[Surgical treatment of metastatic urothelial carcinoma of the bladder: Review of the Cancer Committee of the French Association of Urology]. / Traitement chirurgical du carcinome urothélial de vessie métastatique : revue du Comité de cancérologie de l'Association française d'urologie.

INTRODUCTION: The role of surgery in the treatment of patients with metastatic urothelial bladder cancer is controversial. The aim was to review situations where surgical resection of the bladder tumor and/or metastatic urothelial carcinoma has been reported and analyze its results. MATERIALS AND METHODS: A bibliographic research in French and English using the keywords BCG, bladder cancer, metastases, cystectomy, metastasectomy, radiotherapy, curative treatment and palliative treatment was performed, 177 articles have been reviewed, and 18 have been selected. RESULTS: Synchronous or metachronous urothelial carcinoma metastases were diagnosed in 4 and 50% of the cases, respectively. The surgical treatment of metastatic urothelial carcinoma of the bladder has been proposed to achieve oncologic resection of all detectable lesions after a first-line chemotherapy or to treat symptoms, which were refractory to other treatment modalities. In achieving complete resection of the primary tumor and metastases after MVAC chemotherapies, the 5years overall survival was 28%. CONCLUSION: There was no evidence in favouring surgical treatment of metastatic urothelial carcinoma. Considering the high perioperative mortality rate of cystectomy in imperative indications, particularly in the case of hematuria, all therapeutic alternatives must have been exhausted and urine derived in the simplest way.

[Bacillus Calmette-Guerin maintenance treatment in non-invasive bladder tumors: 1 year follow-up results of multicenter URO-BCG-4 trial]. / Traitement d'entretien par BCG-thérapie des tumeurs de vessie n'infiltrant pas le muscle (TVNIM): résultats à un an de l'étude multicentrique URO-BCG-4.

INTRODUCTION: Intravesical instillations of BCG remains the gold standard for intermediate and high risk NMIBC management. Maintenance treatment is recommended, however, the frequency of side effects responsible for the discontinuation of maintenance therapy over four out of five patients before the third year suggest a reduction or even spacing instillations. The objective of the study URO-BCG-4 was the evaluation of a new maintenance schedule by intravesical instillations of BCG combined reduced dose (third dose) and a decrease number of instillations per cycle (two or three). MATERIAL AND METHODS: Multicenter study of the French Association Oncologic Committee (12 university hospital centers), randomized, prospective, comparing reference diagram of BCG maintenance therapy one third of usual dose (group I) to a regimen combining third dose and decrease the number of instillations per cycle (two instead of three) (group II). We present the preliminary results at 1year of this Program of Clinical Research (CHU Rouen Promoter 2003-081). RESULTS: The rate of recurrence was respectively 9 and 7% (P=0.678) in groups I and II. The rate of tumor progression are 3 and 2.8% in groups I and II (P=1). Tolerance of intravesical instillations of BCG scored according to the WHO classification (Geneva 1979) was similar in the two groups. CONCLUSION: The decrease in the BCG dose (third dose) and the changes in the number and rate of instillations did not alter free tumor recurrence survival. The toxicity of intravesical instillations of BCG was identical in both groups. The use of the WHO classification has shown its limitations in the study of side effects of BCG as too complex and often not exhaustive. The rate of increase muscle was comparable in the two groups; however, a larger clinical experience is required.

[Primary angiosarcoma of the kidney: case report and literature review]. / Angiosarcome primitif du rein : à propos d'un cas et revue de la littérature.

The primary angiosarcoma of the kidney is a rare tumor. We report a case of angiosarcoma of the right kidney in a man of 60 years. The CT-scan appearance is the one of a solid tumor compatible with renal cell carcinoma. Histological examination of the piece of nephrectomy straightens diagnosis and reveals the angiosarcomatous nature. In this patient with bone and lung synchronous metastasis, evolution has been a lightning death in less than three months. The literature review confirms the high potential of malignancy of these tumors (metastases almost constant and very short survival in spite of local and systemic treatment).

[Diagnosis and management of adverse events occuring during BCG therapy for non-muscle invasive bladder cancer (NMIBC): review of the Cancer Committee of the French Association of Urology]. / Diagnostic et prise en charge des événements indésirables survenant au décours des instillations endovésicales de BCG pour le traitement des tumeurs de vessie n'infiltrant pas le muscle (TVNIM) : revue du comité de cancérologie de l'Association française d'urologie.

INTRODUCTION: Intravesical BCG immuno-therapy with maintenance therapy is considered as the standard treatment for non-muscle invasive bladder cancer with high risk of recurrence and progression. In practice, adverse events (AEs) of BCG therapy could restrict its prescription by urologists. The aim of this article was to present a review of these AEs and of their management. MATERIALS AND METHODS: A bibliographic research in French and English using Medline(®) and Embase(®) with the keywords "BCG", "bladder", "complication", "toxicity", "adverse reaction", "prevention" and "treatment" was performed. RESULTS: The main mechanism of AEs of BCG are infectious (cystitis, fever), immuno-allergic (granulomatous prostatitis, epididymo-orchitis, and granulomatous reactions) and auto-immune (arthralgies, rash). Management of AEs is based on their pathophysiological mechanisms. Classifications of BCG therapy AEs based on clinical features allow to adapt their treatments. CONCLUSION: The combination of antibiotics directed against BCG, steroid or non-steroidal anti-inflammatory medication and symptomatic treatment is currently the triad on which is set up the appropriate treatment of severe AEs. Reductions of BCG doses and ofloxacin medication after instillation decrease the frequency and severity of minor and moderate AEs. Severe or more than 7 days long infectious AEs, immuno-allergic AEs or auto-immune during more than 7 days impose cessation of BCG immuno-therapy.

[Chemoradiotherapy for muscle-invasive cancer: methods, surveillance and results. An update from the cancer committee of the French National Association of Urology]. / Radiochimiothérapie pour le traitement des cancers de vessie infiltrant le muscle: modalités, surveillance et résultats. Mise au point du comité de cancérologie de l'Association française d'urologie.

Radical cystectomy is the treatment of choice for non-metastatic, muscle infiltrating bladder cancer. However, bladder-sparing approaches can be discussed in carefully selected patients. Bladder-preservation protocols aim to guaranty local control and survival with a functional bladder and a good quality of life. The ideal candidate for bladder-preservation therapy is a patient with a small tumor, stage T2, in whom a complete trans-urethral resection of the bladder tumor is achievable, who has no associated carcinoma in situ or hydronephrosis, and who is medically fit to receive chemotherapy. The 5- and 10-year survival rates for muscle-invasive tumors are approximately 50% and 35%, comparable to the results achievable with cystectomy. Approximately 80% of long-term survivors will preserve a native bladder, and approximately 75% of them will have a normal-functioning bladder.

[Benefit of bladder and upper urinary tract urothelial tumors lymph node dissection: review from the Bladder Cancer Committee of the French National Association of Urology ("CC-AFU Vessie")]. / Intérêt du curage ganglionnaire dans les tumeurs urothéliales infiltrantes de la vessie (TVIM) et de la voie excrétrice supérieure (TVES) : article de revue du Comité de cancérologie de l'Association française d'urologie.

INTRODUCTION: Lymph node dissection during radical cystectomy or nephroureterectomy confers improved prognosis and eventually therapeutic advantage. The aim of this update is to clarify the anatomical limits of the lymph node dissection, imaging related techniques, possible difficulties related to pathological analysis, its prognostic value and adjuvant treatments. METHOD: A literature review was performed using PubMed database with a combination of the following keywords: "urothelial carcinoma", "lymph node excision", "imaging", "pathology analysis", "prognosis", "chemotherapy" and "radiotherapy". RESULTS: Regarding bladder tumours, extended lymph node dissection is usually performed up to the division of the iliac vessels and the crossing of the ureters. The CT scan is the recommended imaging technique for lymph node staging but its sensitivity is low. Pathological examination should include perivesicle lymph nodes analysis and report the number of normal and metastatic lymph nodes separately. The prognosis is correlated to the total number of lymph nodes removed and to the extent of the excision. The lymph node density (number of metastatic nodes/normal nodes) is the most important prognosis factor. Adjuvant chemotherapy has not demonstrated a clear advantage. Its most efficient modality is a combination including cisplatin. For upper urinary tract tumours, lymph node dissection may have an impact on survival but definitive conclusion is limited by the lack of surgical technique and indications standardisation. CONCLUSION: Extended lymph node dissection improves survival of bladder cancer and prognosis assessment that could eventually be used to stratify patient requiring adjuvant treatment (level of evidence 3). Improvement on survival was also suggested for upper urinary tract tumors (level of evidence 4).

[Intradiverticular bladder tumours: review of the Cancer Committee of the French Association of Urology]. / Tumeurs de vessie intradiverticulaires: revue du Comité de cancérologie de l'Association française d'urologie.

INTRODUCTION: Cancer Committee of the French Association of Urology (CCAFU) conducted a review of the epidemiology, diagnosis and treatment of intradiverticular bladder tumours (TVID) and proposed therapeutic management. MATERIAL AND METHODS: A bibliographic research in French and English using Medline(®) with the keywords "tumor", "bladder" and "diverticulum" was performed. RESULTS: TVID are more frequently of stage T ≥ 3a and with non urothelial histology than classical bladder tumors. At diagnosis, the risk of underestimation of the extent and multifocality of the tumor was described. Their prognosis, that was more pejorative than conventional tumors, should impelled to limit the indications of conservative treatment. The evidence levels of analyzed publications were low, with C level according to Sackett score. CONCLUSION: the specificities of the TVID have lead the CCAFU to propose specific therapeutic guidelines, based on poor evidence level. Ta-T1 low grade TVID can be treated by transurethral resection alone or followed by BCG therapy in cases of associated carcinoma in situ. High-grade TVID, unifocal and without associated carcinoma in situ, can be treated by diverticulectomy associated with pelvic lymphadenectomy. High grade TVID, multiple or associated with carcinoma in situ, warranted total cystectomy.

Combination of gemcitabine and doxorubicin in rapidly progressive metastatic renal cell carcinoma and/or sarcomatoid renal cell carcinoma.

BACKGROUND/AIMS: Metastatic renal cell carcinoma (mRCC) can be rapidly progressive when tumors exhibit sarcomatoid or Fuhrman grade 4 features. Efficacy of gemcitabine (Gem) with doxorubicin (Dox) in sarcomatoid or rapidly progressive mRCC has been reported. We retrospectively evaluated Gem + Dox in a consecutive cohort of this particular patient population. PATIENTS AND METHODS: Patients had an Eastern Cooperative Oncology Group performance status of 2 or more and rapidly progressive mRCC or mRCC with sarcomatoid features. Gem (1,500 mg/m(2)) and Dox (50 mg/m(2)) were given every 2 weeks with granulocyte colony-stimulating factor. RESULTS: Twenty-nine patients were treated. Sarcomatoid features were predominant in 6 patients, while 14 tumors were Fuhrman grade 4. All patients had progressive mRCC within 4 months. No grade 4 toxicity or drug-related death was reported. One partial response (7 months), 1 mixed response, and 14 stable diseases (≥4 months for 9 patients) were observed and no response was seen in sarcomatoid tumors. The median disease-free survival was 3.7 months (≥6 months for 8 patients) and the median overall survival was 4.8 months (>12 months for 5 patients). CONCLUSION: This study showed a lower response rate than previously reported. Nevertheless, some patients had prolonged survival outcomes. This combination could be an option in sarcomatoid histology (NCCN guidelines) or rapidly progressive disease, but this population represents an unmet medical need.

[Diagnostic test for bladder cancer: the NMP22®]. / Actualités urologiques concernant les tests diagnostiques utilisés pour les tumeurs de vessie: le NMP22.

INTRODUCTION: Diagnosis and follow-up of bladder cancer is based on cytology and cystoscopic exams. Cytology is highly specific but remains with a highly variable sensitivity. Cystoscopy is an invasive exam and has shown specific limits. Urinary test, highly specific and highly sensitive, might be ideal to replace the couple cytology-cystoscopy. MATERIAL AND METHODS: Through a literature review, using MeSH system and Pubmed system (keywords: NMP22 and bladder cancer), authors pointed to the value of NMP22 to replace cystoscopy and cytology. RESULTS: Between 1996 and 2010, 193 publications were identified with these keywords. Seventeen original articles have been selected based on their quality and methodology. NMP22 was more sensitive than cytology for follow-up and screening of bladder cancer. As screening test, NMP22 has shown positive predictive value between 0 and 70%. As follow-up test, NMP22 has shown more stable positive predictive value close to 70%. Coupled to cytology, NMP22 has shown predictive positive value up to 90%. CONCLUSION: For screening test, NMP22 should be the referent test for best selection cases (tobacco, hematuria) and for systemic elimination of false positive cases (ureteral stent, lithiasis). For follow-up test, NMP22-cytology should be the new reference. Moreover, when NMP22 is positive with negative cystoscopy, follow-up may be carefully proposed (recurrence risk×10).

[The role and method of fluorescence-guided cystoscopy in 2011 for management of bladder cancer: Review of the Oncology Committee of the French Urology Association]. / Intérêt et modalités pratiques de la cystoscopie de fluorescence en 2011 pour la prise en charge des carcinomes urothéliaux de la vessie : une revue du Comité de cancérologie de l'Association française d'urologie.

AIM: Fluorescence-guided cystoscopy is a useful tool for bladder tumour detection in association with white-light cystoscopy and decreases the residual tumour rate. The aim of the study was to provide an overview of the pertinent literature on this subject. MATERIALS AND METHODS: The data were provide from a Medline(®) research by using the follow keywords: urinary bladder neoplasms; cystoscopy; fluorescence; prognosis; intraepithelial neoplasm. RESULTS: No evidence 1 level data was available. The fluorescence-guided cystoscopy improves the bladder cancer detection rate, especially the flat lesions, and improve the recurrence-free survival by decreasing the residual tumour rate. The specific indications for fluorescence-guided cystoscopy in the diagnosis and management of non-muscle invasive bladder cancer (NMIBC) should benefit the patients. CONCLUSION: The fluorescence-guided cystoscopy is a benefical tool in association with white-light cystoscopy in NMIBC diagnosis. It has been shown to have a positive impact on recurrence-free survival but not on progression-free survival. More investigations with significant follow-up should be lead in the future to accurately assess its therapeutic impact on patients.

Embolization of polycystic kidneys as an alternative to nephrectomy before renal transplantation: a pilot study.

In autosomal polycystic kidney disease, nephrectomy is required before transplantation if kidney volume is excessive. We evaluated the effectiveness of transcatheter arterial embolization (TAE) to obtain sufficient volume reduction for graft implantation. From March 2007 to December 2009, 25 patients with kidneys descending below the iliac crest had unilateral renal TAE associated with a postembolization syndrome protocol. Volume reduction was evaluated by CT before, 3, and 6 months after embolization. The strategy was considered a success if the temporary contraindication for renal transplantation could be withdrawn within 6 months after TAE. TAE was well tolerated and the objective was reached in 21 patients. The temporary contraindication for transplantation was withdrawn within 3 months after TAE in 9 patients and within 6 months in 12 additional patients. The mean reduction in volume was 42% at 3 months (p = 0.01) and 54% at 6 months (p = 0.001). One patient required a cyst sclerosis to reach the objective. The absence of sufficient volume reduction was due to an excessive basal renal volume, a missed accessory artery and/or renal artery revascularization. Embolization of enlarged polycystic kidneys appears to be an advantageous alternative to nephrectomy before renal transplantation.

[Chemotherapy in early stage of hormone-resistant metastatic prostate cancer: what are the indications?]. / Chimiothérapie en phase précoce d'hormonorésistance des cancers de prostate métastatiques: quelles indications?

Treatment of hormone-refractory prostate cancer remains a source of debate. Since 2004, docétaxel-based chemotherapy has become the standard treatment as it has demonstrated efficacy on overall survival in two randomized studies. In some studies, chemotherapy seems to be also effective on pain relief. The adverse effects occur more frequently than with others chemotherapy (mitoxantrone) but are moderated and aren't responsible of specific mortality. These facts encourage to begin the chemotherapy as earlier as possible even before metastases appear. Some studies have even raised the issue of an initiation of chemotherapy before the onset of hormone independence. However these arguments might be use with caution. The treated patients have a limited life expectancy and a 2 months gain of survival may be of limited value. Furthermore, even low side effects can generate a morbidity on these fragile patients especially when they are initially asymptomatic. Thus, an early initiation of chemotherapy must be discussed case by case, on an individual basis. The prognosis factors and alternative therapeutic options based on new molecules used in metastatic cancer might also be considered for the therapeutic decision.

[Checkup and management of upper urinary tract tumours in 2010: An update from the committee of cancer from the French National Association of Urology]. / Bilan et prise en charge d'une tumeur de la voie excrétrice urinaire supérieure en 2010 : mise au point du comité de cancérologie de l'Association francaise d'urologie.

Urothelial carcinoma of the upper urinary tract (UUT-UCC) are rare tumours and represent about 5 % of urothelial tumours. There is a history of bladder cancer in 30 % of patients with UUT-UCC but less than 2 % of patients with bladder cancer have a location in the upper urinary tract. The main prognostic factors are age, grade and tumour stage. A High-MSI status is predictive of improved survival, especially in patients under 70years with invasive tumour. During the preoperative assessment, improved staging of UUT-UCC is now essential. The couple urine cytology and uro-CT is an element of staging that underestimates or overestimates some UUT-UCC. The diagnostic ureteroscopy has become a fundamental step in the preoperative evaluation of the tumour. Ureteroscopy allows to explore visually at least 95 % of the upper urinary tract and to perform biopsies of the tumour that help to determine the grade cell. It can also detect a possible secondary location unnoticed with imaging. An exhaustive preoperative assessment, including a systematic diagnostic ureteroscopy, should allow to explore UUT-UCC in a better manner and to increase the number of potential candidates for conservative treatment. The treatment of choice is currently nephroureterectomy with open approach. Superficial and/or low-grade UUT-UCCs have favourable outcomes similar to noninvasive tumours of the bladder (80 % specific survival at five years). Their surgical management is gradually evolving towards the maximum preservation of the upper urinary tract and of the renal parenchyma. The good oncologic results obtained after conservative endoscopic treatment (ureteroscopy, percutaneous treatment) make it a credible alternative to the radical surgery for the management of tumours with non-aggressive behaviour. However, the high cost of endoscopy equipment and supplies currently remains a factor limiting their distribution in France.

[Intravesical chemotherapy and bladder cancer]. / Instillations endovésicales et cancer de la vessie.

Superficial bladder cancer is treated by transuretral resection and in some cases by intravesical chemotherapy. Modalities, ways of administration and indications of these treatments will be presented and discussed.

[Treatment of infiltrating nonmetastatic bladder cancers in elderly patients]. / Traitement des cancers infiltrants non métastatiques de la vessie chez les patients âgés.

Total cystectomy is the reference treatment for infiltrating nonmetastatic bladder cancers. With the progress in anesthesia and postoperative intensive care, this treatment can be applied to a population of elderly subjects provided there is a strict oncological and geriatric evaluation of the patient. Recent series reporting total cystectomies in subjects over 75 years of age report comparable morbidity and mortality rates to the general population. Strategies to preserve the vesical reservoir can be indicated in selected cases. Their objectives are to guarantee local control and follow-up identical to radical cystectomy, while preserving a functional bladder and good quality of life. The strategies including transurethral resection with radiochemotherapy are analyzed. Thus, with multidisciplinary consensus and adapted management, elderly patients with significant comorbidities should not be automatically excluded from access to effective treatment of these cancers.

[Targeted therapy for locally advanced and/or metastatic bladder cancer]. / Les thérapeutiques ciblées du cancer de vessie localement avancé et/ou métastatique.

Cancer is a complex disease characterized by a multitude of molecular and genetic abnormalities affecting cell proliferation and differentiation, apoptosis, and mobility (invasion). Each of these alterations represents a potential target for the development of targeted therapy. These new therapies inhibit cell growth and are said to be "cytostatic" in contrast with conventional "cytotoxic" chemotherapy. As a result of a better understanding of the molecular biology of bladder cancers, various signalling pathways involved in both carcinogenesis and tumour progression have been defined, and some of the key molecules in these pathways have been isolated and can be used as prognostic markers and as potential therapeutic targets. Locally advanced, and/or metastatic bladder cancer, is characterized by mutations of the p53 and retinoblastoma (Rb) genes, regulators of the cell cycle, which interact with the Ras-mitogen activated protein kinase (MPAK) transduction pathway. Overexpression of tyrosine kinase receptors, including EGFR, VEFGR and HER2/neu, is correlated with tumour progression and activation of the phosphatidyl-inositol-3 kinase (PI-3K) pathway is involved in tumour invasion and inhibition of apoptosis. Due to their molecular heterogeneity, optimal targeted therapy of bladder cancers will require the combined use of several molecules. Modulation of signalling pathways by these new molecules can restore chemosensitivity to cytotoxic drugs, which can then be associated with targeted therapy.

[The advantages of antiangiogenics in neoadjuvant and adjuvant locally advanced and metastatic kidney cancer: two case studies]. / Intérêt des anti-angiogéniques dans le cancer du rein localement avancé et métastatique en situation néo-adjuvante: à propos de 2 cas.

New antiangiogenic molecules have proven an advantage in term of survival in metastatic renal cell carcinoma. We describe herein two clinical cases showing the efficacy of antiangiogenic agent in locally advanced or metastatic renal cell carcinoma. In this cases the surgical management has been altered in front of an important tumor necrosis provided by this treatment. The role of antiangiogenic agents as adjuvant or neo adjuvant therapy has not yet been defined precisely. However, these new molecules open new perspectives in the therapeutic field of metastatic renal cell carcinoma notably in case of bulky tumors which appeared difficult to remove surgically at first look or in case of early recurrence after radical nephrectomy.

[Benign urachus abnormalities: embryology, diagnosis and treatments]. / Pathologies bénignes de l'ouraque chez l'adulte : origine embryologique, présentation clinique et traitements.

Urachus pathologies are very rare but require to be known by urologists. Lack of appropriate treatment exposes the patients to the risks of symptoms recurrence, infectious complications or adenocarcinomatous degeneration. A partial or total defect of obliteration of the urachus channel after the fifth month of gestation can be at the origin of four benign pathologies. The ombilicovesical fistula (47.6%) is diagnosed at the native period. In the adult, the most frequent form is the cyst (30.7%) whereas the external (16.4%) and internal sinus (3.2%) are rarer. Diagnosis depends on the clinical examination and the association of sonography and TDM. The risk of complications must systematically result in proposing a surgical treatment for these benign pathologies. The umbilicus resection is not recommended, but the surgeon has to remove the urachus and its implantation base on the bladder. Laparoscopic surgery seems to be an interesting route for this intervention.

["Superficial bladder cancers" do not exist anymore]. / Les << tumeurs superficielles de vessie >> n'existent plus.

"Superficial bladder tumours" term is progressively abandoned in the urological community because of its ambiguity leading possibly to harmful confusions. The French Oncologic Society proposes to designate by non-infiltrating bladder neoplasm by the muscle Ta, T1 and Tis tumours.

[What is the clinical practice of partial nephrectomy in France?]. / Quelle pratique de la néphrectomie partielle en France ?

OBJECTIVE: To describe the practice of partial nephrectomy (PN) in France and assess its results in terms of morbidity and cancer control. MATERIAL AND METHOD: Seven French University Hospitals in which nephron sparing surgery represents at least 30% of the total number of nephrectomies for renal tumour, participated in this study. All centres included, as exhaustively as possible, all their PN cases. For each patient, 70 variables were harvested in order to characterize the patient population, the indications, the operative technique, the per- and postoperative course and complications, the tumor specificities, the carcinologic control and renal function follow-up. RESULTS: Seven hundred and forty-one PN, of which 579 for malignant tumours were analysed. The mean tumour size was 3.4+/-2.1 cm (0.1-18) and 20.8% of the tumours were larger than 4 cm. In 30.1% of cases, the indication was imperative. Among the PN, 12.2% were performed laparoscopically. The mean operating time was 151+/-54.2 min (55-420). The medical and surgical complications rates were respectively 15.2 and 14.7%. At a mean 38 months follow-up, the local recurrence rate was 3.5% and the specific death rate was 4.5%. CONCLUSION: PN is nowadays getting a more and more widely used technique in France. This expansion is completely justified by its results and urologists must consider nephron sparing surgery as the gold standard treatment for renal tumours measuring less than 4 cm.