1 Instituto Valenciano de Oncología.CANCRO DA BEXIGA BLADDER CANCER Bladder Preservation Preservasao da Bexiga Eduardo Solsona Servicio de Urologia Instituto Valenciano de Oncología. Valencia

2 Therapeutic AlternativesRadical Treatment: Cystectomy (CTx) 2. Conservative Treatments: ● Monoterapy: PCx/ Radical TUR, RT, Chemotherapy ● Bimodal Treatments: TUR+Chemotherapy Chemo-Radiotherapy ● Trimodals Treatments: TUR ± Radiotherapy ± Chemotherapy

3 } Radical TUR (complete & fractionated) NegativeExophitic part (1st sample) Endophitic part (2nd sample) Biopsies on clean tumoural bed (3th sample) x Negative } Biopsies on perivesical fat (4th sample) ● NO obstructive uropathy and cN0 & M0 (CT-scan) ● NO T2 en re-TUR in pts. refered from other Hospitals - MSKCC - MD Anderson

4 Radical TUR: Rational Incidence of pT0 in CTx specimen (x=12%(9-14%)● cT2 ►:pT0 = 11.5%; cTa-Tis-1= 31.7%1 ● cT2 con RTU completa►: pT0=31.3%2 ● Microscopic unaccuracy of TUR radicality - frontal o tentacular growth ● Infrastaging: 36% cT2 son pT≥3 Problems Solution ● Inclusion criteria –aims-: - Identify tumours limited to the muscle (pT2) - Achieve a TUR microscopically complete 1Isbarn H J Urol (09)182:459; 2Volkmer BG Cancer (05)104:2384 1Shariat SF Eur Urol (07) 51: 137

5 Inclusion criteria ● NEGATIVE Bx on apparently healthy muscular layer and perivesial fat ● NO obstructive uropathy and negative nodes and metastasis ● NO T2 on re-TUR (2-6 weeks) in pts. refered from other Hospitals - MSKCC and MD Anderson 83 ( mos) 100 (75.2) 107 (80.5) 7 (5.3) 30 (22.4) 37 (27.7) 35 (26.2) 133 Solsona1 Median FU. Bladder preservation (%) Cancer-specífic survival (%) -cT0M1 -cT2 Progression (%) Recurrence -cTa-1- (%) No. Pts 29 mos 19 (70) 1 (3.7) 5 (18.5) 6 (22.2) 9 (33.3) 27 Leivobici3 5.1 (3-7 yrs.) 30 (67) 2 (93) 37 (82.2) 2 (4.4) 13 (28.8) 15 (33.3) 21 (46.6) 45 Herr2 Series 1 Solsona E J Urol (98)159: 95; 2 Herr HW J Clin Oncol (01)19:89. 3 Leibovici D Urology (07) 70:473

6 Radical TUR: at 10 yrs. ResultsSlight increase of progression and cancer-specific survival decrease Authors Solsona2 10-yr 75 57 - 8 -26 34 56 Herr1 99 Evaluation at 10-yr No. patients 133 % recurrence 25.2 % progression 28.5 -T2 -23.3 -T0M1 - 5.2 % Cancer-specific survival 79.5 % Bladder preservation 64.9 1Herr HW J Clin Oncol (01)19:89; 2Solsona E J Urol (98)159: 95

7 Radical TUR: at 15 yrs. Results133 patients with minimum follow-up of 15 years Patient’ status No. (%) Median FU mos. (range) Recurrence 40 (30) 21 (3-247) Progression 40 (30) 26 (3-135) - T2M0 - 30 (22.5) 29 (4-135) - T2M1 - 3 (2.2) 12 (3-36) - T0M1 - 7 (5.2) 21 (11-30) Lost of follow-up 9 (6.7) 159 ( ) Died of tumor 27 (20.3) 34 (11-183) Alive free of tumor 14 (10.7) 220 ( ) Died free of tumor 83 (62.4) 99 (44-305) 1Solsona E. J.Urol (10) 184:475

8 Radical TUR: at 15 yrs. ResultsCancer-specific survival: stable after 10 years 15 yrs 10 yrs 5 yrs Survival 79.5 81.9 % Cancer-specific 24.8 39.8 73.7 % Overall 61.9 70.2 81.8 % Local progression-free with bladder preserved 57.8 64.9 75.5 % Progression-free with bladder preserved 30.0 27.7 25.5 % Progression 151 pts with same inclusion criteria: 99 prefered TURB and 53 CTx Herr’ series3 1Solsona E. J.Urol (10) 184:475; 3 Herr H.W. JCO (01) 19:89

9 Bimodal Treatment: TUR+ChemotherapyInclusion Criteria 1. Complete TUR 2. POSITIVE Bx on apparently healthy muscular layer 3. NO - hydronephrosis - cN / M+ (CT-scan, chest x-ray) 1989 Solsona E Eur Urol (09) 55:911

10 Comparative trial: TUR+chemotherapy vs CTxScheme: 1. 3 cycles of Cispatin-based chemotherapy (MVAC/CG) 2. After 3rd cycle: CT-scan, TUR of scar or residual tumour, cytology, random bladder Bx, bimanal examination under anaesthesia Response to Chemotherapy Criteria N0 and M0 Distant M+ T2 Non response (cNR) Ta-1-Tis, cytology & random Bx positive Partial (cPR) T0, cytology & random Bx negative Complete (cCR) Local stage Clinical response or N01-3 or M1

11 Pts characteristics: TUR+Chemotherapy vs CTxTURB+ chemotherapy Cystectomy Characteristics No % No % p-value Numbe of patients 75 71 Age at baseline, years. Mean age (range) Median age 60.8 (36-82) 62 62.8 (35-71) 64 0.1782 Sex Male Female 0.6010 Antecedent history Primary tumor Recurrent tumor 0.1823 Morphology of tumors Sesile tumor Papillary tumor 0.2001 Size of tumors, cm. 3 >3 0.7438 Number of tumor Solitary Multiple 0.1223 Grade of tumor 2 3 0.1508 Bladder Tis Yes No 0.3099 Follow-up, months Mean follow-up (range) Median 65.1 (9-211) 45 67.5 (1-215) 45 0.7906

12 Initial and Durable ResponseTUR + Chemotherapy Initial and Durable Response 1 22 5 32 15 (29.4) * 6 (50) 4 9 (22.5) T0M1 T2M1 T2M0 Total (%) Progression 16 (31.3) * 2 (16.6) 14 (35) Total (%) Recurrence Response No. (%) cCR 40 (53.3) cPR 12 (16) cNR* 23 (30.6) Total 75 (*) percentage on 51 patients with bladder preserved

13 No difference between both approachesTUR + Chemotherapy vs CTx Comparative study between TUR+ Chemotherapy vs CTx Log rank test (p= 0.544) S. específica 5a 10a CTx 63.4 63.4 TUR+ Chemth. 64.5 59.8 No difference between both approaches

14 Oncological and Functional OutcomeTUR + Chemotherapy Oncological and Functional Outcome Bladder preservation: 44 (58.6%) Pts Alive with bladder preserved: 39 (52%) Bladder preservation in responders: 43 /52 (82.6%) 52.6% 64.5% Cancer-specífic 34.5% 10 años 59.8% 5 años With Bladder preserved Survival Toxicity Chemotherapy - High but no death by toxicity

15 54 (72%) pts with complementary therapy 34 (45.3%) CTxTUR + Chemotherapy Rescue treatment Pts Rescue Characteristics Death by tumour Intravesical therapy (*) 10 Ta-1 recurrence after cCR or cPR CTx 34 T2M0: progression or cNR (27) Tis in ducts in cPR (1) G3-Tis refractary to BCG (4) 17 Radiotherapy 1 T2M0 progression or unfit for CTx 1 RTU+ quimioterapia 2 T2M0 late recurrence (135 ms) T2M0 (personal election sfter cNR) Quimioterapia 7 T2M0 unrresectable (1) T2M1 (1) T0M1 (5) 7 (*) only one therapy 54 (72%) pts with complementary therapy 34 (45.3%) CTx

16 Trimodal Treatment: MGH ProgramSlide handed over by Dr. Lopez-Torrecillas

17 Trimodal Treatment: MGH ProgramDemography ( ): - 348 pts; Md FU= 7,7yrs - T2 (54%) T3 (38%); T4 (8%); - complete TUR (65%) Outcome: - Complete Response: 72% - Bladder preservation: 51% 57 59 64 Specífic (%) 22 35 52 Overall (%) 15yr 10yr 5yr Survival 56% 68% 5yr-specífic s. No complete Complete .03 P-value) TUR Prognostic Factors J.A. Efstathiou SUO 2010

18 } Complete TUR: 65% Bladder Preservation Programs MGH vs IVO cT2 (54%)MGH (TUR+Chem-RT) IVO (radical TUR) IVO (TUR+Chem) C-Specific Survival 5a a a 5a a a 5a a cT (%) Global series cT3-4 (%) cT (%) cT3-4 (%) cT (%) 51 Bladder Pres. (%) 59.8 75.5 cT2 (54%) cT3 (38%) cT4a (8%) } Complete TUR: 65%

19 Trimodal Treatment: Erlangen ProgramSlide Diapositiva handed over by Dr. Lopez-Torrecillas Rödel C. JCO 2006

20 Trimodal Treatment: Erlangen ProgramOverall Survival for cT2 - 4a Overall survival Nº 5 yr. 10 yr. 15 yr. cT2-3 328 45% 26% 16% cT4a 34 25% 7% R0* 142 (30%) 70% 46% 35% R1* 152 (32.1%) 47% 30% 16% R2* 160 (33.8%) 33% 7% R0: no microscopic residual tumour after TUR; R1: microscopic residual tumour; R2: macroscopic residual tumour Krause F.S. Eurol. Urol (2010), abstract EAU Congress

21 Macroscopic incompleteErlangen vs IVO Erlangen: evaluation criteria . R0= complete TUR with histological comprobation . R1= complete TUR with microsocpic residual tumour . R2 = incomplete TUR with macroscopic residual tumour Erlangen vs IVO Incomplete (biopsy) Evaluation TUR Macroscopic incomplete (1982) R2 Biopsies (-) Biopsies (+) (1989) R0 R1 CTx no chemotherapy 298 (pts.) Radical TUR (133 pts.) TUR + chem (75pts.) o CTx (71 pts.)

22 Erlangen vs IVO Specific survival1. If no microsocpic residual tumour: rTUR can be sufficient 73% (10yr) R0 79.5% (10yr) radical TUR 2. In cases of microscopic residual tumour: TUR + 3 cycles of chemotherapy is equivalent to trimodal therapy 60% (5yr) R1 63.5% (5yr) TUR+chem 40% (5yr) R2 61.5% (5yr) (CTx) 3. In cases of macroscopic residual tumour: trimodal therapy is inferior to CTx Krause (09) (trimodal) Solsona (98),(05),(09) (mono/bimodal)

23 Conclusions With long-term follow-up, strict selected pts with Invasive Bladder Cancer can be treated with TUR alone 2. In pts with microscopic residual tumour, 3 cycles of Chemotherapy can be sufficient to preserve the bladder witout compromising cancer-specific survival 3. Pts with macroscopic residual tumours, CTx achieves better survival than trimodal programs. If pts like to preserve his bladder or unfit for CTx, Trimodal Therapy is a valid option.

24

25 IVO: Uniendo ambas estrategiasCancer-specific survival Recurrences (yes / no) 0.6903 Biopsies of tumour bed (+ /-) ; Age 0.9716 Grade (2 /3) 0.097 Morphology (papillary / sesil) 0.0452 No. tumours 0.4284 Sex (women / men) 0.1381 Size 0.7421 Tis (yes / no) 0.3955 Treatment: rTURB vs. .rTURB + chemotherapy vs. 0.0007 .CTx 0.0015 Variables p-value RR ; p-value Univariate Multivariate Cancer-specific survival 21 31 42 56 65 71 84 89 96 110 123 138 0.2 0.4 0.6 0.8 1 TURB+ chemotherapy Radical TURB Cystectomy 1. rTURB vs. TURB + chemotherapy (p<0.001) 2. rTUR vs. CTx (p<0.001) 3. TURB + chemotherapy vs. CTx (p>0.05) Negative biopsies on healthy appearance muscular layer select patients with good prognosis and define a microscopic complete TURB Solsona E. Text Book edited b S Lerner, MP Schoenberg, Sternberg C, Taylor & Francis (08) pp:535

26 Conservación vesical: MultimodalEsquemas de los tratamientos Bimodales Revisión de la literatura Series 9 64.5% Supervivencia (5a) 59.8% Conservación vesical 75 Pts 53.3% cCR 31% Recidiva 43.3% CTR rescate 29.4% Progresión Serie IVO: RTU + 3 ciclos PQT Pts 447 cCR 53.8 (33-7) Supervivencia (5a) 54.4% ( ) Conservación vesical 41.7% (26-79) CTR rescate 33.8% ( )

27 Conservación vesical: MultimodalEsquemas de los tratamientos Bimodales Revisión de la literatura Series 9 64.5% Supervivencia (5a) 59.8% Conservación vesical 75 Pts 53.3% cCR 31% Recidiva 43.3% CTR rescate 29.4% Progresión Serie IVO: RTU + 3 ciclos PQT Pts 447 cCR 53.8 (33-7) Supervivencia (5a) 54.4% ( ) Conservación vesical 41.7% (26-79) CTR rescate 33.8% ( )

28 Conservación vesical: MultimodalComparación de estrategias de conservación vesical C. vesical Superv. (5a) Pts Modalidad 54.4% 41.7% 447 Bimodal 37.4% 1284 Trimodal 60.2% 3083 RCT cCR 53.8% 67.9% Revisión de la literatura Log rank test (p= 0.544) Estudio comparativo RTU+ PQT vs CTR (mismos criterios de inclusión: cT2)

29 ¿ Que significan las recidivas tras cCR?3. Recidivas: T 2 (10-43%) 17% (12-26) 12 estudios Hagan 03) (Sternberg, Pieras, Solsonal,Hall) Impact of T 2 (incidence: 14 pts (35.8%) recurrence on survival 12 (63.1%) 18 22 Initial non response (T2) 2 (22%%) 9 14 After progression (T2) Pts. died of cancer No. RCT Pts. RCT Solsona E. Eur. Urol. 2004, Abst. 690

30 Resultados (objetivo 1)Fiabilidad de los criterios de inclusión. P0: 1 (1.4%) P1-Pis N0: 7 (9.9%) P2-4N0 46 (64.7%) P0-4N1-3: 17 (24%) Estadio No. (%) Fiabilidad patológico P4 3 (3.9) Infraestadiaje P3b 19 (25) 40.7% P3a 9 (11.8) P2b 29 (38.1) P2a 7 (9.2) 47.3% Estadiaje adecuado P1 8 (10.5) P0 1 (1.3) 11.8% Supraestadiaje

31 34 CTx de rescate: 5 (5.5%) P0n= 2 (2.5%) Pis N0 15 (55.8%) p2-4 N0 11 (32.3%) P2N1-3

32 RTU radical y fraccionadaExophitic part (1st sample) Endophitic part (2nd sample) Biopsies on clean tumor bed (3th sample) x X Biopsies on perivesical fat (4th sample) x x x x x x

33 TVI: Tto. multimodal Estrategia de Tratamiento de los TVI (IVO)RTU fraccionada y radical: - exeresis completa del tumor - exéreis de la base hasta dejar libre de tumor el detrusor - biopsias sobre músculo sano (5) biopsias de capa grasa Desaparición de áreas pre-RTU induradas (post-RTU) No hidronefrosis ni adenopatías Solsona E Eur Urol (09) 55:911

34 7. ¿Que calidad de vida? 5. Q of L: Toxicity (807 pts)TUR + Chemotherapy (%) - Acute side effects 40-70 - Dose reduction 20 Trimodales - Scheme completed 71 - Cystitis (induction) 50 - Cystitis (2-4 weeks after) 10 - Bowel toxicity 10-20 - Cystectomy due to toxicity 1 - Mortality by scheme 1.1 Thurman SA Urol. Oncol. 2002; 18:

35 5.¿Que calidad de vida? Impact of Quality of Life: radio-chemotherapyPts.: total / alive with bladder / analysed 221 / 71 / 32 Normal bladder functioning 24 (75%) Decrease compliance 7 (22%) (6%) Hypersensitivity +Incontinence women 2 (6%) Flow symptoms 6% Urgency 15% Pads (women) 11% Intestinal toxicity 22% Control urinary problems 19% Zietman A. J.Urol. 2003;170:1772

36 2. ¿Cual es el esquema mas adecuado?104 (bimodal Sternberg (03) 47 (trimodal) Hagan (03) 75 (bimodal 820 (trimodal) Pacientes Solsona (06) Hagan (revisión) X seguimiento 41 ms 26 ms. 88 ms 62.7 ms. 48% 74% 52% 78% cRC 36% 17% 44% 18.2% CTR 47% 69% 48% 61% 45.6% Conserv. vesical 62.8% Supervivencia 5.6% 4.0% . T 2,M1 9.8% 12% 10.6% 17.2% Progr.: . T 2 23% 10.6% 15% 13% . N1-3 13.3% 29% 30.7% . M1

37

38 TVI: Estrataegia terapéuticaCistectomía Radical como tratamiento estándar Conservación vesical en tumores vesical infiltrantes 1- Pacientes aptos para CTR pero desean conservar la vejiga . Monoterapia: RTU /CP /RT . Multimodales: RTU + Quimioterapia ± Radioterapia 2- Pacientes no aptos para CTR . Tto. Adaptado al riesgo de co-morbilidad . Tratamientos paliativos

39 Conservación Vesical (TVI)Estrategia de Tratamiento de los TVI (IVO) RTU fraccionada y radical: - exeresis completa del tumor - exéreis de la base hasta dejar libre de tumor el detrusor - biopsias sobre músculo sano (5) biopsias de capa grasa Desaparición de áreas pre-RTU induradas (post-RTU) No hidronefrosis ni adenopatías Solsona E Eur Urol (09) 55:911

40 RTUr: Bases racionales2. Estudios retrospectivo Supervivvencia cancer-especifica (5 a.) Autor (a.) Pacientes General B1(cT2a) B2 (cT2b) Holmäng (97) 44* 25 Flocks (51) 126 53 54 43 Milner (54) 190 53 57 23 Barnes (77) 114 40 O’Flynn (75) 123 52 59 20 Barnes (66) 75 31 Henry (88) 43 52 63 38 Kondas (93) 27 48.8 54.6 20 * Pacientes no aptos para cistctomía, 26 pacientes T4 Un grupo seleccionado de estos patientes pueden ser controlados con RTU sola

41 RTUr: Infraestadio Factores de predicción de progresión e infraestadioUnivariate analysis: Variables True progression Understaging Tumor size ( 3cm. vs. >3 cm.) 0.813 0.057 Age (65 vs. >65 yrs.) 0.791 0.652 Grade (2 vs. 3) 0.445 0.117 Tumor morphology (papillary vs. sessile) 0.517 0.135 Number of tumors (unique vs. multiples) 0.968 0.532 Primary vs. recurrent tumors 0.698 0.250 Sex (women vs. men) 0.686 0.072 Bladder Tis (yes vs. no) 0.013 0.346 Recurrence (Ta-1) after TURB (yes vs. No) 0.104 Multivariate analysis: Variables Bladder Tis HR=2.27 (p=0.026); (p=0.132) Pts con tumores papilares: tamaño ≤3cm vs >3cm (p=0.647) Pts con tumor sésil: tamaño ≤3cm vs >3cm (p=0.0236) Infraestadio: 11.9% (1992) vs 6.7% (1998)

43 Conservación Vesical (TVI)15-Year Survival Rates of Transurethral Resection of Radiochemotherapy or Radiation in Bladder Cancer Treatment: Validation

44 multidisciplinar en el cáncer urológicoIII Jornada multidisciplinar en el cáncer urológico Conservación vesical: visión del Urólogo Eduardo Solsona Servicio Urología. Instituto Valenciano de Oncología. Valencia Madrid 8 de Julio de 2011

45 Servicio Urología. Instituto Valenciano de Oncología (IVO)Estrategias de Preservación Vesical en Cáncer de Vejiga Músculo-infiltrante (CVMI) Eduardo Solsona Servicio Urología. Instituto Valenciano de Oncología (IVO) Valencia Lima 1-3 Septiembre 2011

46 RTUr: Impacto de la edadImpacto de la mediana y cuartiles sobre supervivencia1 Overall survival Age: NEGATIVE impact on overall survival Cancer-specific survival Age: NO impact on cancer-specific survival 1Solsona E. J.Urol (10) 184:475

47 RTUr + Quimioterapia Programa de Conservación Vesical con RTU radical mas 3 ciclos de quimioterapia basada en el Cisplatino Criterios de inclusión RTU completa del tumor Biopsias del lecho tumoral positivas a tumor EBBA: no induración vesical tras RTU Ausencia de hidronefrosis TAC: no adenomegalias PAL normales Esquema conservación vesical: 3 ciclos de Quimioterapia basada en Cispatino (MVAC/CG) Tras 2º ciclo cistoscopia para descartar progresión local Tras 3º ciclo; TAC, RTU de la cicatriz, citología y biopsias al azar Esquema CTx (convencional)

48 ¿Qué significan la recidiva tras conservación?RTUr + Quimioterapia ¿Qué significan la recidiva tras conservación? Recidivas: Ta-1 ( %) Patología de la recidiva Recidiva/ cCR Tis vesical cT1G2-3 Ta Zietman (01) 32 /124 (26%) 60% 28% 12% Pieras (03) 18 / 42 (43%) 61% 28% 11% Solsona (04) 10 /49 (20.5%) 50% 40% 10%

49

50 Conservación vesical: MultimodalEsquemas de los tratamientos multimodales - Bimodales: RTU + 3 ciclos quimioterapia (MVAC o CG) - Trimodales: Inducción Consolidación . Secuencial: RTU + Qimioterapia  RT+C  Quimioterapia . Concurrente: RTU + Quimioterapia + RT  Quimioterapia - Inducción  valoración respuesta  R. completa  consolidación  R. parcial o no respuesta  CTR - Seguimiento estrecho Recidiva infiltrante  CTR Secuencia - MVAC - C + 5-FU (Cisplatino, 5-Fluorouracilo) - CG Esquemas de quimioterapia

51 Programas de la RTOG: RTU +PQT-RTAutor Esquema Nº pRC S. Global 5 años Con vejiga RTOG RTU→RT+ Cispla 42 66% 52% 42% RTOG RTU→MCV→RT+Cispla 91 75% 62% 44% RTOG RTU→MCVx2 vs NO→RT+Cispla 123 61vs65% 49-48% 36 vs 40% RTOG RTU→RT(bid) + Cispla+5FU 34 67% 83%* 66%* RTOG RTU→RT(bid) + Cispla 47 74% 61%* 48%* Global 337 61-75% 48-83% 36-66% 70%-80% pacientes Supervivencia 5 años conservan vejiga J.A. Efstathiou SUO 2010

52 Estrategía Terapéutica IVO1983 1989 Solsona E Eur Urol (09) 55:911

53 RTUr: Definición/ Criterios inclusiónRTU radical y fraccionada 2. Criterios de inclusion 1 Confirmación invasión muscular (2nd) biopsias negativas sobre el lecho tumoral aparentemente sano (3th) biopsias negativas sobre la grasa perivesical si esta se alcanza (3th& 4th) desaparición de áreas endurezsidas de la pared vesical tras RTU TAC y Rx de tórax: NO uropatía obstructiva ni cN+/ M+ NO T2 en re-RTU (2-6 sem) en ptes. remitidos desde otro Hospital. Exophitic part (1st sample) Endophitic part(2nd sample) Biopsies on clean tumoural bed (3th sample) Biopsies on perivesical fat (4th sample) x 3. Criterios de inclusion del MSKCC2 y MD Anderson3 - NO T2 en re-RTU (2-6 sem.) tras RTU completa 1 Solsona E J Urol (98)159: 95; 2 Herr HW J Clin Oncol (01)19:89. 3 Leibovici D Urology (07) 70:473

54 } Programa del MGH Demografía: Características clínico-patológicas:- 348 ptes ( ) - Edad media 66,3 años - Segto. medio 7,7 años Características clínico-patológicas: - T2 (54%); T3 (38%); T4a (8%) - RTU macroscópica completa: 65% - Hidronefrosis 17% Resultados post-tratamiento: - Respuesta completa: 72% - Conservación vesical: 51% - Requerimiento de Cistectomías: 29% . 17% inmediatas (no RC) y . 12% salvación (post-recidiva) } 29% 57 59 64 Específica (%) 22 35 52 Global (%) 15a 10a 5a Supervivencia J.A. Efstathiou SUO 2010

55 Resultados a largo plazo 1986-2002. Valor de la RTUPrograma del MGH Resultados a largo plazo Valor de la RTU Diapositiva cedida por el Dr. Lopez-Torrecillas

56 Supervivencia en función del estadio clínicoPrograma del MGH Supervivencia en función del estadio clínico J.A. Efstathiou SUO 2010

57 Bases Racionales dela RTUr1. Incidencia de pT0 in pieza de CTx - pT0 en CTx: x=12% (9-14%) . cT2 ►:pT0 = 11.5%; cTa-Tis-1= 31.7%1 . cT2 con RTU completa►: pT0=31.3%2 Supervivencia - Series Globales pT0= % (5a.) - En cT2 (pT0)= 89-95% (5a.); % (10a.) 1,2 1Isbarn H J Urol (09)182:459; 2Volkmer BG Cancer (05)104:2384

58 RTUr: Problemas Inseguridad microscópica de la radicalidad ---- crecimiento frontal o tentacular 2. Infraestadio: - 36% cT2 son pT≥31 Soluciones potenciales: Criterios inclusion . Objetivos: - Identificar tumores limitados al músculo (pT2) - Conseguir una RTU microscópica completa 1Shariat SF Eur Urol (07) 51: 137

59 RTUr vs CTx Literature overview Survival Herr’ series3- CTx (pts con cT2 -pT0): % (10yr)1,2 - rTURB (prospective studies): % (10yr)3,4 151 pts with same inclusion criteria: 99 prefered TURB and 53 CTx Herr’ series3 1Isbarn H J Urol (09)182:459; 2Volkmer BG Cancer (05)104:2384; 3 Herr H.W. JCO (01) 19:89; 4 Solsona E J Urol (98)159: 95

60 } Radical TUR (complete & fractionated) NegativeExophytic part (1st sample) Endophytic part (2nd sample) Biopsies on clean tumoural bed (3th sample) x Negative } Biopsies on perivesical fat (4th sample)

61 RTUr: Seguimiento Estudio secuencial Intervalo: Esquema:- Cada 3 meses durante 3 años; cada 4 meses hasta el 5º año y luego anual Esquema: - Cada evaluación: . Cistoscopia, citología urinaria, biopsias añeatorias y sobre áreas sospechosas y exploración bimanual . RTU de la cicatriz al menos las 2 primeras evaluaciones. - Rx tórax y TAC al 3º mes y cada 6 meses durante 3 años

62 } Complete TUR: 65% Bladder Preservation Programs MGH vs IVO cT2 (54%)MGH (TUR+Chem-RT) IVO (radical TUR) IVO (TUR+Chem) C-Specific survival 5a. 10a. 15a. 5a. 10a. 15a. 5a. 10a. cT2 (%) 74 67 63 81.9 79.5 79.5 49 53 cT3-4ª (%) 52.6 64.5 57 59 64 Global Series (%) 52.6 64.5 51 Bladder Pres. (%) 59.8 75.5 cT2 (54%) cT3 (38%) cT4a (8%) } Complete TUR: 65%

63 } Complete TUR: 65% Bladder Preservation Programs MGH vs IVO cT2 (54%)MGH (TUR+Chem-RT) IVO (radical TUR) IVO (TUR+Chem) C-Specific survival 5a. 10a. 15a. 5a. 10a. 15a. 5a. 10a. cT2 (%) 74 67 63 81.9 79.5 79.5 49 53 cT3-4ª (%) 52.6 64.5 57 59 64 Global Series (%) 52.6 64.5 51 Bladder Pres. (%) 59.8 75.5 cT2 (54%) cT3 (38%) cT4a (8%) } Complete TUR: 65%