From the Guidelines
PD-L1 CPS (Combined Positive Score) is a more comprehensive and preferred method for measuring PD-L1 expression in cancer tissues compared to TPS (Tumor Proportion Score), as it includes immune cells in its assessment, providing a more accurate representation of the tumor microenvironment's immunological status. The key difference between CPS and TPS is that CPS calculates the ratio of PD-L1 positive cells (including tumor cells, lymphocytes, and macrophages) to the total number of viable tumor cells, multiplied by 100, whereas TPS only measures the percentage of viable tumor cells showing partial or complete membrane PD-L1 staining 1. This distinction is clinically important, as certain cancers like gastric, esophageal, and cervical cancers rely on CPS scoring for immunotherapy decisions, while lung cancer typically uses TPS. For example, pembrolizumab may be indicated in esophageal cancer with CPS ≥10, whereas in non-small cell lung cancer, TPS ≥1% might determine eligibility 1.
Key Differences Between CPS and TPS
- CPS includes immune cells in its assessment, providing a more comprehensive understanding of the tumor microenvironment
- TPS focuses exclusively on tumor cells, measuring the percentage of viable tumor cells showing partial or complete membrane PD-L1 staining
- CPS is preferred for maximum sensitivity, although a TPS score indicating ≥1% positivity is correlated with benefit to immune checkpoint inhibitor (ICI) therapy and may be interpreted as positive if available 1
Clinical Implications
- Understanding the differences between CPS and TPS is essential for oncologists when selecting appropriate patients for immune checkpoint inhibitor therapy
- Certain cancers, such as gastric, esophageal, and cervical cancers, rely on CPS scoring for immunotherapy decisions, while lung cancer typically uses TPS
- Pembrolizumab may be indicated in esophageal cancer with CPS ≥10, whereas in non-small cell lung cancer, TPS ≥1% might determine eligibility 1
Evidence-Based Recommendations
- CPS is the preferred method for measuring PD-L1 expression in cancer tissues, due to its comprehensive assessment of the tumor microenvironment 1
- A lower threshold for defining CPS positivity of ≥1 is also preferred, as it is associated with superior overall survival (OS) in certain cancers 1
From the FDA Drug Label
for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test. as a single agent for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-approved test
The main difference between PD-L1 Combined Positive Score (CPS) and Tumor Proportion Score (TPS) is the type of cancer they are used for:
- TPS is used for Non-Small Cell Lung Cancer (NSCLC)
- CPS is used for Head and Neck Squamous Cell Cancer (HNSCC) 2
From the Research
Definition of PD-L1 Scoring Methods
- Programmed Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) and Tumor Proportion Score (TPS) are two methods used to score PD-L1 expression in cancer cells.
- TPS measures the percentage of tumor cells that express PD-L1, while CPS measures the number of PD-L1-positive cells (tumor cells, lymphocytes, and macrophages) per total number of tumor cells [ 3(https://doi.org/10.1038/s41379-021-00733- erotisch) ].
Comparison of CPS and TPS
- Studies have shown that CPS and TPS are similar in predicting response to immunotherapy in non-small cell lung cancer (NSCLC) [ 4 ].
- In head and neck cancer, CPS ≥ 50 appeared equivalent to TPS ≥ 50% for predicting objective response rate, overall survival, and progression-free survival [ 3 ].
- CPS may be more sensitive than TPS at lower cutoffs, such as CPS ≥ 1 [ 3 ].
Clinical Applications of CPS and TPS
- Both CPS and TPS have been used as predictive biomarkers for response to PD-1/PD-L1 inhibitors in various types of cancer, including NSCLC, head and neck cancer, and triple-negative breast cancer [ 5, 6 ].
- The choice of scoring method may depend on the specific cancer type and the clinical context [ 7 ].