[Evaluation of a prostate cancer aftercare app from the patient perspective: A qualitative study]. / Evaluation einer Prostatakrebsnachsorge-App aus Patientensicht: Eine qualitative Studie.

INTRODUCTION: The project "Digital unterstützte Prostatakrebsnachsorge in Schleswig-Holstein" (Digitally supported prostate cancer aftercare in Schleswig-Holstein) funded by the federal state of Schleswig-Holstein aims to test the app "Nachsorge-Pass" (Patient Aftercare Book) in the care of prostate cancer patients after seed brachytherapy. In order to evaluate the app from the patient perspective a qualitative study was conducted which examined usability, usefulness and potential for improvement. METHODS: All patients using the app at the start of the study were invited to participate in semi-structured telephone interviews; 12 of 20 users (60%) followed the invitation. In addition, the questionnaire "System Usability Scale" (SUS) was applied. Qualitative content analysis was used to interpret the interviews. RESULTS: The evaluation revealed that, overall, the app was regarded as very user-friendly, though some users encountered difficulties during the installation of the app and technical problems afterwards. Some patients experienced a feeling of security resulting from the symptom monitoring. Other participants did not see a personal benefit, but made suggestions for improvement in order to make the app more useful. DISCUSSION: Symptom monitoring through the app "Nachsorge-Pass" has shown to be feasible. Potential for improvement includes the representation of the symptom course for patients, a stronger focus on psychosocial aspects, and a better integration of the app into the ongoing aftercare process. As soon as the number of users is high enough, a randomised controlled trial should be conducted in order to collect reliable evidence on the effectiveness of the app. CONCLUSION: The present study provides first clues about a patient-oriented design of an app for prostate cancer aftercare, which has shown a high level of user-friendliness in the first test with patients. Further development should take place in iterative cycles involving both users and health care professionals.

International Bladder Cancer Group Consensus Statement on Clinical Trial Design for Patients with Bacillus Calmette-Guérin-exposed High-risk Non-muscle-invasive Bladder Cancer.

CONTEXT: A large proportion of patients with non-muscle-invasive bladder cancer (NMIBC) fall in the gap between bacillus Calmette-Guérin (BCG)-naïve and BCG-unresponsive disease. As multiple therapeutic agents move into this gray area, there is a critical need to define the disease state and establish recommendations for optimal trial design. OBJECTIVE: To develop a consensus on optimal trial design for patients with BCG-exposed NMIBC, defined as high-grade recurrence after BCG treatment that does not meet the criteria for BCG-unresponsive disease. EVIDENCE ACQUISITION: We conducted a literature review using the Cochrane Library, Medline, and Embase and a review of clinical trials in ClinicalTrials.gov as a basis to generate consensus recommendations for clinical trial design in BCG-exposed NMIBC. EVIDENCE SYNTHESIS: BCG-exposed NMIBC encompasses BCG resistance (presence of high-grade Ta or carcinoma in situ [CIS] at 3-mo evaluation after induction BCG) and delayed relapse. Randomized controlled trials are required to compare experimental therapies to a control arm receiving additional BCG, although ongoing BCG shortages may impact our ability to follow an optimal trial design. A placebo should be used in combination with BCG if the treatment arm includes BCG plus a study drug. Trials will either need to separate patients with and without CIS into two cohorts, or stratify by the presence of CIS at the time of randomization. If two cohorts are used, the primary endpoint for CIS patients should be complete response within a predetermined time. The primary endpoint in a cohort with Ta/T1 only, or if a single combined cohort is used, should be the duration of event-free survival. Suggested efficacy thresholds and corresponding sample sizes are provided. CONCLUSIONS: The International Bladder Cancer Group has developed recommendations regarding definitions, endpoints, and clinical trial design for BCG-exposed NMIBC to encourage uniformity among studies in this disease state. PATIENT SUMMARY: Our consensus provides a precise definition of the disease state for bladder cancer not invading the bladder muscle and exposed to bacillus Calmette-Guérin (BCG) treatment. Clear guidance for conducting optimal clinical trials in this disease setting was established and we believe that this will promote further progress in this field.

Potential Benefit of Lymph Node Dissection During Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the European Association of Urology Guidelines Panel on Non-muscle-invasive Bladder Cancer.

CONTEXT: The oncological efficacy of routine lymphadenectomy (lymph node dissection [LND]) at the time of radical nephroureterectomy (RNU) remains controversial. OBJECTIVE: To systematically review the available literature assessing the impact of LND in upper tract urothelial carcinoma (UTUC) patients. EVIDENCE ACQUISITION: Embase, Medline, and Cochrane databases were searched for all studies comparing outcomes of patients undergoing RNU without LND versus any form of LND. We identified nine retrospective studies eligible for inclusion in this systematic review. We took cancer-specific survival (CSS) as the primary end point, and performed a narrative review and risk of bias assessment. EVIDENCE SYNTHESIS: Six studies compared outcomes of no LND versus LND. Three studies compared complete LND versus incomplete LND versus no LND. The incidence of pN+ in patients with high-stage (≥pT2) tumours ranged from 14.3% to 40%. Pre- and postoperative characteristics differed among the study groups, potentially biasing the results, as demonstrated by the risk of bias assessment, potentially favouring the LND group. Oncological outcomes such as cancer-specific, overall, recurrence-free, and metastasis-free survival were reviewed, demonstrating a survival benefit with LND in high-stage disease of the renal pelvis. CONCLUSIONS: Template-based and complete LND improves CSS in patients with high-stage (≥pT2) UTUC and reduces the risk of local recurrence. The impact of LND in ureteral tumours remains uncertain. PATIENT SUMMARY: Studies comparing radical nephroureterectomy with or without the removal of nodes (lymph node dissection [LND]) were analysed. LND improves survival in patients with high-stage disease of the renal pelvis, if it is performed according to an anatomical template-based approach.

EAU Guidelines on Non-Muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016.

CONTEXT: The European Association of Urology (EAU) panel on Non-muscle-invasive Bladder Cancer (NMIBC) released an updated version of the guidelines on Non-muscle-invasive Bladder Cancer. OBJECTIVE: To present the 2016 EAU guidelines on NMIBC. EVIDENCE ACQUISITION: A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines published between April 1, 2014, and May 31, 2015, was performed. Databases covered by the search included Medline, Embase, and the Cochrane Libraries. Previous guidelines were updated, and levels of evidence and grades of recommendation were assigned. EVIDENCE SYNTHESIS: Tumours staged as TaT1 or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection of the bladder (TURB) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TURB is essential for the patient's prognosis. If the initial resection is incomplete, there is no muscle in the specimen, or a high-grade or T1 tumour is detected, a second TURB should be performed within 2-6 wk. The risks of both recurrence and progression may be estimated for individual patients using the European Organisation for Research and Treatment of Cancer (EORTC) scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups is pivotal to recommending adjuvant treatment. For patients with a low-risk tumour and intermediate-risk patients at a lower risk of recurrence, one immediate instillation of chemotherapy is recommended. Patients with an intermediate-risk tumour should receive 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. In patients at highest risk of tumour progression, immediate radical cystectomy (RC) should be considered. RC is recommended in BCG-refractory tumours. The long version of the guidelines is available at the EAU Web site (www.uroweb.org/guidelines). CONCLUSIONS: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. PATIENT SUMMARY: The European Association of Urology has released updated guidelines on Non-muscle-invasive Bladder Cancer (NMIBC). Stratification of patients into low-, intermediate-, and high-risk groups is essential for decisions about adjuvant intravesical instillations. Risk tables can be used to estimate risks of recurrence and progression. Radical cystectomy should be considered only in case of failure of instillations or in NMIBC with the highest risk of progression.

Oncologic Outcomes of Kidney-sparing Surgery Versus Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the EAU Non-muscle Invasive Bladder Cancer Guidelines Panel.

CONTEXT: There is uncertainty regarding the oncologic effectiveness of kidney-sparing surgery (KSS) compared with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). OBJECTIVE: To systematically review the current literature comparing oncologic outcomes of KSS versus RNU for UTUC. EVIDENCE ACQUISITION: A computerised bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting comparative oncologic outcomes of KSS versus RNU. Approaches considered for KSS were segmental ureterectomy (SU) and ureteroscopic (URS) or percutaneous (PC) management. Using the methodology recommended by the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, we identified 22 nonrandomised comparative retrospective studies published between 1999 and 2015 that were eligible for inclusion in this systematic review. A narrative review and risk-of-bias (RoB) assessment were performed using cancer-specific survival (CSS) as the primary end point. EVIDENCE SYNTHESIS: Seven studies compared KSS overall (n=547) versus RNU (n=1376). Information on the comparison of SU (n=586) versus RNU (n=3692), URS (n=162) versus RNU (n=367), and PC (n=66) versus RNU (n=114) was available in 10, 5, and 2 studies, respectively. No significant difference was found between SU and RNU in terms of CSS or any other oncologic outcomes. Only patients with low-grade and noninvasive tumours experienced similar CSS after URS or PC when compared with RNU, despite an increased risk of local recurrence following endoscopic management of UTUC. The RoB assessment revealed, however, that the analyses were subject to a selection bias favouring KSS. CONCLUSIONS: Our systematic review suggests similar survival after KSS versus RNU only for low-grade and noninvasive UTUC when using URS or PC. However, selected patients with high-grade and invasive UTUC could safely benefit from SU when feasible. These results should be interpreted with caution due to the risk of selection bias. PATIENT SUMMARY: We reviewed the studies that compared kidney-sparing surgery versus radical nephroureterectomy for upper tract urothelial carcinoma. We found similar oncologic outcomes for favourable tumours when using ureteroscopic or percutaneous management, whereas indications for segmental ureterectomy could be extended to selected cases of aggressive tumours.

Definitions, End Points, and Clinical Trial Designs for Non-Muscle-Invasive Bladder Cancer: Recommendations From the International Bladder Cancer Group.

PURPOSE: To provide recommendations on appropriate clinical trial designs in non-muscle-invasive bladder cancer (NMIBC) based on current literature and expert consensus of the International Bladder Cancer Group. METHODS: We reviewed published trials, guidelines, meta-analyses, and reviews and provided recommendations on eligibility criteria, baseline evaluations, end points, study designs, comparators, clinically meaningful magnitude of effect, and sample size. RESULTS: NMIBC trials must be designed to provide the most clinically relevant data for the specific risk category of interest (low, intermediate, or high). Specific eligibility criteria and baseline evaluations depend on the risk category being studied. For the population of patients for whom bacillus Calmette-Guérin (BCG) has failed, the type of failure (BCG unresponsive, refractory, relapsing, or intolerant) should be clearly defined to make comparisons across trials feasible. Single-arm designs may be relevant for the BCG-unresponsive population. Here, a clinically meaningful initial complete response rate (for carcinoma in situ) or recurrence-free rate (for papillary tumors) of at least 50% at 6 months, 30% at 12 months, and 25% at 18 months is recommended. For other risk levels, randomized superiority trial designs are recommended; noninferiority trials are to be used sparingly given the large sample size required. Placebo control is considered unethical for all intermediate- and high-risk strata; therefore, control arms should comprise the current guideline-recommended standard of care for the respective risk level. In general, trials should use time to recurrence or recurrence-free survival as the primary end point and time to progression, toxicity, disease-specific survival, and overall survival as potential secondary end points. Realistic efficacy thresholds should be set to ensure that novel therapies receive due review by regulatory bodies. CONCLUSION: The International Bladder Cancer Group has developed formal recommendations regarding definitions, end points, and clinical trial designs for NMIBC to encourage uniformity among studies in this disease.

European Association of Urology Guidelines on Upper Urinary Tract Urothelial Cell Carcinoma: 2015 Update.

CONTEXT: The European Association of Urology (EAU) guidelines panel on upper urinary tract urothelial cell carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice. OBJECTIVE: To provide a brief overview of the EAU guidelines on UTUC as an aid to clinicians. EVIDENCE ACQUISITION: The recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified following a systematic search of Medline. Data on urothelial malignancies and UTUC were searched using these 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; and survival. References were weighted by a panel of experts. EVIDENCE SYNTHESIS: Due to the rarity of UTUC, there are insufficient data to provide strong recommendations (ie, grade A). However, the results of recent multicentre studies are now available, and there is a growing interest in UTUC. The 2009 TNM classification is recommended. Recommendations are given for diagnosis and risk stratification as well as radical and conservative treatment, and prognostic factors are discussed. A single postoperative dose of intravesical mitomycin after nephroureterectomy reduces the risk of bladder tumour recurrence. Recommendations are also provided for patient follow-up after different therapeutic strategies. CONCLUSIONS: These guidelines contain information on the management of individual patients according to a current standardised approach. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen, based on the proposed risk stratification of these tumours. PATIENT SUMMARY: Urothelial carcinoma of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, an appropriate diagnosis is most important. A number of known risk factors exist.

Defining and treating the spectrum of intermediate risk nonmuscle invasive bladder cancer.

PURPOSE: Low, intermediate and high risk categories have been defined to help guide the treatment of patients with nonmuscle invasive bladder cancer (Ta, T1, CIS). However, while low and high risk disease has been well classified, the intermediate risk category has traditionally comprised a heterogeneous group that does not fit into either of these categories. As a result, many urologists remain uncertain about the categorization of patients as intermediate risk as well as the selection of the most appropriate therapeutic option for this patient population. We review the current literature and clinical practice guidelines on intermediate risk nonmuscle invasive bladder cancer and, based on our findings, provide urologists with a better understanding of this heterogeneous risk group as well as practical recommendations for the treatment of intermediate risk patients. MATERIALS AND METHODS: The IBCG analyzed published clinical trials, meta-analyses and current clinical practice guidelines on intermediate risk nonmuscle invasive bladder cancer available as of September 2013. The definitions of intermediate risk, patient outcomes and guideline recommendations were considered, as were the limitations of the available literature and additional parameters that may be useful in guiding treatment decisions in intermediate risk patients. RESULTS: Current definitions and management recommendations for intermediate risk nonmuscle invasive bladder cancer vary. The most simple and practical definition is that proposed by the IBCG and the AUA of multiple and/or recurrent low grade Ta tumors. The IBCG suggests that several factors should be considered in clinical decisions in intermediate risk disease, including number (greater than 1) and size (greater than 3 cm) of tumors, timing (recurrence within 1 year) and frequency (more than 1 per year) of recurrence, and previous treatment. In patients without these risk factors a single, immediate instillation of chemotherapy is advised. In those with 1 to 2 risk factors adjuvant intravesical therapy (intravesical chemotherapy or maintenance bacillus Calmette-Guérin) is recommended, and previous intravesical therapy should be considered when choosing between these adjuvant therapies. For those patients with 3 to 4 risk factors, maintenance bacillus Calmette-Guérin is recommended. It is also important that all intermediate risk patients are accurately risk stratified at initial diagnosis and during subsequent followup. This requires appropriate transurethral resection of the bladder tumor, vigilance to rule out carcinoma in situ or other potential high risk tumors, and review of histological material directly with the pathologist. CONCLUSIONS: Intermediate risk disease is a heterogeneous category, and there is a paucity of independent studies comparing therapies and outcomes in subgroups of intermediate risk patients. The IBCG has proposed a management algorithm that considers tumor characteristics, timing and frequency of recurrence, and previous treatment. Subgroup analyses of intermediate risk subjects in pivotal EORTC trials and meta-analyses will be important to validate the proposed algorithm and support clear evidence-based recommendations for subgroups of intermediate risk patients.

Defining progression in nonmuscle invasive bladder cancer: it is time for a new, standard definition.

PURPOSE: Despite being one of the most important clinical outcomes in nonmuscle invasive bladder cancer, there is currently no standard definition of disease progression. Major clinical trials and meta-analyses have used varying definitions or have failed to define this end point altogether. A standard definition of nonmuscle invasive bladder cancer progression as determined by reproducible and reliable procedures is needed. We examine current definitions of nonmuscle invasive bladder cancer progression, and propose a new definition that will be more clinically useful in determining patient prognosis and comparing treatment options. MATERIALS AND METHODS: The IBCG (International Bladder Cancer Group) analyzed published clinical trials and meta-analyses that examined nonmuscle invasive bladder cancer progression as of December 2012. The limitations of the definitions of progression used in these trials were considered, as were additional parameters associated with the advancement of nonmuscle invasive bladder cancer. RESULTS: The most commonly used definition of nonmuscle invasive bladder cancer progression is an increase in stage from nonmuscle invasive to muscle invasive disease. Although this definition is clinically important, it fails to include other important parameters of advancing disease such as progression to lamina propria invasion and increase in grade. CONCLUSIONS: The IBCG proposes the definition of nonmuscle invasive bladder cancer progression as an increase in T stage from CIS or Ta to T1 (lamina propria invasion), development of T2 or greater or lymph node (N+) disease or distant metastasis (M1), or an increase in grade from low to high. Investigators should consider the use of this new definition to help standardize protocols and improve the reporting of progression.

EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013.

CONTEXT: The first European Association of Urology (EAU) guidelines on bladder cancer were published in 2002 [1]. Since then, the guidelines have been continuously updated. OBJECTIVE: To present the 2013 EAU guidelines on non-muscle-invasive bladder cancer (NMIBC). EVIDENCE ACQUISITION: Literature published between 2010 and 2012 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the levels of evidence and grades of recommendation were assigned. EVIDENCE SYNTHESIS: Tumours 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 patient's prognosis. Where the initial resection is incomplete, where there is no muscle in the specimen, or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. The risks of both recurrence and progression may be estimated for individual patients using the EORTC scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups is pivotal to recommending adjuvant treatment. For patients with a low-risk tumour, one immediate instillation of chemotherapy is recommended. Patients with an intermediate-risk tumour should receive one immediate instillation of chemotherapy followed by 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or by further instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. In patients at highest risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is recommended in BCG-refractory tumours. The long version of the guidelines is available from the EAU Web site: http://www.uroweb.org/guidelines/. CONCLUSIONS: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. PATIENT SUMMARY: The EAU Panel on Non-muscle Invasive Bladder Cancer released an updated version of their guidelines. Current clinical studies support patient selection into different risk groups; low, intermediate and high risk. These risk groups indicate the likelihood of the development of a new (recurrent) cancer after initial treatment (endoscopic resection) or progression to more aggressive (muscle-invasive) bladder cancer and are most important for the decision to provide chemo- or immunotherapy (bladder installations). Surgical removal of the bladder (radical cystectomy) should only be considered in patients who have failed chemo- or immunotherapy, or who are in the highest risk group for progression.

European guidelines on upper tract urothelial carcinomas: 2013 update.

CONTEXT: The 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. OBJECTIVE: To provide a brief overview of the EAU guidelines on UTUC as an aid to clinicians in their daily clinical practice. EVIDENCE ACQUISITION: The 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. EVIDENCE SYNTHESIS: There 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. CONCLUSIONS: These 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.

Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) with emphasis on the use of bacillus Calmette-Guérin (BCG): results of an international individual patient data survey (IPDS).

OBJECTIVES: To examine the management of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), particularly with regard to the use of bacillus Calmette-Guérin (BCG) therapy, in North America and Europe. To compare NMIBC management practices to European Association of Urology (EAU) and American Urological Association (AUA) guideline recommendations for the management of intermediate- and high-risk NMIBC. PATIENTS AND METHODS: In all, 102 urologists from Europe and North America participated in this retrospective on-line chart review, which was conducted between 1 April 2011 and 30 April 2012. Participants selected the charts of the first 10 intermediate- (defined as multiple or recurrent low-grade tumours) or high-risk (defined as any T1 and/or high-grade/G3 tumours and/or carcinoma in situ) patients who underwent transurethral resection of bladder tumour in 2009. Physicians retrospectively reviewed the charts and completed an on-line survey consisting of questions related to diagnosis, planned treatment, treatment status and follow-up. In all, 971 patients (197 intermediate-risk; 774 high-risk) were included in the analysis; frequency counts and associated percentages were used to analyse treatment variables. RESULTS: In all, 47% of intermediate-risk patients received EAU or AUA guideline-recommended intravesical therapy: intravesical chemotherapy, BCG induction therapy or BCG induction plus maintenance. Of the high-risk patients, 50% received maintenance BCG as recommended by the EAU and the AUA; although not recommended for high-risk NMIBC, 12.5% received intravesical chemotherapy. Of patients prescribed maintenance BCG, 93% were scheduled for at least 1 year of therapy. Notably, only 15% discontinued BCG maintenance and, of these discontinuations, 65% were due to reasons unrelated to BCG-associated adverse events. CONCLUSIONS: There is significant non-adherence to EAU and AUA guideline recommendations for BCG use in intermediate- and high-risk NMIBC. However, most of those patients prescribed BCG maintenance therapy are scheduled for at least 1 year of therapy, as recommended by current guidelines for NMIBC management, and BCG maintenance discontinuation is low.

A review of current guidelines and best practice recommendations for the management of nonmuscle invasive bladder cancer by the International Bladder Cancer Group.

PURPOSE: Although the European Association of Urology, First International Consultation on Bladder Tumors, National Comprehensive Cancer Network and American Urological Association guidelines all provide an excellent evidence-based framework for the management of nonmuscle invasive bladder cancer, these guidelines vary with respect to important issues such as risk level definitions and management strategies for these risk categories. Therefore, we built on the existing framework provided by current guidelines, and provide consensus on the definitions of low, intermediate and high risk nonmuscle invasive bladder cancer, as well as practical recommendations for the treatment of patients in each of these risk categories. MATERIALS AND METHODS: An international committee of experts on bladder cancer management identified and analyzed the European Association of Urology, First International Consultation on Bladder Tumors, National Comprehensive Cancer Network and American Urological Association guidelines as well as the published English language literature related to the treatment and management of nonmuscle invasive bladder cancer available as of April 2010. RESULTS: Based on review of the current guidelines and literature, the International Bladder Cancer Group developed practical recommendations for the management of nonmuscle invasive bladder cancer. CONCLUSIONS: Complete transurethral bladder tumor resection is recommended for all patients with nonmuscle invasive bladder cancer. For low risk disease a single, immediate chemotherapeutic instillation after transurethral bladder tumor resection is recommended. For intermediate or high risk disease there is no significant benefit from an immediate, postoperative chemotherapeutic instillation. For intermediate risk disease intravesical bacillus Calmette-Guérin with maintenance or intravesical chemotherapy is recommended. For high risk disease bacillus Calmette-Guérin induction plus maintenance is recommended. The appropriate management of recurrence depends on the patient level of risk as well as previous treatment, while the management of treatment failure depends on the type of failure as well as the level of risk for recurrence and disease progression.

EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update.

CONTEXT AND OBJECTIVE: To present the 2011 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC). EVIDENCE ACQUISITION: Literature 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. EVIDENCE SYNTHESIS: Tumours 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 patient's 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). CONCLUSIONS: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice.

The role of bacillus Calmette-Guérin in the treatment of non-muscle-invasive bladder cancer.

CONTEXT: Bacillus Calmette-Guérin (BCG) remains the most effective intravesical treatment for non-muscle-invasive bladder cancer (NMIBC), but the clinical development of BCG has been accompanied by controversy. Recent publications have called into question a number of aspects related to its use. OBJECTIVE: To review the current clinical role of BCG in NMIBC, focusing on efficacy and tolerability as primary objectives and on strategies to predict response and decrease toxicity as secondary objectives. EVIDENCE ACQUISITION: We performed a systematic literature search of published articles in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases for the period from 1976 to November 2008. The following "free text" combination was used in the first instance: "BCG and intravesical and bladder cancer." Further free text searches were performed by separately adding the following keywords to the combination "BCG and intravesical": survival, progression, recurrence, maintenance, dosing, toxicity, tolerability, side effects, prognostic factors. EVIDENCE SYNTHESIS: BCG is the most effective intravesical agent for preventing NMIBC recurrence, but its role in disease progression remains controversial. In intermediate-risk NMIBC, the superiority of BCG over chemotherapy is well established for disease recurrence but not for progression and needs to be balanced against higher toxicity. With regard to high-risk NMIBC, there is sufficient evidence to show that BCG is the most effective treatment of carcinoma in situ for ablation, disease-free interval, and progression, but the impact of BCG on the natural history of T1G3 tumors relies on a low level of evidence. Maintenance remains crucial for efficacy. The dose can be safely and effectively reduced to decrease its toxicity, which is slightly greater than chemotherapy. CONCLUSIONS: BCG should still be viewed as the most effective intravesical agent, but its role in the progression of papillary tumors needs to be clarified. BCG remains an alternative to intravesical chemotherapy in intermediate-risk NMIBC, and it is recommended as the standard of care for high-risk NMIBC.

[EAU guidelines on non-muscle-carcinoma of the bladder]. / Guía clínica del carcinoma urotelial no mísculo invasivo de la Asociación Europea de Urología.

CONTEXT AND OBJECTIVE: To present the updated version of 2008 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer. EVIDENCE ACQUISITION: A 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. EVIDENCE SYNTHESIS: The 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. CONCLUSIONS: These 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.

Single postoperative instillation of gemcitabine in patients with non-muscle-invasive transitional cell carcinoma of the bladder: a randomised, double-blind, placebo-controlled phase III multicentre study.

BACKGROUND: Recurrence prophylaxis with intravesical gemcitabine (GEM) was effective and safe in patients with non-muscle-invasive bladder cancer (NMIBC); efficacy as single-shot instillation remains to be proved. OBJECTIVE: To compare the efficacy of a single GEM instillation versus placebo (PBO) immediately after transurethral resection (TUR) of tumour in patients with histologically confirmed NMIBC (pTa/pT1,G1-3). DESIGN, SETTING, AND PARTICIPANTS: This was a double-blind, randomised, PBO-controlled study in patients with clinical evidence of primary or recurrent NMIBC (Ta/T1,G1-3). Of 355 patients randomised at 24 urologic centres, 328 underwent TUR and received instillation (92.4%; GEM/PBO: 166/162). In case of nonmalignancy, carcinoma in situ (CIS), > or = pT2 disease, or intraoperative complications, patients were discontinued. INTERVENTION: We used a single, postoperative 30-40-min instillation of GEM (2000 mg/100 ml of saline) or PBO (100 ml of saline) followed by continuous bladder irrigation for > or = 20 h. A second TUR (no instillation) and adjuvant bacillus Calmette-Guérin (BCG) instillations were allowed. MEASUREMENTS: Primary outcome was recurrence-free survival (RFS). Secondary outcomes included type of recurrence and adverse events. To detect a difference in RFS, 191 recurrences were required (80% power, log-rank-test, alpha = 0.050). RESULTS AND LIMITATIONS: Two hundred forty-eight patients (69.9%, GEM, PBO: 124, 124) had histologically confirmed pTa/pT1 G1-3 Gx tumour and were eligible for efficacy (GEM: 76.6% male; median age: 65 yr; PBO: 83.1% male; median age: 67 yr). Treatment groups were balanced (pTa: 75.0%, 71.0%; G1-G2: 85.5%, 87.9%; recurrent tumour: 24.2%, 21.0%; BCG: 10.5%, 16.9%). After a median follow-up of 24 mo, there were only 94 recurrences and 11 deaths. The study was terminated early based on predefined decision criteria. RFS was high in both groups (12-mo RFS [95% confidence interval (CI)]: GEM: 77.7% [68.8-84.3]; PBO: 75.3% [66.3-82.3]). There was no significant group difference (hazard ratio [HR]: 0.946 [0.64-1.39], log-rank test, p=0.777). CONCLUSIONS: In this study of NMIBC, the immediate single instillation of GEM 2000 mg/100 ml of saline after TUR was not superior to PBO in terms of RFS. Rigid continuous irrigation and improved TUR/cystoscopy techniques may have contributed to the high RFS in both groups.