Yoshiaki Yamamoto1, Junji Yatsuda2, Mototsugu Shimokawa3, Nakanori Fuji4, Akihiko Aoki5, Shigeru Sakano6, Mitsutaka Yamamoto7, Akinobu Suga8, Yasuhide Tei9, Satoru Yoshihiro10, Seiji Kitahara11, Kazuhiro Nagao12, Kimio Takai13, Yoriaki Kamiryo14, Jumpei Akao15, Shiro Yamaguchi16, Kazuo Oba17, Tomoyuki Shimabukuro18, Hiroaki Matsumoto1, Tomomi Kamba2, Hideyasu Matsuyama19. 1. Department of Urology, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan. 2. Department of Urology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. 3. Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Japan. 4. Department of Urology and Nephrology, Tokuyama Central Hospital, Shunan, Japan. 5. Department of Urology, Masuda Red Cross Hospital, Masuda, Japan. 6. Department of Urology, Kokura Memorial Hospital, Kitakyusyu, Japan. 7. Department of Urology, Yamaguchi Grand Medical Center, Hofu, Japan. 8. Department of Urology, Yamaguchi Red Cross Hospital, Yamaguchi, Japan. 9. Department of Urology, Kanmon Medical Center, 1-1-1, Shimonoseki, Japan. 10. Department of Urology, Shimonoseki City Hospital, Shimonoseki, Japan. 11. Department of Urology, Sanyo-Onoda Municipal Hospital, Sanyo-Onoda, Japan. 12. Department of Urology, Shuto General Hospital, Yanai, Japan. 13. Department of Urology, Saiseikai Shimonoseki General Hospital, Shimonoseki, Japan. 14. Department of Urology, Shimonoseki Saiseikai Toyoura Hospital, Shimonoseki, Japan. 15. Department of Urology, Ogori Daiichi General Hospital, Yamaguchi, Japan. 16. Department of Urology, Shimonoseki Medical Center, Shimonoseki, Japan. 17. Department of Urology, Saiseikai Yamaguchi General Hospital, Yamaguchi, Japan. 18. Department of Urology, Ube-kohsan Central Hospital Corp, Ube, Japan. 19. Department of Urology, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-kogushi, Ube, Yamaguchi, 755-8505, Japan. hidde@yamaguchi-u.ac.jp.
Abstract
BACKGROUND: Pembrolizumab is effective in a limited number of patients with advanced urothelial carcinoma (UC). Therefore, we evaluated the prognostic value of clinical biomarkers following pembrolizumab treatment in patients with advanced UC. METHODS: We retrospectively reviewed the medical records of 121 patients with platinum-refractory advanced UC who received pembrolizumab. Inflammation-based prognostic scores before and 6 weeks after the treatment were recorded. The categorical variables influencing overall survival (OS) and objective response rate (ORR) were analyzed. RESULTS: Multivariate analyses showed that pretreatment Eastern Cooperative Oncology Group (ECOG) performance score (PS), presence of only lymph node metastasis (only LN mets), C-reactive protein (CRP), and neutrophil/lymphocyte ratio (NLR) were independent prognostic factors for OS (P = 0.0077; RR = 2.42, P = 0.0049; RR = 0.36, P = 0.0047; RR = 2.53, and P = 0.0079; RR = 2.33, respectively). The pretreatment risk stratification using ECOG PS, only LN mets, CRP, and NLR was used for estimating the OS (P < 0.0001) and ORR (P < 0.0001). Furthermore, changes in NLR in response to pembrolizumab were significantly associated with the OS (P = 0.0002) and ORR (P = 0.0023). This change was also significantly correlated with OS even in the high-risk group stratified by this pretreatment risk stratification (P = 0.0069). CONCLUSIONS: This pretreatment risk stratification may be used for estimating the OS and ORR of patients with advanced UC treated with pembrolizumab. If changes in NLR in response to pembrolizumab treatment improve, pembrolizumab should be continued.
BACKGROUND:Pembrolizumab is effective in a limited number of patients with advanced urothelial carcinoma (UC). Therefore, we evaluated the prognostic value of clinical biomarkers following pembrolizumab treatment in patients with advanced UC. METHODS: We retrospectively reviewed the medical records of 121 patients with platinum-refractory advanced UC who received pembrolizumab. Inflammation-based prognostic scores before and 6 weeks after the treatment were recorded. The categorical variables influencing overall survival (OS) and objective response rate (ORR) were analyzed. RESULTS: Multivariate analyses showed that pretreatment Eastern Cooperative Oncology Group (ECOG) performance score (PS), presence of only lymph node metastasis (only LN mets), C-reactive protein (CRP), and neutrophil/lymphocyte ratio (NLR) were independent prognostic factors for OS (P = 0.0077; RR = 2.42, P = 0.0049; RR = 0.36, P = 0.0047; RR = 2.53, and P = 0.0079; RR = 2.33, respectively). The pretreatment risk stratification using ECOG PS, only LN mets, CRP, and NLR was used for estimating the OS (P < 0.0001) and ORR (P < 0.0001). Furthermore, changes in NLR in response to pembrolizumab were significantly associated with the OS (P = 0.0002) and ORR (P = 0.0023). This change was also significantly correlated with OS even in the high-risk group stratified by this pretreatment risk stratification (P = 0.0069). CONCLUSIONS: This pretreatment risk stratification may be used for estimating the OS and ORR of patients with advanced UC treated with pembrolizumab. If changes in NLR in response to pembrolizumab treatment improve, pembrolizumab should be continued.