Marko Babjuk

EAU Guidelines on Non–Muscle-Invasive Urothelial Carcinoma of the Bladder, the 2011 Update

CONTEXT AND OBJECTIVEnTo present the 2011 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC).nnnEVIDENCE ACQUISITIONnLiterature published between 2004 and 2010 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the level of evidence (LE) and grade of recommendation (GR) were assigned.nnnEVIDENCE SYNTHESISnTumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection (TUR) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TUR is essential for the patients prognosis. Where the initial resection is incomplete or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. In papillary tumours, the risks of both recurrence and progression may be estimated for individual patients using the scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups-separately for recurrence and progression-is pivotal to recommending adjuvant treatment. For patients with a low risk of tumour recurrence and progression, one immediate instillation of chemotherapy is recommended. Patients with an intermediate or high risk of recurrence and an intermediate risk of progression should receive one immediate instillation of chemotherapy followed by a minimum of 1 yr of bacillus Calmette-Guérin (BCG) intravesical immunotherapy or further instillations of chemotherapy. Papillary tumours with a high risk of progression and CIS should receive intravesical BCG for 1 yr. Cystectomy may be offered to the highest risk patients, and it is at least recommended in BCG failure patients. The long version of the guidelines is available from the EAU Web site (www.uroweb.org).nnnCONCLUSIONSnThese abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice.

EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder.

CONTEXT AND OBJECTIVEnTo present the updated version of 2008 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer.nnnEVIDENCE ACQUISITIONnA systematic review of the recent literature on the diagnosis and treatment of non-muscle-invasive bladder cancer was performed. The guidelines were updated and the level of evidence and grade of recommendation were assigned.nnnEVIDENCE SYNTHESISnThe diagnosis of bladder cancer depends on cystoscopy and histologic evaluation of the resected tissue. A complete and correct transurethral resection (TUR) is essential for the prognosis of the patient. When the initial resection is incomplete or when a high-grade or T1 tumour is detected, a second TUR within 2-6 wk should be performed. The short- and long-term risks of both recurrence and progression may be estimated for individual patients using the scoring system and risk tables. The stratification of patients to low, intermediate, and high-risk groups-separately for recurrence and progression-represents the cornerstone for indication of adjuvant treatment. In patients at low risk of tumour recurrence and progression, one immediate instillation of chemotherapy is strongly recommended. In those at an intermediate or high risk of recurrence and an intermediate risk of progression, one immediate instillation of chemotherapy should be followed by further instillations of chemotherapy or a minimum of 1 yr of bacillus Calmette-Guerin (BCG). In patients at high risk of tumour progression, after an immediate instillation of chemotherapy, intravesical BCG for at least 1 yr is indicated. Immediate cystectomy may be offered to the highest risk patients and in patients with BCG failure. The long version of the guidelines is available on www.uroweb.org.nnnCONCLUSIONSnThese EAU guidelines present the updated information about the diagnosis and treatment of non-muscle-invasive bladder cancer and offer the recent findings for the routine clinical application.

European Guidelines on Upper Tract Urothelial Carcinomas: 2013 Update

CONTEXTnThe European Association of Urology (EAU) guideline group for upper tract urothelial carcinoma (UTUC) has prepared updated guidelines to aid clinicians in assessing the current evidence-based management of UTUC and to incorporate present recommendations into daily clinical practice.nnnOBJECTIVEnTo provide a brief overview of the EAU guidelines on UTUC as an aid to clinicians in their daily clinical practice.nnnEVIDENCE ACQUISITIONnThe recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified using a systematic search of Medline. Data on urothelial malignancies and UTUCs in the literature were searched using Medline with the following keywords: urinary tract cancer; urothelial carcinomas; upper urinary tract, carcinoma; renal pelvis; ureter; bladder cancer; chemotherapy; nephroureterectomy; adjuvant treatment; instillation; neoadjuvant treatment; recurrence; risk factors; nomogram; and survival. References were weighted by a panel of experts.nnnEVIDENCE SYNTHESISnThere is a lack of data in the current literature to provide strong recommendations (ie, grade A) due to the rarity of the disease. A number of recent multicentre studies are now available, and there is a growing interest in UTUC in the recent literature. Overall, 135 references have been included here, but most of these studies are still retrospective analyses. The TNM 2009 classification is recommended. Recommendations are given for diagnosis as well as radical and conservative treatment (ie, imperative and elective cases); additionally, prognostic factors are discussed. Recommendations are also provided for patient follow-up after different therapeutic options.nnnCONCLUSIONSnThese guidelines contain information for the management of individual patients according to a current standardised approach. Physicians must take into account the specific clinical characteristics of each individual patient when determining the optimal treatment regimen including tumour location, grade, and stage; renal function; molecular marker status; and medical comorbidities.

European Guidelines for the Diagnosis and Management of Upper Urinary Tract Urothelial Cell Carcinomas: 2011 Update

CONTEXTnThe European Association of Urology (EAU) Guideline Group for urothelial cell carcinoma of the upper urinary tract (UUT-UCC) has prepared new guidelines to aid clinicians in assessing the current evidence-based management of UUT-UCC and to incorporate present recommendations into daily clinical practice.nnnOBJECTIVEnThis paper provides a brief overview of the EAU guidelines on UUT-UCC as an aid to clinicians in their daily practice.nnnEVIDENCE ACQUISITIONnThe recommendations provided in the current guidelines are based on a thorough review of available UUT-UCC guidelines and papers identified using a systematic search of Medline. Data on urothelial malignancies and UUT-UCCs in the literature were searched using Medline with the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, chemotherapy, nephroureterectomy, adjuvant treatment, neoadjuvant treatment, recurrence, risk factors, and survival. A panel of experts weighted the references.nnnEVIDENCE SYNTHESISnThere is a lack of data in the current literature to provide strong recommendations due to the rarity of the disease. A number of recent multicentre studies are now available, whereas earlier publications were based only on limited populations. However, most of these studies have been retrospective analyses. The TNM classification 2009 is recommended. Recommendations are given for diagnosis as well as for radical and conservative treatment; prognostic factors are also discussed. Recommendations are provided for patient follow-up after different therapeutic options.nnnCONCLUSIONSnThese guidelines contain information for the diagnosis and treatment of individual patients according to a current standardised approach. When determining the optimal treatment regimen, physicians must take into account each individual patients specific clinical characteristics with regard to renal function including medical comorbidities; tumour location, grade and stage; and molecular marker status.

ICUD-EAU international consultation on bladder cancer 2012: Non-muscle-invasive urothelial carcinoma of the bladder

CONTEXTnOur aim was to present a summary of the Second International Consultation on Bladder Cancer recommendations on the diagnosis and treatment options for non-muscle-invasive urothelial cancer of the bladder (NMIBC) using an evidence-based approach.nnnOBJECTIVEnTo critically review the recent data on the management of NMIBC to arrive at a general consensus.nnnEVIDENCE ACQUISITIONnA detailed Medline analysis was performed for original articles addressing the treatment of NMIBC with regard to diagnosis, surgery, intravesical chemotherapy, and follow-up. Proceedings from the last 5 yr of major conferences were also searched.nnnEVIDENCE SYNTHESISnThe major findings are presented in an evidence-based fashion. We analyzed large retrospective and prospective studies.nnnCONCLUSIONSnUrothelial cancer of the bladder staged Ta, T1, and carcinoma in situ (CIS), also indicated as NMIBC, poses greatly varying but uniformly demanding challenges to urologic care. On the one hand, the high recurrence rate and low progression rate with Ta low-grade demand risk-adapted treatment and surveillance to provide thorough care while minimizing treatment-related burden. On the other hand, the propensity of Ta high-grade, T1, and CIS to progress demands intense care and timely consideration of radical cystectomy.

Hexyl Aminolevulinate–Guided Fluorescence Cystoscopy in the Diagnosis and Follow-up of Patients with Non–Muscle-invasive Bladder Cancer: A Critical Review of the Current Literature

CONTEXTnControversy exists regarding the therapeutic benefit and cost effectiveness of photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) or hexyl aminolevulinate (HAL) in addition to white-light cystoscopy (WLC) in the management of non-muscle-invasive bladder cancer (NMIBC).nnnOBJECTIVEnTo systematically evaluate evidence regarding the therapeutic benefits and economic considerations of PDD in NMIBC detection and treatment.nnnEVIDENCE ACQUISITIONnWe performed a critical review of PubMed/Medline, Embase, and the Cochrane Library in October 2012 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) and Standards for the Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forty-four publications were selected for inclusion in this analysis.nnnEVIDENCE SYNTHESISnIncluded reports used 5-ALA (in 26 studies), HAL (15 studies), or both (three studies) as photosensitising agents. PDD increased the detection of both papillary tumours (by 7-29%) and flat carcinoma in situ (CIS; by 25-30%) and reduced the rate of residual tumours after transurethral resection of bladder tumour (TURBT; by an average of 20%) compared to WLC alone. Superior recurrence-free survival (RFS) rates and prolonged RFS intervals were reported for PDD, compared to WLC in most studies. PDD did not appear to reduce disease progression. Our findings are limited by tumour heterogeneity and a lack of NMIBC risk stratification in many reports or adjustment for intravesical therapy use in most studies. Although cost effectiveness has been demonstrated for 5-ALA, it has not been studied for HAL.nnnCONCLUSIONSnModerately strong evidence exists that PDD improves tumour detection and reduces residual disease after TURBT compared with WLC. This has been shown to improve RFS but not progression to more advanced disease. Further work to evaluate cost effectiveness of PDD is required.

Impact of Smoking and Smoking Cessation on Oncologic Outcomes in Primary Non–muscle-invasive Bladder Cancer

BACKGROUNDnCigarette smoking is the best-established risk factor for urothelial carcinoma (UC) development, but the impact on oncologic outcomes remains poorly understood.nnnOBJECTIVEnTo analyse the effects of smoking status, cumulative exposure, and time from smoking cessation on the prognosis of patients with primary non-muscle-invasive bladder cancer (NMIBC).nnnDESIGN, SETTING, AND PARTICIPANTSnWe collected smoking data from 2043 patients with primary NMIBC. Smoking variables included smoking status, average number of cigarettes smoked per day (CPD), duration in years, and time since smoking cessation. Lifetime cumulative smoking exposure was categorised as light short term (≤ 19 CPD, ≤ 19.9 yr), light long term (≤ 19 CPD, ≥ 20 yr), heavy short term (≥ 20 CPD, ≤ 19.9 yr) and heavy long term (≥ 20 CPD, ≥ 20 yr). The median follow-up in this retrospective study was 49 mo.nnnINTERVENTIONSnTransurethral resection of the bladder with or without intravesical instillation therapy.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnUnivariable and multivariable logistic regression and competing risk regression analyses assessed the effects of smoking on outcomes.nnnRESULTS AND LIMITATIONSnThere was no difference in clinicopathologic factors among never (24%), former (47%), and current smokers (29%). Smoking status was associated with the cumulative incidence of disease progression in multivariable analysis (p=0.003); current smokers had the highest cumulative incidences. Among current and former smokers, cumulative smoking exposure was associated with disease recurrence (p<0.001), progression (p<0.001), and overall survival (p<0.001) in multivariable analyses that adjusted for the effects of standard clinicopathologic factors and smoking status; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation >10 yr reduced the risk of disease recurrence (hazard ratio [HR]: 0.66; 95% confidence interval [CI], 0.52-0.84; p<0.001) and progression (HR: 0.42; 95% CI, 0.22-0.83; p=0.036) in multivariable analyses. The study is limited by its retrospective nature.nnnCONCLUSIONSnSmoking status and a higher cumulative smoking exposure are associated with worse prognosis in patients with NMIBC. Smoking cessation >10 yr abrogates this detrimental effect. These findings underscore the need for integrated smoking cessation and prevention programmes in the management of NMIBC patients.

Follow-up After Surgical Treatment of Bladder Cancer: A Critical Analysis of the Literature

CONTEXTnFollow-up of patients treated for bladder cancer (BCa) is of great importance for both non-muscle-invasive BCa (NMIBC) and muscle-invasive BCa (MIBC) because of the high incidence of recurrence and progression. The schedule and methods of follow-up should reflect the individual clinical situation.nnnOBJECTIVEnTo evaluate the existing evidence for intensity and duration of follow-up recommendations in patients after surgical treatment of BCa.nnnEVIDENCE ACQUISITIONnWe searched the Medline, Embase, and Cochrane databases for published data on the follow-up of patients with NMIBC and MIBC after radical cystectomy (RC).nnnEVIDENCE SYNTHESISnFollow-up in patients with NMIBC is necessary because of the high probability of tumour recurrence and the risk of progression. Cystoscopy plus cytology are the standard methods for follow-up. Cystoscopy should be done 3 mo after the transurethral resection in every patient, and the frequency after that depends on the individual recurrence/progression risk. Cytology should be used as an adjunctive method to cystoscopy in intermediate- and high-risk patients. None of the currently available urinary markers or imaging methods can substitute for cystoscopy-based follow-up. High-risk NMIBC patients require regular lifelong upper urinary tract monitoring. Follow-up in MIBC is based on the fact that early detection of recurrence after RC allows for timely treatment with the aim of improving outcomes. Patients with extravesical and lymph node-positive disease should have the most intensive follow-up because of the highest recurrence risk. Routine upper urinary tract imaging is advisable for all patients and should continue in the long term. Follow-up also allows for early detection of urinary diversion-related complications, the rate of which increases with time.nnnCONCLUSIONSnFollow-up in BCa is necessary for diagnosing recurrence and progression, as well as for evaluating complications after radical treatment. Since randomised studies investigating the most appropriate follow-up schedule are lacking, most recommendations are based on only the retrospective experience. Nonetheless, reasonable recommendations can be made until further prospective randomised studies testing different follow-up schedules have been performed.

Impact of Smoking and Smoking Cessation on Outcomes in Bladder Cancer Patients Treated with Radical Cystectomy

BACKGROUNDnCigarette smoking is the best-established risk factor for urothelial carcinoma development.nnnOBJECTIVEnTo elucidate the association of pretreatment smoking status, cumulative exposure, and time since smoking cessation on outcomes of patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC).nnnDESIGN, SETTING, AND PARTICIPANTSnWe retrospectively collected clinicopathologic and smoking variables, including smoking status, number of cigarettes per day (CPD), duration in years, and time since smoking cessation, for 1506 patients treated with RC for UCB. Lifetime cumulative smoking exposure was categorized as light short-term (≤20 CPD for ≤20 yr), light long-term (≤20 CPD for >20 yr), heavy short-term (>20 CPD for ≤20 yr), and heavy long-term (>20 CPD for >20 yr).nnnINTERVENTIONnRC and bilateral lymph node (LN) dissection without neoadjuvant chemotherapy.nnnOUTCOME MEASUREMENTS AND STATISTICAL ANALYSISnLogistic regression and competing risk analyses assessed the association of smoking with disease recurrence, cancer-specific mortality, and overall mortality.nnnRESULTS AND LIMITATIONSnThere was no difference in clinicopathologic factors between patients who had never smoked (20%), former smokers (46%), and current smokers (34%). Smoking status was associated with the cumulative incidence of disease recurrence (p=0.004) and cancer-specific mortality (p=0.016) in univariable analyses and with disease recurrence in multivariable analysis (p=0.02); current smokers had the highest cumulative incidences. Among ever smokers, cumulative smoking exposure was associated with advanced tumor stages (p<0.001), LN metastasis (p=0.002), disease recurrence (p<0.001), cancer-specific mortality (p=0.001), and overall mortality (p=0.037) in multivariable analyses that adjusted for standard characteristics; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation ≥10 yr mitigated the risk of disease recurrence (hazard ratio [HR]: 0.44; p<0.001), cancer-specific mortality (HR: 0.42; p<0.001), and overall mortality (HR: 0.69; p=0.012) in multivariable analyses. The study is limited by its retrospective nature.nnnCONCLUSIONSnSmoking is associated with worse prognosis after RC for UCB. This association seems to be dose-dependent, and its effects are mitigated by >10 yr smoking cessation. Health care practitioners should counsel smokers regarding the detrimental effects of smoking and the benefits of smoking cessation on UCB etiology and prognosis.

Predictors of cancer-specific mortality after disease recurrence following radical cystectomy.

Study Type – Therapy (case series)