Research & Education

CAP IASLC AMP Molecular Testing Guideline

Leading Health Care Organizations issue Guideline recommendations for Molecular Testing and Targeted Therapies
April 3, 2013

The College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP) have developed an evidence-based guideline, “Molecular Testing Guideline for the Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors,” which establishes standards for EGFR and ALK testing, helping to guide targeted therapies. The guideline was released on April 3, 2013, in Archives of Pathology & Laboratory Medicine, the Journal of Thoracic Oncology, and the Journal of Molecular Diagnostics.

The IASLC offers the following resources:

View the full article on the JTO Website

Download a Summary of the Recommendations

View the Patient Guide

View the slide deck of the webcast

View the webcast with the lead authors of the guideline

View the Videos about the guideline


Frequently Asked Questions are listed below:

Q: What has changed from the draft recommendations posted for public comment in November/December 2011?

A: There have been several changes to the final recommendation and we encourage you to read the final document completely. Since the time that the draft recommendations were posted for comment, another literature search was performed and the evidence graded, resulting in changes to the strength of the recommendations.

Q: Why does the guideline recommend only the two biomarkers EGFR and ALK? And not next generation sequencing?

A: EGFR and ALK are the two biomarkers with the most compelling published evidence to support a role in determining therapy for patients with lung cancer. KRAS may have some value in excluding therapies, and this role is addressed in the guideline. Several other genetic changes may show promise as markers to guide therapy, but remain to be proven in larger studies before an evidence-based recommendation can be made; these are also discussed in the document. Similarly, the published evidence about the analytical performance of “next generation” sequencing is insufficient at this time to make a defensible statement either for or against. This is a guideline about what should be done today, not what we speculate about what should be done tomorrow, regardless of how confident we may feel about what the future will bring.

Q: The diagnosis of adenocarcinoma is usually established before the stage is known. In the majority of institutions, the pathologist will not know whether the patient is early or late stage. What should the pathologist do in that setting?

A: Communication, where practical, is always recommended. The pathologist should make a reasonable effort to determine stage, or an institutional decision should be made to determine, in advance, what the policy should be in this circumstance. In the absence of clinical evidence or an institutional policy to argue against testing, our opinion is that analysis of EGFR and ALK should be performed.

Q: How do I work with my oncologists to implement these guidelines?

A: Pathologist- oncologist communication is critical. Pathologists need to share with their oncologists the types of molecular tests that are available, along with the strengths and weaknesses of each test. Pathologists need to engage with oncologists as to which tests should be used and when to use them. The guideline makes recommendations when data was extremely clear about what should be done. There are a number of issues that have been left up to the institutions to make a decision in their patients’ best interest. And that should be done prospectively on an institution-wide base basis – not managed case by case

Q: Why perform testing when such a small percentage of patients are EGFR and ALK positive?

A: One of the important findings in recent years is that if you don’t test patients for these 2 abnormalities (EGFR and ALK) and you just give chemotherapy – the patients whose tumors contain EGFR do significantly worse with chemotherapy than they would with targeted therapy. So you’re actually doing harm by not testing patients with abnormalities and very likely the same thing will apply to patients with same subset ALK gene fusion. Also, 20-25% is not a small percentage, especially with such a common and lethal cancer. Approximately 20,000 patients per year in the US can receive life-prolonging therapy from these tests.

Q: When will we be required to be compliant with these guidelines?

A: Laboratories are encouraged to adopt these international guideline recommendations to support best practices for EGFR and ALK testing. The CAP Accreditation Program will review and determine whether these recommendations will be incorporated into accreditation requirements.