High Pretreatment Serum PD-L1 Levels Are Associated with Muscle Invasion and Shorter Survival in Upper Tract Urothelial Carcinoma
Ádám Széles,
Petra Terézia Kovács,
Anita Csizmarik,
Melinda Váradi,
Péter Riesz,
Tamás Fazekas,
Szilárd Váncsa,
Péter Hegyi,
Csilla Oláh,
Stephan Tschirdewahn,
Christopher Darr,
Ulrich Krafft,
Viktor Grünwald,
Boris Hadaschik,
Orsolya Horváth,
Péter Nyirády,
Tibor Szarvas
Affiliations
Ádám Széles
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Petra Terézia Kovács
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Anita Csizmarik
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Melinda Váradi
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Péter Riesz
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Tamás Fazekas
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Szilárd Váncsa
Centre for Translational Medicine, Ulloi ut 26, 1085 Budapest, Hungary
Péter Hegyi
Centre for Translational Medicine, Ulloi ut 26, 1085 Budapest, Hungary
Csilla Oláh
Department of Urology, University of Duisburg-Essen, German Cancer Consortium (DTKK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
Stephan Tschirdewahn
Department of Urology, University of Duisburg-Essen, German Cancer Consortium (DTKK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
Christopher Darr
Department of Urology, University of Duisburg-Essen, German Cancer Consortium (DTKK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
Ulrich Krafft
Department of Urology, University of Duisburg-Essen, German Cancer Consortium (DTKK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
Viktor Grünwald
Department of Urology, University of Duisburg-Essen, German Cancer Consortium (DTKK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
Boris Hadaschik
Department of Urology, University of Duisburg-Essen, German Cancer Consortium (DTKK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
Orsolya Horváth
Department of Genitorurinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology, Ráth György utca 7-9., 1122 Budapest, Hungary
Péter Nyirády
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Tibor Szarvas
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
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 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.
