Résumé
Abstract only 4550 Background: Intravesical BCG instillation (IBI) is the gold standard adjuvant treatment after transurethral resection of the bladder in high risk non muscle invasive bladder cancer (HR-NMIBC). IBI induce a type of Th1 immune response requiring a recruitment of cytotoxic cells. This response is downregulated by the PD-1/PD-L1 checkpoint inhibitors through an inhibition of the action of CD8+ T cells against their target. Our purpose was to assess whether PD-1/PD-L1 expression was associated with IBI response in HR-NMIBC. Methods: Histologically confirmed HR-NMBC from 5 academic French institutions which underwent maintenance IBI were retrospectively included. The following data were collected: pathological stage, grade, concomitant carcinoma in situ, number of lesions and size. From a paraffin embedded samples of initial resection, a unique dedicated uropathologist quantified immunochemistry expression of CD3, CD8, PD-L1 (antibody SP263/ SP142, E1L3N, 28 8) in both tumour cells and tumoral microenvironment. Univariate and multivariate analyses were performed using Cox proportional hazards model. Results: Overall 140 patients (median age 66.5 years, range:35-87; sex ratio male vs female:6:1) were included. The distribution of NMIBC tumour for stage and grade was: Ta 37.2% (n = 52), T1 62.8% (n = 88) and high grade 100% (n = 140) respectively. The median number of IBI which were delivered was 12 (range 7-36). The median length of follow-up was 54.24 mo (95% CI = 49.91-58.68). Overall, 25 patients (17.9%) had a recurrence/or progression. The 72mo Disease free survival (DFS) rate was 81.11% (95% CI = 72.20-87.41). Using univariate analysis, we found that Age (HR = 1.07; [1.02-1.12] p = 0.005), CD3/CD8 ratio (HR per 10 units = 3.43 [1.62-7.23] p = 0.014) and PD-L1(HR per 10 units = 1.65 [1.15-2.38] p = 0.046) were associated with DFS. In multivariate analysis, Age (HR = 1.07 [1.02-1.13] p = 0.009), CD3/CD8 ratio (HR per 10 units = 1.96 [1.28-3.00] p = 0.02) and PD-L1 expression in tumour cells (HR per 10 units = 3.38 [1.61-7.11] p = 0.01) remained significantly associated with DFS. Conclusions: PD-L1 expression in tumour cells and the T cells population in tumour microenvironment were both predictive factors of BCG response in HR-NMIBC. These results build a scientific rationale for pharmacological intervention on a molecular target using immuno-oncology.