The prognostic value of expressions of STAT3, PD-L1, and PD-L2 in Ta/T1 urothelial carcinoma before and after BCG treatment

Integrating the PD-L1 Prognostic Biomarker in Non-Muscle Invasive Bladder Cancer in Clinical Practice—A Comprehensive Review on State-of-the-Art Advances and Critical Issues

“…Conversely, in the study by Civriz et al, no association was found between PD-L1 (E1L3N) status, assessed through different scoring systems and cut-offs, and recurrence after BCG treatment [53], in keeping with the findings of previous studies [50,59]. According to Aydin et al [59], neither pre-treatment nor post-treatment PD-L1 (SP142) expression was associated with RFS or progression-free survival (PFS), even using different cut-offs (≥3% or ≥5%), in a large study cohort of 117 HG-NMIBCs.…”

“…In this setting, a closer monitoring of the disease for a few years after the first diagnosis of NMIBC, through a protocol that includes more frequent cystoscopies with a shorter interval between them, would be advisable [46]. The occurrence of a statistically significant difference in PD-L1 expression based on the stage has been observed by some authors [47,48,51,53], possibly due to discrepancies in the tumor microenvironment or genomic drivers between MIBC and NMIBC [54]. For instance, Huang et al [55] examined a cohort of BCs of different stages, finding that increased levels of PD-L1 mRNA expression in tumors with higher stage and shorter survival.…”

“…Putative reasons which may contribute to affect the consistency and comparability of available findings in this setting (and more generally the assessment of PD-L1 expression as a biomarker in BC) are (1) intrinsic to the study population, including a small number of patients overall [50,58,62], an exceedingly low recurrence rate after BCG treatment, and/or unbalanced subgroup size (i.e., BCG responders vs. non responders) [53]; (2) intrinsic to the treatment, including the frequency and/or timing of BCG administration and type of BCG reagents; (3) intrinsic to the method, such as PD-L1 assessment through heterogeneous assays, antibody clones, cellular populations, scoring systems, and cut-off points (see next section); and (4) intrinsic to the tumor/tissue sample, due to the intra-tumoral heterogeneity of PD-L1 expression and the dynamic nature of the tumor microenvironment [66,67]. Furthermore, the constantly changing of the molecule over time (temporal heterogeneity) has been proven by the discrepancy over different tumor stages, as well as between metastatic sites and corresponding primary tumors, revealed by several authors [68,69].…”

PD-L1 Expression in High-Risk Non-Muscle-Invasive Bladder Cancer Is Influenced by Intravesical Bacillus Calmette–Guérin (BCG) Therapy

“…A study by Roumiguiè et al was able to show a correlation between PD-L1 expression in tumor cells and disease-free survival (DFS) [12]. On the other hand, a recent study by Civriz et al found no predictive value for PD-L1 expression in response to BCG treatment [13].…”

Enhancing Therapeutic Efficacy and Safety of Immune Checkpoint Inhibition for Bladder Cancer: A Comparative Analysis of Injectable vs. Intravesical Administration

“…Despite being the cornerstone of first-line therapy for BC, intravesical administration of Bacillus Calmette-Guérin (BCG) [8] is hindered by the resistance encountered in a significant proportion of patients [9,10]. BCG resistance is hallmarked by the expression of immunosuppressive molecules: programmed death (PD)L1, PDL2 ligands by BCG resistant tumor engages with the PD1 receptor on T cells to suppress anti-tumor response [10] (Figure 1).…”