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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.

Bladder cancer detection and follow-up is based on cystoscopy and/or cytology, but it remains imperfect and invasive. Current research focuses on diagnostic biomarkers that could improve bladder cancer detection and follow-up by discriminating patients at risk of aggressive cancer who need confirmatory TURBT (Transurethral Resection of Bladder Tumour) from patients at no risk of aggressive cancer who could be spared from useless explorations.To perform a systematic review of data on the clinical validity and clinical utility of eleven urinary biomarkers (VisioCytAll available studies on the 11 biomarkers published between May 2010 and March 2021 and present in MEDLINEMost studies on urinary biomarkers had a prospective design and high level of evidence. However, their results should be interpreted with caution given the heterogeneity among studies. Most of the biomarkers under study displayed higher detection sensitivity compared with cytology, but lower specificity. Some biomarkers may have clinical utility for NMIBC surveillance in patients with negative or equivocal cystoscopy or negative or atypical urinary cytology findings, and also for recurrence prediction.Urinary biomarkers might have a complementary place in bladder cancer diagnosis and NMIBC surveillance. However, their clinical benefit remains to be confirmed.

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.

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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

Precise 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 2) 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

OBJECTIVES To compare the oncological outcomes of percutaneous cryoablation (PCA) vs robot-assisted partial nephrectomy (RAPN) for the treatment of T1 renal tumours. PATIENTS AND METHODS We conducted a retrospective study in all patients treated by RAPN or PCA for malignant renal tumours in one of four centres between 2009 and 2016. Tumours were paired one by one using radiological tumour stage and RENAL nephrometry score (package matchit, R software version 3.2.2). Malignancy was confirmed by biopsy for all patients in the PCA group. Patient characteristics before and after matching and oncological results were compared between the two groups. Cox regression, adjusted for age, treatment type, histological type and margins, was used to identify factors associated with time to local recurrence. Positive margins were defined histologically in the RAPN group and radiologically in the PCA group. RESULTS A total of 647 patients were identified; 470 underwent RAPN and 177 underwent PCA. After matching, there was no significant difference between the two groups (RAPN, n = 177; PCA, n = 177) with regard to tumour stage, RENAL nephrometry score, tumour size (27.6 vs 25.9 mm; P = 0.07) and gender ratio. Patients in the PCA group remained significantly older (69.9 vs 59.8 years; P < 0.001). The absolute recurrence rate was 2.8% in the RAPN group vs 8.4% in the PCA group (P = 0.03). The 5-year recurrence-free survival rate was 85% in the PCA group vs 95% in the RAPN group (log-rank P = 0.02). In multivariate analysis, the presence of positive margins and the type of treatment were the two factors significantly associated with local recurrence (P < 0.001 and P = 0.046, respectively). CONCLUSION The local recurrence rate after PCA was significantly higher than after RAPN for T1 renal tumours. Incomplete treatment was the main criterion associated with recurrence. The recurrence rate may have been overestimated in the PCA group because of closer radiological follow-up in these patients.

Objective: Fibroblast growth factor receptor 3 (FGFR3) is a potentially actionable target in bladder cancer (BC). FGFR3 mutations are associated with favorable prognosis in non-muscle invasive (NMI) BC and MIBC. Overexpression of FGFR3 was reported in up to 40% of FGFR3 wild-type MIBC. p53 alterations rarely coincide with FGFR3 mutations. We analyzed FGFR3 mutations and protein-expression of FGFR3 and p53 and assessed their prognostic value in a multicenter, multilaboratory setting. Methods: We included 1,000 cN0M0, chemotherapy-naive patients who underwent radical cystectomy (RC) with pelvic node dissection. Specimens were reviewed by eight uropathologists. At seven laboratories, FGFR3 mutation status was examined using PCR-SNaPshot. p53 and FGFR3 expression were determined by immunohistochemistry (IHC). FGFR3 mutation status, p53 and FGFR3 protein expression were correlated to each other, clinicopathologic parameters, and disease-specific survival (DSS). Results: FGFR3 mutations were found in 107/1,000 RCs (11%), of which 67 were S249C. Overexpression of FGFR3 was found in 279/1,000 (28%) of tumors. p53 overexpression (cut-off>10%) was found in 638/926 (69%) of available cases. Among FGFR3 mutant tumors, 73% had FGFR3 overexpression. Among FGFR3 wild-type tumors, 22% had FGFR3 overexpression. FGFR3 mutations were associated with lower pT-stage (P Conclusions: FGFR3 mutations identified patients with favorable BC with fewer p53 alterations at RC. FGFR3 overexpression was not associated with DSS in patients with FGFR3 wild-type tumors. Our results suggest that FGFR3 mutations (driver effect) have a distinct functional role than FGFR3 overexpression (passenger effect). Hence, patients with FGFR3 mutations may be more likely to benefit from anti-FGFR3 therapy than patients with only overexpression of FGFR3. Citation Format: Bas van Rhijn, Laura Mertens, Roman Mayr, Peter Bostrom, Mirari Marques, Geert van Leenders, Stefanie Gotz, Michiel van der Heijden, Michael Jewett, Francisco Real, Robert Stohr, Alexandre Zlotta, Markus Eckstein, Yanish Soorojebally, Max Burger, Wolfgang Otto, Francois Radvanyi, Damien Pouessel, Theo van der Kwast, Nuria Malats, Arndt Hartmann, Yves Allory, Deric van der Schoot, Ellen Zwarthoff, Tahlita Zuiverloon. FGFR3 mutations and their relation to FGFR3 expression and clinical outcome in a large radical cystectomy cohort: Implications for anti-FGFR3 bladder cancer treatment? [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B23.

Objectifs La cryotherapie per cutanee pourrait etre une alternative therapeutique a la nephrectomie partielle qui est le traitement de reference des tumeurs renales de moins de 4 cm. L’objectif de cette etude etait de comparer les resultats oncologiques de la cryotherapie par rapport a la tumorectomie robot assistee pour le traitement des tumeurs renales de stade T1. Methodes Les patients traites par tumorectomie robot vs cryotherapie pour tumeur renale maligne dans 4 centres entre 2009 et 2016 ont ete inclus retrospectivement. Les deux groupes furent appareilles un pour un sur le stade tumoral radiologique et le score RENAL (package Matchit, R software version 3.2.2). Tous les patients du groupe cryo ont ete biopsies. Les caracteristiques des patients avant et apres match ainsi que les resultats oncologiques ont ete compares entre les deux groupes. Une regression de Cox ajustee sur l’âge, le type de traitement, le type histologique et les marges a ete conduite pour identifier les facteurs associes a la recidive locale. Les marges positives etaient definies histologiquement dans le groupe robot et radiologiquement dans le groupe cryo. Resultats Au total, 647 patients ont ete identifies, 470 robots et 177 cryo. Apres appariement, on ne retrouvait pas de difference significative entre les deux groupes (177 robot et 177 cryo) pour le stade tumoral, le score RENAL, la taille tumorale (27,6 vs 25,9, p = 0,07), et le sexe. L’âge des patients du groupe cryo restait significativement superieur (69,9 vs 59,8 ans, p p = 0,03). La survie sans recidive a 5 ans etait de 85 % dans le groupe cryo vs 95 % dans le groupe robot ( log rank p = 0,02, Fig. 1 ). En analyse multivariee, seule la presence de marges positives etait significativement associee a la recidive locale ( p Conclusion Le taux de recidive locale apres cryotherapie etait significativement plus eleve qu’apres tumorectomie robot pour tumeur renale de stade T1. La realisation d’un traitement incomplet etait le principal critere associe a la recidive. Le taux de recidive pourrait etre surestime dans le groupe cryo en raison d’un suivi radiologique plus strict.

International audience; Objective - Evaluate the feasibility of laparoscopic nephrectomy for big tumors. Material and methods - Data from 116 patients were retrospectively collected from 16 tertiary centres. Clinical and operative parameters, tumor characteristics, pre- and postoperative parameters, and renal function before and after surgery were analyzed. Results - Mean age and body mass index were 61 years and 27.8 kg/m(2), respectively. Males represented 63.8% of patients, 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 minutes and 200 mL respectively. Conversion to open surgery was necessary in 20.7% of cases. Intraoperative complications related to massive hemorrhage occurred in 16.4% of patients, resulting in open conversion in 62.5%. Major postoperative complications occurred in only 10 patients (8.6%). In univariate analysis, intraoperative 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. Conclusion - Laparoscopic nephrectomy 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.