High PDL1 mRNA expression predicts better survival of stage pT1 non-muscle-invasive bladder cancer (NMIBC) patients

• Published in: Cancer Immunology, Immunotherapy Vol. 67; no. 3; pp. 403 - 412
• Main Authors: Breyer, Johannes, Wirtz, Ralph M., Otto, Wolfgang, Erben, Philipp, Worst, Thomas S., Stoehr, Robert, Eckstein, Markus, Denzinger, Stefan, Burger, Maximilian, Hartmann, Arndt
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2018; Springer Nature B.V
• Subjects: Aged; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Bladder cancer; Cancer Research; CD3 antigen; Data processing; Female; Follow-Up Studies; Gene expression; Humans; Immunology; Immunotherapy; Invasiveness; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Oncology; Original; Original Article; Paraffin; PD-1 protein; PD-L1 protein; Regression analysis; Retrospective Studies; RNA, Messenger - genetics; RNA, Messenger - metabolism; Survival; Survival Rate; Tissues; Urinary bladder; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - mortality; Urinary Bladder Neoplasms - pathology; mRNA; Prognosis; NMIBC; PD1; PDL1
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-017-2093-9

Introduction and objectives Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification. Materials and methods We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder. mRNA expression of PD1, PDL1 and CD3 was measured by single step RT-qPCR and correlated to clinicopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS) and carcinoma-specific survival (CSS). Results We have analyzed 334 patients with NMIBC at stage pT1 for mRNA analysis. Data from 296 patients (79% male, median age: 72 years) could be used. Spearman correlation revealed significant associations between mRNA expressions of PD1/PDL1 ( ρ : 0.6024, p  < 0.0001), CD3/PDL1 ( ρ : 0.5728, p  < 0.0001) and CD3/PD1 ( ρ : 0.7005, p  < 0.0001). Kaplan–Meier analysis revealed that high PDL1 mRNA expression (≥ 33.83) is a favorable prognostic factor with regard to better RFS ( p  = 0.0018), PFS ( p  = 0.021) and CSS ( p  = 0.012). Multivariate Cox-regression analysis proved PDL1 expression to be an independent prognosticator for RFS [HR 0.48 (0.31–0.72), p  = 0.0005], PFS [HR 0.45 (0.24–0.80), p  = 0.0059] and CSS [HR 0.31 (0.13–0.67), p  = 0.0021]. Conclusion High mRNA expression of PDL1 predicts improved RFS, PFS and CSS of pT1 NMIBC. Following prospective validation, this objective measurement of PD-L1 might help stratify patients with NMIBC for immunotherapy and identify patients who might benefit from early cystectomy.