Campedel Luca, Compérat Eva, Cancel-Tassin Géraldine, Varinot Justine, Pfister Christian, Delcourt Clara, Gobet Françoise, Roumiguié Mathieu, Patard Pierre-Marie, Daniel Gwendoline, Bigot Pierre, Carrouget Julie, Eymerit Caroline, Larré Stéphane, Léon Priscilla, Durlach Anne, Ruffion Alain, de Mazancourt Emilien Seizilles, Decaussin-Petrucci Myriam, Bessède Thomas, Lebacle Cédric, Ferlicot Sophie, Robert Grégoire, Vuong Nam-Son, Philip Magali, Crouzet Sébastien, Matillon Xavier, Mège-Lechevallier Florence, Lang Hervé, Mouracade Pascal, Lindner Véronique, Gougis Paul, Cussenot Olivier, Rouprêt Morgan, Seisen Thomas
Department of Medical Oncology, Pitié-Salpêtrière Hospital, AP-HP, Paris, France.
GRC n°5, Predictive Onco-Urology, Sorbonne Université, Paris, France.
BJU Int. 2023 Nov;132(5):581-590. doi: 10.1111/bju.16129. Epub 2023 Aug 10.
To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC).
A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-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%) patients with UTUC 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 pathological tumour stage ≥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 (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, 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 3.82, 95% CI 2.13-6.85; 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.
评估程序性死亡配体1（PD-L1）和程序性死亡1（PD-1）表达在上尿路尿路上皮癌（UTUC）患者中的预后价值。
对2000年至2015年期间在法国10家医院接受根治性肾输尿管切除术（RNU）治疗的283例UTUC患者进行了一项回顾性多中心研究。使用含有NAT105®和28.8®抗体的2毫米核心组织微阵列进行免疫组织化学分析，以5%的肿瘤细胞和肿瘤浸润淋巴细胞阳性率为界值分别评估PD-L1和PD-1的表达。采用多变量Cox回归模型确定无复发生存期（RFS）、癌症特异性生存期（CSS）和总生存期（OS）的独立预测因素。
总体而言，UTUC患者中分别有63例（22.3%）和220例（77.7%）为PD-L1阳性和阴性疾病，而分别有91例（32.2%）和192例（67.8%）为PD-1阳性和阴性疾病。与未表达PD-L1或PD-1的患者相比，表达PD-L1或PD-1的患者更有可能患有病理肿瘤分期≥pT2（分别为68.3%对49.5%，P = 0.009；以及69.2%对46.4%，P < 0.001）、高级别（分别为90.5%对70.0%，P = 0.001；以及91.2%对66.7%，P < 0.001）疾病且伴有淋巴管浸润（分别为52.4%对17.3%，P < 0.001；以及39.6%对18.2%，P < 0.001）。在相互调整的多变量Cox回归分析中，PD-L1和PD-1表达与RFS降低显著相关（风险比[HR] 1.83，95%置信区间[CI] 1.09 - 3.08，P = 0.023；以及HR 1.59，95% CI 1.01 - 2.54，P = 0.049）、CSS（HR 2.73，95% CI 1.48 - 5.04，P = 0.001；以及HR 1.96，95% CI 1.12 - 3.45，P = 0.019）和OS（HR 2.08，95% CI 1.23 - 3.53，P = 0.006；以及HR 1.71，95% CI 1.05 - 2.78，P = 0.031）。此外，评估PD-L1和PD-1表达四层组合的多变量Cox回归分析显示，与PD-L1/PD-1阴性疾病患者（n = 167 [59.0%]）相比，仅PD-L1/PD-1阳性患者（n = 38 [13.4%]）的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）和OS（HR 3.82，95% CI 2.13 - 6.85；P < 0.001）显著降低。
我们观察到，PD-L1和PD-1表达均与不良病理特征相关，这在接受RNU治疗的UTUC患者中转化为独立且累积的不良预后价值。
