Laura-Maria Krabbe1, Barbara Heitplatz2, Sina Preuss3, Ryan C Hutchinson4, Solomon L Woldu4, Nirmish Singla4, Martin Boegemann3, Christopher G Wood5, Jose A Karam5, Alon Z Weizer6, Jay D Raman7, Mesut Remzi8, Nathalie Rioux-Leclercq9, Andrea Haitel10, Leonid M Rapoport11, Peter V Glybochko11, Marco Roscigno12, Christian Bolenz13, Karim Bensalah14, Arthur I Sagalowsky4, Shahrokh F Shariat8, Yair Lotan4, Evanguelos Xylinas15, Vitaly Margulis16. 1. Department of Urology, University of Muenster Medical Center, Muenster, Germany; Department of Urology, University of Texas Medical Center, Dallas, Texas. 2. Department of Pathology, University of Muenster Medical Center, Muenster, Germany. 3. Department of Urology, University of Muenster Medical Center, Muenster, Germany. 4. Department of Urology, University of Texas Medical Center, Dallas, Texas. 5. Department of Urology, M. D. Anderson Cancer Center, Houston, Texas. 6. Department of Urology, University of Michigan Cancer Center, Ann Arbor, Michigan. 7. Division of Urology, Penn State Health Milton S.Hershey Medical Center, Hershey, Pennsylvania. 8. Department of Urology, Medical University Vienna, Vienna, Austria. 9. Department of Pathology, Centre Hospitalier Universitaire de Rennes, Rennes, France. 10. Department of Pathology, Medical University Vienna, Vienna, Austria. 11. Department of Uronephrology and Reproductive Health, Sechenov First Moscow State Medical University, Moscow, Russia. 12. Department of Urology, Ospedali Riuniti of Bergamo, Bergamo, Italy. 13. Department of Urology, University of Ulm, Ulm, Germany. 14. Department of Urology, Centre Hospitalier Universitaire de Rennes, Rennes, France. 15. Department of Urology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris, France. 16. Department of Urology, University of Texas Medical Center, Dallas, Texas. Electronic address: Vitaly.margulis@utsouthwestern.edu.
Abstract
PURPOSE: We investigated the prognostic value of PD-1 and PD-L1 expression in patients with high grade upper tract urothelial carcinoma. MATERIALS AND METHODS: Tissue microarrays of 423 patients treated with extirpative surgery for high grade upper tract urothelial carcinoma from the International Upper Tract Urothelial Carcinoma collaboration were stained for PD-1 and PD-L1 using antibodies, including Cell Marque™ NAT105 diluted 1:250 and prediluted E1L3N® via immunohistochemistry. A 1% or greater staining rate of tumor infiltrating lymphocytes (PD-1) and tumor cells (PD-L1) was considered positive. Univariate and multivariate analyses were performed to assess independent prognosticators of survival outcomes. RESULTS: Median patient age was 70.0 years and median followup was 37.0 months. PD-1 and PD-L1 were positive in 37.2% and 26.2% of patients, respectively. PD-1 positivity was significantly associated with adverse pathological characteristics while PD-L1 positivity was associated with favorable pT stage. On univariate analysis PD-1 expression was associated with worse recurrence-free, cancer specific and overall survival. On multivariate analysis PD-1 expression was an independent prognosticator of cancer specific survival (HR 1.7, 95% CI 1.03-2.66, p = 0.039) and overall survival (HR 1.5, 95% CI 1.05-2.24, p = 0.029) but not recurrence-free survival (HR 1.4, 95% CI 0.9-2.16, p = 0.139). On univariate analysis PD-L1 expression was not significantly associated with survival outcomes. However, on multivariate analysis in patients with organ confined disease (pT2 or less, pN0/x and cM0), PD-L1 positivity was an independent prognosticator of recurrence-free survival (HR 0.2, 95% CI 0.06-0.98, p = 0.046) and overall survival (HR 0.3, 95% CI 0.11-0.63, p = 0.003). CONCLUSIONS: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and independent prognostication of worse survival outcomes. PD-L1 positivity of tumor cells was an independent prognosticator of favorable survival outcomes in cases of organ confined disease.
PURPOSE: We investigated the prognostic value of PD-1 and PD-L1 expression in patients with high grade upper tract urothelial carcinoma. MATERIALS AND METHODS: Tissue microarrays of 423 patients treated with extirpative surgery for high grade upper tract urothelial carcinoma from the International Upper Tract Urothelial Carcinoma collaboration were stained for PD-1 and PD-L1 using antibodies, including Cell Marque™ NAT105 diluted 1:250 and prediluted E1L3N® via immunohistochemistry. A 1% or greater staining rate of tumor infiltrating lymphocytes (PD-1) and tumor cells (PD-L1) was considered positive. Univariate and multivariate analyses were performed to assess independent prognosticators of survival outcomes. RESULTS: Median patient age was 70.0 years and median followup was 37.0 months. PD-1 and PD-L1 were positive in 37.2% and 26.2% of patients, respectively. PD-1 positivity was significantly associated with adverse pathological characteristics while PD-L1 positivity was associated with favorable pT stage. On univariate analysis PD-1 expression was associated with worse recurrence-free, cancer specific and overall survival. On multivariate analysis PD-1 expression was an independent prognosticator of cancer specific survival (HR 1.7, 95% CI 1.03-2.66, p = 0.039) and overall survival (HR 1.5, 95% CI 1.05-2.24, p = 0.029) but not recurrence-free survival (HR 1.4, 95% CI 0.9-2.16, p = 0.139). On univariate analysis PD-L1 expression was not significantly associated with survival outcomes. However, on multivariate analysis in patients with organ confined disease (pT2 or less, pN0/x and cM0), PD-L1 positivity was an independent prognosticator of recurrence-free survival (HR 0.2, 95% CI 0.06-0.98, p = 0.046) and overall survival (HR 0.3, 95% CI 0.11-0.63, p = 0.003). CONCLUSIONS: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and independent prognostication of worse survival outcomes. PD-L1 positivity of tumor cells was an independent prognosticator of favorable survival outcomes in cases of organ confined disease.
Authors: Daniel Benamran; Thomas Seisen; Elias Naoum; Christophe Vaessen; Jérome Parra; Pierre Mozer; Shahrokh F Shariat; Morgan Rouprêt Journal: Transl Androl Urol Date: 2020-08