7
PCO 1.5
➤ Germline testing for genetic alterations linked to approved therapies
should be performed in patients with metastatic or advanced solid
tumors considered for such treatment. It should not be limited
by family history-based or clinical criteria used for familial risk
assessment. Patients with P/LP variants should be referred for
genetic counseling for education about secondary cancer risks,
possible inheritance of germline mutations among blood relatives,
and the differences between germline and somatic mutations, if they
did not receive pretest counseling. (Strong recommendation)
Qualifying statement: Germline testing and genetic counseling may still be needed
in patients with personal or family histories suggestive of an inherited predisposition,
even when no germline alterations are identified during tumor genomic sequencing
using various sequencing panels.
Section 2: Assessment of dMMR and/or MSI-H Status, and TMB
PCO 2.1
➤ dMMR status should be evaluated on patients with metastatic or
advanced solid tumors who are candidates for immunotherapy.
• There are multiple approaches, including using large multigene panel-based
testing to assess MSI.
• Consider the prevalence of dMMR and/or MSI-H status in individual tumor
types when making this decision. (Strong recommendation)
PCO 2.2
➤ When TMB may influence the decision to use immunotherapy,
testing should be performed with either large multigene panels
with validated TMB testing or whole-exome analysis. (Strong
recommendation)
