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Guidelines on Bladder Cancer$ European Urology European Urology 41 2002) 105±112 Guidelines on Bladder Cancer$ Willem Oosterlincka,*, Bernard Lobelb, Gerhard Jaksec, Per-Uno MalmstroÈmd, Michael StoÈcklee, Cora Sternbergf The EAU Working Group on Oncological Urology$$ aDepartment of Urology, University Hospital Ghent, De Pintelaan 185, B-9000 Gent, Belgium bCHRU Pontchaillou, Rennes, France cUniversity Clinics RWTH, Aachen, Germany dUniversity Hospital, Uppsala, Sweden eUniversity Saarland, Homburg, Saar, Germany fClinic Pio XI, Rome, Italy Abstract Objectives: On behalf of the European Association of Urology EAU) guidelines for diagnosis, therapy and follow- up of bladder cancer patients were established. Criteria for recommendations were evidence based, and included aspects of cost-effectiveness and clinical feasibility. Method: A systematic literature research using Medline Services was conducted. References were weighted by a panel of experts. Results: TNM 1997 classi®cation and WHO grading 1998 are recommended. Recommendations are developed for diagnosis for bladder cancer in general, treatment of super®cial and in®ltrative bladder cancer, and follow-up after different types of treatment modalities, such as intravesical instillations, radical cystectomy, urinary diversions, radiotherapy and chemotherapy. # 2002 Elsevier Science B.V. All rights reserved. Keywords: Bladder cancer; Super®cial bladder cancer; Guidelines 1. Classification of bladder cancer transurethral resection TUR), imaging studies and histopathological ®ndings. The use of the TNM classi®cation 1997 and WHO There is also important inter observer variability in grading, 1999, is encouraged, as it corresponds best classifying stage T1 versus Ta tumours and grading with the clinical outcome of the tumours [1]. tumours [2]. More than 90% of bladder cancers are transitional cell carcinoma TCC); the remainder are squamous cell or adenocarcinoma. 2. Diagnosis Bladder tumours are considered super®cial TIS-Ta- T1) or in®ltrative T2-T3-T4) based on cystoscopy, 2.1. Early detection Early symptom recognition in bladder tumours is a key to better prognosis [6,7]. Haematuria is the most common ®nding in bladder cancer. The degree of haematuria does not correlate with the extent $ For more extensive information consult the EAU Guidelines presented of the disease. at the XVI EAU Annual Congress, Geneva, Switzerland ISBN: Bladder cancer may also present with voiding irritability. 90-806179-3-9). $$ EAU Working Group on Oncological Urology Chairman: Prof. Dr. C.C. Abbou): Membersof the EAU Working Group on 2.2. Imaging Oncological Urology are the EAU Working Groupson Bladder Intravenous pyelography is considered as an important exam- Cancer, Penile Cancer, Prostate Cancer and Testis Cancer. ination to evaluate haematuria but the necessity to perform routi- * Corresponding author. Tel. 32-9-240-2276; Fax: 32-9-240-3889. nely is now questioned because of the low incidence of important E-mail address: [email protected] W. Oosterlinck). ®ndings obtained [3]. Ultrasonography combined with plain 0302-2838/02/$ ± see front matter # 2002 Elsevier Science B.V. All rights reserved. PII:S0302-283801)00026-4 106 W. Oosterlinck et al. / European Urology 41 52002) 105±112 abdominal ®lm was found to be as accurate in the diagnosis of the progression, side effects and cost-effectiveness. The cause of haematuria as IVP. recurrence rate of super®cial bladder cancer SBC), Computed tomography scanning may be part of the evaluation of even after adequate treatment, is widely documented invasive bladder tumours and the evaluation of pelvic and abdom- inal lymph node metastasis. Its usefulness in predicting the local [6,7]. The riskof progression to invasive cancer is extent of the disease is reduced by artefactual abnormalities in the low in the majority of cases, but goes up to 50% in perivesical tissues. high-grade T1G3 [7,8], which represents around 10% The signi®cance of routine bone scans before total cystectomy in of cases. in®ltrative tumours is questionable. The riskof recurrence and progression can be pre- dicted on the basis of clinical and pathological data. 2.3. Urinary cytology Examination of a voided urine or bladder barbotage specimen for exfoliated cancer cells is particularly useful when a high-grade 3.1.1. Prognostic factors malignancy or CIS is present. It remains often negative in low- The prognostic factors for recurrence in descending grade tumours. importance) [9,10] are the following. 2.4. Cystoscopy and TUR 1. The number of tumours present at diagnosis. A bimanual examination should be performed ®rst to assess 2. Recurrence rate in the previous period; a recur- whether or not a mass is palpable in the bladder and, if so, whether rence at 3 months. it is ®xed to the pelvic wall. TUR of the bladder tumour should be 3. Size of the tumour: the larger the tumour, the done so as to maximise the preservation of architectural detail and the relation of the tumour to the various layers of the bladder wall. higher the riskof recurrence. The more super®cial component of the tumour should be 4. Anaplasia grade of the tumour. resected separately from its deeper component. Biopsy specimens of the tumour and suspected area should be For evolution to invasive disease, anaplasia grade taken to map the extent of the disease. Random biopsies of normal and the T-category are of outmost importance. mucosa are indicated in the presence of positive cytology, even in Based on the prognostic factors, SBC can be divided the absence of a tumour, or in any non-papillary tumour. Random into the following riskgroups: biopsies in patients with solitary papillary lesions are not indicated because of the absence of additional information [4] and because it Low-risktumours: single, Ta, G1, 3 cm diameter. may be nocious, as lesions to the mucosa can provoke implantation High-risktumours: T1, G3, multifocal or highly of tumour cells. Prostatic urethra biopsies by TUR are indicated for recurrent, CIS TIS). suspicion of TIS of the bladder in view of the high frequency of Intermediate: all other tumours, Ta-1, G1-2, multi- involvement of the prostatic urethra [5]. focal, >3 cm diameter. Immediate instillation after TUR with a chemother- 3. Treatment apeutic agent should be encouraged in all cases as it is able to reduce recurrence rate by about 50% [11,12]. In Ta-1 are superficial bladder tumours. Treatment will intermediate risktumours that needs a further instilla- be directed towards the prevention of recurrence and tion, an early instillation can reduce the need for progression of the disease. maintenance therapy [13]. Low-risktumours need no T1G3 has a high tendency to progression. The role of further treatment. early cystectomy still is a matter of debate. Tumours with a higher riskof recurrence should be TIS is a potential highly malignant disease that can treated with a 4±8-week-course of bladder instillation. still be treated in the majority of cases with bladder Severe bladder irritation is a reason to delay or stop the instillations of BCG. A cystectomy is necessary treatment to avoid invalidating symptoms for the when this fails to cure the disease after two cycles patient and later bladder contraction. Side effects are of six weekly instillations. related to the intensity of the treatment regimen. Tumours of T2 or higher category are infiltrating The usefulness of repeated instillations with che- tumours and cystectomy will be necessary in the motherapeutic agents is not clearly de®ned. majority of cases. Bladder preservation can be an There is no proof that chemotherapeutic instillations option in selected cases. longer than 6 months are worthwhile, if no recurrence N and metastatic diseases needs additional ther- is noticed. Intravesical therapy may be effective mainly apeutic approaches. by reducing the hazard of recurrence in the ®rst phase after therapy. 3.1. Treatment of Ta and T1 lesions On recurrence, the initial instillation schedule is The therapeutic regimen for a Ta and T1 tumour restarted. In case of highly recurrent SBC or multiple will take into account the risk of recurrence and recurrences it is advocated to change to BCG therapy W. Oosterlinck et al. / European Urology 41 52002) 105±112 107 because of its proven results in these circumstances 4.1. Indications [14]. Progression of T1 tumours involves muscle The indication for cystectomy is a patient with in®ltration and should be treated accordingly. muscle-invasive bladder cancer T2-T4a, N0-NX, M0. Other indications are patients with high-risksuper®cial 3.1.2. BCG tumours and BCG resistant TIS and T1G3 and exten- It has been found more effective in high-riskSBC sive papillary disease that cannot be controlled with BCG is able to prevent progression. conservative measures. Six weekly induction instillations of BCG are neces- sary to provoke an immunological response and three 4.2. Technique cycles are necessary as a booster to obtain the same Radical cystectomy consists of removal of the blad- immunological reaction. In papillary T1-a G1-2 der and neighbouring organs, such as the prostate and lesions, one can reduce the dose to 25% with the same seminal vesicles in men and uterus and adnexa in effectiveness as the full dose and less general side women. The distal part of the ureters is also usually effects [15]. resected and in cases with CIS a frozen section of the BCG is not indicated in low-riskgroups in which the margin is advisable. The indications for urethrectomy potential danger of BCG does not counterbalance its are controversial. Currently, urethrectomy is recom- advantage. mended if the tumour involves the bladder neckin Lower recurrence rates have been reported after women and the prostatic urethra in men. maintenance therapy of up to 3 years [14]. Whether A radical cystectomy also includes a dissection of or not this heavy schedule is necessary for all patients is the regional lymph nodes, which will give valuable uncertain. prognostic information. No controlled studies exist supporting the curative value of lymph node dissection 3.2.
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