Download FASGO 2005 CONSENSO CANCER DE ENDOMETRIO AAGO

FASGO 2005
CONSENSO CANCER DE ENDOMETRIO
AAGO
Coordinador
Gustavo Maya
Expertos
Daniel Falugue
Gustavo Irico
Roberto Orti
Jorge Sarrouf
1
Epidemiologia
Existe una gran variación en la incidencia en el mundo, 170.000 nuevos casos
fueron estimados en el año 1997. Está relacionado con la endocrinología, la
obesidad y por lo tanto más frecuente en países desarrollados.
Incidencia:
Para el 2001 fue de 24.7 por 100.000 (EEUU).
Mujeres blancas: 26.1 por 100.000
Mujeres negras: 18.5 por 100.000
Morbimortalidad:
De 40.300 casos en el 2004 morirán 7.000 de la enfermedad. Representan el
4º cáncer más común entre las mujeres.
Raza:
La mortalidad es más alta en las negras 7 de 100.000, en las blancas, 38 de
100.000.
Edad:
Reproductiva y menopáusica. La edad media es la 7º década pero la mayoría
tienen entre 50 y 59 años.
Sólo el 5% de las mujeres son menores de 40 años.
El 20% se diagnostica antes de la menopausia.
Etiología y Factores de Riesgo
Parece haber dos tipos patogénicos del cáncer de endometrio. El más
frecuente
ocurre
en
mujeres
perimenopáusicas,
más
jóvenes,
con
antecedentes de exposición a los estrógenos sin oposición, ya sean endógenos
o exógenos, se inician como endometrio hiperplásico y progresan a carcinoma.
Estos tumores son DEPENDIENTES de los ESTRÓGENOS, tienden a estar
mejor diferenciados y su pronóstico es más favorable.
El otro tipo de carcinoma endometrial se produce en mujeres que no han
recibido estimulación del endometrio. Estos cánceres no se relacionan con las
hiperplasias y pueden originarse sobre un fondo atrófico. Están menos
diferenciados y se acompañan de peor pronóstico. Estos tumores son
INDEPENDIENTES de los ESTRÓGENOS.
Múltiples factores de riesgo epidemiológicos han sido identificados.
2
•
Factores Endógenos:
Obesidad: incrementa el riesgo.
Nuliparidad: 2 a 3 veces comparada con la paridad.
Menopausia tardía: > 52 Años.
•
Estrógenos sin oposición:
Como terapia hormonal
Endógenos (tumores de la granulosa u ovarios poliquísticos)
Anovulación
•
Tamoxifeno
Un estudio reciente de control usando el SERM indica que cuando es
correctamente utilizado no se incrementa el riesgo de cáncer de
endometrio.
•
Combinación con ACOs disminuye el riesgo de desarrollar cáncer de
endometrio, cuando se usa por más de 12 meses y permanece por 12
años después del uso de los ACOs. Es más notable en las mujeres
multíparas.
•
El hábito de fumar aparentemente disminuye el riesgo, las mujeres que
fuman tienen la menopausia 1 a 2 años antes que las que no fuman.
Epidemiología y factores de riesgo:
–
Postmenopausia (sólo 7% ca de endometrio premenop.).
–
Obesidad, hipertensión arterial, diabetes mellitus.
–
Nuliparidad.
–
Menarca temprana, menopausia tardía.
–
Terapia hormonal sin oposición.
–
Tamoxifeno.
–
Antecedentes de cáncer de mama, ovario, colon.
–
Hiperplasias endometriales con atipía.
–
Cáncer hereditario colorrectal no polipoideo (HNPCC) 25-50%.
Screening
Los procedimientos para screening no logran reducir la mortalidad por
cáncer de endometrio
3
Diagnóstico
A continuación mostramos en forma resumida los procedimientos
diagnósticos para cáncer de endometrio.
Modalidades para evaluar Endometrio
Muestreo endometrial:
–
Dilatación y curetaje-Histeroscopía
–
Biopsia (Pipelle-cureta de Novack)
–
Cepillado
Ecografía transvaginal
Conclusiones
•
7% cánceres de endometrio son en mujeres menores de 50 años.
•
90% de las portadoras de un Ca. de Endometrio tienen síntomas.
•
Solamente el 10 al 12% de las pacientes con metrorragia de la
postmenopausia son portadoras de un ca de endometrio.
•
Definir perfil de Riesgo.
•
ETV suma utilidad en el algorritmo diagnóstico.
•
Endometrio igual ó menor de 4 mm tiene alta sensibilidad y un V.P
negativo alto para excluir ca. de endometrio.
•
En pacientes con tamoxifeno el grosor promedio es de 8 mm.
•
Post menopausia, sin sangrado, y sin factores de riesgo:
–
<11mm. Control (R.Ca.E 0.02%)
–
>11 mm. Considerar biopsia (R.Ca E 6.7%)
Evaluación Preoperatoria
•
Estudio completo de sangre.
•
Radiografía de tórax como parte del chequeo clínico.
•
La tomografía computada es innecesaria salvo que se sospeche
enfermedad extrapélvica.
•
La resonancia magnética puede ser útil para evaluar involucro
ganglionar y la invasión miometrial, pero es innecesaria si la
estadificación quirúrgica planeada es completa.
•
Dosaje de Ca 125 es útil como predictor de invasión extrauterina del
cáncer de endometrio y para el seguimiento de las pacientes después de
4
iniciado el tratamiento. Pero no es suficientemente sensible para ocupar
el lugar de la estadificación quirúrgica.
A partir de 1988 la FIGO estableció la estadificación quirúrgica. La
estadificación clínica solo se usa para pacientes inoperables.
Estadificación clínica (FIGO 1971):
tumor limitado al cuerpo
histerometría hasta 8 cm
histerometría mayor de 8 cm
subtipos histológicos G1-2-3
E II propagado al cuello
E III fuera del utero pero dentro de la pelvis
E IV fuera de la pelvis o vejiga o recto
EI
IA
IB
Estadificación quirúrgica (FIGO 1988)
Estadio I - Tumor confinado al cuerpo uterino
• IA Tumor limitado al endometrio
• IB Tumor invade menos de la mitad del espesor del miometrio
• IC Tumor invade más de la mitad del espesor del miometrio
Estadio II - Tumor se extiende al cuello uterino
• IIA sólo compromiso de las glándulas endocervicales
• IIB Invasión del estroma cervical
Estadio III - Diseminación locoregional
• IIIA tumor compromete serosa y/o anexos (por extensión directa o
metástasis) y/o citología peritoneal positiva (ascitis o lavado peritoneal)
• IIIB Compromiso vaginal (por extensión directa o metástasis)
• IIIC Metástasis a ganglios pelviano y/o lumboaórticos
Estadio IV – extensión a otros órganos
• IVA Tumor invade mucosa vesical y/o mucosa rectal
• IVB Metástasis a disancia (excluyendo metástasis a la vagina, serosa
uterina, anexos, e incluyendo metástasis a ganglios intrabdominales
otros que los pelvianos y lumboaórticos)
Los casos de cáncer de endometrio deberán ser agrupados según el grado de
diferenciación del adenocarcinoma en:
5
•
•
•
G1: cuando 5% o menos tienen características de crecimiento sólido no
escamoso o no morular.
G2: de 6% a 50% tienen características de crecimiento sólido no
escamoso o no morular.
G3: más del 50% tienen características de crecimiento sólido no
escamoso o no modular.
En caso de presentar atipía nuclear importante, inapropiada para el grado de
diferenciación arquitectónico, se deberá aumentar en 1 el grado tumoral.
Aquellos pacientes con diagnóstico de cáncer de endometrio que no puedan
ser intervenidas quirúrgicamente y que por ende sean tratadas con
radioterapia, deberán estadificarse según la estadificación FIGO 1971, pero se
deberá anotar que esa fue la estadificación utilizada
ESTADIFICACIÓN QUIRÚRGICA:
La estadificación deberá evaluar invasión al miometrio, propagación al cuello
uterino y extensión extrauterina.
La estadificación quirúrgica descripta por la FIGO incluye:
• Incisión mediana
• Lavado peritoneal
• Examen cuidadoso de cavidad abdominal (omento, hígado, fondos de
saco, ovarios)
• Anexo histerectomía total extrafacial (AHT)
• Linfadenectomía pelviana y lumboaórtica.
De esto se derivan varias situaciones, con conductas intraoperatorias
diferentes:
1.
2.
3.
4.
Enfermedad aparentemente localizada en el cuerpo uterino
Extensión a cuello,
Enfermedad extrauterina,
Tipos histológicos particulares
1. Cuando la enfermedad está aparentemente localizada en el cuerpo
uterino:
Se realiza la anexo histerectomía total. El compromiso miometral deberá ser
valorado por un anátomo patólogo durante el acto quirúrgico.
Para la valoración del grado de diferenciación histológica se tomará el de la
biopsia de diagnóstico (legrado o histeroscopia).
La indicación de la linfadenectomía se basará entonces en la posibilidad de
progresión al retroperitoneo.
6
•
•
Tumores bien diferenciados (G1), sin invasión o con invasión menor al
50% del miometrio (M0 o M1) es el grupo en el que puede no realizarse
la linfadenectomía. (riesgo de progresión a retroperitoneo menor al 5%)
En los tumores con invasión menor al 50% (M1), G2, G3 o tumores con
invasión mayor al 50% del miometrio (M2) independientemente del
grado de diferenciación, la probabilidad de progresión al retroperitoneo
justifica la realización de la linfadenectomía sistemática
El abordaje laparoscópico es factible si es llevado a cabo por cirujano
experimentado conservando los mismos criterios oncológicos que en la cirugía
a cielo abierto
Estadificación por laparoscopia
Se ha establecido por distintos autores que es posible realizarla con toda
seguridad.Falta por determinar todavía si es el procedimiento más adecuado.
Para ello se está realizando un estudio comparativo prospectivo y aleatorio, en
el que la única variable diferencial es la vía de abordaje (GOG).Se realiza así el
mismo estudio de extensión, siendo los objetivos la distribución por estadios y
si existen diferencias entre supervivencias entre estos estadios.
Vía laparoscópico-vaginal
La combinación del acceso laparoscópico con la vía vaginal permite la
realizacion, con menos riesgo para la paciente, de todos los objetivos que, hoy
en día, se estima deberían formar parte del plan lógico de tratamiento del
adenocarcinoma de endometrio.El alcance del tiempo laparoscópico y del
vaginal, varía, dentro de límites, en función de las condiciones operatorias y de
la experiencia, laparoscópica o vaginal, del cirujano.
El abordaje laparoscópico permite llevar a cabo una exploración abdominal
sistemática, la realización de lavados peritoneales con fines de verificación
citológica, la anexectomía y la linfadenectomía pélvica, lumbo-aórtica, según
criterios oncológicos protocolizados en cada centro, así como preparar la
extirpación del útero por vía vaginal.
El grado de asistencia laparoscópica puede variar desde una simple lisis de
adherencias hasta la resección total del útero. Sin embargo, la principal ventaja
del acceso laparoscópico, además de la realización de todos aquellos gestos
que forman parte del estadiaje quirúrgico y que no son practicables por vía
vaginal, es el tratamiento de los anexos.
Al igual que en cirugía abierta, el principal factor limitante de la práctica de la
linfadenectomía (pélvica y paraórtica) por vía laparoscópica es la obesidad.
Por otra parte, los factores de riesgo quirúrgico que contraindican la vía
abdominal son los mismos que pueden hacer desaconsejable -o incluso
contraindicar formalmente- la práctica de la laparoscopia.
7
El procedimiento laparoscópico-vaginal sólo debe ser realizado por quienes
posean la capacitación y experiencia necesaria para la práctica de la
linfadenectomía con técnica abierta. No puede ni debe haber "límites" entre la
cirugía laparoscópica y la convencional sino que, por el contrario, hay que
contar con el conocimiento y dominio de ambos métodos operatorios.
Los resultados preliminares del tratamiento laparoscópico - transvaginal
parecen demostrar que los índices de supervivencia obtenidos con esta nueva
estrategia son similares a los registrados en los controles tradicionales.
Por otra parte, si se respetan los criterios de efectuar la intervención por
cirujanos expertos en oncología y laparoscopia quirúrgica avanzada, el uso de
instrumentos adecuados y la estricta selección de las pacientes, las
complicaciones pueden reducirse al mínimo.
El GOG ha diseñado sendos estudios clínicos aleatorizados con el objetivo de
responder a los interrogantes actualmente abiertos sobre la factibilidad y
morbilidad de esta modalidad terapéutica.
La ventaja potencial (o justificación) de la linfadenectomía sistemática es:
primero, que de documentar la ausencia de retroperitoneo comprometido, se
evitaría la necesidad de realizar radioterapia adyuvante y segundo, el potencial
rol terapéutico de la linfadenectomía
No hay sin embargo unanimidad entre las diferentes sociedades
internacionales en la recomendación de la linfadenectomía sistemática o del
sampling ganglionar.
2. Cuando la enfermedad está extendida al cuello uterino:
•
•
Cuando hay diagnóstico previo de compromiso cervical y factibilidad
quirúrgica se podrá realizar una anexo histerectomía radical más
linfadenectomía pelviana y lumboaórtica
Cuando en la biopsia por congelación de la pieza de AHT, se detecta el
compromiso cervical, se deberá realizar la linfadenectomía pelviana y
lumboaórtica. Igual criterio (AHT más linfadenectomia pelviana y
lumboaórtica), en los casos con imposibilidad de realización de
histerectomía radical).
3. Enfermedad extrauterina
En el caso de hallazgo de enfermedad extrauterina intraoperatoria:
• MTS en ovario o pelvis: agregar linfadenectomía pelviana y
lumboaórtica
• Ante difusión extrauterina macroscopica pelviana o abdominal se
deberá realizar la citoreducción quirúrgica
8
4. Estadificación en tipos histológicos especiales
En el caso de diagnóstico patológico de tumor seroso papilar o tumor de células claras
se agregará a la estadificación quirúrgica completa la realización de la omentectomía y
biopsias peritoneales (incluyendo subdiafragmáticas), estadificación similar a la del
cáncer de ovario.
MANEJO POR ESTADIOS (INDICACIÓN DE TRATAMIENTO ADYUVANTE)
ESTADIO I (estadificación completa)
IA
IB
IC
G1
G2
G3
G1
G2
G3
Seguimiento
seguimiento
Seguimiento o RT cúpula vaginal
Seguimiento
Seguimiento o RT cúpula vaginal
RT cúpula vaginal
G1
G2
G3
Seguimiento o RT cúpula vaginal
Seguimiento o RT cúpula vaginal
RT pelviana ± RT cúpula vaginal
ESTADIO I (estadificación incompleta)
IB
G2
G3
Seguimiento o RT en cúpula
RT pelviana ± RT cúpula vaginal
IC
RT pelviana ± RT cúpula vaginal o reestadificación
ESTADIO II (estadificación completa + Op Wertheim Meigs)
IIA
IIB
Similar manejo que en estadio I
G1
G2
G3
Seguimiento o RT cúpula vaginal
RT pelviana ± RT cúpula vaginal
RT pelviana ± RT cúpula vaginal
ESTADIO II (estadificación incompleta o realización de
anexohisterectomia total no radical)
IIA
RT pelviana ± RT cúpula vaginal
IIB
RT pelviana ± RT cúpula vaginal
9
ESTADIO III (estadificación completa)
IIIA
•
•
sólo por compromiso de citologia, M0, cervix negativo:
seguimiento
Todos los otros IIIA: RT pelviana ± RT cúpula vaginal
IIIB
RT pelviana ± RT cúpula vaginal
IIIC
Ganglios pelvianos (+)
RT pelviana hasta bifurcación aórtica ± RT
cúpula vaginal
Ganglios lumboaórticos (+) RT pelviana y lumboaórtica ± RT cúpula vag.
ESTADIO III (estadificación incompleta)
•
•
Sin evidencia clínica de enfermedad persistente: RT pelviana y
lumboaórtica ± RT cúpula vaginal
Si hay evidencia clínica de enfermedad macroscópica, se deberá
plantear reestadificación quirúrgica.
ESTADIO IV
Control local de la enfermedad
Tratamiento sistémico
AHT
RT adbominopelviana
Quimioterapia
Hormonoterapia
CARCINOMA SEROSO PAPILAR
Estadio IA
RT cúpula vagina o RT pelviana
Estadio IB, IC, II RT pelviana ± RT cúpula vaginal
Estadio III, IV
Quimioterapia o RT abdominopelviana
PACIENTES INOPERABLES:
Estadíos I y II
RT pelviana + RT intracavitaria
En los tipos histológicos desfavorables (seroso papilar y celulas claras)
considerar, según performance status, tratamiento sistémico con QT:
CT (Carboplatino-Paclitaxel)
AP (Doxirrubicina-Cis -Platino)
TAP(Paclitaxel- Doxirrubicina-Cis-platino)
Se estadifican clínicamente según FIGO
Si se confirmaran GLAO+ y/o múltiples GP+ ( por ejemplo: por
punción biopsia guiada) se agrega RT de campo extendido a
10
región para-aórtica y se considera administrar tratamiento sistémico
Si el performance status lo permite: Considerar QT (idealmente
dentro de protocolos de investigación)
Si el performance status no admite QT: Considerar Hormonoterapia ,
especialmente en tumores endometroides G1-G2 con RPG+: Acetato
de Medroxiprogesterona
Estadíos III y IVA
RT externa con dosis adicional en parametrio (dependiendo de la evidencia
clínica de invasión parametrial) + RT intracavitaria.
Si hay GLAO + o enfermedad en el abdomen superior: RT de campo extendido
o WART.
Si el performance status lo permite: Considerar QT
Si el performance status no lo permite: considerar HT.
Estadíos IV B
El tratamiento es considerado paliativo.
Tratamiento locorregional y abdomen:
RT: GLAO+: RT pelvis + campo extendido o WART
Si se verifica enfermedad en el abdomen superior: WART
Tratamiento sistémico: QT u HT según perfomance status
ESTADIOS AVANZADOS OPERABLES: est. quir., citorred. y trat. adyuvante
Estadío IIIA:
Sólo citología peritoneal +:
T. endometroides G1-G2, sin otros factores de riesgo: Observación
T. Endom. con fact. riesgo (G3, Invasión miometrial profunda, ILV) : WART
Seroso pap. y cel. claras si el performance status lo permite: RT pelviana + QT
Estadío IIIA con mts. anexial o serosa uterina:
RT pelviana
QT u HT según perf. status
Estadío IIIB: RT pelviana y Braquiterapia.
QT u HT según perfomance status
Estadíos IIIC: GP+ : RT pelviana
GLAO+: RT pelviana + RT campo extendido o WART
QT u HT según perfomance status
Estadío IV:
IVA operables (con citorreducciòn óptima): Exenteración pelviana
IVB intraabdominal (con citorreduciòn óptima): WART
QT u HT según perf. status.
11
ENF. RECURRENTE Y METASTASICA. Recurrencias a distancia o IVB
Pacientes SIN RT previa:
Recurrencia vaginal aislada:
Evaluación quir. Pelv. y abd.: resecable: agregar RT pelviana más BT
irresecable: RT pelviana más BT.
Si en la evaluación quirúrgica aparece enfermedad extravaginal:
Si es GP+: RT pelviana más BT
Si es GLAO+: ídem más RT de campo extendido
Si hay recurrencia en abd. sup.:citorr. óptima seguida de RT : WART
En la enfermedad metastásica a distancia: en general el tratamiento es
paliativo, aunque en ocasiones se logran sobrevidas prolongadas. El
tratamiento es sistémico. A veces es necesario efectuar RT localizada en el
sitio de la MTS para disminuir síntomas.
En todos los casos (enf. recurrente y met.): QT u HT según perfomance status
Pacientes CON RT previa:
Exenteraciòn (excepcional, sólo con intento curativo)
Evaluar RT acorde a tipo y dosis de RT previa
QT u HT según perfomance status
SEGUIMIENTO LUEGO DEL TRATAMIENTO:
Consulta y exámen físico cada 3 a 6 meses por 2 años. Luego cada 6 meses a
1 año.
Si el CA 125 estaba elevado de entrada, solicitarlo en cada visita.
Rx tórax anual
PAP vaginal cada 6 meses por 2 años, luego anualmente.
Avisar a las pacientes que concurran si hay síntomas (dolor, sangrado,pérdida
de peso o disminución del apetito, edemas, tos), y estudiar los síntomas a
fondo.
Asociar al seguimiento específico, el cuidado de la salud (TA, peso, DBT, etc,)
así como hacer screening de otros cánceres asociados al endometrial (mama,
colon, etc)
12
APÉNDICE
Grados de Recomendación basados en la Evidencia disponible
Recomendacion grado sobre la Significado
que se basa
Grado Existe evidencia satisfactoria, por lo Hay buena o muy buena
general de nivel 1 (meta-análisis o evidencia
A
para
ensayos clínicos randomizados y
recomendarla.
controlados)
que
sustenta
la
recomendación. (*)
Grado Evidencias de nivel 2 (ensayos Existe
evidencia
clínicos bien diseñados y controlados razonable
B
para
aunque no randomizados)
recomendarla.
Grado Existe pobre evidencia. Hallazgos Después de analizar las
inconsistentes. Deben ser sometidas evidencias
C
disponibles
a la aprobación del grupo de
con
relación
a posibles
consenso.
sesgos, el grupo de
consenso las admite y
recomienda
la
intervención.
Grado Existe muy pobre evidencia. Los estudios disponibles
Evidencia empírica pobre o no no pueden ser utilizados
D
sistemática.
como evidencia, pero el
grupo
de
consenso
considera por experiencia
que la intervención es
favorable y la recomienda
(*) En situaciones muy especiales, cuando el evento es mortalidad,
especialmente ante una enfermedad previamente fatal, ésta puede deberse a
evidencias de menor nivel.
CATEGORÍAS DEL CONSENSO
Categoría 1: El consenso es uniforme entre los especialistas, basado en
alto nivel de evidencia que la recomendación es apropiada
Categoría 2: El consenso es uniforme entre los especialistas, basado en bajo nivel de
evidencia y en la experiencia clínica que la recomendación es apropiada
Categoría 3: El consenso no es uniforme entre los especialistas, basado en bajo nivel
de evidencia y en la experiencia clínica que la recomendación es apropiada. A pesar
de lo anterior no existe importante desacuerdo.
Categoría 4: No existe acuerdo entre los especialistas que la recomendación sea
apropiada
13
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