Programmed death ligand-1 (PD-L1) is an immune checkpoint molecule and a widely used
therapeutic target in urothelial cancer. Its circulating, soluble levels (sPD-L1)
were recently suggested to be associated with the presence and prognosis of various
malignancies but have not yet been investigated in upper tract urothelial carcinoma
(UTUC). In this study, we assessed sPD-L1 levels in 97 prospectively collected serum
samples from 61 UTUC patients who underwent radical nephroureterectomy (RNU), chemotherapy
(CTX), or immune checkpoint inhibitor (ICI) therapy. In addition to pretreatment samples,
postoperative and on-treatment sPD-L1 levels were determined in some patients by using
ELISA. In the RNU group, elevated preoperative sPD-L1 was associated with a higher
tumor grade (p = 0.019), stage (p < 0.001) and the presence of metastasis (p = 0.002).
High sPD-L1 levels were significantly associated with worse survival in both the RNU
and CTX cohorts. sPD-L1 levels were significantly elevated in postoperative samples
(p = 0.011), while they remained unchanged during CTX. Interestingly, ICI treatment
caused a strong, 25-fold increase in sPD-L1 (p < 0.001). Our results suggest that
elevated preoperative sPD-L1 level is a predictor of higher pathological tumor stage
and worse survival in UTUC, which therefore may help to optimize therapeutic decision-making.
The observed characteristic sPD-L1 flare during immune checkpoint inhibitor therapy
may have clinical significance.
