Clinical Medicine I. (Poster discussion will take place in the Aula during the Coffee Break)
Adam Daniel Széles 1,2, Tamás Fazekas 1,2, Anita Csizmarik 1, Melinda Váradi 1, Petra Terézia Kovács 1, Szilárd Váncsa 2, Péter Nyirády 1, Tibor Szarvas 1,2,3
1 Department of Urology, Semmelweis University, Budapest, Hungary
2 Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
3 Department of Urology, University of Duisburg-Essen and German Cancer Consortium, Essen, Germany
Introduction: Programmed death-ligand 1 (PD-L1) is a widely used therapeutic target and an emerging tissue biomarker in oncology. Recently, its circulating, soluble levels (sPD-L1) were shown to be associated with the prognosis of various malignancies but have not been investigated in upper tract urothelial carcinoma (UTUC) yet. We performed a systematic review and a meta-analysis of the prognostic relevance of sPD-L1 in patients with various tumors who underwent anti-PD-L1 or -PD-1 targeting therapy and conducted a post hoc serum PD-L1 analysis in different treatment settings of UTUC.
Aim: The aim of this project is to assess the prognostic value of sPD-L1 in various cancers.
Methods: For the meta-analysis, we conducted the systematic search on the 21st of October, 2021 in PubMed, Scopus, Cochrane, and Embase databases. The primary outcome was overall survival and progression-free survival. Furthermore, we assessed sPD-L1 levels in 97 prospectively collected serum samples of 61 UTUC patients who underwent radical nephroureterectomy, chemotherapy, or immune checkpoint inhibitor (ICI) therapy. In addition to pretreatment samples, postoperative and on-treatment sPD-L1 levels were determined with ELISA.
Results: Our meta-analysis identified 14 eligible studies with 1009 patients in 6 different cancer types. ICI-treated patients with high sPD-L1 had shorter survival (OS) (HR: 1.67; 95% CI: 1.26-2.23; p<0.001), but this effect was not uniformly observable in all tumor types. In the surgically treated UTUC subgroup, elevated preoperative sPD-L1 was associated with higher tumor stage (p<0.001) and the presence of metastasis (p=0.002). In addition, high sPD-L1 levels were associated with poor OS in both surgically- and chemotherapy-treated UTUC cohorts.
Conclusions: Pretreatment sPD-L1 levels could be a useful prognostic marker for various tumors. However, its prognostic value in ICI-treated patients should be interpreted in a tumor-specific context. Furthermore, our results suggest preoperative sPD-L1 level as a predictor of higher pathological stage and the presence of metastasis in UTUC which may have influence on therapeutic decision-making.
Funding: National Research Development and Innovation Fund (K139059). János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00451/20/5) and by the New National Excellence Program (ÚNKP-21-5-SE-3).