Non-muscle-invasive Bladder Cancer

Full Text Guidelines Summary of Changes Scientific Publications & Appendices Pocket Guidelines Archive Panel


M. Babjuk (Chair), M. Burger (Vice-chair), E. Compérat, P. Gontero, F. Liedberg, A. Masson-Lecomte, A.H. Mostafid, J. Palou, B.W.G. van Rhijn, M. Rouprêt, S.F. Shariat, R. Sylvester
Guidelines Associates: O. Capoun, D. Cohen, J.L. Dominguez Escrig, T. Seisen, V. Soukup

1.INTRODUCTION

1.1.Aim and scope

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 recommendations on the clinical management of NMIBC with a focus on clinical presentation and recommendations.

Separate EAU Guidelines documents are available addressing upper tract urothelial carcinoma (UTUC) [1], muscle-invasive and metastatic bladder cancer (MIBC) [2] and primary urethral carcinoma [3]. It must be emphasised that 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 help to focus decisions - also taking personal values and preferences/individual circumstances of patients into account. Guidelines are not mandates and do not purport to be a legal standard of care.

1.2.Panel composition

The EAU Guidelines Panel on NMIBC consists of an international multidisciplinary group of clinicians, including urologists, uro-oncologists, a pathologist and a statistician. Members of this Panel have been selected based on their expertise and to represent the professionals treating patients suspected of suffering from bladder cancer. All experts involved in the production of this document have submitted potential conflict of interest statements which can be viewed on the EAU website Uroweb: https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/.

1.3.Available publications

A quick reference document (Pocket guidelines) is available, both in print and as an app for iOS and Android devices. These are abridged versions which may require consultation together with the full text version. Several scientific publications are available, the latest publication dating to 2019 [4], as are a number of translations of all versions of the EAU NMIBC Guidelines. All documents are accessible through the EAU website Uroweb: https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/.

1.4.Publication history and summary of changes

1.4.1.Publication history

The EAU Guidelines on Bladder Cancer were first published in 2000. This 2021 NMIBC Guidelines document presents a limited update of the 2020 publication.

1.4.2.Summary of changes

Additional data has been included throughout this document text. In particular in chapters/sections:

  • 4.4 - Histological grading of non-muscle-invasive bladder urothelial carcinomas. New Section 4.5.1 - Prognostic value of histological grading, has been included, and Table 4.3 WHO 2004/2016 histological classification for flat lesions, was revised, resulting in changes to:

4.9 Summary of evidence and guidelines for bladder cancer classification

Summary of evidence

LE

Histological grading of urothelial NMIBC is classified according to the WHO 1973 (G1-G3) and/or the WHO 2004/2016 (PUNLMP, LG/HG) systems.

2a

Both the WHO 1973 and 2004/2016 classification systems are prognostic for progression, but not for recurrence.

2a

The WHO 1973 was a stronger prognosticator of progression in Ta/T1 NMIBC than the WHO 2004/2016. However, a four-tier combination (LG/G1, LG/G2, HG/G2 and HG/G3) of both classification systems proved to be superior to either classification system alone.

2a

PUNLMP lesions have the same prognosis as Ta/LG carcinomas.

2a

  • Chapter 6 - Predicting disease recurrence and progression, has been completely revised based on the findings of a recent IPD analysis [5]. New risk groups have been developed (Table 6.1) as well as a new table addressing disease progression (Table 6.2), resulting in changes to Sections 6.5, 7.6 and new Section 7.7:

6.5 Summary of evidence and guidelines for stratification of non-muscle-invasive bladder cancer

Summary of evidence

LE

The EAU NMIBC 2021 scoring model and risk tables predict the short- and long-term risks of disease progression in individual patients with primary non-muscle-invasive bladder cancer (NMIBC) using either the WHO 1973 or the WHO 2004/2016 classification system (see Section 6.1.2.1).

2a

The 2006 EORTC scoring model and risk tables predict the short- and long-term risks of disease recurrence and progression in individual patients with NMIBC using the WHO 1973 classification system (see Section 6.1.1.1).

2a

Patients with TaG1/G2 tumours receiving chemotherapy have been further stratified into three risk groups for recurrence, taking into account the history of recurrences, history of intravesical treatment, tumour grade (WHO 1973), number of tumours and adjuvant chemotherapy (see Section 6.1.1.2).

2a-b

In patients treated with 5-6 months of BCG, the CUETO scoring model predicts the short- and long-term risks of disease recurrence and progression using the WHO 1973 classification system (see Section 6.1.1.3).

2a

In patients receiving at least one year of BCG maintenance; prior recurrence rate and number of tumours are the most important prognostic factors for disease recurrence. Stage and grade are the most important prognostic factors for disease progression and disease-specific survival; patient age and grade (WHO 1973) are the most important prognostic factors for overall survival (see Section 6.1.1.4).

2a

Recommendations

Strength rating

Stratify patients into four risk groups according to Table 6.1. A patient’s risk group can be determined using the EAU risk group calculator available at www.nmibc.net.

Strong

For information about the risk of disease progression in a patient with primary TaT1 tumours, use data from Table 6.2

Strong

Use the 2006 EORTC scoring model to predict the risk of tumour recurrence in individual patients not treated with bacillus Calmette-Guerin (BCG).

Strong

Use the 2016 EORTC scoring model or the CUETO risk scoring model to predict the risk of tumour recurrence in individual patients treated with BCG intravesical immunotherapy (the 2016 EORTC model is calculated for 1–3 year of maintenance, the CUETO model for 5 to 6 months of BCG).

Strong

  • In Chapter 7, Section 7.2.2.4 - Optimal BCG schedule, has been expanded; new section: 7.3 - Individual treatment strategy in primary or recurrent tumours after TURB without previous BCG intravesical immunotherapy, has been added. Sections 7.4.2 - Treatment failure after intravesical BCG immunotherapy and 7.4.3. - Treatment of BCG unresponsive tumours, late BCG-relapsing tumours, low-grade recurrences after BCG treatment and patients with BCG intolerance, have been revised. The following recommendations were changed:

7.6 Guidelines for adjuvant therapy in TaT1 tumours and for therapy of carcinoma in situ

Recommendations

Strength rating

The type of further therapy after transurethral resection of the bladder (TURB) should be based on the risk groups shown in Section 6.3 and Table 6.1. For determination of a patient’s risk group use the 2021 EAU risk group calculator available at www.nmibc.net.

In patients with tumours presumed to be at low risk and in those with small papillary recurrences (presumably Ta LG/HG) detected more than one year after previous TURB, offer one immediate chemotherapy instillation.

Strong

In patients with very high-risk tumours discuss immediate radical cystectomy (RC) (see Section 7.5).

Strong

Offer transurethral resection of the prostate, followed by intravesical instillation of BCG to patients with CIS in the epithelial lining of the prostatic urethra.

Weak

The definition of BCG unresponsive should be respected as it most precisely defines patients who are unlikely to respond to further BCG instillations.

Weak

7.7 Guidelines for the treatment of TaT1 tumours and carcinoma in situ according to risk stratification

Recommendations

Strength rating

EAU risk group: Low

Offer one immediate instillation of intravesical chemotherapy after transurethral resection of the bladder (TURB).

Strong

EAU Risk Group: Intermediate

In all patients either one-year full- dose Bacillus Calmette-Guerin (BCG) treatment (induction plus 3-weekly instillations at 3, 6 and 12 months), or instillations of chemotherapy (the optimal schedule is not known) for a maximum of one year is recommended. The final choice should reflect the individual patient’s risk of recurrence and progression as well as the efficacy and side effects of each treatment modality. Offer one immediate chemotherapy instillation to patients with small papillary recurrences detected more than one year after previous TURB.

Strong

EAU risk group: High

Offer intravesical full-dose BCG instillations for one to three years or radical cystectomy (RC).

Strong

EAU risk group: Very High

Consider RC and offer intravesical full-dose BCG instillations for one to three years to those who refuse or are unfit for RC.

Strong

  • Chapter 8 Follow-up of patients with NMIBC, was expanded resulting in amended recommendations:

    8.1 Summary of evidence and guidelines for follow-up of patients after transurethral resection of the bladder for non-muscle-invasive bladder cancer

Recommendations

Strength rating

Patients with high-risk and those with very high-risk tumours treated conservatively should undergo cystoscopy and urinary cytology at three months. If negative, subsequent cystoscopy and cytology should be repeated every three months for a period of two years, and every six months thereafter until five years, and then yearly.

Weak

Regular (yearly) upper tract imaging (computed tomography-intravenous urography [CT-IVU] or IVU) is recommended for high-risk and very high-risk tumours.

Weak

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