Prognostic value of the fluctuation in the neutrophil–lymphocyte ratio at 6 weeks of pembrolizumab treatment is specific to the clinical response in metastatic urothelial carcinoma

Purpose: Most patients with metastatic urothelial carcinoma experience no objective response to pembrolizumab and have poor overall survival (OS). Here, we investigated the prognostic value of fluctuation in the neutrophil–lymphocyte ratio (NLR) at 6 weeks of pembrolizumab treatment, focusing on its association with the achievement of objective response. Materials and Methods: The clinical records of 177 metastatic urothelial carcinoma patients treated with pembrolizumab were retrospectively analyzed. Results: The median age was 72 years, and the median OS was 14 months. The objective response rate in the total cohort was 26.5% (47 of 177 patients). Multivariable analysis showed that objective response achievement (hazard ratio 0.3 [95% confidence interval 0.15–0.59], P < 0.001) and decline in NLR from that at baseline at 6 weeks of treatment (0.54 [0.34–0.88], P = 0.013) were independent prognostic factors for improved OS. For 47 (26.5%) patients who achieved an objective response, OS was similar regardless of NLR fluctuation at 6 weeks of treatment (P = 0.723). Intriguingly, of the 130 (73.5%) patients with no objective response, those who showed a decreased NLR at 6 weeks of pembrolizumab treatment (57 patients) from that at baseline had significantly longer OS than those with elevated NLR (73 patients) (14 vs. 6 months, P = 0.007). Conclusions: The fluctuation in NLR from that at baseline at 6 weeks of pembrolizumab treatment may be useful for patients without an objective response. This could potentially aid decision-making for post pembrolizumab therapies.