The collaboration between the College of American Pathologists (CAP) and esteemed organizations such as the International Association for the Study of Lung Cancer (IASLC), Pulmonary Pathology Society (PPS), Association for Molecular Pathology (AMP), and LUNGevity Foundation has yielded groundbreaking guidelines for the testing of immunotherapy biomarkers in lung cancer. These guidelines, published in the Archives of Pathology & Laboratory Medicine, are pivotal in addressing the complexities surrounding the selection and implementation of tests for PD-L1 expression and tumor mutation burden (TMB) due to the considerable variability in available methodologies.
One of the key challenges highlighted by the expert panel is the dynamic and heterogeneous nature of PD-L1 expression, which complicates the process of selecting appropriate samples for testing. To provide clarity and consistency, CAP has outlined six guidelines aimed at ensuring pathologists validate their chosen testing methods, select the correct subset of patients, and report results uniformly.
The importance of utilizing validated PD-L1 immunohistochemistry assays, in conjunction with genomic biomarker assays, is emphasized to optimize patient selection for immune checkpoint inhibitor therapy in advanced non-small cell lung cancer (NSCLC). Extensive research showcased a significant correlation between PD-L1 expression status and the efficacy of immunotherapy, particularly in NSCLC patients without specific genetic mutations.
Furthermore, the guidelines underscore the necessity of validating all specimen types and fixatives for PD-L1 testing, acknowledging the potential for discordant results due to sample heterogeneity. Despite the prevalence of laboratory-developed tests (LDTs), CAP recommends their validation against approved companion diagnostics before implementation, citing prior studies that have highlighted limited analytical compatibility between LDTs and approved assays.
In terms of reporting PD-L1 results, the guidelines advocate for the use of percentage expression scores, particularly tumor proportion scores (TPS), as they have demonstrated a strong correlation with patient response and survival rates on immunotherapy. Notably, NSCLC patients with high PD-L1 expression levels (>50%) have shown elevated response rates and improved outcomes.
Lastly, while acknowledging the potential of TMB as a biomarker, the expert panel urges caution against solely relying on it for patient selection in advanced NSCLC cases. Insufficient evidence exists to support its efficacy in predicting response and survival outcomes on immunotherapy. These guidelines represent a significant milestone in standardizing the testing and reporting of immunotherapy biomarkers in lung cancer, with the overarching goal of improving patient care and treatment outcomes in this challenging clinical landscape.
