Table 2 Risks associated with PD-L1 biomarkers for clinical practice
From: Applicability of PD-L1 tests to tailor triple-negative breast cancer treatment in Brazil
| Risk | Details | Recommendation |
|---|---|---|
| Patient safety | ||
| False-positive or false-negative | Incorrect results lead to inappropriate therapy and put patient safety at risk. | When both primary and metastatic samples are available, test both. |
| Tumor heterogeneity | Heterogeneity of PD-L1 expression between primary and metastatic lesions in TNBC can lead to erroneous classification. | |
| Logistical risks | ||
| Sample collection and processing issues | Poor quality tissues can result in unclear test results. | Ensure correct sample fixation for 6 to 72 h and processing. Determine tissue adequacy on H&E: the presence of TC and tumor-associated IC. Cut 4um-thick slices for PD-L1 IHC testing and sections for other IHC to preserve tissue in biopsy samples. Use within 2 months of cutting. |
| Biomarker risks | ||
| PD-L1 expression prevalence among clones | Clones differ in quantitative expression for TC and IC, therefore analytical comparison does not reflect clinical performance. | An assay must identify patients who will most likely respond based on clinical trial data, thereby identifying a more significant proportion of PD-L1 positive patients. |
| Multiple scoring systems | Multiple scoring systems for PD-L1 clones complicate reproducibility. | For BC, PD-L1 expressed in IC and not in TC is predictive of response in the SP142 assay. |
| Inter-pathologist variability for report results | PD-L1 on IC is not reproducible. | Ensure real-world training on the expected staining profile and cut-off for pathologists in clinical practice. Assess interobserver variability with a sufficiently large and statistically powered number of pathologists to guarantee reproducibility. |