(Limited text update March 2018)

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


The EAU Working Group has published guidelines on Non-muscle-invasive bladder cancer (NMIBC), TaT1 tumours and carcinoma in situ (CIS).

Staging and classification systems

The 2017 TNM (Tumour, Node, Metastasis Classification) is used for staging (Table 1). For grading, both the 1973 and 2004 WHO Grading classifications are used (Table 2).

Non-muscle-invasive (TaT1, CIS) Bladder Cancer 9

Table 1: TNM Classification 2017

T - Primary Tumour

TX Primary tumour cannot be assessed

T0 No evidence of primary tumour

Ta Non-invasive papillary carcinoma

Tis Carcinoma in situ:’flat tumour’

T1 Tumour invades subepithelial connective tissue

T2 Tumour invades muscle

T2a Tumour invades superficial muscle (inner half)

T2b Tumour invades deep muscle (outer half)

T3 Tumour invades perivesical tissue

T3a Microscopically

T3b Macroscopically (extravesical mass)

T4 Tumour invades any of the following: prostate stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall

T4a Tumour invades prostate stroma, seminal vesicles, uterus or vagina

T4b Tumour invades pelvic wall or abdominal wall

N – Regional Lymph Nodes

NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Metastasis in a single lymph node in the true pelvis (hypogastric, obturator, external iliac, or presacral)

N2 Metastasis in multiple regional lymph nodes in the true pelvis (hypogastric, obturator, external iliac, or presacral)

N3 Metastasis in common iliac lymph node(s)

10 Non-muscle-invasive (TaT1, CIS) Bladder Cancer

M - Distant Metastasis

M0 No distant metastasis

M1a Non-regional lymph nodes

M1b Other distant metastases

The prognostic value of both WHO 1973 and 2004 grading systems has been confirmed. The WHO 2004 system has not yet been fully incorporated into prognostic models.

Carcinoma in situ
Carcinoma in situ (CIS) is a flat, high-grade, non-invasive urothelial carcinoma, and classified into the following clinical types:

  • Primary: isolated CIS with no previous or concurrent

    papillary tumours and no previous CIS;

  • Secondary: CIS detected during follow-up of patients with

    a previous tumour that was not CIS;

  • Concurrent: CIS in the presence of any other urothelial

    tumour in the bladder.

    Table 2: WHO grading in 1973 and in 2004

1973 WHO grading

Grade 1: well differentiated
Grade 2: moderately differentiated Grade 3: poorly differentiated

2004 WHO grading system (Papillary lesions)
Papillary urothelial neoplasm of low malignant potential (PUNLMP)
Low-grade (LG) papillary urothelial carcinoma High-grade (HG) papillary urothelial carcinoma

Non-muscle-invasive (TaT1, CIS) Bladder Cancer 11

Recommendations for bladder cancer classification (NMIBC)

Strength rating

Use the 2017 TNM system for classification of the depth of tumour invasion (staging).


Use both the 1973 and 2004/2016 WHO grading systems for histological classification.


Do not use the term “superficial bladder cancer”.


Mention the tumour stage and grade whenever the terminology NMIBC is used in individual cases.



A comprehensive patient history is mandatory. Haematuria is the most common finding. Physical examination does not reveal NMIBC.

Recommendations for the primary assessment of non-muscle-invasive bladder cancer (NMIBC)

Strength rating

Take a patient history, focusing on urinary tract symptoms and haematuria.


Renal and bladder ultrasound and/or computed tomography-intravenous urography may be used during the initial work-up in patients with haematuria.


Once a NMIBC has been detected, perform a computed tomography urography in selected cases (e.g., tumours located in the trigone, multiple- or high-risk tumours).


12 Non-muscle-invasive (TaT1, CIS) Bladder Cancer

Perform cystoscopy in patients with symptoms suggestive of bladder cancer or during surveillance. It cannot be replaced by cytology or by any other non-invasive test.


In men, use a flexible cystoscope, if available.


Describe all macroscopic features of the tumour (site, size, number and appearance) and mucosal abnormalities during cystoscopy. Use a bladder diagram.


Use voided urine cytology as an adjunct to cystoscopy to detect high-grade tumour.


Perform cytology on fresh urine or urine with adequate fixation. Morning urine is not suitable because of the frequent presence of cytolysis.


Use the Paris system for cytology reporting.


Repeat urine cytology in patients with initial cytology results suspicious for high-grade urothelial carcinoma.


Papillary (TaT1) tumours

The diagnosis of papillary bladder cancer ultimately depends on cystoscopic examination of the bladder and histological evaluation of the tissue resected during transurethral resection (TURB). TURB is a crucial procedure in the diagnosis and treatment of TaT1 tumours and should be performed systematically in individual steps (see recommendations below). The strategy of resection depends on the size of the lesion. In selected cases, due to the risk of tumour persistence and understaging after initial TURB, a second resection

(2nd TURB) is recommended.

Non-muscle-invasive (TaT1, CIS) Bladder Cancer 13

Carcinoma in situ
Carcinoma in situ is diagnosed by a combination of cystoscopy, urine cytology, and histological evaluation of multiple bladder biopsies. Carcinoma in situ cannot be eradicated by TURB and further treatment is mandatory.

Recommendations for transurethral resection of the bladder (TURB), biopsies and pathology report

Strength rating

In patients suspected of having bladder cancer, perform a TURB followed by pathology investigation of the obtained specimen(s) as a diagnostic procedure and initial treatment step.


Perform TURB systematically in individual steps:
• bimanual palpation under anaesthesia; • insertion of the resectoscope, under

visual control with inspection of the

whole urethra;
• inspection of the whole urothelial lining

of the bladder;
• biopsy from the prostatic urethra

(if indicated);
• cold-cup bladder biopsies (if indicated); • resection of the tumour;
• recording of findings in the surgery

• precise description of the specimen for

pathology evaluation.


14 Non-muscle-invasive (TaT1, CIS) Bladder Cancer

Performance of individual steps

Perform en-bloc resection or resection in fractions (exophytic part of the tumour, the underlying bladder wall and the edges of the resection area). The presence of detrusor muscle in the specimen is required in all cases except for TaG1/LG tumours.


Avoid cauterisation as much as possible during TURB to avoid tissue deterioration.


Take biopsies from abnormal-looking urothelium. Biopsies from normal-looking mucosa (trigone, bladder dome, and right, left, anterior and posterior bladder wall) are recommended when cytology is positive

or when high-risk exophytic tumour is expected (non-papillary appearance). If equipment is available, perform fluorescence-guided (PDD) biopsies.


Take biopsy of the prostatic urethra in cases of bladder neck tumour, when bladder carcinoma in situ is present or suspected, when there is positive cytology without evidence of tumour in the bladder, or when abnormalities of the prostatic urethra are visible. If biopsy is not performed during the initial procedure, it should be completed at the time of the second resection.


Non-muscle-invasive (TaT1, CIS) Bladder Cancer 15

Take the biopsy from abnormal areas in the prostatic urethra and from the precollicular area (between the 5 and 7 o’ clock position) using a resection loop. In primary non- muscle-invasive tumours when stromal invasion is not suspected, cold-cup biopsy with forceps can be used.


Use methods to improve tumour visualisation (FC, NBI) during TURB, if available.


Refer the specimens from different biopsies and resection fractions to the pathologist in separately labelled containers.


The TURB protocol must describe tumour appearance, all steps of the procedure, as well as the extent and completeness of resection.


In patients with positive cytology, but negative cystoscopy, exclude an upper tract urothelial carcinoma, CIS in the bladder (random biopsies or PDD-guided biopsies) and tumour in the prostatic urethra (prostatic urethra biopsy).


Perform a second TURB in the following situations:

• • •

after incomplete initial TURB, or in
case of doubt about completeness of a TURB);
if there is no muscle in the specimen after initial resection, with the exception of TaLG/G1 tumours and primary CIS;

in T1 tumours.


16 Non-muscle-invasive (TaT1, CIS) Bladder Cancer

If indicated, perform a second TURB within two to six weeks after initial resection. This second TURB should include resection of the primary tumour site.


Register the pathology results of a second TURB as it reflects the quality of the initial resection.


Inform the pathologist of prior treatments (intravesical therapy, radiotherapy, etc.).


Pathological report

The pathological report should specify tumour location, tumour grade, depth of tumour invasion, presence of CIS, and whether the detrusor muscle is present in the specimen.


The pathological report should specify the presence of lymphovascular invasion or unusual (variant) histology.


Predicting disease recurrence and progression

After TURB, patients should be stratified, according to prognostic factors, into risk groups which will facilitate treatment recommendations (see Table 3). For individual prediction of the risk of tumour recurrence and progression at different intervals after TURB, application of EORTC risk tables and calculator (http://www.eortc.be/tools/bladdercalculator/) is strongly recommended.

For bacillus Calmette-Guerin (BCG)-treated patients, scoring models have been created by the CUETO and the EORTC. The CUETO risk calculator is available at: http://www. aeu.es/Cueto.html.

Non-muscle-invasive (TaT1, CIS) Bladder Cancer 17

Table 3: Treatment recommendations in TaT1 tumours and carcinoma in situ according to risk stratification

Risk category


Treatment recommendation

Low-risk tumours

Primary, solitary, TaG1 (PUNLMP, LG*),<3cm,no CIS.

One immediate instillation of intra- vesical chemotherapy after TURB.

Intermediate- risk tumours

All tumours not defined in the two adjacent categories (between the category of low and high-risk).

In patients with previous low recurrence rate (≤ one recurrence per year) and expected EORTC recurrence score < 5, one immediate instillation of intravesical chemotherapy after TURB. In all patients either one-year full- dose BCG treatment (induction plus three- weekly instillations at three, six and twelve months), or instillations of chemotherapy (the optimal schedule is not known) for a maximum of one year.

18 Non-muscle-invasive (TaT1, CIS) Bladder Cancer

High-risk tumours

Any of the following:
• T1 tumours;
• G3 (HG**) tumour; • CIS;
• Multiple,

recurrent and large (> 3 cm) TaG1G2/LG tumours (all features must be present)*.

Intravesical full-dose BCG instillations for one to three years or radical cystectomy (in highest-risk tumours - see below).

Subgroup of highest-risk tumours

T1G3/HG associated with concurrent bladder CIS, multiple and/ or largeT1G3/HG and/or recurrent T1G3/HG, T1G3/HG with CIS in the prostatic urethra, some forms of variant histology
of urothelial carcinoma, LVI.

Radical cystectomy (RC) should be considered.

In those who refuse or are unfit for RC

intravesical full-dose BCG instillations for one to three years.

BCG-refractory tumours.

Radical cystectomy is recommended.

*Low grade is a mixture of G1 and G2.
** High grade is a mixture of some G2 and all G3.

Non-muscle-invasive (TaT1, CIS) Bladder Cancer 19

Recommendations for stratification of non-muscle-invasive bladder cancer

Strength rating

Stratify patients into three risk groups according to Table 3.


Apply the EORTC risk tables and calculator for the prediction of the risk of tumour recurrence and progression in different intervals after transurethral resection of the bladder, in individual patients.


Use the CUETO risk tables and the new EORTC risk groups for the prediction of the risk of tumour recurrence and progression in individual patients treated with bacillus Calmette-Guérin.


Disease management

Adjuvant treatment

Since there is considerable risk for recurrence and/or progression of tumours after TURB, adjuvant intravesical therapy is recommended for all stages (TaT1, and CIS).

  • Immediate single post-operative instillation of chemo-

    therapy within six hours after TURB can reduce recurrence rate in patients with low-risk and selected intermediate- risk tumours. The difference of efficacy between individual drugs (mitomycin C, epirubicin, or doxorubicin) has not been confirmed.

  • Further chemotherapy instillations can improve recurrence-free survival in intermediate-risk tumours, but do not prevent progression. These instillations are associated with minor side-effects.

  • Intravesical immunotherapy with BCG (induction and maintenance) is superior to intravesical chemotherapy in reducing recurrences and in preventing or delaying progression to muscle-invasive bladder cancer. However, intravesical BCG is more toxic.

20 Non-muscle-invasive (TaT1, CIS) Bladder Cancer

The individual choice of further intravesical adjuvant therapy depends on the patient’s risk (Table 3). In patients at highest risk of progression, radical cystectomy (RC) should be considered. Patients with BCG failure are unlikely to respond to further BCG therapy; RC is therefore the preferred option.

General recommendations for adjuvant therapy in TaT1 tumours and for therapy of CIS

Strength rating

Counsel smokers with confirmed non- muscle-invasive bladder cancer to stop smoking.


The type of further therapy after transurethral resection of the bladder should be based on the risk groups shown in Table 3.


In patients with tumours presumed to be at low risk and in those presumed to be at intermediate risk with previous low recurrence rate (≤ one recurrence per year) and expected EORTC recurrence score < 5, one immediate chemotherapy instillation is recommended.


Non-muscle-invasive (TaT1, CIS) Bladder Cancer 21

In patients with intermediate-risk tumours (with or without immediate instillation), one-year full-dose bacillus Calmette- Guérin (BCG) treatment (induction plus three-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.


In patients with high-risk tumours, full-dose intravesical BCG for one to three years (induction plus three-weekly instillations
at 3, 6, 12, 18, 24, 30 and 36 months), is indicated. The additional beneficial effect of the second and third years of maintenance should be weighed against its added costs and inconveniences.


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


Discuss immediate radical cystectomy (RC) with patients at highest risk of tumour progression.


Perform a RC in patients with BCG failure.


In patients with BCG-refractory tumours, who are not candidates for RC due to comorbidities, use preservation strategies (intravesical chemotherapy, chemotherapy and microwave-induced hyperthermia).


22 Non-muscle-invasive (TaT1, CIS) Bladder Cancer

Recommendations – technical aspects for treatment

Intravesical chemotherapy

If given, administer a single immediate instillation of chemotherapy within
24 hours after TURB.


Omit a single immediate instillation of chemotherapy in any case of overt or suspected bladder perforation or bleeding requiring bladder irrigation.


Give clear instructions to the nursing staff to control the free flow of the bladder catheter at the end of the immediate instillation.


The optimal schedule and duration of further intravesical chemotherapy instillation is not defined; however, it should not exceed one year.


If intravesical chemotherapy is given, it is advised to use the drug at its optimal pH and to maintain the concentration of the drug by reducing fluid intake before and during instillation.


The length of individual instillation should be one to two hours.


BCG intravesical immunotherapy

Absolute contraindications of BCG intravesical instillation are:
• during the first two weeks after TURB; • in patients with visible haematuria;
• after traumatic catheterisation;
• in patients with symptomatic urinary

tract infection.


Non-muscle-invasive (TaT1, CIS) Bladder Cancer 23


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

    non-muscle-invasive recurrence is crucial because a delay

    in diagnosis and therapy can be life-threatening.

  • Tumour recurrence in the low-risk group is nearly always

    low stage and LG/G1. Small, TaLG/G1 papillary recurrence does not present an immediate danger to the patient and early detection is not essential for successful therapy. Fulguration of small papillary recurrences on an outpatient basis could be a safe option that reduces the therapeutic burden. Multiple authors have even suggested temporary surveillance in selected cases.

  • The first cystoscopy after TURB at three months is a very important prognostic indicator for recurrence and progression. Therefore, the first cystoscopy should always be performed three months after TURB in all patients with TaT1 tumours and CIS.

  • In tumours at low risk, the risk of recurrence after five recurrence-free years is low.

  • Discontinuation of cystoscopy or its replacement with less invasive methods can be considered.

  • In tumours originally intermediate- or high risk, recurrences after ten years tumour-free are not unusual. Therefore, life-long follow-up is recommended.

  • The follow-up strategy must reflect the risk of extravesical recurrence (prostatic urethra in men and upper urinary tract in both genders).

24 Non-muscle-invasive (TaT1, CIS) Bladder Cancer

  • The risk of upper urinary tract recurrence increases in patients with multiple- and high-risk tumours.

  • Positive urine test results have a positive impact on the quality of performed follow-up cystoscopy, supporting the adjunctive role of urine tests during follow-up.

  • In patients initially diagnosed with TaLG/G1-2 BC, US of the bladder may be a mode of surveillance in case cystoscopy is not possible or refused by the patient.

Recommendations for follow-up in patients after transurethral resection of the bladder

Strength rating

Base follow-up of TaT1 tumours and carcinoma in situ (CIS) on regular cystoscopy.


Patients with low-risk Ta tumours should undergo cystoscopy at three months. If negative, subsequent cystoscopy is advised nine months later, and then yearly for five years.


Patients with high-risk tumours 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.


Patients with intermediate-risk Ta tumours should have an in-between (individualised) follow-up scheme using cystoscopy.


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


Non-muscle-invasive (TaT1, CIS) Bladder Cancer 25

Endoscopy under anaesthesia and bladder biopsies should be performed when office cystoscopy shows suspicious findings or if urinary cytology is positive.


Consider random (R)-biopsies or photodynamic diagnosis (PDD)-guided biopsies after intravesical treatment (at three or six months) in patients with CIS.


During follow-up in patients with positive cytology and no visible tumour in the bladder, R-biopsies or PDD-guided biopsies (if equipment is available) and investigation of extravesical locations (CT urography, prostatic urethra biopsy) are recommended.


In patients initially diagnosed with TaLG/ G1-2 bladder cancer, use ultrasound of the bladder during surveillance in case cystoscopy is not possible or refused by the patient.


This short booklet text is based on the more comprehensive
EAU Guidelines (ISBN: 978-94-92671-01-1), available to all members of the European Association of Urology at their website: http://www.uroweb.org/guidelines/.

26 Non-muscle-invasive (TaT1, CIS) Bladder Cancer