Prognostic Value of Testing PD-L1 Expression After Radical Cystectomy in High-risk Patients

The use of cisplatin-based adjuvant chemotherapy (AC) after radical cystectomy (RC) is a highly controversial issue and has been infrequently used owing to the high rates of postoperative complications, cisplatin ineligibility, and lack of randomized trials. Checkpoint inhibitors such as nivolumab, pembrolizumab, or atezolizumab are currently being tested in phase III studies in the adjuvant setting owing to their more favorable safety profile compared with chemotherapy. The aim of the present study was to investigate whether compartmentalization of programmed cell death ligand 1 (PD-L1) expression in different locations of RC specimens influences recurrence-free survival (RFS) after RC.

PD-L1 expression was quantified on tumor cells and immune cells by immunohistochemistry in 83 "high-risk" patients (stage ≥ pT3a and/or pN+ disease) who had undergone RC without cisplatin-based AC.

PD-L1 (≥ 1%) was expressed on tumor cells in 33 patients (39.8%) and immune cells in 51 patients (61.4%), respectively. PD-L1 positivity on tumor cells was not associated with RFS (P = .455). In contrast, PD-L1⁺ expression on immune cells was significantly associated with shorter RFS compared with PD-L1^- expression (P = .015).

We have confirmed the high heterogeneity of PD-L1 cell type-dependent expression, with the resulting divergent outcomes. Ultimately, no clear statement about PD-L1 expression as a prognostic biomarker for further AC after RC could be made, although PD-L1 expression on immune cells seemed to have the greatest effect in predicting the outcome.