The pretreatment neutrophil-to-lymphocyte ratio is a novel biomarker for predicting clinical responses to pembrolizumab in platinum-resistant metastatic urothelial carcinoma patients

Koichiro Ogihara, Eiji Kikuchi, Keisuke Shigeta, Takashi Okabe, Seiya Hattori, Ryo Yamashita, Shunsuke Yoshimine, Suguru Shirotake, Ryuto Nakazawa, Kazuhiro Matsumoto, Ryuichi Mizuno, Satoshi Hara, Masafumi Oyama, Takeshi Masuda, Masashi Niwakawa, Mototsugu Oya

Research output: Contribution to journalArticle


Purpose: We investigated the relationship between pretreatment neutrophil-to-lymphocyte ratio (pre-NLR) levels just before the initiation of treatment with pembrolizumab and clinical outcomes in platinum-resistant metastatic urothelial carcinoma (UC) patients treated with pembrolizumab. Methods: Our study population comprised 78 patients diagnosed with metastatic UC and treated with pembrolizumab after platinum-based chemotherapy at our institutions between December 2017 and April 2019. We examined the relationships between pre-NLR levels just before pembrolizumab treatment and clinical outcomes. A pre-NLR level of ≥3.35 was defined as elevated according to a calculation by a receiver-operating curve analysis. Results: The high pre-NLR group consisted of 33 patients (42.3%). Overall, 29.5% of patients had a clinical response and the sum of the target lesion longest diameter was decreased in 18.8% of the high pre-NLR group, which was significantly lower than that in the low pre-NLR group (58.1%, P = 0.005). Six-month progression-free survival and cancer-specific survival rates for the high pre-NLR group were 9.1 and 58.0%, which were significantly lower than those for their counterpart (45.9 and 89.1%, P < 0.001 and P = 0.002, respectively). The pre-NLR level was an independent indicator of disease progression and cancer-specific death (P < 0.001 and P = 0.003). Furthermore, patients with a postpembrolizumab NLR level that had decreased ≥25% from the pre-NLR level had significantly lower disease progression and cancer-specific death rates than their counterparts (P = 0.01 and P = 0.022, respectively). Conclusions: Elevated pre-NLR may be a novel biomarker for identifying poor responders to pembrolizumab among platinum-resistant metastatic UC patients.

Original languageEnglish
JournalUrologic Oncology: Seminars and Original Investigations
Publication statusAccepted/In press - 2020 Jan 1



  • Neutrophil-to-lymphocyte ratio
  • Pembrolizumab
  • Platinum-resistant urothelial carcinoma
  • Prognosis
  • Progression

ASJC Scopus subject areas

  • Oncology
  • Urology

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