Implications of PD-L1 Positivity for Patients With Papillary Thyroid Cancer
According to a retrospective biomarker analysis of a real-world Greek cohort of patients with papillary thyroid cancer (PTC), nearly half of the patients were found to have PD-L1 expression which was associated with multiple adverse features and an increased risk of recurrence.
While PD-L1 expression is an established prognostic biomarker for various disease states and is required for the use of immune checkpoint inhibitors in many cases, the significance of this expression among patients with PTC is controversial. There may be an associated between PD-L1 overexpression in PTC and adverse features as well as poor survival outcomes. However, these association have not been confirmed and the current evidence, as Dimitra Spyroulia, MD, Korgialenio-Benakio Hellenic Red Cross Hospital, Athens, Greece, and coauthors, wrote, “remains inconclusive, and a consensus has yet to be reached.”
This retrospective, single-center analysis included data from 81 patients with a confirmed diagnosis of PTC following complete thyroidectomy in Greece between 2007 and 2018. All patients had a primary tumor of at least 0.5 cm and at least 5 years of follow-up at the time of analysis. Most patients had thyroid carcinoma (localized, 34.6%; suspected metastatic, 16.0%) with other histologies including multinodular goiter (28.4%), solitary thyroid nodule (13.6%), substernal goiter (3.7%), and Grave’s disease (3.7%).
There were 37 patients (45.7%) identified to have a PD-L1 combined positive score (CPS) ≥ 10. Those patients with CPS ≥ 10 had tumors that were significantly larger (median size 1.20 cm vs 0.50 cm; P = .002) and were more likely to have advanced primary tumor stage (pT1 vs pT2: 35.1% vs 86.4%; pT3 to pT4: 64.9% vs 13.6%), extrathyroidal extension (64.9% vs 11.4%; P = .001) and lymph metastasis (45.9% vs 2.3%; P = .001), when compared to those with CPS < 10. Those patients with CPS ≥ 10 were also more likely to have aggressive histologies (43.2% vs 4.5%; P < .001), ≥ 4 tumor foci (24.3% vs 4.5%) and coexisting Hashimoto’s thyroiditis (45.9% vs 13.6%; P < .001). Additionally, patients with CPS ≥ 10 were more likely to have radioactive iodine (RAI) administered then the CPS < 10 group (81.1% vs 31.8%; P < .001).
With a median follow-up of 9 years, the disease recurrence rate was 8.6% overall. Disease recurrence was significantly more frequent among patients with CPS ≥ 10 than those with CPS < 10 (16.2% vs 2.3%). There was. When the disease-free survival (DFS) was stratified by PD-L1 expression, those patients with CPS ≥ 10 experienced a significantly shorter DFS than those with CPS < 10 (median DFS was not reached in either group). There was no significant difference in overall survival between the 2 groups, with median OS not reached in either group. There was 1 disease-specific mortality, in the CPS ≥ 10 group, due to distant lung metastases. There were 8 deaths that were not disease related, 5 in the CPS ≥ 10 group and 3 in the CPS < 10 group.
According to Dr Spyroulia et al, the association between PD-L1 positivity and larger tumor size, higher pT stage, lymph node metastasis, and the presence of aggressive histologic variants “support a link between PD-L1 expression and biologically aggressive tumor features.” They added that the findings regarding PD-L1 expression and disease-free survival “suggest that PD-L1 may serve as a biomarker of early recurrence and more aggressive clinical behavior in PTC,” while noting that, because of the overall low number of recurrences in this cohort, this observation should be taken with caution.
Study authors concluded this analysis “underscores the potential association between PD-L1 expression and adverse clinicopathological features in PTC.” They added that “future prospective, multicenter studies with larger cohorts are warranted to validate these findings and further elucidate the prognostic and therapeutic relevance of targeting the PD-1/PD-L1 axis in appropriately selected PTC populations.”
Source:
Spyroulia D, Lefantzis D, Lygeros S, et al. Prognostic value of programmed cell death ligand 1 (PD-L1) expression in patients with papillary thyroid carcinoma: A retrospective biomarker study. Cureus. Published online: August 30, 2025.
