, chemotherapy-naive BC patients who underwent RC with pelvic lymph-node dissection at 8 hospitals. The specimens were reviewed by uro-pathologists. Mutations in the FGFR3 gene were examined using PCR-SNaPshot; p53 and Ki-67 expression were determined by standard IHC. FGFR3 mutation status as well as p53 (cut-off>10%) and Ki-67 (cut-off>20%) expression were correlated to clinicopathological parameters and disease specific survival (DSS). Results: pT-stage was <pT2 in 80, pT2 in 266, pT3 in 513 and pT4 in 199 patients, respectively. Cancer-positive nodes were found in 410 (39%) patients. An FGFR3 mutation was detected in 107 (10%) and aberrant p53 and Ki-67 expression in 718 (68%) and 581(55%) tumors, respectively. The FGFR3 mutation was associated with lower pT-stage (P<0.001), lower grade (P<0.001), pN0 (P=0.001) and prolonged DSS (P<0.001). Aberrant Ki-67 and p53 expression were associated with higher pT-stage and G3-tumors, but not with pN-stage or worse DSS, even if these IHC-biomarkers were combined (P=0.81). Significant predictors for DSS in multivariable analysis were pT-stage (HR1.5, 95%CI:1.3-1.6; P<0.001), lympho-vascular invasion (LVI) (HR1.4, 95%CI:1.2-1.7; P=0.001), pN-stage (HR1.9, 95%CI:1.6-2.4; P<0.001) and FGFR3 mutation status (HR1.6, 95%CI:1.1-2.2; P=0.011). Conclusion: The FGFR3 mutation selectively identified patients with favorable BC at RC while p53 and Ki-67 were only associated with adverse tumor characteristics. Our results suggest that, besides tumor-stage, nodal-status and LVI, the oncogenic FGFR3 mutation may represent a valuable tool to guide adjuvant treatment and follow-up strategies after RC