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Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette–Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment. Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety. Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to erdafitinib (n = 49) and chemotherapy (n = 24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6 months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy. Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy. • Erdafitinib prolonged RFS versus intravesical chemotherapy in papillary-only FGFR -altered BCG-treated high-risk NMIBC. • At median follow-up of 13.4 months, median RFS was not reached for erdafitinib and was 11.6 months for chemotherapy. • The observed RFS benefit for erdafitinib was further reflected by the 6- and 12-month RFS rates and subgroups tested. • In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy. • These trial results validate FGFR inhibition as a promising treatment approach for NMIBC. [ABSTRACT FROM AUTHOR]

The aim of this article is to describe the natural history and peculiarities of carcinogenesis of upper tract urothelial carcinoma (UTUC). A systematic review of the scientific literature was performed on the Medline database (Pub- Med) using different combinations of the following key words: upper tract urothelial carcinoma, clonality, carcinogenesis, mutation, chromosomal instability, Lynch syndrome, and genetic polymorphism. Local development of UTUC is characterized by a highly prevalent multifocality that might be explained by the overlap of 'field change' and 'intra-luminal seeding and implantation' theories. UTUC and bladder tumors share common carcinogenesis mechanisms, such as mutations of FGFR3 and TP53, defining two distinct pathways of pathogenesis. The estimated UTUC incidence is 1.2 cases/100,000 inhabitants per year in Europe. The incidence of renal pelvis tumor has been stable for 30 years, while the frequency of ureteral locations has increased over time. Locally advanced stage and high grade are more frequent factors at the time of diagnosis. The median age for diagnosis is 70 years. Male-to-female ratio is nearly 2. Main carcinogenic factors are tobacco consumption and occupational exposure. There are specific risk factors for UTUC, such as Aristolochic acid (Balkan nephropathy and Chinese herbes nephropathy). Furthermore, specific genetic risk factors for UTUC includes Lynch syndrome, and different polymorphisms might explain an individual's susceptibility for developing these tumors. [ABSTRACT FROM AUTHOR]

Résumé: Objectifs de l’étude: La radiothérapie prostatique est parfois responsable de séquelles vésicosphinctériennes qui peuvent nécessiter une prise en charge chirurgicale. L’objectif de cette étude était de rapporter les résultats obtenus après traitement chirurgical de l’incontinence urinaire post-radique. Patients et méthode: Les dossiers médicaux des patients traités par chirurgie pour des séquelles vésicosphinctériennes après radiothérapie prostatique entre septembre 2004 et février 2012 ont été revus rétrospectivement. Résultats: Au total, sept hommes âgés en moyenne de 70ans±4,1 ont été inclus. Le suivi moyen a été de 32,3mois±29 (3–86). Une cystectomie sustrigonale avec entérocystoplastie d’agrandissement a permis de traiter les troubles de complication urinaire post-radique dans tous les cas. Le taux de fistule vésicocutanée était de 33 %, avec un délai moyen de survenue de 18,5jours±2,1 (17–20). Les durées moyennes de sondage vésical et d’hospitalisation étaient respectivement de 16jours±8,4 (12–35) et de 18jours±7,8 (13–37). Dans cinq cas, il y a eu nécessité de recourir à l’implantation asynchrone d’un sphincter urinaire artificiel pour tarir les fuites urinaires persistantes. Le délai moyen entre la cystectomie sustrigonale avec entérocystoplastie d’agrandissement et l’implantation d’un sphincter urinaire artificiel a été de 27,6mois±26,4 (7–72). Conclusion: Le traitement chirurgical des séquelles vésicosphinctériennes post-radiques après irradiation de la prostate offre des résultats fonctionnels satisfaisants au prix d’une morbidité non négligeable qui doivent être proposés par des centres qui en ont l’expertise. [ABSTRACT FROM AUTHOR]

It is advocated that patients with high-risk non-muscle-invasive bladder cancer (NMIBC) receive an adjuvant course of intravesical Bacille Calmette-Guerin (BCG) as first-line treatment. However, a substantial proportion of patients will 'fail' BCG, either early with persistent (refractory) disease or recur late after a long disease-free interval (relapsing). Guideline recommendation in the 'refractory' setting is radical cystectomy, but there are situations when extirpative surgery is not feasible due to competing co-morbidity, a patient's desire for bladder preservation or reluctance to undergo surgery. In this review, we discuss the contemporary management of NMIBC in patients who have failed prior BCG and are not suitable for radical surgery and highlight the potential options available. These options can be categorised as immunotherapy, chemotherapy, device-assisted therapy and combination therapy. However, the current data are still inadequate to formulate definitive recommendations, and data from ongoing trials and maturing studies will give us an insight into whether there is a realistic efficacious second-line treatment for patients who fail intravesical BCG but are not candidates for definitive surgery. [ABSTRACT FROM AUTHOR]

Cancer of the prostate is the commonest form of cancer in the male and it is increasingly being diagnosed by screening at an earlier stage. This means that we should try to limit the side effects of surgical treatment as much as possible. Total prostatectomy is recognised as a procedure which is effective in treating the cancer but also for its high rate of complications (incontinence and erectile dysfunction) with a significant effect on the quality of life. Surgery has continued to develop less invasive techniques, first with the adoption of laparoscopy and now with the Da Vinci® system of robot-assisted surgery. In this article we aim to describe the results obtained with this treatment, both in removal of the cancer and on function. In the hands of a suitably trained surgeon, robot-assisted surgery can reduce the operative risk of bleeding and also shorten the hospital stay. The precision of its manoeuvrability facilitates dissection that spares the structures surrounding the prostate and seems to allow a rapid return of continence and possibly of erectile function when the neurovascular bundles are preserved. [ABSTRACT FROM AUTHOR]

Abstract: Five hundred and twenty one abstracts (26.51 %) were dedicated to prostate cancer during the 2007 annual meeting of the American Urological Association (AUA) which took place in Anaheim from 19-24th of May. The aim of the current article was to provide a summary of the most debated topics and to highlight the most original subjects in this specific field of urology. This year, the main topics of prostate cancer were diversified and concern notably : statin treatment, PSA kinetic, surgical margins, robotic surgery, molecular markers from bodily fluids and adjuvant therapy after surgery. [Copyright &y& Elsevier]

We compared the outcomes of robotic-assisted partial nephrectomy (RPN) and open partial nephrectomy (OPN) using contemporary data to respond to unmet clinical needs. Data from patients included in the registry who underwent partial nephrectomy between January 01, 2014 and June 30, 2017 within 20 centres of the French Network for Research on Kidney Cancer UroCCR were collected (NCT03293563). Statistical methods included adjusted multivariable analyses. Rates of peri- and post-operative transfusion, and of surgical revision, were lower in the RPN (n = 1434) than the OPN (n = 571) group (2.9% vs. 6.0%, p = 0.0012; 3.8% vs. 11.5%, p < 0.0001; 2.4% vs. 6.7%, p < 0.0001, respectively). In multivariable analyses, RPN was independently associated with fewer early post-operative complications than OPN (overall: odds-ratio [95% confidence interval, CI] = 0.48 [0.35–0.66]; severe: 0.29 [0.16–0.54], p < 0.0001 for both) and shorter hospital stays (34% [30%; 37%], p < 0.0001). RPN was also a significantly associated with a decresedrisk of post-operative acute renal failure, and new-onset chronic kidney disease at 3 and 12 months post-surgery. There were no between-group differences in oncological outcomes. In comparison with OPN, RPN was associated with improved peri- and post-operative morbidity, better functional outcomes, and shorter hospital stays. Our results support the use of RPN, even for large and complex tumours. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The objective of this study was to analyze, during a transversal study, the predictive sociodemographic and individual factors to be ranked within the first 500 medical students in the 2009 French national ranking exam (NRE). Methods: In September 2009, 5570 medical students have chosen their subspecialty. They were invited to fill-up a questionnaire that included sociodemographics and educational items. Logistic regression was used to identify factors that were associated with being ranked within the first 500 medical students. Results: A total of 4712 students (two third of women) responded to the questionnaire (92.3% response rate). The mean age of respondents was 24.7 years (±1.79). In the multivariate analysis, independent factors associated with being ranked within the first 500 medical students at the NRE were: being less than 25-year-old (odds ratio [OR]: 1.8; 95%CI: 1.3–2.5; P <0.001), region of origin (Île de France) (OR: 3.7; 95%CI: 2.3–5.8; P <0.0001), to succeed at the first medical year examination for the first time (OR: 1.7; 95%CI: 1.2–2.4; P <0.001), being in the first 20% of the medical students during externship (P <0.0001), critical reading test (CRT) teaching by graduate doctors (OR: 1.5; 95%CI: 1.05–2.1; P <0.001), and to participate in a national practicing ranking exam with a CRT (OR: 1.96; 95%CI: 1.3–3.03; P =0.002). Conclusion: Our study identified six factors independently associated with being ranked within the first 500 medical students in the French NRE. Education and training of the CRT, newly introduced test in 2009, seem to play an important role. [Copyright &y& Elsevier]

Objective: To perform an external validation of this RC-pentafecta. Method: Between January 2014 and December 2019, 104 consecutive patients who underwent RARC with ICUD within 6 urological centers were analyzed retrospectively. Patients who simultaneously demonstrated negative soft tissue surgical margins (STSMs), a lymph node (LN) yield ≥ 16, absence of major (Clavien–Dindo grade III–V) 90-day postoperative complications, absence of UD-related long-term sequelae, and absence of 12-month clinical recurrence were considered to have achieved RC-pentafecta. A multivariable logistic regression model was used to measure predictors for achieving RC-pentafecta. We analyzed the influence of this RC-pentafecta on survival, and the impact ofthe surgical experience. Results: Since 2014, 104 patients who had completed at least 12 months of follow-up were included. Over a mean follow-up of 18 months, a LN yield ≥ 16, negative STSMs, absence of major complications at 90 days, and absence of UD-related surgical sequelae and clinical recurrence at ≤ 12 months were observed in 56%, 96%, 85%, 81%, and 91% of patients, respectively, resulting in a RC-pentafecta rate of 39.4%. Multivariate analysis showed that age was an independent predictor of pentafecta achievement (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.90. 0.99; p = 0.04). The surgeon experience had an impact on the validation of the criteria. Conclusion: This study confirmed that the RC-pentafecta is reproducible and could be externally used for the outcome assessment after RARC with ICUD. Therefore, the RC-pentafecta could be a useful tool to assess surgical success and its impact on different outcomes. [ABSTRACT FROM AUTHOR]

La prise en charge des cancers de la prostate à haut risque a fortement évolué ces dernières années. Les progrès de l'imagerie permettent de mieux définir l'agressivité réelle de la maladie, de planifier le geste chirurgical, et d'améliorer l'évaluation pronostique de ces maladies à haut risque de récidive. Les informations obtenues par l'IRM et par les biopsies ciblées améliorent la prise en charge en amont de la chirurgie. Les progrès de la médecine nucléaire et la généralisation des TEP-scanographie au prostate-specific membrane antigen (PSMA) commencent à bouleverser l'étape initiale diagnostique, et améliorent la détection des métastases ganglionnaires et à distance. L'intérêt oncologique de ces nouvelles imageries, qui influencent ensuite le plan thérapeutique, reste à définir. L'impact curatif d'un curage ganglionnaire étendu, comme recommandé à l'heure actuelle, reste à prouver et les essais randomisés récemment publiés ne permettent pas de conclure. Les nouvelles hormonothérapies ouvrent la voie à une intensification du traitement systémique périopératoire, avec une action réelle sur le tissu tumoral, mais un impact en survie qui reste à définir dans le cadre d'essais randomisés en cours. The management of high-risk prostate cancer has greatly evolved in recent years. Advances in imaging helps to better define the actual aggressiveness of the disease, to plan the surgical procedure, and to improve the prognostic evaluation of this high-risk of recurrence disease. The information obtained by MRI and by targeted biopsies improves management before surgery. Advances in nuclear medicine and generalization of PSMA-PET scans are beginning to improve the initial stage of diagnosis, thanks to a better detection of lymph node and distant metastases. The oncological interest of these new imaging techniques, which then influence the therapeutic plan, remains to be defined. The curative impact of an extensive lymph node dissection, as currently recommended, remains to be proved, and recently published randomized trials do not provide firm conclusions. The new hormone therapies pave the way for an intensification of perioperative systemic treatment, with a significant action on the tumor tissue, but an impact on survival, which remains to be defined in the context of ongoing randomized trials. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to determine the significance of androgen receptor (AR) expression in urothelial carcinoma of the upper urinary tract (UTUC). Methods: AR expression was assessed on tissue microarrays containing specimens of 737 patients with UTUC who underwent radical nephroureterectomy with curative intent. AR expression was correlated with clinical and pathological tumor features as well as recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Results: Overall, AR was expressed in 11 % of tumors. AR expression was significantly associated with tumor necrosis as well as sessile and multifocal tumor growth but not with RFS, CSS or OS. AR was detected nearly twice as often in tumors of the ureter than of the pelvicalyceal system ( p = 0.005). Subgroup analyses showed that the significant associations of AR with unfavorable pathologic features were exclusively attributable to tumors located in the ureter. However, in both ureteral and pelvicalyceal tumors, AR status was independent of RFS, CSS and OS. Conclusions: In this cohort of patients treated with RNU, AR expression was found in approximately 10 % of UTUCs, twice as often in ureteral than in pelvicalyceal tumors. While AR expression had no impact on postoperative prognosis, it was significantly associated with unfavorable pathologic features in ureteral tumors. Steroid hormone signaling might be relevant for future investigations of differences between ureteral and pelvicalyceal tumors. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of hospital volume on partial nephrectomy indications and outcomes. Materials and methods: Data were extracted from the National Observational Registry on the Practice and Hemostasis in Partial Nephrectomy registry. Four groups were created according to the number of partial nephrectomy (PN) performed: very high (VH, ≥19 PN), high (H, 10-18 PN), moderate (M, 4-9 PN) and low (L, <4 PN) PN activity. Indications and surgical outcomes were compared among all groups. The effect of hospital volume on postoperative complications and positive margin rate was examined by a multivariable analysis. Results: Fifty-three centers included a total of 570 PN. There were 9 VH, 13 H, 12 M and 19 L volume centers which performed 270 (47.4 %), 179 (31.4 %), 74 (13 %) and 47 (8.2 %) PN, respectively. Patients in higher volume centers were significantly younger ( p = 0.008), had a lower BMI ( p = 0.002) and decreased ASA score ( p < 0.001). PN was more frequently performed in higher volume centers ( p = 0.006) particularly in case of renal masses <4 cm ( p = 0.005). Open surgery was the most common approach in all groups, but laparoscopic PN was more frequent in M volume hospitals ( p < 0.001). Positive margin ( p = 0.06) and complications ( p = 0.022) rates were higher in M group. In multivariable analysis, renal chronic disease was an independent predictor of positive margin rate ( p < 0.001, OR 3.91). Conclusions: PN is more frequently performed in high volume institutions particularly for small renal masses. We observed increase positive margin and complication rates in moderate volume centers that might be explained by an increased use of laparoscopy. [ABSTRACT FROM AUTHOR]

Résumé: Propos: Analyser les résultats du système de gestion et d’analyse des publications scientifiques (SIGAPS) au sein de l’Assistance publique–Hôpitaux de Paris (AP–HP) et comparer la production scientifique entre les différentes disciplines médicales et chirurgicales du CHU de Paris. Méthodes: Toutes les publications importées par SIGAPS depuis PubMed entre 2006 et 2008 ont été incluses. Les données suivantes ont été prises en compte et analysées : service hospitalier d’origine, nombre d’articles publiés, nombre de titulaires dans l’unité, score SIGAPS. Résultats: Au total, 38 709 publications ont été analysées. Les 747 services étaient composés de 5719 titulaires (1895 [33,1 %] PU–PH, MCU ou PHU ; 2772 [48,4 %] PH et 1052 [18,4 %] CCA ou AHU). Le nombre moyen de titulaires par service était de 7,7±6,7 (min-max : 1–69). La moyenne du nombre total de publications par service était de 51,8±49,4 (min-max : 1–453). Le score SIGAPS moyen était plus important en médecine qu’en chirurgie (621,2±670,1 vs. 401±382,2 ; p =0,01) mais pas le nombre moyen d’article par titulaires entre ces deux filières (8,1±8,3 en médecine vs. 6,6±6,2 ; p =0,08). Le nombre de moyen de publication par temps plein était de 7,9±7,8 (1–45), soit un nombre moyen de 2,7±2,6 par temps plein et par an. Conclusion: L’AP–HP a une production scientifique relativement importante mais avec un nombre moyen de 2,7 articles par temps plein par an. Il n’existait pas de différence notable entre les disciplines médicales et chirurgicales. [ABSTRACT FROM AUTHOR]

Background:Owing to the scarcity of upper urinary tract urothelial carcinoma (UUT-UC) it is often necessary for investigators to pool data. A patient-specific survival nomogram based on such data is needed to predict cancer-specific survival (CSS) post nephroureterectomy (NU). Herein, we propose and validate a nomogram to predict CSS post NU.Patients and methods:Twenty-one French institutions contributed data on 1120 patients treated with NU for UUT-UC. A total of 667 had full data for nomogram development. Study population was divided into the nomogram development cohort (397) and external validation cohort (270). Cox proportional hazards regression models were used for univariate and multivariate analyses and to build a nomogram. A reduced model selection was performed using a backward step-down selection process, and Harrell's concordance index (c-index) was used for quantifying the nomogram accuracy. Internal validation was performed by bootstrapping and the reduced nomogram model was calibrated.Results:Of the 397 patients in the nomogram development cohort, 91 (22.9%) died during follow-up, of which 66 (72.5%) died as a consequence of UUT-UC. The actuarial CSS probability at 5 years was 0.76 (95% CI, 71.62-80.94). On multivariate analysis, T stage (P<0.0001), N status (P=0.014), grade (P=0.026), age (P=0.005) and location (P=0.022) were associated with CSS. The reduced nomogram model had an accuracy of 0.78. We propose a nomogram to predict 3 and 5-year CSS post NU for UUT-UC.Conclusion:We have devised and validated an accurate nomogram (78%), superior to any single clinical variable or current model, for predicting 5-year CSS post NU for UUT-UC. [ABSTRACT FROM AUTHOR]