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High Pretreatment Serum PD-L1 Levels Are Associated with Muscle Invasion and Shorter Survival in Upper Tract Urothelial Carcinoma

Affiliation
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Széles, Ádám;
Affiliation
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Kovács, Petra Terézia;
Affiliation
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Csizmarik, Anita;
Affiliation
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Váradi, Melinda;
Affiliation
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Riesz, Péter;
Affiliation
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Fazekas, Tamás;
ORCID
0000-0002-9347-8163
Affiliation
Centre for Translational Medicine, Ulloi ut 26, 1085 Budapest, Hungary
Váncsa, Szilárd;
Affiliation
Centre for Translational Medicine, Ulloi ut 26, 1085 Budapest, Hungary
Hegyi, Péter;
ORCID
0000-0002-4775-2432
Affiliation
Department of Urology, University of Duisburg-Essen, German Cancer Consortium (DTKK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
Oláh, Csilla;
Affiliation
Department of Urology, University of Duisburg-Essen, German Cancer Consortium (DTKK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
Tschirdewahn, Stephan;
Affiliation
Department of Urology, University of Duisburg-Essen, German Cancer Consortium (DTKK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
Darr, Christopher;
Affiliation
Department of Urology, University of Duisburg-Essen, German Cancer Consortium (DTKK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
Krafft, Ulrich;
ORCID
0000-0003-2083-7687
Affiliation
Department of Urology, University of Duisburg-Essen, German Cancer Consortium (DTKK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
Grünwald, Viktor;
Affiliation
Department of Urology, University of Duisburg-Essen, German Cancer Consortium (DTKK)-University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany
Hadaschik, Boris;
Affiliation
Department of Genitorurinary Medical Oncology and Clinical Pharmacology, National Institute of Oncology, Ráth György utca 7-9., 1122 Budapest, Hungary
Horváth, Orsolya;
Affiliation
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Nyirády, Péter;
Affiliation
Department of Urology, Semmelweis University, Ulloi ut 78/b, 1082 Budapest, Hungary
Szarvas, Tibor

Simple Summary This study aimed to assess the prognostic relevance of soluble serum PD-L1 in upper tract urothelial carcinoma (UTUC) patients who underwent surgical or systemic (chemo- or immune checkpoint inhibitor) therapy. We found that high preoperative sPD-L1 levels were correlated with higher pathological tumor stage, grade and the presence of metastasis. In addition, higher pretreatment serum PD-L1 concentrations were associated with shorter survival in both surgically and chemotherapy-treated UTUC patients. We detected a characteristic increase in serum PD-L1 levels in UTUC patients after 3 months of anti-PD-L1 therapy. Based on these results sPD-L1 is a promising prognostic biomarker in UTUC. Abstract 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.

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