Prognostic value of programmed death ligand‐1 and programmed death‐1 expression in patients with upper tract urothelial carcinoma
Authors: 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 
Published: July 2023

Objective

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).

Patients and methods

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).

Results

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%]).

Conclusions

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.