Tamización contra el cáncer

1. Tamización contra el cáncer (1/2)
Creado por: Mauricio Lema Medina - LemaTeachFiles© - 2021

2. Objetivo
• Comprender los conceptos esenciales para la tamización contra el cáncer
• Entender las fuentes potenciales de error en la tamización contra el
cáncer
• Sobrediagnóstico (y sesgo de duración de la enfermedad)
• Sesgo de adelanto del diagnóstico
• Discriminar los desenlaces que sustentan la tamización contra el cáncer
• Mortalidad cáncer específica
• Entender cómo la mortalidad general (de toda causa) no se afecta
sustancialmente con el tamizaje contra el cáncer

3. Recomendación tamización para el cáncer en Colombia (riesgo promedio)
Grupo de edad Cérvix Mama Colon Próstata Pulmón1
21-29
CCU 25—29 cada
3 años* - - - -
30-39 VPH2 a los 30 y 35 - - - -
40-49 VPH a los 40 y 45 - - - -
50-59 VPH a los 50 y 55
MMG3 cada 2
años
FOBT4 cada 2 años
Colono5 cada 10 años
Oportunista6 LD-CT7 anual,
desde los 55
60-69 VPH a los 658 MMG cada 2 años
FOBT cada 2 años
Colono cada 10 años
Oportunista LD-CT anual
70-80 - -
FOBT cada 2 años
Colono cada 10 años,
hasta los 75
Se recomienda
NO realizar
LD-CT anual
1 Se realiza tamizaje de cáncer de pulmón en pacientes con tabaquismo (>30 ppy) que no hayan cesado en los últimos 15 años.
2 VPH: ADN-VPH en cérvix uterino
3 MMG: Mamografía
4 FOBT: Sangre oculta en fecales
5 Colono: colonoscopia total
6 Oportunista: se permite la realización de antígeno específico de próstata en paciente asintomático que vaya a consulta por otras causas
7 LD-CT: Tomografía de tórax de baja dosis de radiación
8 Se puede suspender el tamizaje de cáncer de cérvix a los 65 si no se detectaron anormalidades en los últimos 10 años.
* CCU: citología cervicouterina. Para mujeres con vida sexual activa (futura recomendación (post 2020), según información de doctora Lina Tujillo)

4. Palabras
La Real Academia Española define tamizar como depurar,
elegir con cuidado y minuciosidad.
En Inglés existe la palabra screening que significa la
evaluación o examen sistemático para la detectar una
sustancia o atributo indeseado.
Cribar es definido como realizar un examen médico a un
conjunto de personas para detectar una determinada
enfermedad y descartar otras.
Ni tamizaje, ni screening son castizas, pero se usan con
mayor frecuencia que cribado, que sería la más apropiada en
el castellano.
En este documento se utilizarán las tres palabras en forma
indistinta.

5. Tamización
La tamización consiste en la realización de
exámenes a personas asintomáticas con el fin de
detectar anormalidades intervenibles y evitar
desenlaces desfavorables.
En la tamización del cáncer se busca la detección
de lesiones premalignas, en fases preinvasivas o
en estadíos tempranos siempre y cuando las
intervenciones terapéuticas en estas fases de la
enfermedad se traduzcan en una mejor
supervivencia en la población tamizada.

6. La tamización del cáncer se
realiza en asintomáticos

7. Screening for a disease
Going out and trying to find a disease early,
before it has caused symptoms.
The logic is that if we find a disease early, we can
cure it.
We hope people will live longer than if we waited
until the disease became symptomatic
Prasad V, Ending Medical Reversal, 2016

8. Effective cancer screening should accomplish
IT SHOULD FIND CANCERS EARLY IT SHOULD LOWER THE RATE OF
DYING FROM THE CANCER IT IS
MEANT TO FIND
IT SHOULD IMPROVE OVERALL
SURIVIVAL
Prasad V, Ending Medical Reversal, 2016

9. Los 10 principios de detección de la
Organización Mundial de la Salud
1. La afección que se busca debe ser un
problema de salud importante
2. Debe haber un tratamiento aceptado
para pacientes con enfermedad
reconocida.
3. Deben estar disponibles instalaciones
para el diagnóstico y el tratamiento.
4. Debe haber una etapa sintomática
latente o temprana reconocible
5. Debe haber una prueba o examen
adecuado
6. La prueba debe ser aceptable para la
población.
7. La historia natural de la afección,
incluido el desarrollo de una
enfermedad latente a una declarada,
debe entenderse adecuadamente.
8. Debe haber una política acordada
sobre a quién tratar como pacientes.
9. El costo de la detección de casos
(incluido el diagnóstico y el tratamiento
de los pacientes diagnosticados) debe
estar económicamente equilibrado en
relación con el posible gasto en
atención médica en su conjunto.
10. La búsqueda de casos debe ser un
proceso continuo y no un proyecto "de
una vez por todas".

10. How to evaluate screening programmes?
The 2002 Handbook further stated that: “Routine
screening programmes can be evaluated most
readily by time trends and differential mortality
from the disease for which screening is being
performed. Probably the best known is screening
for cervical cancer. The substantial differences
among the Nordic countries in the extent of
organised screening were closely matched by the
mortality rates from cervical cancer”
IARC

11. Inspired by: Prasad V, Ending Medical Reversal, 2016
Measured
incidence
Time
How a screening test should work
Incidence of
early cancers
Incidence of
Advanced cancers
Screening programme

12. Laara E, Day NE, Hakama M. Trends in mortality from cervical cancer in the Nordic countries: association with organised screening programmes. Lancet 1987;1(8544):1247e9.
Cervical cancer mortality after screening
“Compliance of some
80%, with screening
every 3-5 years, should
give an overall reduction
in mortality of 65 to
70%”

13. Schoen RE, PLCO trial. NEJM, 2012
Colorectal cancer mortality after screening
Procedure: basal sigmoidoscopy in 84%, q3-5 yrs in 54% (median follow-up 11.9 yrs, n= 77.445)
Variable Screened Usual care Delta
Incidence 11.9/10.000 p.a. 15.2/10.000 p.a. 21%
Colorectal cancer-related mortality 2.9/10.000 p.a. 3.9/10.000 p.a 26%

14. Colon cancer screening: 30 years of follow-up?
Prasad V, Ending Medical Reversal, 2016
N Screened Not screened
Deaths due to
colon cancer
All deaths
Deaths due to
colon cancer
All deaths
For every
10.000
persons
128 7,111 192 7,109
33%

15. NLST. NEJM, 2011
Lung cancer mortality after screening (NLST)
Intervention: Low-dose CT q1yr x3 in high-risk patients (n= 53,454)
Variable Screened Usual care Delta
Positive screening 24.2% 6.9%
False-positive test 96.4% 94.5%
Incidence 645/100.000 p.a. 572/100.000 p.a. 13%
Lung cancer-related mortality 247/100.000 p.a. 309/100.000 p.a 20%
All cause mortality: ↓6.7%

18. La cosa se
complica

19. Inspired by: Prasad V, Ending Medical Reversal, 2016
Measured
incidence
Time
Incidence of
early cancers
Incidence of
Advanced cancers
What actually happened with breast and prostate cancer
screening
Actual Incidence of
early cancers
Actual Incidence of
Advanced cancers
Screening programme

20. Breast cancer screening: 30 years of follow-up?
Prasad V, Ending Medical Reversal, 2016
N Before mammography
After 30 yr of screening
mammography
Early cancers Advanced Early cancers All deaths
For every
100.000
women
112/yr 102/yr 234/yr 94/yr

21. Effect of Three
Decades of Screening
Mammography on
Breast-Cancer
Incidence
https://www.nejm.org/doi/full/10.1056/NEJMoa1206809
Bleyer A, Welch HG. NEJM, 2012.

22. Autier P, Boniol M. Mammography screening: A major issue in medicine. Eur J Cancer. 2018 Feb;90:34-62. doi: 10.1016/j.ejca.2017.11.002. Epub 2017 Dec 20. PMID: 29272783.
Stage II-IV breast cancers have not decreased
with screening mammography (Netherlands)
No discernible difference in
breast cancer mortality with the
adoption of screening
mammography between the US
(1980s), Norway (1995), and
Switzerland (less than half
engaged in active screening in
2018)

23. Autier P, Boniol M. Mammography screening: A major issue in medicine. Eur J Cancer. 2018 Feb;90:34-62. doi: 10.1016/j.ejca.2017.11.002. Epub 2017 Dec 20. PMID: 29272783.
Breast cancer incidence after the introduction of
screening mammography in the US and Sweeden
Screening
mammography
increased the number of
both in-situ and invasive
breast cancer in the US
US
Sweeden

24. Overdiagnosis bias
1000 patients with
progressive cancer 600 dead
5-years
5-year survival: 80%
2000 patients with non-
progressive cancer 2400 alive
400 alive
1000 patients with
progressive cancer 600 dead
5-years
5-year survival: 40%

25. Overdiagnosis in screening mammography
Screen-detected ductal carcinoma in-situ is considered a form of overdiagnosis
Mälmo/Canadian UK Age Trial As a denominator
of screen detected
cancers
Range of overdiagnosis
with screening
mammography
19% 35% 30% 15-50%
Autier P, Boniol M. Mammography screening: A major issue in medicine. Eur J Cancer. 2018 Feb;90:34-62. doi: 10.1016/j.ejca.2017.11.002. Epub 2017 Dec 20. PMID: 29272783.

26. Dead at age 70
Cancer diagnosis because of
symptoms at age 67
Lead-time bias
No screening mammography
5-year survival: 0%

27. Dead at age 70
Cancer diagnosis because of
screening at age 60
Lead-time bias
Screening mammography
5-year survival: 100%

28. Dead at age 70
Cancer diagnosis because of
symptoms at age 67
Dead at age 70
Cancer diagnosis because of
screening at age 60
Lead-time bias
No screening mammography
Screening mammography
5-year survival: 0%
5-year survival: 100%

29. Løberg, M. Breast Cancer Res. 2015
Outcomes after screening mammography
(for every 1000 women screened over 20 years)

30. Nelson HD. Ann Internal Med. 2015
Outcomes after screening mammography
(for every 10.000 women screened over 10 years)

31. PLCO
The PLCO trial may be viewed as a trial of organized vs opportunistic screening for prostate
cancer because of the substantial screening rate in the control group and the high screening
rate among men in both the control and intervention groups prior to study enrollment.
Men in the intervention group were screened more often than men in the control group, and
more men in the intervention group were diagnosed with prostate cancer than in the control
group.
The trial found no difference between groups in death from prostate cancer after almost 15
years of follow-up (absolute risk, 4.8 per 1000 person-years in the intervention group vs 4.6
per 1000 person-years in the control group; relative risk [RR], 1.04 [95% CI, 0.87-1.24]).

32. ERSPC
In the ERSPC trial, the results suggest that, overall, the number needed to screen is 781 men aged 55 to 69 years at
enrollment (95% CI, 490-1929) to prevent 1 man from dying of prostate cancer after 13 years.
The results varied across the individual ERSPC sites, and prostate cancer mortality was significantly reduced only at the
sites in the Netherlands and Sweden.
However, point estimates were in favor of screening at all sites except Switzerland.
At the largest site (Finland), there was no significant benefit observed for prostate cancer mortality (rate ratio, 0.91
[95% CI, 0.75-1.10]), and in Sweden there was an absolute risk reduction of 0.72% (95% CI, 0.50%-0.94%), a 42%
relative reduction.

33. ERSPC
Four ERSPC trial sites reported data on the effect of PSA-based screening
for prostate cancer on the development of metastatic cancer after 12 years
of follow-up.
The risk of developing metastatic prostate cancer was 30% lower among
men randomized to screening than among men in the control group
(absolute risk, 7.05 per 1000 men in the screening group vs 10.14 per
1000 men in the control group [calculated from numbers in the study]).
This translates to an absolute reduction in the long-term risk of
metastatic prostate cancer of 3.1 cases per 1000 men screened.

34. Autier P, Boniol M. Mammography screening: A major issue in medicine. Eur J Cancer. 2018 Feb;90:34-62. doi: 10.1016/j.ejca.2017.11.002. Epub 2017 Dec 20. PMID: 29272783.
Screening characteristics of selected cancers

35. Do cancer-screening tests fulfill their goals?
Screening-test Early detection /
prevention
Decrease cancer-related
mortality
Improve overall
survival
Mammography Yes 19% (50-74 yo) No
PSA Yes 3% No
Sigmoidoscopy and FOBT Yes 20% No
Chest-CT Yes 20% Yes
Pap-smear Yes Yes, indirect evidence Not proven
FOBT: Fecal occult blood test Prasad V, Ending Medical Reversal, 2016