Prognostic value of manual and digital PD-L1 expression in pT3 and pT4 colon cancer

Programmed death ligand 1 (PD-L1) is a prognostic marker in several malignancies, but the prognostic value of PD-L1 expression in colorectal cancer (CRC) is inconclusive. Lack of standardized scoring systems for PD-L1 evaluation in CRC has led to inconsistent findings. This exploratory study aimed to evaluate PD-L1 expression using manual and digital methods and correlate the results to overall survival (OS) in a cohort of patients with pT3 and pT4 colon cancer (CC).

From a previously published study, 162 patients with pT3 and pT4 CC were included. One tumor slide representing the invasive margin was selected and stained for PD-L1 (22C3). PD-L1 was evaluated according to the tumor proportion score (TPS), the immune cell score (ICS), and the combined positive score (CPS). Additionally, a digital algorithm for detecting PD-L1 positive cells was developed. The manual and digital PD-L1 expression scores were correlated to OS in the entire cohort, and in subgroups according to mismatch repair (MMR) status.

Only 1 case was classified with a TPS of ≥ 1%. The ICS was classified as < 1%, 1-9%, and ≥ 10% in 66%, 30.2% and 3.7% of the tumors, respectively. The CPS was classified as < 1, 1-9, and ≥ 10 in 82.7%, 15.4%, and 1.9% of the tumors, respectively. A high digital PD-L1 expression score was an independent prognostic factor for longer OS, adjusted for age, pT-category and adjuvant chemotherapy (aHR = 0.40, 95% CI = 0.19-0.86, p = 0.018). In the pMMR subgroup, both a CPS ≥ 1 and a high digital score were significantly associated with longer OS in the multivariate analyses (aHR = 0.24, 95% CI = 0.06-0.99, p = 0.049, and aHR = 0.34, 95% CI = 0.12-0.97, p = 0.043, respectively).

Our results suggest that high PD-L1 expression is associated with longer OS. In future studies examining PD-L1 expression as a prognostic biomarker in CC, assessing PD-L1 expression using a digital approach or the CPS can be recommended.