Más criticas al cribado de cáncer de mama

Visión crítica sobre la detección de cáncer de mama mediante mamografía (Revisión Cochrane)

 Desde el excelente blog de Rincón Docente, Luis Lozano, nos informa de esta nueva iniciativa de colaboración Cochrane.

 Luis Lozano | Dejar un comentario

Cochrane Collaboration (Photo credit: Wikipedia)

Peter C. Gøtzsche es un conocido investigador danés líder del Centro Nórdico Cochrane de Copenhague, Dinamarca. Ha escrito numerosas evaluaciones dentro de la colaboración Cochrane.

Además de sus trabajos criticos sobre la investigación con placebos y los posibles sesgos de los metaanálisis es especialmente conocido por su voz crítica sobre el cribado del cancer de mama, sobre los que ya publicó un artículo de 2000 en Lancet (Is screening for breast cancer with mammography justifiable?).
Acaba de publicarse una revisión Cochrane sobre el screening de cancer de mama mediante mamografía escrita por él en colaboración con Karsten Juhl Jørgensen. Creo que se trata de una revisión que invita a la reflexión. Me he permitido traducir las conclusiones:

Shown is a breast being compressed to get the optimum mammographic image. (Photo credit: Wikipedia)

Implicaciones para la Práctica Clínica

Creemos que ha llegado el momento de reevaluar si la mamografía de cribado universal debería ser recomendada para cualquier grupo de edad. La disminución de las tasas de mortalidad por cáncer de mama se deben principalmente a la mejora de los tratamientos y la concienciación sobre el cáncer de mama, por lo que no estamos seguros de los beneficios del cribado en la actualidad. El sobrediagnóstico tiene costes humanos y aumenta el número de mastectomías y muertes. La probabilidad de que una mujer se beneficie del asistir a las pruebas  de cribado es pequeña, y en el mejor de los casos – si nos basamos en los resultados de ensayos aleatorios – diez veces más pequeño que el riesgo de que pueda experimentar daños graves en términos de sobrediagnóstico. Las mujeres, los médicos y los responsables políticos deben valorar cuidadosamente ventajas y desventajas cuando se decide si es adecuado o no asistir o apoyar programas de cribado.

Los defensores del cribado y de diversas  organizaciones en general han hecho hincapié en los beneficios y omitido información sobre los principales daños en sus materiales de información (Dixon-Woods, 2001; Gøtzsche 2012; Jørgensen 2004; Folleto NHS 2001; Folleto NHS 2010; EE.UU. Task Force 2002) y en cartas de invitación (Jørgensen 2006; Gøtzsche 2009). Por tanto la mayoría de las mujeres tienden a exagerar considerablemente los beneficios y no ser conscientes de los principales efectos nocivos del cribaje (Barratt 1997; Barratt 1999; Domenighetti 2003, Schwartz 2000).

Para intentar ayudar a asegurar que la mujer reciba una información adecuada para decidir si acudir o no a un programa de cribado, hemos redactado un folleto para pacientes basado en la evidencia disponible (Gøtzsche 2009). El folleto ha sido probado cuidadosamente entre los médicos generales y pacientes. Está disponible en el sitio web de BMJ en Inglés (Gøtzsche 2009) y en varios idiomas en el sitio web del Centro Nórdico Cochrane en http://www.cochrane.dk (acceso al folleto en español)

Se ha sugerido que estos recursos podrían redirigirse a intervenciones con beneficios comprobados en el cáncer de mama (Baum 2000) o utilizarse para otros fines (NBCC 2002). En comparación, el beneficio es al menos 200 veces mayor en las mujeres con cáncer de mama con ganglios positivos que son tratados con tamoxifeno ya que la extensión media de vida es de seis meses a los 10 años (EBCTCG 1998).

Implicaciones para la investigación

La mortalidad por cáncer de mama resulta poco fiable como medida de resultado de las pruebas de cribado (y por tanto también de los estudios de cohortes sobre eficacia de los programas nacionales) y exagera su beneficio. Debido a los problemas metodológicos de los ensayos de detección y los análisis reaalizados, sería útil que investigadores independientes realizaran un metanálisis basado en datos de pacientes individuales, donde no se permitiera la exclusión de las mujeres al azar. También sería útil obtener datos sobre todas las muertes por cáncer  de todos los ensayos ya que la clasificación errónea de la causa de la muerte a menudo se refiere a muertes por otros cánceres. Por último, es necesario investigar en métodos que permitan diferenciar los cánceres susceptibles de producir mayor mortalidad de los muchos tumores benignos identificados que no necesitarían tratamiento.

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Influence of Study Features and Methods on Overdiagnosis Estimates in Breast and Prostate Cancer Screening

Ruth Etzioni, PhD; Roman Gulati, MS; Leslie Mallinger, MPH; and Jeanne Mandelblatt, MD, MPH

Source: Ann Intern Med. 2013;158(11):831-838. doi:10.7326/0003-4819-158-11-201306040-00008

Knowledge of the likelihood that a screening-detected case of cancer has been overdiagnosed is vitally important to make treatment decisions and develop screening policy. An overdiagnosed case is an excess case detected by screening. Estimates of the frequency of overdiagnosis in breast and prostate cancer screening vary greatly across studies. This article identifies features of overdiagnosis studies that influence results and shows their effect by using published research. First, different ways to define and measure overdiagnosis are considered. Second, contextual features and how they affect overdiagnosis estimates are examined. Third, the effect of estimation approach is discussed. Many studies use excess incidence under screening as a proxy for overdiagnosis. Others use statistical models to make inferences about lead time or natural history and then derive the corresponding fraction of cases that are overdiagnosed. This article concludes with questions that readers of overdiagnosis studies can use to evaluate the validity and relevance of published estimates and recommends that authors of studies quantifying overdiagnosis provide information about these features.

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An Avastin Recommendation & Conflicts Of Interest

 Bevacizumab = Avastin

Earlier this month, the National Comprehensive Cancer Network, a non-profit group of oncologists whose guidance is closely followed by leading treatment centers, voted overwhelmingly in favor of maintaining its recommendation that Avastin should be used to treat breast cancer. The vote came shortly after an FDA panel voted 6-to-0 to revoke the breast cancer indication for Avastin.

The endorsement is important because oncologists will likely continue to use Avastin even if FDA commish Margaret Hamburg rescinds the breast cancer indication. Roche and its Genentech unit had appealed a decision last December by the agency to pull the indication for their best-selling med after new studies showed the med does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh significant risks. This prompted the unusual two-day hearing last month (back stories here and here).

However, 10 of the 33 members of the NCCN breast cancer panel members have ties to Roche or Genentech, either as advisory board members, speakers, consultants, expert witnesses or having received clinical research support. These connections are disclosed on the NCCN web site (look here). And 25 members of the panel participated in the recent vote to maintain the recommendation.

Specifically, the NCCN panel voted 24 in favor, 0 against and 1 abstention. The simple math suggests that at least one panel member - and possibly two - with ties to Roche voted to support the metastatic breast cancer recommendation. Perhaps more panel members with connections voted, although there is now way to know ascertain this since the NCCN press release does not specify who participated in the voting.

As we have noted previously, the NCCN endorsement is likely to be a boon for Roche, since treatment for breast cancer has typically generated about $1 billion or more in annual sales. Avastin rings registers - worldwide sales last year totaled about $6.8 billion and rose 9 percent, which meant this one drug accounted for 14 percent of total Roche sales. In other words, much is at stake.

Meanwhile, the stated NCCN policy conflicts of interest requires “disclosure of external relationships and recusal of NCCN Guidelines Panel Members with conflicting interests so that the integrity of the NCCN Guidelines is not compromised or diminished by conflicts or by the perception of conflicts,” according to the NCCN web site.

The policy also states that a panel member with a significant and direct or indirect relationship with “an external entity” that constitutes a conflict shall not participate in NCCN Guidelines Panel discussions, when the panel’s action on the topic under discussion “may advantage or disadvantage an external entity.” An exception is granted when requested by the panel chair “to participate for the purpose of providing or presenting information to the NCCN Guidelines Panel.”

More specifically, certain “direct relationships,” such as a panel member who is a beneficial owner of stock in an “external” entity or a director of such an organization” would be considered to have a de facto conflict. The policy also defines “direct relationships” as anyone “who receives compensation for services including, but not limited to, management or consulting services to the organization” (here is the policy).

So we asked NCCN whether this policy was followed for the recent breast cancer panel, given that the vote tally suggested otherwise. The spokeswoman repeatedly declined to discuss specifics and referred us back to the recent press release which, again, offers no information on the topic. In fact, she refused to answer whether NCCN has a recusal policy, even though this exists on the web site. “I’m only allowed to discuss what is in the press release,” she told us over and over.

We also reached out to the 10 panel members who have ties to Roche and Genentech. One responded. Antonio Wolff wrote us to confirm that “Genentech provides funding to Johns Hopkins University (where I am employed as School of Medicine faculty) to support research costs associated with an ongoing early phase clinical trial, and I am the site PI for that study. As for your specific question regarding my activities within NCCN, I will ask (you) to contact it directly as NCCN requires all panel members to adhere to its confidentiality policy.”

And so, an influential panel with ties to a drugmaker - which has a lot of sales on the line - voted to maintain a key recommendation. In this instance, NCCN panel members fully disclosed their ties to Roche, but is this sufficient? Supposedly, there is a reason NCCN has a disclosure and recusal policy, but in this instance, there would appear to have been a breach. If none occurred, the organization should be willing to discuss specifics and defend its policy. Yet NCCN refused to do so. What do you think?

Source: Pharmalot