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Trends in bladder cancer treatments
Professor Morgan Rouprêt Pitié-Salpétrière Hospital University Paris 6, Paris, France
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Disclosures Consultant and advisory role, Ipsen
Consultant and advisory role, Sanofi Pasteur Member of the EAU- guidelines panel NMIBC Head of the French association- guidelines panel Bladder Cancer
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95% are Urothelial Carcinomas
Renal pelvis Ureter UTUC 5-10% Bladder Cancer 90-95% Siegel R, CA Cancer J Clin, 2012
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Bladder cancer There are 104.000 new cases per year in Europe
Smoking increases the risk by 2 to 5-fold 2/3 of patients with bladder urothelial cell carcinoma are Ta, T1 or CIS (NMIBC) and 1/3 MIBC. Recurrence and progression are the two main problems in the management of NMIBC
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Medico-Economic 5th most expensive cancer on a global perspective
Bladder Cancer Time Consuming (nurses, urologists) Costly +++ (TURBT, Urinary culture, cytology, cystoscopy,…) Range $ / patient Botteman, Pharmacoeconomics 2001 60% treatment et 30% follow-up & complications Avritscher, Urology 2006 5th most expensive cancer on a global perspective THE most expensive Ca/ patient
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MEDIAN AGE at diagnosis
Classification Classification TNM Bladder Cancer NMIBC MIBC Frequency at diagnosis NMIBC : 70-80% MIBC : 20-30% MEDIAN AGE at diagnosis 65 years
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NMIBC vs. MIBC
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Mortality Bladder Cancer
database Surveillance Epidemiology and End Results (SEER) NCI, USA
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Mortality Bladder Cancer
database Surveillance Epidemiology and End Results (SEER) NCI, USA
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STOP SMOKING
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GUIDELINES
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BC: daily practice
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NON MUSCLE INVASIVE BLADDER CANCER
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NMIBC Stratification: Why and How?
PROGNOSIS PRACTICE Recurrence Progression Specific survival Blue light Day care Surveillance TREATMENTS IPOI 2nd TURBT adjuvant instillation early cystectomy
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Stratification PROGNOSIS
EORTC CUETO Scores Stage Grade Size Number Past BCa CIS Stage Grade Number Past BCa CIS Sexe Age Probability of RECURRENCE and of PROGRESSION Sylvester R et al. Eur Urol. 2006 Fernandez-Gomez J et al. J Urol. 2009
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Stratification PROGNOSIS
EORTC CUETO Scores Recurrence 17 1 4 5 9 10 Recurrence 16 9 10 Progression 23 6 7 13 14 2 Progression 16 9 10 LOW HIGH LOW HIGH RISK GROUP Sylvester R et al. Eur Urol Fernandez-Gomez J et al. J Urol. 2009
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Stratification PROGNOSIS
EORTC CUETO Scores Stage Grade Size Number Past BCa CIS Stage Grade Number Past BCa CIS Sex Age STATISTICAL WEIGHT FOR THE RISK OF PROGRESSION Sylvester R et al. Eur Urol. 2006 Fernandez-Gomez J et al. J Urol. 2009
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NMIBC Stratification PROGNOSIS PRACTICE TREATMENTS Recurrence
Progression Blue light Day care Surveillance TREATMENTS IPOI 2nd TURBT Adjuvant instillation Early cystectomy
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NMIBC – risk stratification group
Low risk: primary, unique Ta low grade <3 cm Intermediate risk: Ta low grade, multifocal and/or recurrent, low grade High risk: CIS; TI tumour; High grade; multiple/ recurrent large > 3 cm Ta, G1, G2 tumours EAU GUIDELINES
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TURBT crucial step mandatory must be complete
In the OR, under anesthesia
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？ ？ ？ Causal lesions of intravesical recurrence are
“the endoscopic invisible lesions” Tiny lesion Flat lesion Concomitant flat lesion ？ ？ ？ To detect these invisible lesions
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Concomitant flat lesion
ALA-PDD visualization of bladder lesions Tiny lesion Flat lesion Concomitant flat lesion
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Current European guidelines and the recommendations
PDD in NMIBC: The value of fluorescence cystoscopy for improvement of the outcome in relation to progression rate or survival remains to be demonstrated
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If feasible, tissue preservation would be better
TURB TUR en bloc F #witjes #EAU15
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BLADDER INSTILLATION : BCG or CHEMOTHERAPY
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BCG strains: are all the same?
Not clear! Connaught may be superior Morbidity similar Neuzillet Y t al, Prog en Urol 2015
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Non-grade 3 NMIBC that failed to BCG N= 34 patients
Chemo-Hyperthermia with MMC that employs conductive heating: Unithermia Non-grade 3 NMIBC that failed to BCG N= 34 patients 5 patients toxicity grade 3 No recurrence at one year: 59 % Median followup 41 m: 35.3 % recurrence and 23.5 % progression Soria F et al, World J Urol 2015
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NMIBC Treatment - - TURBT TURBT 2nd TURBT NMIBC low risk
IPOIC + Surveillance TURBT MMC x8 ± + 1/month 2 years NMIBC intermediate risk Failure BCG x6 + 3 BCG x3 + BCG m - - BCG x3 + BCG maintenance TURBT 2nd F/u cystoscopy NMIBC High risk TURBT NMIBC interm. BCG x6 Cystoscopy BCG x6 NMIBC High risk Failure CT MIBC MIBC MIBC
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MUSCLE INVASIVE BLADDER CANCER
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What would be a « Triple A »
Radical Cystectomy ?
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Length of time
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Lymphadenectomy
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Influence of hospital surgical volume
complications, post-operative care, nursing, immunonutrition,..
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Radical Cystectomy
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Surgical approach Oncological outcomes= similar? ?
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WE NEED MORE BASIC RESEARCH
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Boormans and Zwarthoff, Bladder cancer 2016
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Checkpoint clinical trails in bladder cancer
NMIBC MIBC metastatic BCa Low grade High grade Neoadjuvant Adjuvant BCG refractory 1st line Fit for cisplatin 2nd line and more Unfit for cisplatin Pembrolizumab MPDL3280A Cisplatin refractory Maintenance Pembrolizumab (Phase III) MPDL3280A (Phase III) MEDI4736 AMP-514 MSB C MGA271 ongoing Pembrolizumab / BCG Nivolumab + ipilimumab Nivolumab/carbozantinib + ipilimumab Pembrolizumab/radiation MPDL3280A + Bevacizumab MEDI MEDI4736
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Bladder Cancer: treatments
NMIBC TURBT Instillation Stratification MIBC Cystectomy Neo adjuvant chemo NEW DRUGS Immunotherapy Molecular status
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Professor Morgan Rouprêt
Trends in bladder cancer treatments Professor Morgan Rouprêt Paris, France
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