Risk Classification for Overall Survival by the Neutrophil–Lymphocyte Ratio and the Number of Metastatic Sites in Patients Treated with Pembrolizumab—A Multicenter Collaborative Study in Japan

SIMPLE SUMMARY: Pembrolizumab improves overall survival (OS) in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas objective response was observed in a modest number of patients (<25%) for this treatment, implying the distinct survival outcomes for those patients. Thus, the optimal risk stratification to predict survival outcomes at the initiation of pembrolizumab treatment would be helpful for physicians. In the present study, we examined a risk model developed using two clinical factors, including the number of metastatic sites and neutrophil–lymphocyte ratio (NLR), for predicting OS at the initiation of pembrolizumab treatment. This risk stratification seemed to be well-balanced (26.5%, 44.3%, and 29.2% in the favorable-risk, intermediate-risk, and poor-risk groups, respectively), and Kaplan–Meier curves illustrated clear discrimination of OS among the risk groups. Since the model proposed in the present study can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice. ABSTRACT: Pembrolizumab has emerged as the new standard of care in patients with platinum-refractory metastatic urothelial carcinoma (mUC), whereas the optimal risk stratification to predict survival outcomes is still controversial. We examined a risk model for overall survival (OS) in mUC treated with pembrolizumab using our multi-institutional dataset (212 patients). The median age was 72 years old. Median OS from the initiation of pembrolizumab treatment was 11.7 months. The objective response rate (ORR) was 26.4%. On multivariate analysis, multiple metastatic sites and an NLR > 3.50 at the initiation of pembrolizumab treatment were identified as independent predictors for OS. We next developed a risk model using those two predictors. Patients without any factors were assigned to the favorable-risk group (26.5%). Patients with either factor and both factors were assigned to the intermediate-risk group (44.3%), and poor-risk group (29.2%), respectively. Kaplan–Meier curves showed clear discrimination of OS among the risk groups (p < 0.001). The ORR in each group was 35.7% in the favorable-risk group, 27.7% in the intermediate-risk group, and 17.7% in the poor-risk group. Given that the model can be concisely determined at the initiation of pembrolizumab treatment, physicians may be encouraged to consider the risk group for daily practice.