Positive Ki-67 and PD-L1 expression in post-neoadjuvant chemotherapy muscle-invasive bladder cancer is associated with shorter overall survival: a retrospective study

Bladder Cancer
13/07/2020

Rubino S, et al. World J Urol 2020.

ABSTRACT

PURPOSE: There is an unmet need to develop prognostic biomarkers in post-neoadjuvant chemotherapy (NAC) muscle-invasive bladder cancer (MIBC) patients. We examine whether Ki-67 and PD-L1 expression can be used to guide adjuvant therapy.

METHODS: Tissue microarrays were constructed from 130 post-NAC radical cystectomy samples. Up to 5 cores per sample were included. Expressions of Ki-67 and PD-L1 were evaluated using immunohistochemistry (IHC).

RESULTS: Using a Cox regression model, positive Ki-67 expression in post-NAC radical cystectomy samples was associated with poorer overall survival (OS) (HR = 2.412, 95% CI, 1.076-5.408), independent of the pathological lymph node/N-stage. Positive Ki-67 expression was also associated with lack of tumor downstaging in a multivariable logistic regression model analysis (OR = 0.081, 95% CI, 0.014-0.464). PD-L1- and PD-L1+ expression was associated with a median OS of 49.8 months and 26.9 months, respectively, which did not reach statistical significance. Patients with Ki-67/PD-L1 double-negative tumors had a significantly longer median OS of 98.2 months versus 29.9 and 26.9 months in PD-L1-/Ki-67+ and PD-L1+/Ki-67+ tumors, respectively. Lack of tumor downstaging was significantly associated with positive Ki-67 and positive PD-L1 expression.

CONCLUSION: Positive Ki-67 and PD-L1 expression in post-NAC radical cystectomy samples was associated with inferior OS and absence of tumor downstaging. IHC on Ki-67 and PD-L1 would help to select patients for adjuvant therapy in post-NAC muscle-invasive bladder cancer.