Guía de Práctica Clínica - Problema de Salud AUGE N°70
Cáncer Colorectal en personas de 15 años y más
Recomendación – T3 / Juicio del Panel y Evidencia
T.3.En personas con diagnóstico de cáncer de colon en etapa II operado y factores de riesgo de recurrencia*, el Ministerio de Salud SUGIERE realizar quimioterapia adyuvante por sobre no realizarla.
* Factores de riesgo de recurrencia destacan: Etapa T4, obstructivo o perforado, bajo recuento ganglionar, permeaciones vasculares, brotes tumorales, infiltración perineural.
Comentarios del Panel de Expertos:
►Antes de iniciar quimioterapia adyuvante es deseable evaluar la inestabilidad microsatelital en la biopsia, ya que pacientes que presentan tumores con esta característica podrían no beneficiarse de la quimioterapia adyuvante.
El panel de expertos analizó y debatió cada uno de las preguntas de la “Tabla de la evidencia a la decisión”, considerando tanto la evidencia de investigación, experiencia clínica, conocimiento de gestión o experiencia de los pacientes. Una vez consensuada la postura del panel respecto a las preguntas, emitieron un juicio seleccionando la opción de respuesta que mejor representaba la opinión del conjunto (destacada con color). Finalmente cuando el panel emitió su juicio sobre todas las preguntas, se emitió la recomendación.
A continuación se presenta la “Tabla de la evidencia a la decisión” con el resumen de los juicios, la evidencia de investigación evaluada, consideraciones adicionales y comentarios planteados por el panel.
1.- ¿El problema es una prioridad?
| No | Probablemente no | Probablemente sí | Sí | Varía | No lo sé |
|---|
El problema ha sido definido como prioritario en el marco de las Garantías Explícitas en Salud (GES), régimen integral de salud que prioriza un grupo de patologías o problemas de salud, garantizando el acceso a tratamiento oportuno y de calidad.
2.- ¿Qué tan significativos son los efectos deseables anticipados?
| Triviales | Pequeños | Moderados | Grandes | Varía | No lo sé |
|---|
Moderados: El panel de expertos de la Guía estimó que los efectos deseables de «realizar quimioterapia adyuvante» en comparación a «no realizarla» son moderados, considerando la evidencia, experiencia clínica, conocimiento de gestión o experiencia de las personas con la condición o problema de salud.
Evidencia de investigación
|
Quimioterapia adyuvante para cáncer de colon etapa II operado y con factores de riesgo de recurrencia. |
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|
Pacientes |
Personas con diagnóstico de cáncer de colon en etapa II operado y factores de riesgo de recurrencia (Etapa T4, obstructivo o perforado, bajo recuento ganglionar, permeaciones vasculares, brotes tumorales, infiltración perineural). |
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|
Intervención |
Realizar quimioterapia adyuvante |
|||||
|
Comparación |
No realizarla. |
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|
Desenlaces |
Efecto relativo (IC 95%) — Pacientes / estudios |
Efecto absoluto estimado* |
Certeza de la evidencia (GRADE) |
Mensajes clave en términos sencillos |
||
|
SIN Quimioterapia adyuvante |
CON Quimioterapia adyuvante |
Diferencia (IC 95%) |
||||
|
Mortalidad |
RR 0,96 (0,87 a 1,05) — 7097 pacientes / 16 ensayos en una revisión sistemática [1] |
215 |
206 |
Diferencia: (28 menos a 11 más) |
⊕⊕⊕◯1 Moderada |
Quimioterapia adyuvante probablemente disminuye la mortalidad en cáncer de colon etapa II operado con factores de riesgo de recurrencia. |
|
Recurrencia |
RR 0,83 (0,75 a 0,91) — 8642 pacientes / 18 ensayos en una revisión sistemática [1] |
213 |
177 |
Diferencia: (19 a 53 menos) |
⊕⊕⊕⊕ Alta |
Quimioterapia adyuvante disminuye las recurrencias en cáncer de colon etapa II operado con factores de riesgo de recurrencia. |
|
Efectos adversos |
Ninguna de las revisiones identificadas entrega una medida de efecto, sin embargo en general concluyen que existe un aumento de los efectos adversos con terapia adyuvante. |
— |
— |
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IC 95%: Intervalo de confianza del 95%.
RR: Riesgo relativo.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* El riesgo SIN Quimioterapia adyuvante está basado en el riesgo del grupo control en los estudios. El riesgo CON quimioterapia adyuvante(y su intervalo de confianza) está calculado a partir del efecto relativo (y su intervalo de confianza).
1 Se disminuyó un nivel de certeza de evidencia por imprecisión, ya que cada extremo del intervalo de confianza conlleva una decisión diferente.
Fecha de elaboración de la tabla: Octubre, 2018.
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Búsqueda y Síntesis de Evidencia
Búsqueda y síntesis de evidencia de efectos deseables e indeseables
3.- ¿Qué tan significativos son los efectos indeseables anticipados?
| Grandes | Moderados | Pequeños | Triviales | Varía | No lo sé |
|---|
Moderados: El panel de expertos de la Guía estimó que los efectos indeseables de «realizar quimioterapia adyuvante» en comparación a «no realizarla» son moderados, considerando la evidencia, experiencia clínica, conocimiento de gestión o experiencia de las personas con la condición o problema de salud. La quimioterapia adyuvante aumenta los efectos adversos, sobre todo agudos, por ejemplo los gastrointestinales o los hematológicos. Sin embargo la mayoría no son crónicos y son tratables.
Evidencia de investigación
|
Quimioterapia adyuvante para cáncer de colon etapa II operado y con factores de riesgo de recurrencia. |
||||||
|
Pacientes |
Personas con diagnóstico de cáncer de colon en etapa II operado y factores de riesgo de recurrencia (Etapa T4, obstructivo o perforado, bajo recuento ganglionar, permeaciones vasculares, brotes tumorales, infiltración perineural). |
|||||
|
Intervención |
Realizar quimioterapia adyuvante |
|||||
|
Comparación |
No realizarla. |
|||||
|
Desenlaces |
Efecto relativo (IC 95%) — Pacientes / estudios |
Efecto absoluto estimado* |
Certeza de la evidencia (GRADE) |
Mensajes clave en términos sencillos |
||
|
SIN Quimioterapia adyuvante |
CON Quimioterapia adyuvante |
Diferencia (IC 95%) |
||||
|
Mortalidad |
RR 0,96 (0,87 a 1,05) — 7097 pacientes / 16 ensayos en una revisión sistemática [1] |
215 |
206 |
Diferencia: (28 menos a 11 más) |
⊕⊕⊕◯1 Moderada |
Quimioterapia adyuvante probablemente disminuye la mortalidad en cáncer de colon etapa II operado con factores de riesgo de recurrencia. |
|
Recurrencia |
RR 0,83 (0,75 a 0,91) — 8642 pacientes / 18 ensayos en una revisión sistemática [1] |
213 |
177 |
Diferencia: (19 a 53 menos) |
⊕⊕⊕⊕ Alta |
Quimioterapia adyuvante disminuye las recurrencias en cáncer de colon etapa II operado con factores de riesgo de recurrencia. |
|
Efectos adversos |
Ninguna de las revisiones identificadas entrega una medida de efecto, sin embargo en general concluyen que existe un aumento de los efectos adversos con terapia adyuvante. |
— |
— |
|||
IC 95%: Intervalo de confianza del 95%.
RR: Riesgo relativo.
GRADE: Grados de evidencia Grading of Recommendations Assessment, Development and Evaluation.
* El riesgo SIN Quimioterapia adyuvante está basado en el riesgo del grupo control en los estudios. El riesgo CON quimioterapia adyuvante(y su intervalo de confianza) está calculado a partir del efecto relativo (y su intervalo de confianza).
1 Se disminuyó un nivel de certeza de evidencia por imprecisión, ya que cada extremo del intervalo de confianza conlleva una decisión diferente.
Fecha de elaboración de la tabla: Octubre, 2018.
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58. McCollum AD, Catalano PJ, Haller DG, Mayer RJ, Macdonald JS, Benson AB, Fuchs CS. Outcomes and toxicity in african-american and caucasian patients in a randomized adjuvant chemotherapy trial for colon cancer. Journal of the National Cancer Institute. 2002;94(15):1160-7.
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87. Taal BG, Van Tinteren H, Zoetmulder FA, NACCP group. Adjuvant 5FU plus levamisole in colonic or rectal cancer: improved survival in stage II and III. British journal of cancer. 2001;85(10):1437-43.
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Búsqueda y Síntesis de Evidencia
Búsqueda y síntesis de evidencia de efectos deseables e indeseables
4.- ¿Cuál es la certeza general de la evidencia sobre efectos?
| Muy baja | Baja | Moderada | Alta | Ningún estudio incluído |
|---|
Moderada: Existe confianza respecto del efecto de «realizar quimioterapia adyuvante» en comparación a «no realizarla». La certeza general de la evidencia se centró en la certeza del desenlace en salud «mortalidad», dado que es considerado crítico para el paciente. El desenlace «recurrencia» aunque importantes no fue considerado crítico.
Evidencia de investigación
|
Desenlaces |
Importancia |
Certeza de la evidencia (GRADE) |
|
Mortalidad |
Crítico |
⨁⨁⨁◯ |
|
Recurrencia |
Importante |
⨁⨁⨁⨁ |
|
Efectos adversos |
– |
– |
a. Se disminuyó un nivel de certeza de evidencia por imprecisión, ya que cada extremo del intervalo de confianza conlleva una decisión diferente.
5.- ¿Hay incertidumbre importante o variabilidad sobre qué tanto valora la gente los desenlaces principales?
| Incertidumbre o variabilidad importantes | Posiblemente hay incertidumbre o variabilidad importantes | Probablemente no hay incertidumbre ni variabilidad importantes | No hay variabilidad o incertidumbre importante |
|---|
Posiblemente hay incertidumbre o variabilidad importantes: En función de la evidencia de investigación, experiencia clínica, conocimiento de gestión o experiencia de las personas con la condición o problema de salud, el panel de expertos de la Guía consideró que posiblemente existe incertidumbre o variabilidad importante respecto a lo que escogería una persona informada de los efectos deseables e indeseables de «realizar quimioterapia adyuvante» y «no realizarla». Según lo indicado en la evidencia, a criterio de los pacientes, pequeños beneficios potenciales de supervivencia compensan los riesgos de efectos secundarios de la quimioterapia adyuvante. Sin embargo, algunos pacientes con poca tolerancia a efectos adversos podrían rechazar la quimioterapia.
Evidencia de investigación
No se encontró un estudio que evaluaran las preferencias de pacientes con cáncer de colon estadio II, sí se encontraron estudios que evaluaban las diferentes alternativas en pacientes estadio III:
Se identificó una revisión (1) que abordaba las preferencias de pacientes respecto al tratamiento adyuvante, dentro de los estudios incluidos 2 abordaba la comparación de agregar quimioterapia adyuvante al tratamientos pacientes con cáncer de colon en estadio II-III operados (2,3). Ambos concluyen que en pacientes con cáncer de colon II-III, los pequeños potenciales beneficios de supervivencia compensaban los riesgos de efectos secundarios de la quimioterapia adyuvante.
En Hofmann et al (2), el 77% pacientes con cáncer colorectal (n=102) optaron por quimioterapia adyuvante por 1 año para pacientes con cáncer de colon III, con un beneficio de supervivencia del 5% y a pesar de los efectos adversos informados (19% posibilidad de nauseas+vómitos; 2% de pérdida de cabello, 2% mucositis oral, 1% mucositis oral+vómitos; 2% vómitos más diarrea).
En Blinman et al (3), el 82% de pacientes con cáncer de colon II – III y que recibieron quimioterapia por al menos 4 semanas, consideraron suficiente un 5% adicional en las tasas de supervivencia a los 5 años y el 90% un 10% adicional supervivencia para considerar la quimioterapia adyuvante. Las preferencias no se asociaron fuertemente con otras características basales de los pacientes, al estadio, características del tratamiento recibido, características de la evolución de la enfermedad, o aspectos de la calidad de vida relacionada con la salud durante la quimioterapia.
En estudio retrospectivo indagó en las razones para no recibir quimioterapia adyuvante tras la cirugía en pacientes cáncer de colon en estadio III. Observaron que el 12% de los 502 pacientes a los que se les recomendó quimioterapia adyuvante la rechazaron, la razón declarada más recurrente fue la preocupación sobre la toxicidad (4), sin embargo en la mayoría de los casos no se registra el motivo del rechazo (4,5).
Referencias
1. Currie A, Askari A, Nachiappan S, Sevdalis N, Faiz O, Kennedy R. A systematic review of patient preference elicitation methods in the treatment of colorectal cancer. Color Dis [Internet]. 2015 Jan 1 [cited 2018 Sep 27];17(1):17–25. Available from: http://doi.wiley.com/10.1111/codi.12754
2. Hofmann S, Vetter J, Wachter C, Henne-Bruns D, Porzsolt F, Kornmann M. Visual AIDS for multimodal treatment options to support decision making of patients with colorectal cancer. BMC Med Inform Decis Mak [Internet]. 2012 Oct 23 [cited 2018 Sep 27];12:118. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23092310
3. Blinman P, Duric V, Nowak AK, Beale P, Clarke S, Briscoe K, et al. Adjuvant chemotherapy for early colon cancer: What survival benefits make it worthwhile? Eur J Cancer [Internet]. 2010 Jul [cited 2018 Sep 27];46(10):1800–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20137908
4. El Shayeb M, Scarfe A, Yasui Y, Winget M. Reasons physicians do not recommend and patients refuse adjuvant chemotherapy for stage III colon cancer: a population based chart review. BMC Res Notes [Internet]. 2012 Jun 7 [cited 2018 Oct 2];5(1):269. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22676354
5. Gilbar P, Lee A, Pokharel K. Why adjuvant chemotherapy for stage III colon cancer was not given: Reasons for non-recommendation by clinicians or patient refusal. J Oncol Pharm Pract [Internet]. 2017 Mar 23 [cited 2018 Oct 2];23(2):128–34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26692241
2. Hofmann S, Vetter J, Wachter C, Henne-Bruns D, Porzsolt F, Kornmann M. Visual AIDS for multimodal treatment options to support decision making of patients with colorectal cancer. BMC Med Inform Decis Mak [Internet]. 2012 Oct 23 [cited 2018 Sep 27];12:118. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23092310
3. Blinman P, Duric V, Nowak AK, Beale P, Clarke S, Briscoe K, et al. Adjuvant chemotherapy for early colon cancer: What survival benefits make it worthwhile? Eur J Cancer [Internet]. 2010 Jul [cited 2018 Sep 27];46(10):1800–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20137908
4. El Shayeb M, Scarfe A, Yasui Y, Winget M. Reasons physicians do not recommend and patients refuse adjuvant chemotherapy for stage III colon cancer: a population based chart review. BMC Res Notes [Internet]. 2012 Jun 7 [cited 2018 Oct 2];5(1):269. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22676354
5. Gilbar P, Lee A, Pokharel K. Why adjuvant chemotherapy for stage III colon cancer was not given: Reasons for non-recommendation by clinicians or patient refusal. J Oncol Pharm Pract [Internet]. 2017 Mar 23 [cited 2018 Oct 2];23(2):128–34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26692241
Búsqueda y Síntesis de Evidencia
Búsqueda y síntesis de evidencia de valores y preferencias de los pacientes
6.- El balance entre efectos deseables e indeseables favorece la intervención o la comparación?
| Favorece la comparación | Probablemente favorece la comparación | No favorece la intervención ni la comparación | Probablemente favorece la intervención | Favorece la intervención | Varía | No lo sé |
|---|
Probablemente favorece la intervención: Considerando que la intervención es «realizar quimioterapia adyuvante» y la comparación es «no realizarla», el panel de expertos de la Guía opinó que el balance entre efectos deseables e indeseables probablemente favorece «realizar quimioterapia adyuvante».
7.- ¿Qué tan grandes son los recursos necesarios (costos)?
| Costos extensos | Costos moderados | Costos y ahorros despreciables | Ahorros moderados | Ahorros extensos | Varía | No lo sé |
|---|
Costos extensos: El panel de expertos de la Guía consideró que los costos de «realizar quimioterapia adyuvante» son grandes si se compara con los costos de «no realizarla», en función de los antecedentes, experiencia clínica, conocimiento de gestión o experiencia de los pacientes.
Evidencia de investigación
A continuación se muestran los costos referenciales, es preciso considerar que estos costos fueron recogidos con el único objetivo de constituir un antecedente aproximado.
|
El porcentaje de cobertura del seguro de salud sobre el precio de las prestaciones sanitarias, dependerá del tipo de seguro de cada paciente. |
|
|
ítem |
Intervención: quimioterapia adyuvante |
|
Canasta GES: Quimioterapia Adyuvante: Bajo Riesgo: Y Estadíos: II (Alto Riesgo) 1 |
$ 286.074 |
|
PPV: Quimioterapia Adyuvante: Bajo riesgo y Estadíos II (alto riesgo) 2 |
$ 359.110 |
|
|
Rango: $286.074 – $359.110 |
Canasta GES: El precio total de la canasta considera exámenes prequirúrgicos, consulta a especialistas y otros requerimientos propios de la cirugía. No todos los pacientes requerirán todas las prestaciones establecidas en la canasta, es por ellos que el precio total considera una frecuencia estimada de utilización de cada prestación.
PPV: Programa de prestaciones valoradas de FONASA donde se establecen aranceles por prestaciones integrales o paquetes de prestaciones sanitarias.
Referencias:
1. Precios indicados en las canastas de Cáncer Colorectal elaboradas en el contexto de las Garantías Explícitas en Salud. Precio inflactados utilizando una tasa de descuento del 3%.
2. Precio obtenido de la base de datos del Programa de Prestaciones Valoradas. Este precio agrupa varias prestaciones.
Búsqueda y Síntesis de Evidencia
Búsqueda de costos
8.- ¿La costo-efectividad de la intervención beneficia la intervención o la comparación?
| Favorece la comparación | Probablemente favorece la comparación | No favorece la intervención ni la comparación | Probablemente favorece la intervención | Favorece la intervención | Varía | Ningún estudio incluído |
|---|
Ningún estudio incluído: No se encontraron estudios que respondieran la preguntan de interés.
Evidencia de investigación
No se encontraron estudios que evaluaran la costo efectividad de «realizar quimioterapia adyuvante» vesus «no realizarla» en la población indicada.
Búsqueda y Síntesis de Evidencia
Búsqueda y síntesis de evidencia de costo efectividad
9.- ¿Cuál sería el impacto en equidad en salud?
| Reducido | Probablemente reducido | Probablemente ningún impacto | Probablemente aumentado | Aumentado | Varía | No lo sé |
|---|
Aumentada: El panel de expertos de la Guía consideró que la equidad en salud aumentaría si se recomendase «realizar quimioterapia adyuvante», dado que en la actualidad existe amplio acceso, ya sea en términos económicos, geográficos u otros.
10.- ¿La intervención es aceptable para las partes interesadas?
| No | Probablemente no | Probablemente sí | Sí | Varía | No lo sé |
|---|
Probablemente sí: El panel de expertos de la Guía consideró que «realizar quimioterapia adyuvante» probablemente SÍ es aceptable para las partes interesadas (profesionales de la salud, gestores de centros de salud, directivos de centros de salud, pacientes, cuidadores, seguros de salud, otros).
11.- ¿Es factible implementar la intervención?
| No | Probablemente no | Probablemente sí | Sí | Varía | No lo sé |
|---|
Sí: El panel de expertos de la Guía consideró que «realizar quimioterapia adyuvante» SÍ es factible implementar, contemplando la capacidad de la red asistencial, los recursos humanos disponibles a nivel país, recursos financieros, etc.