How CPS is Calculated and Specimen Requirements
Combined Positive Score (CPS) is calculated as the number of PD-L1 positive cells (tumor cells, lymphocytes, and macrophages) divided by the total number of viable tumor cells, multiplied by 100. 1
CPS Calculation Formula
The mathematical formula is:
CPS = (Number of PD-L1+ tumor cells + PD-L1+ lymphocytes + PD-L1+ macrophages) / Total number of viable tumor cells × 100
This differs fundamentally from Tumor Proportion Score (TPS), which only counts the percentage of tumor cells expressing PD-L1. CPS has emerged as the superior marker because it captures immune cell expression in addition to tumor cell expression, providing greater sensitivity especially at lower cutoff values 1.
Specimen Types for CPS Testing
Acceptable Specimens (in order of preference):
- Primary tumor resection specimens - Gold standard 2
- Excisional biopsies - Highly reliable 3
- Lymph node metastases - Show substantial concordance (76.7% overall agreement, κ = 0.593) with primary tumor 2
- Preoperative core biopsies - Acceptable but with important caveats (86.7% concordance, κ = 0.688) 2
Critical Caveat for Small Biopsies
CPS scoring should be used with caution in small biopsies and aspirate cell blocks. 3 In core biopsies and cell blocks from head and neck squamous cell carcinoma patients, the sensitivity is only 66% at the 20% cutpoint and 70% at the 1% cutpoint when compared to excisional specimens 3.
A negative CPS result on a small biopsy should prompt consideration of an excisional biopsy and repeat testing to avoid false negatives that could deny patients potentially beneficial immunotherapy 3.
Factors Affecting CPS Accuracy
Several variables can impact CPS assessment 1:
- Intratumoral heterogeneity
- Temporal heterogeneity
- Size of sample stained
- Type of sample stained
The concordance between preoperative biopsies and tumor resections is moderate to substantial (κ = 0.688), and similar concordance exists between primary tumors and lymph node metastases (κ = 0.593) 2. This means that while biopsies and metastatic nodes can be used, there is approximately 13-23% discordance risk.
Clinical Interpretation
CPS ≥ 1 is the preferred threshold for defining PD-L1 positivity to maximize sensitivity for identifying patients who may benefit from immune checkpoint inhibitors 1. While CPS ≥ 20 also correlates with superior outcomes, the lower cutoff of ≥ 1 was adopted to avoid excluding potential responders 1.