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Research ArticleClinical Studies

Early Serum and Hematological Responses to Pembrolizumab Therapy as Predictors of Survival in Metastatic Urothelial Cancer

MOTOHIRO FUJIWARA, RYO FUJIWARA, TETSUYA URASAKI, TOMOHIKO OGUCHI, YOSHINOBU KOMAI, NOBORU NUMAO, SHINYA YAMAMOTO, JUNJI YONESE and TAKESHI YUASA
Anticancer Research April 2022, 42 (4) 2045-2051; DOI: https://doi.org/10.21873/anticanres.15685
MOTOHIRO FUJIWARA
1Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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  • For correspondence: motohiro.fujiwara@gmail.com
RYO FUJIWARA
1Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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TETSUYA URASAKI
2Department of Medical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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TOMOHIKO OGUCHI
1Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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YOSHINOBU KOMAI
1Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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NOBORU NUMAO
1Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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SHINYA YAMAMOTO
1Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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JUNJI YONESE
1Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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TAKESHI YUASA
1Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;
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Abstract

Background: In order to search for predictive biomarkers of efficacy of pembrolizumab therapy for metastatic urothelial cancer (UC), we investigated the relationship between treatment outcomes and early neutrophil-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and C-reactive protein (CRP) responses. Patients and Methods: Medical records of 101 patients with metastatic UC who started pembrolizumab as a second-line or later treatment were reviewed. NLR, LDH, and CRP were recorded after 3 weeks of therapy. In addition, we investigated whether these factors had an association with prolonged progression-free (PFS) or overall (OS) survival. Results: The objective response rate, median PFS, and median OS were 25.7%, 6.3 months, and 15.2 months, respectively. PFS and OS were significantly shorter in patients with NLR>3, LDH>upper limit of normal (ULN), and CRP>0.5 mg/dl after 3 weeks of pembrolizumab treatment (p<0.05). A predictive model comprising these factors (favorable risk group: 0 risk factors; intermediate-risk group: 1-2 risk factors; poor-risk group: 3 risk factors) revealed distinct PFS and OS curves (p<0.001). In the favorable risk group, 12-month OS was 79.6%; in the poor-risk group, it was 12.8%. Harrell’s C-indices for NLR >3, LDH >ULN, CRP >0.5 mg/dl, and all three combined for predicting OS were 0.656, 0.625, 0.633 and 0.678, respectively. Early responses were also non-significantly associated with ORR (p=0.37). Conclusion: Pembrolizumab treatment outcomes are associated with early NLR, LDH, and CRP responses in metastatic urothelial cancer.

Key Words:
  • Pembrolizumab
  • urothelial cancer
  • neutrophil-lymphocyte ratio
  • NLR
  • lactate dehydrogenase
  • LDH
  • C-reactive protein
  • CRP
  • immune checkpoint inhibitor
  • predictive factor
  • Received February 6, 2022.
  • Revision received February 27, 2022.
  • Accepted March 2, 2022.
  • Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Early Serum and Hematological Responses to Pembrolizumab Therapy as Predictors of Survival in Metastatic Urothelial Cancer
MOTOHIRO FUJIWARA, RYO FUJIWARA, TETSUYA URASAKI, TOMOHIKO OGUCHI, YOSHINOBU KOMAI, NOBORU NUMAO, SHINYA YAMAMOTO, JUNJI YONESE, TAKESHI YUASA
Anticancer Research Apr 2022, 42 (4) 2045-2051; DOI: 10.21873/anticanres.15685

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Early Serum and Hematological Responses to Pembrolizumab Therapy as Predictors of Survival in Metastatic Urothelial Cancer
MOTOHIRO FUJIWARA, RYO FUJIWARA, TETSUYA URASAKI, TOMOHIKO OGUCHI, YOSHINOBU KOMAI, NOBORU NUMAO, SHINYA YAMAMOTO, JUNJI YONESE, TAKESHI YUASA
Anticancer Research Apr 2022, 42 (4) 2045-2051; DOI: 10.21873/anticanres.15685
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Keywords

  • pembrolizumab
  • urothelial cancer
  • neutrophil-lymphocyte ratio
  • NLR
  • lactate dehydrogenase
  • LDH
  • C-reactive protein
  • CRP
  • immune checkpoint inhibitor
  • predictive factor
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