To evaluate the prognostic value of PD-L1 and PD-1 expression in upper tract urothelial carcinoma (UTUC) patients.
A retrospective multicenter study was conducted in 283 UTUC patients treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue micro-arrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumor cells and tumor-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS).
Overall, 63 (22.3%) and 220 (77.7%) UTUC patients had PD-L1 positive and negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1 positive and negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have ≥pT2(68.3% vs. 49.5%;p=0.009 and 69.2% vs. 46.4%;p<0.001, respectively) and high-grade(90.5% vs. 70.0%;p=0.001 and 91.2% vs. 66.7%; p<0.001, respectively) disease with lymphovascular invasion(52.4% vs. 17.3%;p<0.001 and 39.6% vs. 18.2%;p<0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (HR=1.83;95%CI=[1.09-3.08];p=0.023 and HR=1.59; 95%CI=[1.00-2.54];p=0.049; respectively), CSS (HR=2.73; 95%CI=[1.48-5.04]; p=0.001 and HR=1.96; 95%CI=[1.12-3.45]; p=0.019; respectively) and OS (HR=2.08;95%CI=[1.23-3.53]; p=0.006 and HR=1.71; 95%CI=[1.05-2.78];p=0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only [PD-L1 / PD-1 positive] patients (n=38; 13.4%) had significantly decreased RFS (HR=3.07; 95%CI=[1.70-5.52];p<0.001), CSS (HR=5.23; 95%CI=[2.62-10.43];p<0.001) and OS (HR=3.07; 95%CI=[1.70-5.52]; p<0.001) as compared to those with [PD-L1 / PD-1 negative] disease (n=167; 59.0%).
We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.
BJU international. 2023 Jul 24 [Epub ahead of print]
Luca Campedel, Eva Compérat, Géraldine Cancel-Tassin, Justine Varinot, Christian Pfister, Clara Delcourt, Françoise Gobet, Mathieu Roumiguié, Pierre-Marie Patard, Gwendoline Daniel, Pierre Bigot, Julie Carrouget, Caroline Eymerit, Stéphane Larré, Priscilla Léon, Anne Durlach, Alain Ruffion, Emilien Seizilles de Mazancourt, Myriam Decaussin-Petrucci, Thomas Bessède, Cédric Lebacle, Sophie Ferlicot, Grégoire Robert, Nam-Son Vuong, Magali Philip, Sébastien Crouzet, Xavier Matillon, Florence Mège-Lechevallier, Hervé Lang, Pascal Mouracade, Véronique Lindner, Paul Gougis, Olivier Cussenot, Morgan Rouprêt, Thomas Seisen
Department of Medical Oncology, Pitié-Salpêtrière Hospital, AP-, HP, Paris, France., Sorbonne Université, GRC n°5, Predictive Onco-Urology, Paris, France., Departement of Pathology, Tenon Hospital, AP-, HP, Paris, France., Department of Urology, Rouen Hospital, Rouen, France., Department of Pathology, Rouen Hospital, Rouen, France., Department of Urology, Toulouse Hospital, Toulouse, France., Department of Pathology, Toulouse Hospital, Toulouse, France., Department of Urology, Angers Hospital, Angers, France., Department of Pathology, Angers Hospital, Angers, France., Department of Urology, Reims Hospital, Reims, France., Department of Pathology, Reims Hospital, Reims, France., Department of Urology, Lyon Hospital, Lyon, France., Department of Pathology, Lyon Hospital, Lyon, France., Department of Urology, Kremlin-Bicêtre Hospital, Le Kremlin-Bicêtre, France., Department of Pathology, Kremlin-Bicêtre Hospital, Le Kremlin-Bicêtre, France., Department of Urology, Bordeaux Hospital, Bordeaux, France., Department of Pathology, Bordeaux Hospital, Bordeaux, France., Department of Urology, Strasbourg Hospital, Strasbourg, France., Department of Pathology, Strasbourg Hospital, Strasbourg, France.