Clinical interest of PD-L1 immuno-histochemistry expression as a predictive factor of Bacillus Calmette Guerin (BCG) efficacy in refractory high-risk non-muscle-invasive bladder cancer (NMIBC)
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To assess PD-L1 expression in tumor (TC) and tumor infiltrating immune cells (IC) as a predictive factor of BCG therapy failure in high-risk NMIBC.
Materials and methods
Patients treated with complete resection followed by bladder BCG instillation for high-risk NMIBC were included. Early recurrence (ER) was defined as tumor recurrence after BCG induction course. The association between ER and immuno-histochemistry PD-L1 (E1L3N clone) expression by tumors cells (TC) and tumor infiltrating immune cells (IC) was investigated using an exact Fisher test variant.
A total of 186 patients were included, of whom 38 (20.4%) were ER, 35 (18.8%) were positive for TC PD-L1 expression and 60 (32.3%) were positive for IC PD-L1. ER was not significantly (p = 0.97) more frequent in the TC PD-L1 ≥ 1% group (n = 7, 20.0%) than in the TC PD-L1-negative group (n = 31, 20.5%). Patients with IC PD-L1 negative had ER in 15 (19.2%) cases and patients with IC PD-L1 ≥ 1% had ER in 23 (21.3%) cases. PD-L1-positive expression for IC (threshold > 1%) was correlated with immune infiltrate density (95.2% dense immune infiltrate vs 47.2% low immune infiltrate, p < 0.05), with increased expression of PD-L1 by IC after BCG therapy (p = 0.006).
No association was observed between immuno-histochemistry PD-L1 positivity and ER after BCG therapy. Nevertheless, the relationship between immune infiltrate and PD-L1 positivity confirmed the interest of assessing the immune infiltrate density to define tumor’s profile.
KeywordsPD-L1 BCG Bladder cancer
CD: project development, data collection, manuscript writing. PG: data collection and histological analysis. FXN: project development, data collection. FG: data collection and histological analysis. AG: data collection and statistical analysis. SF: data collection and histological analysis. JCS: data collection and histological analysis. JI: project development, data collection. CP: project development, data collection, manuscript writing and review for important intellectual contents
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
The study protocol was approved by the respective local Ethics Committee.
All patients gave their written informed consent to be included in the study.
- 1.Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O’Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387(10031):1909–1920CrossRefGoogle Scholar
- 2.Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, Necchi A, Gerritsen W, Gurney H, Quinn DI, Culine S, Sternberg CN, Mai Y, Poehlein CH, Perini RF, Bajorin DF, KEYNOTE-045 Investigators (2017) Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 376(11):1015–1026CrossRefGoogle Scholar
- 4.Liu J, Zhang C, Hu J, Tian Q, Wang X, Gu H, Zhang S, Zhao D, Fan R (2018) Effectiveness of anti-PD-1/PD-L1 antibodies in urothelial carcinoma patients with different PD-L1 expression levels: a meta-analysis. Oncotarget 9(15):12400–12407Google Scholar
- 5.Oddens J, Brausi M, Sylvester R, Bono A, van de Beek C, van Andel G, Gontero P, Hoeltl W, Turkeri L, Marreaud S, Collette S, Oosterlinck W (2013) Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guérin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance. Eur Urol 63(3):462–472CrossRefGoogle Scholar
- 9.Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, Plimack ER, Vaena D, Grimm MO, Bracarda S, Arranz J, Pal S, Ohyama C, Saci A, Qu X, Lambert A, Krishnan S, Azrilevich A, Galsky MD (2017) Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275). A multicentre single-arm phase 2 trial. Lancet Oncol 18(3):312–322CrossRefGoogle Scholar
- 11.Lantuejoul S, Adam J, Girard N, Duruisseaux M, Mansuet-Lupo A, Cazes A, Rouquette I, Gibault L, Garcia S, Antoine M, Vignaud JM, Galateau-Salle F, Sagan C, Badoual C, Penault-Liorca F, Damotte D (2018) PD-L1 testing in non-small cell lung carcinoma: guidelines from the PATTERN group of thoracic pathologists. Ann Pathol 38(2):110–125CrossRefGoogle Scholar
- 13.Le Goux C, Damotte D, Vacher S, Sibony M, Delongchamps NB, Schnitzler A, Terris B, Zerbib M, Bieche I, Pignot G (2017) Correlation between messenger RNA expression and protein expression of immune checkpoint-associated molecules in bladder urothelial carcinoma: a retrospective study. Urol Oncol 35(5):257–263CrossRefGoogle Scholar
- 17.Hashizume A, Umemoto S, Yokose T, Nakamura Y, Yoshihara M, Shoji K, Wada S, Miyagi Y, Kishida T, Sasada T (2018) Enhanced expression of PD-L1 in non-muscle-invasive bladder cancer after treatment with Bacillus Calmette-Guerin. Oncotarget. 25(9):34066–34078Google Scholar
- 19.Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, Rost S, Leabman M, Xiao Y, Mokatrin A, Koeppen H, Hegde PS, Mellman I, Chen DS, Hodi FS (2014) Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515(7528):563–567CrossRefGoogle Scholar