Elsevier

European Urology

Volume 71, Issue 3, March 2017, Pages 447-461
European Urology

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

https://doi.org/10.1016/j.eururo.2016.05.041Get rights and content

Abstract

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.

Introduction

This overview represents the updated European Association of Urology (EAU) guidelines for Non–muscle-invasive Bladder Cancer (NMIBC): TaT1 and carcinoma in situ (CIS). The information presented is limited to urothelial carcinoma, unless specified otherwise. The aim is to provide practical guidance on the clinical management of NMIBC with a focus on clinical presentation and recommendations.

Clinical guidelines present the best evidence available to the experts, but following guideline recommendations will not necessarily result in the best outcome. Guidelines can never replace clinical expertise when making treatment decisions for individual patients, but rather they help to focus decisions, also taking personal values and preferences/individual circumstances of patients into account.

Section snippets

Evidence acquisition

A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines was performed. The search was limited to studies representing high levels of evidence (LE) only published in the English language. The search was restricted to articles published during the period from April 1, 2014, to May 31, 2015. Databases covered by the search included Medline, Embase, and the Cochrane Libraries. A total of 1040 unique records were identified, retrieved, and screened for relevance. A

Epidemiology

Bladder cancer (BCa) is the seventh most commonly diagnosed cancer in the male population worldwide. It drops to 11th when both genders are considered [1]. The worldwide age-standardised incidence rate (per 100 000 person-years) is 9.0 for men and 2.2 for women [1]. In the European Union, the age-standardised incidence rate is 19.1 for men and 4.0 for women [1]. In Europe, the highest age-standardised incidence rate was reported in Belgium (31 in men and 6.2 in women) and the lowest in Finland

Risk factors

Tobacco smoking is the most important risk factor for BCa, accounting for approximately 50% of cases [2], [4] (LE: 3). Occupational exposure to aromatic amines, polycyclic aromatic hydrocarbons, and chlorinated hydrocarbons accounts for about 10% of cases. This type of exposure occurs mainly in industrial plants processing paint, dye, metal, and petroleum products [2], [5]. Genetic predisposition has an influence on susceptibility to other risk factors [2], [6].

The chlorination of drinking

Definition of non–muscle-invasive bladder cancer

Papillary tumours confined to the mucosa or invading the lamina propria are classified as stage Ta or T1, respectively, according to the TNM classification system. Flat high-grade (HG) tumours confined to the mucosa are classified as CIS (Tis). These tumours are grouped under the heading of NMIBC for therapeutic purposes. However, molecular biology techniques and clinical experience have demonstrated the highly malignant potential of CIS and T1 lesions. Consequently, the terms NMIBC and

Patient history, signs, and symptoms

A comprehensive patient history is mandatory. Haematuria is the most common finding in NMIBC. CIS might be suspected in patients with storage lower urinary tract symptoms.

Physical examination

Physical examination does not reveal NMIBC.

Imaging

Computed tomography (CT) urography is used to detect papillary tumours in the urinary tract that can be seen as filling defects or indicated by hydronephrosis. Intravenous urography (IVU) can be an alternative if CT is not available [19] (LE: 3), but particularly in muscle-invasive

Prognosis of TaT1 tumours

To predict separately the short- and long-term risks of disease recurrence and progression in individual patients, the European Organisation for the Research and Treatment of Cancer-Genito-Urinary Cancer Group (EORTC-GUCG) developed a scoring system and risk tables [56]. These tables are based on individual patient data from 2596 patients with TaT1 tumours who were randomised into seven EORTC trials and did not undergo a second TURB or receive maintenance BCG.

The scoring system is based on the

Counselling of smoking cessation

It has been confirmed that smoking increases the risk of tumour recurrence and progression [66], [67] (LE: 3).

Intravesical chemotherapy

Although TURB by itself can eradicate a TaT1 tumour completely, these tumours commonly recur and can progress to muscle-invasive BCa. It is therefore necessary to consider adjuvant therapy in all patients.

Follow-up of patients with non–muscle-invasive bladder cancer

As a result of the risk of recurrence and progression, patients with NMIBC need to be followed up. However, the frequency and duration of cystoscopy and imaging should reflect the individual patient's degree of risk. When planning the follow-up schedule and methods, the following aspects should be considered:

  • The prompt detection of muscle-invasive and HG/G3 NMIBC recurrence is crucial because a delay in diagnosis and therapy can be life threatening.

  • Tumour recurrence in the low-risk group is

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