TITULO DE LA PRESENTACION de vejiga avanzado.pdfmonths for MVAC. The 5-year overall survival rates...
Transcript of TITULO DE LA PRESENTACION de vejiga avanzado.pdfmonths for MVAC. The 5-year overall survival rates...
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TITULO DE LA PRESENTACION
Plataforma de OncologíaUnidad de Radioterapia
13-enero-06
Carcinoma vejigaEstrategias en tumores localmente avanzados
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TNM
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Punto de partida
• Tratamiento estándar: cistectomía• Alternativo: preservación• Supervivencia: 50% a 5 años
30% a 10 años– T2: órgano confinado– T3: extensión extravesical– T4: heterogéneo– Enfermedad ganglionar
• Patrones de fallo– Fallo local: 20-25%– Metástasis: 40-70%
Stein et al. JCO 19: 666, 2001
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Abordaje en ca. vejiga localmente avanzado
•Cirugía conservadora•Cistectomía parcial
•Cirugía radical (cistectomía radical)•Heterotópica•Ortotópica•Quimioterapia de inducción/adyuvante
•Tratamiento conservador•Radioterapia•Quimioradioterapia
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Estrategias en carcinoma avanzado (tto conservador)
RTUInducción
QT neoadyuvante
Valoración Respuesta
Tratamiento local Quimiorradioterapia
Valoración Respuesta
Cirugía
Consolidación Quimiorradioterapia
Quimimioterapia
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Protocolos de la RTOG
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RT radical (Universidad de Erlangen)
• Erlangen. 10 años de experiencia (IJROBP 30: 261, 1994)• 245 pacientes• Dosis max: 56 Gy (min: 50.4 Gy)• QT: CDDP 25 mg/m2 w1-w5/CBCDA 65 mg/m2 (n=139 p)• SV@ 5 años: 47%• Factores pronóstico más importante TURB
– R0: 81% 74%– R1: 53% 21%– R2: 31% 17%
• 79% preservación de vejiga• 40% vivos con vejiga funcionante
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RTU y supervivencia
R-status after TURB was the only independent prognostic factor for survival and bladder preservation.For relapsed patients after cystectomy, the 5- and 10-year CSS were 40 and 33%.
Sauer et al. Int. J. Radiation Oncology Biol. Phys 40: 121, 1998
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Probabilidad de enf. a distancia. Experiencia del MGH
T2
T3-4
< 5 cm
> 5 cm
Estadio Tamaño
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QT neoadyuvante
3 ciclos MVAC
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• 2 ciclos de MCV (QT neoadyuvante) no demostraron un beneficio en la tasa
de CR sobre el brazo control o en aumento del periodo libre de enfermedad
a distancia. Tampoco hubo beneficio en supervivencia.
• Dudoso papel del a QT neoadyuvante.
• Toxicidad.
• Falta de eficacia del esquema.
• Especialmente útil después de R0 y ausencia de hidronefrosis
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Recidiva de ca. superficial
• Seguimiento riguroso.
• 9-28% recidivaran con un Ca. superficial .
• 1-2 años después.
• MGH: 60% en la zona previa.
• Pieras et al.: 60% en otra zona.
• Su tratamiento no compromete la supervivencia.
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Estrategias en la Plataforma
• Cistoscopias (diagnóstico, seguimiento)– Revisión AP, mejorar
• Quimioterapia, qué combinación– Neoadyuvante siempre???
• Consolidación primario (Tóxico)– MCV con RT!!!!!!!!!!!!!!!!!!– Diseño de la RT. Vejiga llena
• Tratamiento después de la consolidación• Cistoscopias
– HAL (hexaminolevulinate) cistoscopy. 96% were detected with HAL imaging compared with 77% using standard cystoscopy (J Urol 2005).
• Seguimiento– Marcadores en orina y suero
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Factores pronósticos (suero/orina)
• VEGF-C. Relacionados con mts ganglionares (Int J Urol 2005)• p53 suero (Int J Urol 2004)• BLCA-4 en orina. Monitorización (Urology 2005)• HYAL-1/ sICAM-1 en suero u orina (Arch Med Res 2006)• Telomerasa orina (JAMA 2005)• Revisión sistemática (Eur Urol 2005):
– Microsatellite analysis – ImmunoCyt– NMP22 (nomogramas Ca. superficial, J Urol 2005)– CYFRA21-1 (monitorización en suero, J Urol 2005) – LewisX– FISH. UroVysion probe set (Abbott Laboratories), J Urol 2005
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Tratamiento combinado. U Erlangen
RTURO si es posible
Radioquimioterapia
Re-evaluación, RTU
Remisión completa
Tumor residualsuperficial
Invasivo
Cistectomía RTU+intravesicalSeguimiento
Superficial Invasivo
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Conservación vesical (T2-T3a)
QT
QT
Hiperfracc CDDP, FU, TXLRT radical -QT
Cistoscopia, RTU
RCNo RC
2 ciclos QTCistectomía
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Conservación vesical (T3b-T4a)
QT
QT
cistoscopiaNo RC RC
2 ciclos QTRT preop + 2 QT
Cistectomía Re-evaluación
2 ciclos QT 2 ciclos QT + RT radical
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Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, with Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients with Bladder Cancer
• 405 patients
• Overall survival was similar in both arms (hazard ratio [HR], 1.09; 95% CI, 0.88 to 1.34; P .66) with a median survival of 14.0 months for GC and 15.2 months for MVAC. The 5-year overall survival rates were 13.0% and 15.3%, respectively (P .53).
• Significant prognostic factors favoring overall survival included performance score (> 70), TNM staging (M0 v M1), low/normal alkaline phosphatase level, number of disease sites (or three), and the absence ofvisceral metastases.
• Conclusion: Longterm overall and progression-free survival after treatment with GC or MVAC are similar.
• These results strengthen the role of GC as a standard of care in patients with locally advanced or metastatic TCC.
J Clin Oncol, 23: 4602–4608, 2005
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Muscle-invading bladder cancer,RTOG Protocol 99-06:
Initial report of a phase I/II trial of selective bladder-conservation employing TURBT, accelerated irradiation
sensitized with cisplatin and paclitaxel followed by 4 cycles of adjuvant Cisplatin and Gemcitabine chemotherapy.
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Inclusion Criteria
• Muscle-invasive bladder cancer• AJC Stages T2 – T4a• No prior chemotherapy or pelvic RT• Cystectomy candidate• ANC > 1800 Platelet count > 100,000• Creatinine clearance > 60 ml/minute
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Exclusion Criteria
• Tumor invasion into prostatic stroma
• Tumor-related hydronephrosis
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RTOG 99-06: COMBINED Chemotherapy and BID Radiation Therapy
TURBT Induction Response Taxol, Cisplatin Evaluation and b.i.d. XRT (week 7) (13 days)
CR ConsolidationTaxol, Cisplatin and b.I.d. XRT(8 days in weeks 9 + 10)
<CR Immediate Cystectomy
Adjuvant chemotherapy – 4 cycles, Cisplatin / Gemcitabine
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INDUCTION THERAPY (Weeks 1-3)
AGENTS Day 1 2 3 4 5 8 9 10 11 12 15 16 17
Taxol 50 mg/m2 X X X
Cisplatin 20 mg/m2 X X X X X X
XRT, bid x 13 days X X X X X X X X X X X X X
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CONSOLIDATION THERAPY (Weeks 8,9)
AGENTS Day 1 2 3 4 5 8 9 10
Taxol 50 mg/m2 X X
Cisplatin 20 mg/m2 X X X X
Pelvic XRT, bid x 8 days X X X X X X X X
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OUTPATIENT ADJUVANT CHEMOTHERAPY (Weeks 21-37 or weeks 17-33)
AGENTS Day 1 8 15
Gemcitabine (1000 mg/m2) X X X
Cisplatin (70 mg/m2) X
Begin 12 weeks post consolidation therapy or 8 weeks following cystectomy. Repeat every 28 days for 4 cycles.
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Pretreatment Characteristics (n=50)
Age Zubrod< 60 14 (28%) 0 46 (92%) > 60 36 (72%) 1 4 (8%)
Gender T StageMale 45 (90%) T2 45 (90%)Female 5 (10%) T3a 4 (8%)
T3b 1 (2%)
Visibly Complete TURBTYes 46 (92%)No 2 (4%)
Unknown 2 (4%)
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Results 1
Completed protocol 34/47 = 72%
CR after induction 41/47 = 87%
Median follow-up 30 months
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Results 4
Estimated Rates
69%80%15Surviving with Bladder Intact
79%88%12Survival
17%10%11Distant Metastases
6%6%4Regional Nodal Failure
18%13%7Local Failure Following Post-Induction CR (n=37)
2-year1-year# FailuresEndpoint (n=49)
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CONCLUSIONS
1. First bladder-sparing study utilizing adjuvant Gemcitabine/Cisplatin
• CR rate = 87% RTOG 95-06 61% RTOG 97-06 74%
3. Protocol completion rate = 72%
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RTOG PROTOCOL 02-33 (Randomized)
TURBT ---> Induction ---> ResponseT vs 5-FU,Cisplatin Evaluationand b.i.d. XRT (week 7)(13 days)
CR ---> ConsolidationT vs 5-FU, Cisplatin and b.i.d. XRT(8 days in weeks 9 + 10)
<CR ---> Immediate Cystectomy
Adjuvant Chemotherapy - 4 cycles, Gemcitabine,Taxol and Cisplatin
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RTOG 05-24: Treatment fornon-cystectomy candidates
Phase I/II- Tolerence and CR ratesChairs: D. Michaelson, A. Pollack, D. Dahl, C-L. Wu
TURBT--->Her-2 stain < 3+---> 65 Gy XRT QDplus Taxol weekly
TURBT--->Her-2 stain 3+---> HERCEPTIN plus65 Gy XRT QDplus Taxol weekly
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Ca. vejiga organoconfinado (T2)
RTU
QuimiorradioterapiaCDDP, TXL
Re-evaluación, RTU/orina
Remisión completa
Tumor residualsuperficial
Invasivo
Cistectomía RTU+intravesicalSeguimiento
Superficial Invasivo
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Ca. vejiga extravesical (T3-T4a)
RTU
3 - 4 ciclos
Re-evaluación
QuimiorradioterapiaCDDP, TXL+/- TT
CistectomiaSeguimiento