aAll recommendations are category 2A unless otherwise indicated.1–4,6–14
bUniversal MMR or MSI testing is recommended.1,2,7
cConsider MSI/MMR testing if metastatic disease is documented or suspected.3,4
dCategory 2B recommendation to consider MSI and/or MMR testing on available tumor tissue.5
eFor metastatic and unresectable disease.6
fValidated tumor molecular testing including MSI or DNA MMR is recommended prior to initiation of therapy for persistent/recurrent disease, if not previously done.8
gPembrolizumab is a category 2B option for patients with MSI-H/dMMR metastatic castration-resistant prostate cancer who have progressed on prior therapy.9
hMSI/MMR testing should be considered in patients with regional or metastatic prostate cancer.9
iMSI/MMR testing if disease progresses after high-dose chemotherapy or third-line therapy.10
jConsider molecular testing, including MSI/MMR testing, in certain patients with unresectable or metastatic disease.6
kPembrolizumab should be considered for certain patients with dMMR or MSI-H adrenocortical tumors that have progressed following prior treatment and have no satisfactory alternative treatment options.11
lThe population of patients with MSI-H/dMMR occult primary tumors is low.12
Category 2A = Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.1–4,6–14
Category 2B = Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.5,9
NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.
MSI-H = microsatellite instability-high; dMMR = mismatch repair deficient; MSI = microsatellite instability; MMR = mismatch repair.
Examples of MMR Test Results
Examples of MSI Test Results
Copyright College of American Pathologists 2015. Used with permission.
- MSI-H is detected by comparing tumor tissue with normal tissue, and showing differences in peak patterns. The arrows represent shifts in base pairs compared with normal tissue.
- NGS is a gene sequencing technique used to identify genetic mutations or variants18,19
IHC = immunohistochemistry; PCR = polymerase chain reaction; NGS = next-generation sequencing.
EGJ = esophagogastric junction; NSCLC = non–small cell lung cancer; PD-1 = programmed death receptor-1.
MSI-H/ dMMR
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MSI/MMR status21
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Potential eligibility for KEYTRUDA across all previously treated MSI-H/dMMR advanced solid tumors based on approved indication
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This is an excerpt from the complete Cancer Protocol Template for DNA Mismatch Repair from the College of American Pathologists.
This template is recommended for tumors other than colon and endometrium. For patients with these cancers, site-specific biomarker reporting templates are available and are recommended.
- To learn more about reporting MSI-H or dMMR, please refer to the complete protocol on reporting results of DNA Mismatch Repair Testing from CAP.
NCI = National Cancer Institute.
KEYTRUDA: The first and only therapy of its kind with a tumor-agnostic indication to treat advanced MSI-H/dMMR cancers.