PD-L1 Expression in Muscle Invasive Urothelial Carcinomas as Assessed via Immunohistochemistry: Correlations with Specific Clinical and Pathological Features, with Emphasis on Prognosis after Radical Cystectomy

Abstract

In the present study, we analyzed Programmed Death Ligand-1 (PD-L1) expression in radical cystectomy (RC) specimens from patients with muscle-invasive urothelial carcinoma (UC), in order to assess any correlations with specific clinicopathological features and its potential prognostic value. A multi-institutional study was performed within the departments of urology and pathology at the Mureș County Hospital, Romania, and Centre Hospitalier Lyon Sud, France. Sixty-nine patients with MIBC were included, for whom tumor histology (conventional versus histological variant/differentiation), tumor extension (T), lymph node involvement (N), and distant metastases (M) were recorded. PD-L1 immunostaining was performed using the 22C3 clone and was interpreted using the combined positive score (CPS) as recommended (Dako Agilent, Santa Clara, CA, USA). Positive PD-L1 immunostaining was more prevalent among UCs with squamous differentiation compared to conventional UCs and trended towards an improved OS (p = 0.366). We found the T stage to be a risk factor for poor survival in PD-L1-positive patients (HR 2.9, p = 0.021), along with the N stage in PD-L1-negative patients (HR 1.98, p = 0.007). No other clinicopathological factor was found to be significantly associated with PD-L1 positivity. Thus, we confirm the need for PD-L1 immunostaining prior to initiating immune checkpoint inhibitor therapy for a more accurate assessment of the patients’ chances of responding to treatment.

Expression and Prognostic Implication of PD-L1 in Patients with Urothelial Carcinoma with Variant Histology (Squamous Differentiation or Micropapillary) Undergoing Radical Cystectomy

“…In our study, concerning the clinicopathological features, PD-L1 expression did not appear to be affected by age or sex, which was consistent with the results of previous studies [22,23]. However, positive PD-L1 expression in TICs was significantly associated with positive LN involvement in patients with MPUC (p = 0.030) and tumor stage in patients with MPUC (p = 0.006).…”

“…These results were consistent with those obtained in a study by Reis et al [3], in which IC2/3 (high PD-L1 expression) levels were 31.6% (6/19) of MPUC and 75.0% (12/16) of UCSD using atezolizumab criteria. Although, it has also been shown that when positive PD-L1 expression was assessed using the combined positive score (CPS ≥10) defined as the number of PD-L1 staining cells (tumor cells, macrophages, and lymphocytes) divided by the total number of viable tumor cells and multiplied by 100, PD-L1 positivity was found in 40.0% (2/5) of MPUC and in 100.0% (5/5) of UCSD [22]. Collectively, there appears to be a vital difference between PD-L1 expression in pure UC and UCV.…”

Prognostic value of programmed cell death ligand-1 expression in patients with bladder urothelial carcinoma undergoing radical cystectomy: A meta-analysis

“…We searched 3297 records from the three electronic databases (PubMed, Embase, and Cochrane Library). Finally, 11 studies ( 11 , 14 – 23 ) and 1393 BUC cases were included in our meta-analysis ( Figure 1 ). This study is the first meta-analysis about the prognostic value of PD-L1 expression in patients with BUC after RC-PLND.…”