PhD Scientific Days 2022

Clinical Medicine I. (Poster discussion will take place in the Aula during the Coffee Break)

Prognostic Significance of Soluble PD-L1 in Upper Tract Urothelial Carcinoma and in Immune Checkpoint Inhibitor-treated Solid Tumors; a Post Hoc Cohort- and Meta-analysis of the Literature

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

Text of the abstract

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).