MANAGEMENT OF CARCINOMA URINARY BLADDER

MANAGEMENT OF CARCINOMA URINARY BLADDERMade by:Dr Isha JaiswalGuided by:Prof Kamal SahniDate:04 December 2015

Urinary bladder cancerNMIBC: non muscle invasive bladder cancerMIBC: muscle invasive bladder cancer:Metastatic Disease

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TREATMENT OPTIONSSurgeryChemotherapyImmunotherapyRadiotherapy

Treatment depends on following factorsTumor related factorTNM categorySizeNumber of tumorsGradePresence of concurrent CISPatient related factorAgeMedical comorbiditiesPerformance statusBladder functionsChoice

Non-muscle-Invasive Bladder Cancer70-80% of patients with bladder cancer present with NMIBCThese are classified as Tis, Ta, and T1 by the TNM classification system.Aim of treatment: prevent recurrence & progression to MIBCPrognostication and management strategy are based on accurate initial staging and grading of the disease.

TURBT: transurethral resection of bladder tumorFirst-line to diagnose, stage, and treat visible tumors.Goal: to make the correct diagnosis and completely remove all visible lesions.EUA done before & after TURBT to asses disease extent & residual tumor. Residual tumor can be as high as 53% in T1 tumors.Muscle must be seen in TURBT specimen before ruling out invasive diseaseBiopsies of apparently uninvolved urothelium should be obtained to rule out occult Tis.Biopsy from the prostatic urethra is necessary in some cases. tumour located on trigone or bladder neck, multiple tumours

TURBT is not effective for carcinoma in situ (CIS) because the disease is often so diffuse and difficult to visualize that surgical removal is not feasible.

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TURBTPathologist should comment on:Sizetumour gradedepth of tumour invasion,presence of CISwhether the detrusor muscle is present in the specimen.specify the presence of LVI or unusual (variant) histology

If there is uncertainty over the pathology, a further early re-resection (2-6 wk.) is indicated.

Second look TURBT?IndicationsResidual disease after initial TURBTWhen specimen contained no muscle High-grade and/or T1 tumor Timing and strategy:Most recommend 2-6 weeks after initial TURShould include resection of primary tumor siteEvidence: 2nd look TURBT in T1 /HG tumor1/2 will have residual disease on 2nd look [EAU 2010]Under stage is more if muscle is absence (50% vs 15%) [Herr JU 1999]1/4 will have upstage [Herr JU1999]1/3 will have to change management [Herr JU 1999]20% increase 5yr DFS [Germen observational study 2003]8European Association of Urology Guidelines 2015.

88Persistent disease after resection of T1 tumours has been observed in 33-55% of patients, and after resectionof TaG3 tumour in 41.4% [111-115].

Moreover, the tumour is often understaged by initial resection. The likelihood that muscle-invasivedisease is detected by second resection of initially T1 tumour ranges from 4-25%, and it increases to 45% ifthere was no muscle in the initial resection [86]. This risk has increased up to 50% in some radical cystectomy(RC) series, although these studies only enrolled selected patients [116-118] (LE: 2a). Treatment of a Ta, T1high-grade tumour and a T2 tumour is completely different; correct staging is therefore important.

It has been demonstrated that a second TURB can increase recurrence-free survival [111, 112](LE: 2a), improve outcomes after BCG treatment [119] (LE: 3) and provide prognostic information [116, 120](LE: 3)

Predicting recurrence and progression of NMIBCEORTC bladder cancer calculator CUETO risk calculator.

NMIBC, can be classified as low, intermediate, or high risk It is based on combined analysis of individual pt. data of 2596 pt. from 7 EORTC trials to predict recurrence and progression in patient with stage Ta, T1 bladder cancerNote: pt. in these trial. does not have 2nd TURBT or maintenance BCG recurrence and progression rates reported here may be higher than those found in current clinical practice.

Sylvester RJ, et al Predicting Recurrence and Progression in Individual Patients with Stage Ta T1 Bladder Cancer Using EORTC Risk Tables: A Combined Analysis of 2596 Patients from Seven EORTC Trials. European Urology 49: 466 - 477, 2006EORTC bladder cancer calculator

European Organisation for Research and Treatment of Cancer. Bladder cancer calculator. Available at:http://www.eortc.be/tools/bladdercalculator/.

Number of tumorsTumor sizePrior recurrence rateT categoryConcomitant carcinoma in situGrade

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Scoring System To Predict 1-yr& 5-yr Recurrence & Progression12

based on six clinical and pathological factors:

most important prognostic factors

for recurrence number of tumorssize,prior recurrence rate.

for progression T categorygradepresence of CIS

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predicts risks of recurrence and progression for BCG-treated patients based on an analysis of 1,062 patients from 4 CUETO trials that compared different intravesical BCG treatments. No immediate postoperative instillation or second TURB was performedThe scoring system is based on evaluation of seven prognostic factorssexageprior recurrence statusnumber of tumoursT categoryassociated CIS;tumour grade.Calculated risk of recurrence is lower than EORTC.Progression risk is lower only in high risk patient. Attributed to BCG therapy in the studies

CUETO risk calculator (Spanish Urological Oncology Group).CUETO risk calculator is available at: http://www.aeu.es/Cueto.html

Implication Of Risk StratificationDecide adjuvant treatmentDecide follow up schedule

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Treatment recommendations in Ta, T1 tumours and CIS according to risk stratificationEuropean Association of Urology Guidelines 2015.

Indications of adjuvant intravesical therapy after TURBT in NMIBCIntermediate & high risk featuresIncomplete excision especially in T1 tumorstumors rapidly recur following TURBT of the initial bladder tumorpersistent tumor cells on urine cytology during surveillance

Adjuvant therapy is given in the form of intravesical administration of immunotherapy or chemotherapy.

Immunotherapy Bacillus Calmette Guerin, live attenuated form of M. bovisActs as immune stimulant: stimulates cellular response releasing cytokines IL-1,2,6,8,TNF and IFN gammaGiven 1-2 weeks after resection, weekly for 6 weeks f/b maintenance as 3 weekly for a 1-3 year .(3yr better)Patient is dehydrated over night. Urine is voided completely.50 mg of TICE in 50cc of 0.9% NS is instilled via catheter. Patient is asked to void urine after 2 hoursS/E : Urinary frequency ,dysuria, hematuriaArthralgia, rash, feverPneumonitis, hepatitis, prostatitis, sepsis

fever, joint pain, granulomatous prostatitis, sinus formation, disseminated tuberculosis, and death; thioTEPA may cause myelosuppression; mitomycin C may cause skin desquamation and rash; and doxorubicin may cause gastrointestinal upset and allergic reactions. The proposed benefit of intravesical chemotherapy is to lessen the rate of recurrences and reduce the incidence of progression. Unfortunately, it cannot be clearly stated that any of these drugs accomplish these goals over the long ter18

Intravesical chemotherapyChemotherapeutic agents used are mitomycin C, doxorubicin, and thiotepa.Similar efficacy in prolonging time to recurrence.Different toxicity profileMitomycin C may cause skin desquamation and rashDoxorubicin may cause G.I upset and local reaction causing urinary urgency.Thiotepa causes myelosuppression

BCG VS MITOMYCINIndividual patient data (IPD) meta-analyses of nine trials that included 2820 patientsOverall, there was no difference in the time to first recurrence (p=0.09) between BCG and MMC. In the trials with BCG maintenance, a 32% reduction in risk of recurrence on BCG compared to MMC was found (p