Breyer, Johannes, Wirtz, Ralph M., Otto, Wolfgang, Erben, Philipp ORCID: 0000-0002-8279-7636, Worst, Thomas S., Stoehr, Robert, Eckstein, Markus, Denzinger, Stefan, Burger, Maximilian and Hartmann, Arndt (2018). High PDL1 mRNA expression predicts better survival of stage pT1 non-muscle-invasive bladder cancer (NMIBC) patients. Cancer Immunol. Immunother., 67 (3). S. 403 - 413. NEW YORK: SPRINGER. ISSN 1432-0851

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Abstract

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 (rho: 0.6024, p < 0.0001), CD3/PDL1 (rho: 0.5728, p < 0.0001) and CD3/PD1 (rho: 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Breyer, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wirtz, Ralph M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Otto, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erben, PhilippUNSPECIFIEDorcid.org/0000-0002-8279-7636UNSPECIFIED
Worst, Thomas S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoehr, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eckstein, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Denzinger, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burger, MaximilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, ArndtUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-193209
DOI: 10.1007/s00262-017-2093-9
Journal or Publication Title: Cancer Immunol. Immunother.
Volume: 67
Number: 3
Page Range: S. 403 - 413
Date: 2018
Publisher: SPRINGER
Place of Publication: NEW YORK
ISSN: 1432-0851
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
UROTHELIAL CARCINOMA; BREAST-CANCER; PD-L1 EXPRESSION; CELL; B7-H1; IMMUNOTHERAPY; ASSOCIATION; RECURRENCEMultiple languages
Oncology; ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/19320

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