Introduction: No reliable biomarker is available for predicting worse clinical outcome in chemo-resistant urothelial carcinoma (UC) patients treated with pembrolizumab. We focused on absolute monocyte count (AMC) that is reported to modulate immune response in the tumor microenvironment and a possible biomarker for predicting prognosis in various malignancies, including UC. Our aim was to evaluate whether high pretreatment AMC (pre-AMC) could predict subsequent clinical outcomes in chemo-resistant UC patients treated with pembrolizumab.
Methods: We identified 90 cases treated with pembrolizumab for chemo-resistant UC between December 2017 and April 2019 at our 6 institutions. We investigated the association between pre-AMC levels and their prognosis. We defined patients with AMC of >342 as the high pre-AMC group according to a calculation by receiver-operating curve analysis.
Results: The high pre-AMC group consisted of 53 cases. In the 85 cases who had measurable lesions, at the point of maximum effect the sum of the target lesion longest diameter (SLD) was decreased in 27 cases compared to baseline. SLD decreased in 9 cases (17.0%) in high pre-AMC group, which was significantly lower than that in low pre-AMC group (18 cases, 48.6%, p=0.001). The disease control rate defined by RECIST ver. 1.1 at best response in high pre-AMC group was 30.6%, which was significantly lower than that in their counterpart (61.1%, p=0.003). No association was observed between pre-AMC levels and the occurrence of adverse events (p=0.184). The 12-month progression-free survival (PFS) rate for high pre-AMC group was 11.8%, which was significantly lower than that for their counterpart (41.4%, p<0.001). Multivariate Cox regression analysis revealed that pre-AMC level of >342 (p=0.007), and liver metastases (p=0.028) were the independent indicators for disease progression. Furthermore, the 12-month cancer-specific survival (CSS) rates for high pre-AMC group was 45.9%, which was significantly lower than that for their counterpart (89.7%, p<0.001). Multivariate analysis revealed that the pre-AMC level of >342 was the only independent indicator for cancer-specific death (p<0.001). The change of AMC level before and after pembrolizumab was elevated in 41 cases (45.6%). However, there was no association between clinical outcome of PFS and CSS and the change of AMC level.
Conclusions: Elevated pre-AMC could identify a population with a poor response to pembrolizumab treatment among chemo-resistant UC patients. Source of