1
|
Hara T, Teishima J, Okamura Y, Suzuki K, Bando Y, Terakawa T, Chiba K, Hyodo Y, Nakano Y, Miyake H. Appearance of New Lesions Associate With Poor Prognosis in Pembrolizumab-Treated Urothelial Carcinoma. Clin Genitourin Cancer 2024; 22:102236. [PMID: 39471702 DOI: 10.1016/j.clgc.2024.102236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/30/2024] [Accepted: 10/05/2024] [Indexed: 11/01/2024]
Abstract
OBJECTIVES This study investigated the variations in response patterns, including target lesion enlargement and the emergence of new lesions, in patients with urothelial carcinoma receiving pembrolizumab therapy and assessed the impact of new lesions on patient outcomes. METHODS This retrospective analysis included patients with urothelial carcinoma treated with pembrolizumab following platinum failure. Response Evaluation Criteria in Solid Tumors criteria were used to assess the target lesion size and appearance of new lesions. Patients were categorized into 2 groups: the primary progressive disease (PD) group, consisting of patients who progressed within 28 to 84 days of treatment initiation, and the secondary PD group, consisting of patients who progressed more than 84 days after treatment initiation. Survival analyses were performed to evaluate the impact of new lesions on patient outcomes. RESULTS In this study, 42 patients experienced primary PD, and 37 experienced secondary PD. Among patients with primary PD, 64.3%, 73.8%, 45.2% had an increase of 20% or more in target lesion size, newly emerged lesions, and both an increase in target lesion size and new lesions, respectively. Kaplan-Meier analysis revealed that patients with primary PD and new lesions had significantly shorter overall survival after PD than those with only target lesion growth and those with secondary PD (both P < .001). CONCLUSION This study revealed the heterogeneity of response patterns during pembrolizumab therapy in patients with urothelial carcinoma and primary pembrolizumab resistance and the presence of new lesions early in treatment. Earlier imaging evaluation should be performed to assess for the appearance of new lesions, leading to sequential treatment.
Collapse
Affiliation(s)
- Takuto Hara
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Jun Teishima
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan.
| | - Yasuyoshi Okamura
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kotaro Suzuki
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yukari Bando
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoaki Terakawa
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Koji Chiba
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yoji Hyodo
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yuzo Nakano
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hideaki Miyake
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| |
Collapse
|
2
|
Çolak R, Erdem GU, Kapar C, Gültürk İ, Aksu F, Erdal GŞ, Yılmaz M, Tural D. Change in the neutrophil-lymphocyte ratio may predict early recurrence in operated bladder cancer. Asia Pac J Clin Oncol 2024. [PMID: 38572819 DOI: 10.1111/ajco.14065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 01/08/2024] [Accepted: 03/20/2024] [Indexed: 04/05/2024]
Abstract
BACKGROUND Recurrence develops in 50% of operated bladder cancer patients. It is important to detect recurrence in advance, and there is no prognostic reliable biomarker for bladder cancer. OBJECTIVE The aim of this study is to show that changes in hematological parameters before radiological imaging can predict recurrence. METHODS We performed a retrospective cohort study of patients undergoing radical cystectomy for urothelial carcinoma of the bladder identified using our institutional database (2010-2022). Disease-free survival (DFS) was evaluated as relapse or death due to any cause. Kaplan-Meier analysis was used for DFS according to the follow-up period. DFS was calculated in two groups neutrophil-lymphocyte ratio (NLR) < 3 and NLR ≥ 3. Log-rank test was used for comparison between groups and p < 0.05 was considered statistically significant. RESULTS In the study, 91 patients were examined. The median age was 61.0 (34-79). 57.1% of the patients were T (1-2) and 42.9% were T (3-4). The lymph node (LN) was negative in 78% and positive in 22%. Median follow-up time and DFS were 53.4 months and 54%, respectively. The median NLR was 2.8 (0.8-8.7). For DFS, there was a significant difference according to age, T stage, and LN status (p: 0.048, 0.019, and 0.040). There was no significant difference in the NLR in terms of DFS at the time of diagnosis (p: 0.654). In follow-ups; While there was no difference in the NLR for DFS 12 months before recurrence (p: 0.231), there was a significant difference 6 months before the relapse and at the time of recurrence (p: 0.023 and 0.031). CONCLUSION The change in the NLR before radiological recurrence in bladder cancer is significant in predicting recurrence. Prospective and multi-center research is needed to confirm our findings.
Collapse
Affiliation(s)
- Rumeysa Çolak
- Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - Gökmen Umut Erdem
- Department of Medical Oncology, Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey
| | - Caner Kapar
- Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - İlkay Gültürk
- Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - Faruk Aksu
- Department of Medical Oncology, Başakşehir Çam and Sakura City Hospital, Istanbul, Turkey
| | - Gülçin Şahingöz Erdal
- Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - Mesut Yılmaz
- Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| | - Deniz Tural
- Department of Medical Oncology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey
| |
Collapse
|
3
|
Taguchi S, Kawai T, Nakagawa T, Kume H. Latest evidence on clinical outcomes and prognostic factors of advanced urothelial carcinoma in the era of immune checkpoint inhibitors: a narrative review. Jpn J Clin Oncol 2024; 54:254-264. [PMID: 38109484 DOI: 10.1093/jjco/hyad172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 11/25/2023] [Indexed: 12/20/2023] Open
Abstract
The management of advanced (locally advanced or metastatic) urothelial carcinoma has been revolutionized since pembrolizumab was introduced in 2017. Several prognostic factors for advanced urothelial carcinoma treated with pembrolizumab have been reported, including conventional parameters such as performance status and visceral (especially liver) metastasis, laboratory markers such as the neutrophil-to-lymphocyte ratio, sarcopenia, histological/genomic markers such as programmed cell death ligand 1 immunohistochemistry and tumor mutational burden, variant histology, immune-related adverse events, concomitant medications in relation to the gut microbiome, primary tumor site (bladder cancer versus upper tract urothelial carcinoma) and history/combination of radiotherapy. The survival time of advanced urothelial carcinoma has been significantly prolonged (or 'doubled' from 1 to 2 years) after the advent of pembrolizumab, which will be further improved with novel agents such as avelumab and enfortumab vedotin. This review summarizes the latest evidence on clinical outcomes and prognostic factors of advanced urothelial carcinoma in the contemporary era of immune checkpoint inhibitors.
Collapse
Affiliation(s)
- Satoru Taguchi
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Taketo Kawai
- Department of Urology, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Tohru Nakagawa
- Department of Urology, Teikyo University School of Medicine, Itabashi-ku, Tokyo, Japan
| | - Haruki Kume
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| |
Collapse
|
4
|
Hara T, Furukawa J, Okamura Y, Bando Y, Terakawa T, Harada K, Takahashi S, Nakano Y, Fujisawa M. The poor antitumor effect of pembrolizumab in advanced upper urothelial carcinoma with renal parenchymal invasion. Int J Urol 2023; 30:779-786. [PMID: 37317886 DOI: 10.1111/iju.15231] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 06/04/2023] [Indexed: 06/16/2023]
Abstract
OBJECTIVES We investigated poor prognosticators in advanced or unresectable urothelial carcinoma, focusing on renal parenchymal invasion (RPI). METHODS This study included 48 bladder cancer (BC) and 67 upper tract urothelial carcinoma (UTUC) patients treated with pembrolizumab from December 2017 to September 2022 at Kobe University Hospital. Medical records were retrospectively reviewed for clinical characteristics, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Multivariate analyses were performed using the Cox proportional hazard regression model to identify parameters associated with either PFS or OS. RESULTS Of 67 UTUC patients, 23 had RPI and 41 patients did not, while 3 cases could not be evaluated. Patients with RPI were predominantly elderly and had liver metastases. ORR for patients with RPI was 8.7%, while it was 19.5% for those without RPI. PFS was significantly shorter for patients with RPI compared with those without RPI. Patients with RPI had significantly shorter OS than those without RPI. On multivariate analysis, performance status (PS) ≥ 2, neutrophil-lymphocyte ratio (NLR) ≥ 3, C-reactive protein ≥0.3 mg/dL and RPI were independent prognostic factors for PFS. PS ≥ 2, NLR ≥ 3, visceral metastasis and RPI were independent prognostic factors for OS. UTUC patient OS was significantly shorter than BC patient OS, while no significant difference in PFS or OS was observed between BC patients and UTUC patients without RPI. CONCLUSIONS RPI was a poor prognostic factor in advanced urothelial carcinoma treated with pembrolizumab, possibly resulting in a poorer prognosis for UTUC compared with BC.
Collapse
Affiliation(s)
- Takuto Hara
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Junya Furukawa
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yasuyoshi Okamura
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yukari Bando
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoaki Terakawa
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kenichi Harada
- Department of Urology, University of Occupational and Environmental Health, Kitakyushu, Japan
| | - Satoru Takahashi
- Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Japan
- Department of Radiology, Takatsuki General Hospital, Takatsuki, Japan
| | - Yuzo Nakano
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masato Fujisawa
- Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan
| |
Collapse
|
5
|
Taguchi S, Kawai T, Buti S, Bersanelli M, Uemura Y, Kishitani K, Miyakawa J, Sugimoto K, Nakamura Y, Niimi F, Kaneko T, Kamei J, Obinata D, Yamaguchi K, Kakutani S, Kanazawa K, Sugihara Y, Tokunaga M, Akiyama Y, Yamada Y, Sato Y, Yamada D, Enomoto Y, Nishimatsu H, Fujimura T, Fukuhara H, Nakagawa T, Takahashi S, Kume H. Validation of a drug-based score in advanced urothelial carcinoma treated with pembrolizumab. Immunotherapy 2023. [PMID: 37191002 DOI: 10.2217/imt-2023-0028] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2023] Open
Abstract
Aim: To validate a 'drug score' that stratifies patients receiving immunotherapy based on concomitant medications (antibiotics/proton pump inhibitors/corticosteroids) in urothelial carcinoma (UC). Materials & methods: We assessed oncological outcomes according to the drug score in 242 patients with advanced UC treated with pembrolizumab. Results: The drug score classified patients into three risk groups with significantly different survivals. Heterogeneous treatment effect analyses showed that the primary cancer site (bladder UC [BUC] or upper-tract UC [UTUC]) significantly affected the prognostic capability of the drug score; it significantly correlated with survivals in BUC, while there were no such correlations in UTUC. Conclusion: A drug score was examined in advanced UC treated with pembrolizumab and was validated in BUC but not in UTUC.
Collapse
Affiliation(s)
- Satoru Taguchi
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
- Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Taketo Kawai
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
- Department of Urology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan
| | - Sebastiano Buti
- Medicine & Surgery Department, University of Parma, Via Gramsci 14, Parma, 43126, Italy
| | - Melissa Bersanelli
- Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, Parma, 43126, Italy
| | - Yukari Uemura
- Biostatistics Section, Department of Data Science, Center of Clinical Sciences, National Center for Global Health & Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan
| | - Kenjiro Kishitani
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Jimpei Miyakawa
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
- Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Kazuma Sugimoto
- Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Yu Nakamura
- Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Fusako Niimi
- Department of Urology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan
| | - Tomoyuki Kaneko
- Department of Urology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan
| | - Jun Kamei
- Department of Urology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan
| | - Daisuke Obinata
- Department of Urology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Kenya Yamaguchi
- Department of Urology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Shigenori Kakutani
- Division of Urology, Mitsui Memorial Hospital, 1 Kanda-izumi-cho, Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Koichiro Kanazawa
- Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokozuna, Sumida-ku, Tokyo, 130-8587, Japan
| | - Yuriko Sugihara
- Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokozuna, Sumida-ku, Tokyo, 130-8587, Japan
| | - Mayuko Tokunaga
- Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokozuna, Sumida-ku, Tokyo, 130-8587, Japan
| | - Yoshiyuki Akiyama
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Yuta Yamada
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Yusuke Sato
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Daisuke Yamada
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Yutaka Enomoto
- Division of Urology, Mitsui Memorial Hospital, 1 Kanda-izumi-cho, Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Hiroaki Nishimatsu
- Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokozuna, Sumida-ku, Tokyo, 130-8587, Japan
| | - Tetsuya Fujimura
- Department of Urology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, 329-0498, Japan
| | - Hiroshi Fukuhara
- Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan
| | - Tohru Nakagawa
- Department of Urology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan
| | - Satoru Takahashi
- Department of Urology, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Haruki Kume
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| |
Collapse
|
6
|
Taguchi S, Kawai T, Nakagawa T, Miyakawa J, Kishitani K, Sugimoto K, Nakamura Y, Kamei J, Obinata D, Yamaguchi K, Kaneko T, Yoshida K, Yamamoto S, Kakutani S, Kanazawa K, Sugihara Y, Tokunaga M, Matsumoto A, Uemura Y, Akiyama Y, Yamada Y, Sato Y, Yamada D, Enomoto Y, Nishimatsu H, Ishikawa A, Tanaka Y, Nagase Y, Fujimura T, Fukuhara H, Takahashi S, Kume H. Improved survival in real-world patients with advanced urothelial carcinoma: A multicenter propensity score-matched cohort study comparing a period before the introduction of pembrolizumab (2003-2011) and a more recent period (2016-2020). Int J Urol 2022; 29:1462-1469. [PMID: 35996761 PMCID: PMC10087413 DOI: 10.1111/iju.15014] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Accepted: 07/24/2022] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Although the treatment strategy for advanced urothelial carcinoma (aUC) has drastically changed since pembrolizumab was introduced in 2017, studies revealing current survival rates in aUC are lacking. This study aimed to assess (1) the improvement in survival among real-world patients with aUC after the introduction of pembrolizumab and (2) the direct survival-prolonging effect of pembrolizumab. METHODS This multicenter retrospective study included 531 patients with aUC undergoing salvage chemotherapy, including 200 patients treated in the pre-pembrolizumab era (2003-2011; earlier era) and 331 patients treated in a recent 5-year period (2016-2020; recent era). Using propensity score matching (PSM), cancer-specific survival (CSS) and overall survival (OS) were compared between the earlier and recent eras, in addition to between the recent era, both with and without pembrolizumab use, and the earlier era. RESULTS After PSM, the recent era cohort had significantly longer CSS (21 months) and OS (19 months) than the earlier era cohort (CSS and OS: 12 months). In secondary analyses using PSM, patients treated with pembrolizumab had significantly longer CSS (25 months) and OS (24 months) than those in the earlier era cohort (CSS and OS: 11 months), whereas patients who did not receive pembrolizumab in the recent era had similar outcomes (CSS and OS: 14 months) as the earlier era cohort (CSS and OS: 12 months). CONCLUSIONS Patients with aUC treated in the recent era exhibited significantly longer survival than those treated before the introduction of pembrolizumab. The improved survival was primarily attributable to the use of pembrolizumab.
Collapse
Affiliation(s)
- Satoru Taguchi
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.,Department of Urology, Kyorin University School of Medicine, Tokyo, Japan.,Department of Urology, Tokyo Teishin Hospital, Tokyo, Japan
| | - Taketo Kawai
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.,Department of Urology, Teikyo University School of Medicine, Tokyo, Japan.,Department of Urology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Tohru Nakagawa
- Department of Urology, Teikyo University School of Medicine, Tokyo, Japan
| | - Jimpei Miyakawa
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kenjiro Kishitani
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kazuma Sugimoto
- Department of Urology, Kyorin University School of Medicine, Tokyo, Japan
| | - Yu Nakamura
- Department of Urology, Kyorin University School of Medicine, Tokyo, Japan
| | - Jun Kamei
- Department of Urology, Jichi Medical University, Tochigi, Japan
| | - Daisuke Obinata
- Department of Urology, Nihon University School of Medicine, Tokyo, Japan
| | - Kenya Yamaguchi
- Department of Urology, Nihon University School of Medicine, Tokyo, Japan
| | - Tomoyuki Kaneko
- Department of Urology, Teikyo University School of Medicine, Tokyo, Japan
| | - Kanae Yoshida
- Division of Urology, Mitsui Memorial Hospital, Tokyo, Japan
| | - Sachi Yamamoto
- Division of Urology, Mitsui Memorial Hospital, Tokyo, Japan
| | | | - Koichiro Kanazawa
- Department of Urology, The Fraternity Memorial Hospital, Tokyo, Japan
| | - Yuriko Sugihara
- Department of Urology, The Fraternity Memorial Hospital, Tokyo, Japan
| | - Mayuko Tokunaga
- Department of Urology, The Fraternity Memorial Hospital, Tokyo, Japan
| | - Akihiko Matsumoto
- Department of Urology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan
| | - Yukari Uemura
- Biostatistics Section, Department of Data Science, Center of Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan
| | - Yoshiyuki Akiyama
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yuta Yamada
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yusuke Sato
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Daisuke Yamada
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yutaka Enomoto
- Division of Urology, Mitsui Memorial Hospital, Tokyo, Japan
| | | | - Akira Ishikawa
- Department of Urology, Tokyo Teishin Hospital, Tokyo, Japan
| | - Yoshinori Tanaka
- Department of Urology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yasushi Nagase
- Department of Urology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan
| | | | - Hiroshi Fukuhara
- Department of Urology, Kyorin University School of Medicine, Tokyo, Japan
| | - Satoru Takahashi
- Department of Urology, Nihon University School of Medicine, Tokyo, Japan
| | - Haruki Kume
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| |
Collapse
|
7
|
Sugimoto K, Taguchi S, Kishitani K, Kawai T, Masuda K, Nakamura Y, Kinjo M, Tambo M, Miyakawa J, Akiyama Y, Yamada Y, Sato Y, Yamada D, Nakagawa T, Fukuhara H, Kume H. Comparison of full-dose gemcitabine/cisplatin, dose-reduced gemcitabine/cisplatin, and gemcitabine/carboplatin in real-world patients with advanced urothelial carcinoma. BMC Urol 2022; 22:177. [DOI: 10.1186/s12894-022-01139-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 10/31/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
While gemcitabine/cisplatin (GC) is the gold standard regimen for patients with advanced urothelial carcinoma (aUC), either dose-reduced GC or gemcitabine/carboplatin (GCa) is an alternative option for “cisplatin-unfit” patients. However, few studies have compared outcomes with these commonly used regimens in the real-world setting.
Methods
We retrospectively reviewed patients with aUC who received full-dose GC, dose-reduced GC, or GCa as first-line salvage chemotherapy at two university hospitals between 2016 and 2020. Progression-free survival, cancer-specific survival, and overall survival, as well as best overall response and adverse event profiles, were compared among these three regimens.
Results
Of 105 patients, 41, 27, and 37 patients received full-dose GC, dose-reduced GC, and GCa, respectively. Significant differences were noted in the patients’ baseline age, primary site, and renal function among the three regimens. Sixty-nine (65.7%) patients died during a median follow-up period of 14 months. There was no significant difference among the three regimens for all survival outcomes and best overall response. However, the complete response rate of dose-reduced GC (2/27, 7.4%) appeared inferior to that of full-dose GC (9/41, 22.0%) or GCa (6/37, 16.2%). Regarding adverse event profiles, no significant difference was observed among the three regimens, except for significantly fewer cases with elevated alanine aminotransferase in the GCa group compared with the other groups.
Conclusions
This study compared the oncological and toxicological outcomes of full-dose GC, dose-reduced GC, and GCa in real-world patients with aUC. Unlike in the clinical trial setting, there were almost no significant differences among the three regimens.
Collapse
|
8
|
Sarrió-Sanz P, Martinez-Cayuelas L, Lumbreras B, Sánchez-Caballero L, Palazón-Bru A, Gil-Guillén VF, Gómez-Pérez L. Mortality prediction models after radical cystectomy for bladder tumour: A systematic review and critical appraisal. Eur J Clin Invest 2022; 52:e13822. [PMID: 35642331 DOI: 10.1111/eci.13822] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 05/18/2022] [Accepted: 05/25/2022] [Indexed: 11/29/2022]
Abstract
INTRODUCTION To identify risk-predictive models for bladder-specific cancer mortality in patients undergoing radical cystectomy and assess their clinical utility and risk of bias. METHODS Systematic review (CRD42021224626:PROSPERO) in Medline and EMBASE (from their creation until 31/10/2021) was screened to include articles focused on the development and internal validation of a predictive model of specific cancer mortality in patients undergoing radical cystectomy. CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS) and Prediction model Risk Of Bias ASsessment Tool (PROBAST) were applied. RESULTS Nineteen observational studies were included. The main predictors were sociodemographic variables, such as age (18 studies, 94.7%) and sex (17, 89.5% studies), tumour characteristics (TNM stage (18 studies, 94.7%), histological subtype/grade (15 studies, 78.9%), lymphovascular invasion (10 studies, 52.6%) and treatment with chemotherapy (13 studies, 68.4%). C-index values were presented in 14 studies. The overall risk of bias assessed using PROBAST led to 100% of studies being classified as high risk (the analysis domain was rated to be at high risk of bias in all the studies), and 52.6% showed low applicability. Only 5 studies (26.3%) included an external validation and 2 (10.5%) included a prospective study design. CONCLUSIONS Using clinical predictors to assess the risk of bladder-specific cancer mortality is a feasibility alternative. However, the studies showed a high risk of bias and their applicability is uncertain. Studies should improve the conducting and reporting, and subsequent external validation studies should be developed.
Collapse
Affiliation(s)
- Pau Sarrió-Sanz
- Urology Services, University Hospital of San Juan de Alicante, Alicante, Spain
| | | | - Blanca Lumbreras
- Department of Public Health, History of Science and Gynecology, Miguel Hernández University, and CIBER en Epidemiología y Salud Pública, Alicante, Spain
| | | | - Antonio Palazón-Bru
- Department of Clinical Medicine, Miguel Hernández University, Alicante, Spain
| | | | - Luis Gómez-Pérez
- Department of Clinical Medicine, Miguel Hernández University, Alicante, Spain
- Urology Services, University General Hospital of Elx, Alicante, Spain
| |
Collapse
|
9
|
Park JH, Park I, Kim IH, Hur JY, Hwang I, Kim C, Kim HJ, Maeng CH, Park K, Lee MY, Lee HJ, Jung JY, Keam B, Park SH, Lee JL. Prognostic model in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitors after platinum failure. Curr Probl Cancer 2022; 46:100848. [PMID: 35344842 DOI: 10.1016/j.currproblcancer.2022.100848] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 02/04/2022] [Accepted: 02/14/2022] [Indexed: 11/26/2022]
|
10
|
Hashimoto M, Fujita K, Nakayama T, Fujimoto S, Hamaguchi M, Nishimoto M, Kikuchi T, Adomi S, Banno E, De Velasco MA, Saito Y, Shimizu N, Mori Y, Minami T, Nozawa M, Nose K, Yoshimura K, Uemura H. Higher neutrophil-to-lymphocyte ratio after the first cycle of the first-line chemotherapy is associated with poor cancer specific survival of upper urinary tract carcinoma patients. Transl Androl Urol 2021; 10:2838-2847. [PMID: 34430386 PMCID: PMC8350230 DOI: 10.21037/tau-21-185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 05/19/2021] [Indexed: 01/29/2023] Open
Abstract
Background Inflammatory cytokines and immature myeloid derived suppressor cells (MDSCs), which increase during cancer progression, could lead to a neutrophil increase and lymphocyte reduction. Thus, the neutrophil-lymphocyte ratio (NLR) was used to predict survival of patients suffering from urological cancers including upper urinary tract carcinoma. We further determined whether the NLR during the first cycle of first-line chemotherapy could predict cancer specific survival. Methods We recruited patients with locally advanced or metastatic upper urinary tract urothelial carcinoma (UTUC) who received chemotherapy between January 2014 and July 2019. We investigated the impact of various clinical variables, including age, sex, performance status, and estimated creatinine clearance (CCr), and NLR before and after the first cycle of the first-line chemotherapy on prognosis. Results A total of 41 patients were included in our study. Cancer specific survival of the patients with lower NLR was significantly better than that of the patients with higher NLR measured after the first cycle of the first-line chemotherapy (log-rank test P=0.005, median 29.2 vs. 11.9 months, respectively). Cox proportional regression analysis showed that higher NLR after the first cycle of the first-line chemotherapy was a significant predictor of cancer specific survival. Conclusions The NLR after the first cycle of the first-line chemotherapy could be an indication for patients with locally advanced or metastatic UTUC to maintain their first-line chemotherapy treatment.
Collapse
Affiliation(s)
- Mamoru Hashimoto
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Kazutoshi Fujita
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Takahito Nakayama
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Saizo Fujimoto
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Mamoru Hamaguchi
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | | | - Takashi Kikuchi
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Shogo Adomi
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Eri Banno
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Marco A De Velasco
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Yoshitaka Saito
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Nobutaka Shimizu
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Yasunori Mori
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Takafumi Minami
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Masahiro Nozawa
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Kazuhiro Nose
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Kazuhiro Yoshimura
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Hirotsugu Uemura
- Department of Urology, Kindai University Faculty of Medicine, Osaka, Japan
| |
Collapse
|
11
|
Taguchi S, Kawai T, Nakagawa T, Nakamura Y, Kamei J, Obinata D, Yamaguchi K, Kaneko T, Kakutani S, Tokunaga M, Uemura Y, Sato Y, Fujimura T, Fukuhara H, Enomoto Y, Nishimatsu H, Takahashi S, Kume H. Prognostic significance of the albumin-to-globulin ratio for advanced urothelial carcinoma treated with pembrolizumab: a multicenter retrospective study. Sci Rep 2021; 11:15623. [PMID: 34341416 PMCID: PMC8329063 DOI: 10.1038/s41598-021-95061-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Accepted: 07/20/2021] [Indexed: 12/16/2022] Open
Abstract
Although the albumin-to-globulin ratio (AGR) is a promising biomarker, no study has investigated its prognostic significance for advanced urothelial carcinoma (UC). This study conformed to the REporting recommendations for tumor MARKer prognostic studies (REMARK) criteria. We retrospectively reviewed 176 patients with advanced UC treated with pembrolizumab between 2018 and 2020. We evaluated the associations between pretreatment clinicopathological variables, including the AGR and performance status (PS), with progression-free survival, cancer-specific survival, and overall survival. The Cox proportional hazards model was used for univariate and multivariable analyses. The AGR was dichotomized as < 0.95 and ≥ 0.95 based on receiver operating characteristic curve analysis. After excluding 26 cases with missing data from the total of 176 cases, 109 (73%) patients experienced disease progression, 75 (50%) died from UC, and 6 (4%) died of other causes (median survival = 12 months). Multivariate analyses identified PS ≥ 2 and pretreatment AGR < 0.95 as independent poor prognostic factors for all endpoints. Furthermore, a prognostic risk model incorporating these two variables achieved a relatively high concordance index for all endpoints. This is the first report to evaluate the significance of AGR in advanced UC. Pretreatment AGR < 0.95 may serve as a prognostic marker for advanced UC treated with pembrolizumab.
Collapse
Affiliation(s)
- Satoru Taguchi
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
- Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan
| | - Taketo Kawai
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Tohru Nakagawa
- Department of Urology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan
| | - Yu Nakamura
- Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan
| | - Jun Kamei
- Department of Urology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Daisuke Obinata
- Department of Urology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Kenya Yamaguchi
- Department of Urology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Tomoyuki Kaneko
- Department of Urology, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo, 173-8605, Japan
| | - Shigenori Kakutani
- Division of Urology, Mitsui Memorial Hospital, 1 Kanda-izumi-cho, Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Mayuko Tokunaga
- Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokozuna, Sumida-ku, Tokyo, 130-8587, Japan
| | - Yukari Uemura
- Biostatistics Section, Department of Data Science, Center of Clinical Sciences, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjyuku-ku, Tokyo, 162-8655, Japan
| | - Yusuke Sato
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Tetsuya Fujimura
- Department of Urology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan
| | - Hiroshi Fukuhara
- Department of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan
| | - Yutaka Enomoto
- Division of Urology, Mitsui Memorial Hospital, 1 Kanda-izumi-cho, Chiyoda-ku, Tokyo, 101-8643, Japan
| | - Hiroaki Nishimatsu
- Department of Urology, The Fraternity Memorial Hospital, 2-1-11 Yokozuna, Sumida-ku, Tokyo, 130-8587, Japan
| | - Satoru Takahashi
- Department of Urology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo, 173-8610, Japan
| | - Haruki Kume
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| |
Collapse
|
12
|
Ito K, Kobayashi T, Kojima T, Hikami K, Yamada T, Ogawa K, Nakamura K, Sassa N, Yokomizo A, Abe T, Tsuchihashi K, Tatarano S, Inokuchi J, Tomida R, Fujiwara M, Takahashi A, Matsumoto K, Shimizu K, Araki H, Kurahashi R, Osaki Y, Tashiro Y, Uegaki M, Ogawa O, Kitamura H, Nishiyama H. Pembrolizumab for treating advanced urothelial carcinoma in patients with impaired performance status: Analysis of a Japanese nationwide cohort. Cancer Med 2021; 10:3188-3196. [PMID: 33931987 PMCID: PMC8124127 DOI: 10.1002/cam4.3863] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 03/04/2021] [Accepted: 03/04/2021] [Indexed: 12/17/2022] Open
Abstract
Background The benefits of pembrolizumab in patients with advanced urothelial carcinoma (UC) and impaired performance status (PS) remain unknown. This study assessed the safety and efficacy of pembrolizumab in patients with platinum‐refractory UC and Eastern Cooperative Oncology Group PS ≥2 to identify which subgroups may benefit from this drug. Methods This retrospective nationwide cohort study collected clinicopathological information for 755 patients from 59 institutions. The overall response rate (ORR) and overall survival (OS) were compared among the patients with PS 0–1, 2, and 3–4. Multivariate analysis was conducted to identify factors predicting OS in patients with PS ≥2. Results The numbers of patients with PS 0–1, 2, and 3–4 were 602, 98, and 55, respectively; the ORRs in these groups were 29.5, 15.3, and 9.1%, respectively, and the median OS times were 14.3, 3.1, and 2.4 months, respectively. In multivariate Cox regression analysis, a neutrophil–lymphocyte ratio (NLR) ≥3.5 (hazard ratio [HR] = 1.897) and liver metastasis (HR = 2.072) were associated with OS in the PS ≥2 subgroup. The median OS of patients with PS ≥2 without either risk factor was 6.8 months, compared with 3.1 months for patients with one risk factor and 2.3 months for patients with both risk factors. Conclusions PS ≥2 portended worse ORR and OS than PS ≤1 despite a comparable safety profile. Among the patients with impaired PS, patients with NLR <3.5 and no liver metastasis may most greatly benefit from pembrolizumab therapy.
Collapse
Affiliation(s)
- Katsuhiro Ito
- Department of Urology, Kyoto University Hospital, Kyoto, Japan.,Department of Urology, Ijinkai Takeda General Hospital, Kyoto, Japan.,Department of Urology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | - Takashi Kobayashi
- Department of Urology, Kyoto University Hospital, Kyoto, Japan.,Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Takahiro Kojima
- Department of Urology, University of Tsukuba, Ibaraki, Japan
| | - Kensuke Hikami
- Department of Urology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
| | - Takeshi Yamada
- Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kosuke Ogawa
- Department of Urology, Kobe City Nishi-Kobe Medical Center, Hyogo, Japan
| | - Kenji Nakamura
- Department of Urology, Japanese Red Cross Osaka Hospital, Osaka, Japan
| | - Naoto Sassa
- Department of Urology, Nagoya University, Aichi, Japan
| | - Akira Yokomizo
- Department of Urology, Harasanshin Hospital, Fukuoka, Japan
| | - Takashige Abe
- Department of Urology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
| | | | | | - Junichi Inokuchi
- Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Ryotaro Tomida
- Department of Urology, Shikoku Cancer Center, Ehime, Japan
| | | | - Atsushi Takahashi
- Department of Urology, Hakodate Goryoukaku Hospital, Hokkaido, Japan
| | | | - Kosuke Shimizu
- Department of Urology, Kyoto Katsura Hospital, Kyoto, Japan
| | - Hiromasa Araki
- Department of Urology, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
| | | | - Yu Osaki
- Department of Urology, National Hospital Organization Himeji Medical Center, Hyogo, Japan
| | - Yu Tashiro
- Department of Urology, Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka, Japan
| | | | - Osamu Ogawa
- Department of Urology, Kyoto University Hospital, Kyoto, Japan.,Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | | | | |
Collapse
|
13
|
Nelson AA, Cronk RJ, Lemke EA, Szabo A, Khaki AR, Diamantopoulos LN, Grivas P, Nezami BG, MacLennan GT, Zhang T, Hoimes CJ. Early Bone Metastases are Associated with Worse Outcomes in Metastatic Urothelial Carcinoma. Bladder Cancer 2021; 7:33-42. [PMID: 38993215 PMCID: PMC11181800 DOI: 10.3233/blc-200377] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Accepted: 12/07/2020] [Indexed: 11/15/2022]
Abstract
BACKGROUND Outcomes of patients with metastatic urothelial carcinoma (mUC) with early bone metastases (eBM) vs no early bone metastases (nBM) have not thoroughly been described in the age of immuno-oncology. OBJECTIVE To compare survival and other clinical outcomes in patients with eBM and nBM. METHODS We used a multi-institutional database of patients with mUC treated with systemic therapy. Demographic, metastatic site, treatment patterns, and clinical outcomes were recorded. Wilcoxon rank-sum, chi-square tests were performed. Survival was estimated by Kaplan-Meier method; multivariable Cox analysis was performed. RESULTS We identified 270 pts, 67% men, mean age 69±11 years. At metastatic diagnosis, 27% had≥1 eBM and were more likely to have de novo vs. recurrent metastases (42% vs 19%, p < 0.001). Patients with eBM had shorter overall survival (OS) vs. those with nBM, (6.1 vs 13.7 months, p < 0.0001). On multivariable analysis, eBM independently associated with higher risk of death, HR = 2.52 (95% CI: 1.75-3.63, p < 0.0001). OS was shorter for patients with eBM who received initial immune checkpoint inhibitor vs platinum-based chemotherapy, (1.6 vs 9.1 months, p = 0.02). Patients with eBM received higher opioid analgesic doses compared to patients with nBM and received quantitatively more palliative radiation. CONCLUSIONS Patients with mUC and eBM have poorer outcomes, may benefit less from anti-PD-1/PD-L1 therapy and represent an unmet need for novel therapeutic interventions. Dedicated clinical trials, biomarker validation to assist in patient selection, as well as consensus on reporting of non-measurable disease are required.
Collapse
Affiliation(s)
- Ariel A. Nelson
- Division of Hematology & Oncology, Department of Medicine, The Medical College of Wisconsin, Milwaukee, WI, USA
- Division of Medical Oncology, Seidman Cancer Center at Case Comprehensive Cancer Center, Cleveland, OH, USA
| | - Robert J. Cronk
- Division of Hematology & Oncology, Department of Medicine, The Medical College of Wisconsin, Milwaukee, WI, USA
| | - Emily A. Lemke
- Division of Hematology & Oncology, Department of Medicine, The Medical College of Wisconsin, Milwaukee, WI, USA
| | - Aniko Szabo
- Division of Biostatistics, The Medical College of Wisconsin, Milwaukee, WI, USA
| | - Ali R. Khaki
- Division of Oncology, Department of Medicine, University of Washington, Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Leonidas N. Diamantopoulos
- Division of Oncology, Department of Medicine, University of Washington, Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Petros Grivas
- Division of Oncology, Department of Medicine, University of Washington, Seattle Cancer Care Alliance, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Behtash Ghazi Nezami
- Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Gregory T. MacLennan
- Department of Pathology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Tian Zhang
- Division of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA
- Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA
| | - Christopher J. Hoimes
- Division of Medical Oncology, Seidman Cancer Center at Case Comprehensive Cancer Center, Cleveland, OH, USA
- Division of Medical Oncology, Department of Medicine, Duke University, Durham, NC, USA
- Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC, USA
| |
Collapse
|
14
|
Bannaga A, Arasaradnam RP. Neutrophil to lymphocyte ratio and albumin bilirubin grade in hepatocellular carcinoma: A systematic review. World J Gastroenterol 2020; 26:5022-5049. [PMID: 32952347 PMCID: PMC7476180 DOI: 10.3748/wjg.v26.i33.5022] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 08/10/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a frequent cause of cancer related death globally. Neutrophil to lymphocyte ratio (NLR) and albumin bilirubin (ALBI) grade are emerging prognostic indicators in HCC.
AIM To study published literature of NLR and ALBI over the last five years, and to validate NLR and ALBI locally in our centre as indicators of HCC survival.
METHODS A systematic review of the published literature on PubMed of NLR and ALBI in HCC over the last five years. The search followed the guidelines of the preferred reporting items for systematic reviews and meta-analyses. Additionally, we also investigated HCC cases between December 2013 and December 2018 in our centre.
RESULTS There were 54 studies describing the relation between HCC and NLR and 95 studies describing the relation between HCC and ALBI grade over the last five years. Our local cohort of patients showed NLR to have a significant negative relationship to survival (P = 0.011). There was also significant inverse relationship between the size of the largest HCC nodule and survival (P = 0.009). Median survival with alpha fetoprotein (AFP) < 10 KU/L was 20 mo and with AFP > 10 KU/L was 5 mo. We found that AFP was inversely related to survival, this relationship was not statically significant (P = 0.132). Mean survival for ALBI grade 1 was 37.7 mo, ALBI grade 2 was 13.4 months and ALBI grade 3 was 4.5 mo. ALBI grades performed better than Child Turcotte Pugh score in detecting death from HCC.
CONCLUSION NLR and ALBI grade in HCC predict survival better than the conventional alpha fetoprotein. ALBI grade performs better than Child Turcotte Pugh score. These markers are done as part of routine clinical care and in cases of normal alpha fetoprotein, these markers could give a better understanding of the patient disease progression. NLR and ALBI grade could have a role in modified easier to learn staging and prognostic systems for HCC.
Collapse
Affiliation(s)
- Ayman Bannaga
- Department of Gastroenterology and Hepatology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, West Midlands, United Kingdom
- Warwick Medical School, University of Warwick, Coventry CV4 7HL, West Midlands, United Kingdom
| | - Ramesh P Arasaradnam
- Department of Gastroenterology and Hepatology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, West Midlands, United Kingdom
- Warwick Medical School, University of Warwick, Coventry CV4 7HL, West Midlands, United Kingdom
| |
Collapse
|
15
|
Yuk HD, Ku JH. Role of Systemic Inflammatory Response Markers in Urothelial Carcinoma. Front Oncol 2020; 10:1473. [PMID: 32974174 PMCID: PMC7471310 DOI: 10.3389/fonc.2020.01473] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 07/10/2020] [Indexed: 12/19/2022] Open
Abstract
Urothelial carcinoma (UC) can occur in various parts of the urinary tract and occurs in different stages and grades. The disease recurs frequently and is monitored through a series of invasive tests, such as cystoscopy or ureteroscopy, over the lifetime of an individual. Although many researchers have attempted to stratify the risks of UC, with the majority being based on cancer characteristics and host factors such as performance status, a risk classification system has yet to be fully developed. Cancer affects various parts of the body through the systemic immune response, including changes in hormones, the number and ratio of white blood cells and platelets, and C-reactive protein (CRP) or albumin levels under the influence of neuroendocrine metabolism, hematopoietic function, and protein and energy metabolism, respectively. Herein, we reviewed various systemic inflammatory response markers (SIRs) related to UC, including CRP, albumin-globulin ratio, albumin, Glasgow prognostic score (GPS), modified GPS, neutrophil-lymphocyte ratio, and platelet-lymphocyte ratio. Our aim was to summarize the role of various SIRs in the treatment of patients with UC.
Collapse
Affiliation(s)
- Hyeong Dong Yuk
- Department of Urology, Seoul National University Hospital, Seoul, South Korea.,College of Medicine, Seoul National University, Seoul, South Korea
| | - Ja Hyeon Ku
- Department of Urology, Seoul National University Hospital, Seoul, South Korea.,College of Medicine, Seoul National University, Seoul, South Korea
| |
Collapse
|
16
|
Zhang L, Li L, Liu J, Wang J, Fan Y, Dong B, Zhu Z, Zhang X. Meta-analysis of multiple hematological biomarkers as prognostic predictors of survival in bladder cancer. Medicine (Baltimore) 2020; 99:e20920. [PMID: 32791672 PMCID: PMC7387011 DOI: 10.1097/md.0000000000020920] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Accumulating emerging studies have demonstrated that systemic inflammation can obviously affect tumor occurrence and progression. Nevertheless, the prognostic value of hematological inflammation biomarkers in bladder cancer is controversial. Thus, we conducted a meta-analysis to evaluate the key hematological biomarkers with various clinical outcomes in bladder cancer. METHODS We used online databases PUBMED and EMBASE to search relevant studies published prior to August 2019. After collecting the basic characteristics and prognostic data from the studies included, overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) were used as primary results. Subgroup analyses were performed according to ethnicity, the number of samples, survival outcomes, the value of cut-off, follow-up time and metastasis stage. RESULTS Thirty-three independent studies with 17,087 bladder cancer patients were added in the present analysis. The collected results showed that the increased neutrophil-to-lymphocyte ratio was associated with a poor OS (hazard ratio [HR] = 1.48, 95% confidence interval [CI]: 1.32-1.67, P < .00001), CSS (HR = 1.71, 95%CI: 1.35-2.18, P < .0001) and PFS (HR = 1.59, 95%CI: 1.38-1.83, P < .00001). Additionally, the elevated platelet-to-lymphocyte ratio was related to a poor OS (HR = 1.29, 95% CI: 1.07-1.54, P = .007), CSS (HR = 1.14, 95%CI = 0.98-1.34, P = .02) and PFS (HR = 1.2, 95%CI: 1.08-1.34, P = .0008). Moreover, a decreased lymphocyte-to-monocyte ratio was associated with a poor OS (HR = 0.77, 95% CI: 0.70-0.84, P = .001), CSS (HR = 0.76, 95%CI: 0.70-0.84). An elevated modified Glasgow prognostic score was also associated with a poor OS (HR = 2.71, 95%CI: 1.08-2.82, P = .003), CSS (HR = 1.50, 95%CI: 0.56-4.05) and PFS (HR = 1.52, 95%CI: 1.23-1.88, P = .001). CONCLUSIONS Our study indicated that the pretreatment hematological biomarkers (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and modified Glasgow prognostic score) were predicative biomarkers of prognosis in bladder cancer patients. Further research is needed to conduct further prospective and multicenter studies to confirm our findings.
Collapse
Affiliation(s)
| | - Longqing Li
- Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR China
| | | | | | | | | | | | | |
Collapse
|
17
|
Suh J, Jung JH, Jeong CW, Kwak C, Kim HH, Ku JH. Clinical Significance of Pre-treated Neutrophil-Lymphocyte Ratio in the Management of Urothelial Carcinoma: A Systemic Review and Meta-Analysis. Front Oncol 2019; 9:1365. [PMID: 31921631 PMCID: PMC6927426 DOI: 10.3389/fonc.2019.01365] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 11/19/2019] [Indexed: 12/13/2022] Open
Abstract
Purpose: We performed a study-level meta-analysis to summarize the current evidence on the correlation between pretreatment neutrophil-to-lymphocyte ratios (NLR) and oncological outcomes in each type of management for urothelial carcinoma. Method: All articles published until February 2017 in PubMed, Scopus, and EMBASE database were collected and reviewed. The current evidence on correlations between pretreatment NLR and oncological outcomes in each type of management for urothelial carcinoma, including transurethral resection of bladder tumor (TURBT), radical cystectomy (RCx), chemotherapy (CTx), and nephroureterectomy (NUx), were summarized. Results: Thirty-eight studies containing clinical information on 16,379 patients were analyzed in this study. Pooled hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals were calculated after weighing each study. Heterogeneity among the studies and publication bias were assessed. Pretreatment NLR was significantly associated with muscle invasiveness (OR: 4.27), recurrence free survival (RFS, HR: 2.32), and progression-free survival (PFS, HR: 2.45) in TURBT patients. In the RCx patients, high NLR was negatively associated with both disease status (extravesical extension and lymph-node positivity, OR: 1.14 and 1.43, respectively) and oncological outcomes [overall survival (OS), PFS], and cancer specific survival (CSS, HR: 1.18, 1.12, and 1.35, respectively). Pretreatment NLR was negatively correlated with pathologic downstaging (OR: 0.79) and positively correlated with PFS (HR: 1.30) and OS (HR: 1.44) in CTx patients. For patients who underwent NUx, pretreatment NLR was significantly associated with OS (HR: 1.72), PFS (HR: 1.63), and CSS (HR: 1.68). Conclusions: Pretreatment NLR is a useful biomarker for disease aggressiveness, oncological outcome, and treatment response in the management of patients with urothelial carcinoma. More evidence is needed to clarify these results.
Collapse
Affiliation(s)
- Jungyo Suh
- Department of Urology, Seoul National University College of Medicine, Seoul, South Korea
- Department of Urology, Seoul Metropolitan Government- Seoul National University Boramae Medical Center, Seoul, South Korea
| | - Jae Hyun Jung
- Department of Urology, Seoul National University College of Medicine, Seoul, South Korea
| | - Chang Wook Jeong
- Department of Urology, Seoul National University College of Medicine, Seoul, South Korea
| | - Cheol Kwak
- Department of Urology, Seoul National University College of Medicine, Seoul, South Korea
| | - Hyeon Hoe Kim
- Department of Urology, Seoul National University College of Medicine, Seoul, South Korea
| | - Ja Hyeon Ku
- Department of Urology, Seoul National University College of Medicine, Seoul, South Korea
| |
Collapse
|
18
|
Chen KH, Tsang NM, Chou WC, Tai SF, Liu SC, Lei KF, Chang KP, Chuang WC, Pai PC. Prognostic significance of pretreatment neutrophil-to-lymphocyte ratio in older patients with metastatic cancer. J Geriatr Oncol 2019; 10:757-762. [PMID: 31085137 DOI: 10.1016/j.jgo.2019.04.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 04/05/2019] [Accepted: 04/20/2019] [Indexed: 01/07/2023]
Abstract
BACKGROUND Treatment options for older patients with malignancies remain suboptimal. An accurate prognostic stratification could inform treatment decisions, which can potentially improve patient outcomes. Here, we sought to investigate whether the neutrophil-to-lymphocyte ratio (NLR) may have prognostic significance in patients with metastatic malignant tumors, with a special focus on older individuals. METHODS We retrospectively reviewed the clinical records of 3981 patients with histology-proven metastatic cancer who underwent radiotherapy between 2000 and 2013. The pretreatment NLR was determined within 7 days before treatment initiation. Patients aged ≥65 years were considered as older. We analyzed the prognostic significance of NLR for overall survival (OS) across all age groups. RESULTS Compared with their younger counterparts, older patients showed a higher NLR (P < 0.001) and a lower OS (P < 0.001). Multivariate analysis revealed that a pretreatment NLR below the median was an independent favorable predictor of OS in both older (hazard ratio [HR]: 0.669, 95.0% CI: 0.605-0.740; P < 0.001) and younger patients (HR: 0.704; 95.0% CI: 0.648-0.765; P < 0.001). Regardless of age, patients who underwent systemic therapy showed more favorable OS, especially when NLR was low. In the older subgroup, the OS of patients with a low pretreatment NLR who did not undergo systemic therapy and of those with high pretreatment NLR who underwent systemic therapy was similar. CONCLUSION A low pretreatment NLR predicts a more favorable OS in older patients with metastatic cancer. The most favorable OS was observed in patients with a low pretreatment NLR who received systemic therapy.
Collapse
Affiliation(s)
| | - Ngan-Ming Tsang
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan
| | - Wen-Chi Chou
- Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taiwan
| | - Shiao Fwu Tai
- Department of Otorhinolaryngology, Linkou Chang Gung Memorial Hospital, Taiwan
| | - Shu-Chen Liu
- Department of Biomedical Sciences and Engineering, National Central University, Taiwan
| | - Kin-Fong Lei
- Graduate Institute of Biomedical Engineering, Chang Gung University, Taiwan
| | - Kai-Ping Chang
- Department of Otolaryngology-Head Neck Surgery, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taiwan
| | | | - Ping-Ching Pai
- Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan.
| |
Collapse
|
19
|
Yoshino Y, Taguchi A, Takao M, Kashiyama T, Furusawa A, Uno M, Okada S, Kino N, Yasugi T. Lymphopenia after induction chemotherapy correlates with incomplete surgical resection in patients with advanced ovarian cancer. Int J Clin Oncol 2018; 24:428-436. [PMID: 30506281 DOI: 10.1007/s10147-018-1374-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2018] [Accepted: 11/27/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Lymphopenia is associated with poor outcomes in patients with various cancers, but little is known about the prognostic impact of lymphopenia in patients with epithelial ovarian cancer (EOC) after induction chemotherapy (IC). This study investigated the prognostic significance of pre- and post-IC lymphopenia in patients with advanced EOC. METHODS We reviewed medical records of 68 patients with stage III/IV ovarian, fallopian tube, or peritoneal cancer treated with IC at our institution between 2009 and 2017. We assessed the associations of pre- and post-IC inflammatory markers, including lymphocyte counts, with several oncological outcomes, such as the implementation of interval debulking surgery (IDS), complete resection, progression-free survival (PFS), and overall survival (OS). RESULTS Lymphocyte counts increased significantly post-IC compared with the pre-IC values (P = 0.009). Pre-IC lymphopenia was observed in 27 patients (40%), whereas only 16 patients (24%) displayed lymphopenia post-IC (P = 0.020). Among several inflammatory markers, only post-IC lymphopenia was significantly associated with incomplete resection outcome during IDS (P = 0.012). Moreover, post-IC lymphopenia was significantly associated with poor PFS (log-rank test, P = 0.009), whereas pre-IC lymphopenia was associated with neither PFS nor OS. CONCLUSIONS Post-IC lymphopenia may predict incomplete resection during IDS and poor prognosis in patients with advanced EOC.
Collapse
Affiliation(s)
- Yasunori Yoshino
- Department of Gynecology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan
| | - Ayumi Taguchi
- Department of Gynecology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.
| | - Maki Takao
- Department of Gynecology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan
| | - Tomoko Kashiyama
- Department of Gynecology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan
| | - Akiko Furusawa
- Department of Gynecology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan
| | - Masaya Uno
- Department of Gynecology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan
| | - Satoshi Okada
- Department of Gynecology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan
| | - Nao Kino
- Department of Gynecology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan
| | - Toshiharu Yasugi
- Department of Gynecology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan
| |
Collapse
|
20
|
Xu N, Jian Y, Wang Y, Tian W. Evaluation of neutrophil-to-lymphocyte ratio and calcitonin concentration for predicting lymph node metastasis and distant metastasis in patients with medullary thyroid cancer. Mol Clin Oncol 2018; 9:629-634. [PMID: 30546892 DOI: 10.3892/mco.2018.1727] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 06/14/2018] [Indexed: 12/18/2022] Open
Abstract
The aim of the present study was to investigate potential predictive factors of lymph node metastasis (LNM) and distant metastasis (DM) of medullary thyroid cancer (MTC). A total of 61 patients newly diagnosed with MTC at the General Hospital of the Chinese People's Liberation Army between January 2001 and January 2016 were enrolled and divided into two groups according to the results of preoperative examinations and surgical histopathology as follows: Group NM (without metastases), and group M (with metastases). Univariate logistic regression analysis demonstrated that sex, tumor size, preoperative peripheral blood neutrophil-to-lymphocyte ratio (NLR), and concentration of carcinoembryonic antigen (CEA) and calcitonin (Ctn), were significantly associated with LNM and DM. The multivariate analysis revealed that a Ctn concentration of >500 pg/ml [odds ratio (OR)=21.422; 95% confidence interval (CI): 2.611-175.731] and the NLR (OR=5.918; 95% CI: 1.147-30.541) were positively correlated with LNM and DM. The optimal cut-off value of the NLR for predicting LNM and DM obtained from receiver operating characteristic curve analysis was 1.784 (sensitivity 68.3% and specificity 80%), and the area under the curve was 0.717. In conclusion, the findings of the present study strongly suggest that inflammation and immune activation of MTC cells promote LNM and DM, and that higher values of NLR and Ctn concentration confer a high risk of metastasis.
Collapse
Affiliation(s)
- Nizhen Xu
- Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, P.R. China
| | - Yanbing Jian
- Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, P.R. China
| | - Yaxi Wang
- Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, P.R. China
| | - Wen Tian
- Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, P.R. China
| |
Collapse
|
21
|
Ohno Y. Role of systemic inflammatory response markers in urological malignancy. Int J Urol 2018; 26:31-47. [PMID: 30253448 DOI: 10.1111/iju.13801] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Accepted: 08/20/2018] [Indexed: 12/14/2022]
Abstract
The systemic inflammatory response is associated with survival in patients with a variety of cancers. This inflammatory response is measured in the peripheral blood, and can be monitored using two categories of indices: concentration of specific serum proteins (albumin, C-reactive protein) and differential blood cell count (neutrophils, lymphocytes and platelets). Furthermore, combinations of these indices, such as the Glasgow Prognostic Score, which consists of the serum C-reactive protein and albumin level; the neutrophil-to-lymphocyte ratio; the platelet-to-lymphocyte ratio; and the prognostic nutritional index, which is based on peripheral blood lymphocyte count and serum albumin level, have also been evaluated and compared in cancer research. To date, there are hundreds of studies that have shown the prognostic value of systemic inflammatory response markers in patients with urological cancer. Most studies have evaluated the prognostic and predictive role of the pretreatment value of the markers, although some have focused on the role of the post-treatment value at specific points during the clinical course. The advantages of systemic inflammatory response markers are that they are easily measurable and inexpensive in the clinical setting. However, it is important to consider how clinicians use these markers in clinical practice. The present review provides a concise overview regarding systemic inflammatory markers in urological cancers, specifically C-reactive protein, Glasgow Prognostic Score/modified Glasgow Prognostic Score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and prognostic nutritional index.
Collapse
Affiliation(s)
- Yoshio Ohno
- Department of Urology, Tokyo Medical University, Tokyo, Japan
| |
Collapse
|
22
|
Morizawa Y, Miyake M, Shimada K, Hori S, Tatsumi Y, Nakai Y, Onishi S, Tanaka N, Konishi N, Fujimoto K. Correlation of Immune Cells and Cytokines in the Tumor Microenvironment with Elevated Neutrophil-To-Lymphocyte Ratio in Blood: An Analysis of Muscle-Invasive Bladder Cancer. Cancer Invest 2018; 36:395-405. [DOI: 10.1080/07357907.2018.1506800] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Affiliation(s)
- Yosuke Morizawa
- Department of Urology, Nara Medical University, Kashihara, Japan
| | - Makito Miyake
- Department of Urology, Nara Medical University, Kashihara, Japan
| | - Keiji Shimada
- Department of Pathology, Nara City Hospital, Nara, Japan
- Department of Pathology, Nara Medical University, Kashihara, Japan
| | - Shunta Hori
- Department of Urology, Nara Medical University, Kashihara, Japan
| | - Yoshihiro Tatsumi
- Department of Urology, Nara Medical University, Kashihara, Japan
- Department of Pathology, Nara Medical University, Kashihara, Japan
| | - Yasushi Nakai
- Department of Urology, Nara Medical University, Kashihara, Japan
| | - Sayuri Onishi
- Department of Urology, Nara Medical University, Kashihara, Japan
| | - Nobumichi Tanaka
- Department of Urology, Nara Medical University, Kashihara, Japan
| | - Noboru Konishi
- Department of Pathology, Nara Medical University, Kashihara, Japan
| | | |
Collapse
|
23
|
Yoshida M, Taguchi A, Kawana K, Ogishima J, Adachi K, Kawata A, Nakamura H, Sato M, Fujimoto A, Inoue T, Tomio K, Mori M, Nagamatsu T, Arimoto T, Koga K, Hiraike OW, Oda K, Kiyono T, Osuga Y, Fujii T. Intraperitoneal neutrophils activated by KRAS-induced ovarian cancer exert antitumor effects by modulating adaptive immunity. Int J Oncol 2018; 53:1580-1590. [PMID: 30066851 PMCID: PMC6086631 DOI: 10.3892/ijo.2018.4504] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 07/04/2018] [Indexed: 12/15/2022] Open
Abstract
Increased neutrophil counts are a hallmark of a poor prognosis for cancer. We previously reported that KRAS promoted tumorigenesis and increased neutrophil counts in a mouse peritoneal cancer model. In the current study, we evaluated the role of increased neutrophils in cancer progression, as well as their influence on the intraperitoneal microenvironment. A mouse peritoneal cancer model was established using the KRAS-transduced mouse ovarian cancer cell line, ID8-KRAS. Neutrophil function was assessed by neutrophil depletion in ID8-KRAS mice. Neutrophil depletion markedly accelerated tumor formation; this was accompanied by an increase in interleukin-6 concentrations in ascites. Neutrophil depletion significantly decreased the amount of local and systemic CD8+ T cells, while increasing the amount of local CD4+ T cells, accompanied by an increased amount of monocytic myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (Tregs) (P<0.05). The roles of peritoneal neutrophils (PENs) in CD8+ T cell activation were assessed in vitro. PENs of ID8-KRAS mice had a strong potential to enhance T cell proliferation with a higher expression of the T cell costimulatory molecules OX40 ligand (OX40L) and 4-1BB ligand (4-1BBL), as compared with peripheral blood neutrophils (PBNs). These findings suggest that neutrophils recruited into the KRAS-induced tumor microenvironment (TME) have antitumor properties with the potential to modulate the numbers of M-MDSCs and Tregs and activate CD8+ T cells through T cell costimulatory molecules.
Collapse
Affiliation(s)
- Mitsuyo Yoshida
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Ayumi Taguchi
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Kei Kawana
- Department of Obstetrics and Gynecology, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
| | - Juri Ogishima
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Katsuyuki Adachi
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Akira Kawata
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Hiroe Nakamura
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Masakazu Sato
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Asaha Fujimoto
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Tomoko Inoue
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Kensuke Tomio
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Mayuyo Mori
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Takeshi Nagamatsu
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Takahide Arimoto
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Kaori Koga
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Osamu Wada Hiraike
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Katsutoshi Oda
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Tohru Kiyono
- Division of Virology, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan
| | - Yutaka Osuga
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| | - Tomoyuki Fujii
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
| |
Collapse
|
24
|
Hsieh MC, Rau KM, Chiang PH, Sung MT, Lan J, Luo HL, Huang CC, Huang CH, Su HYL. Impact of Prognostic Nutritional Index on Overall Survival for Patients with Metastatic Urothelial Carcinoma. J Cancer 2018; 9:2466-2471. [PMID: 30026844 PMCID: PMC6036888 DOI: 10.7150/jca.25061] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2018] [Accepted: 04/17/2018] [Indexed: 12/25/2022] Open
Abstract
Background: Prognostic nutritional index (PNI) has been studied in various types of cancer which is significantly correlated with prognosis. The study aims to investigate the predictive role of PNI in patients with metastatic urothelial carcinoma (mUC) treated with systemic chemotherapy. Methods: We retrospectively reviewed 141 patients with mUC who received systemic chemotherapy. PNI was calculated as 10 × serum albumin concentration (g/dL) + 0.005 × lymphocyte count (number/mm2). The optimal cut-off value for PNI was estimated by using receiver operating curve analysis. Independent factors associated with progression-free survival (PFS) and overall survival (OS) were determined by Cox proportional regression models. Results: The recommended cut-off value for PNI was 40. Patients with a low PNI had more visceral metastases (p < 0.0001), leukocytosis (p = 0.006), and anemia (p < 0.0001). On univariate analysis, patients with a low PNI had poor OS than those with a high PNI (p < 0.0001). The multivariate analysis showed PNI was an independent factor to predict OS (p = 0.001). Conclusions: Our study showed PNI is an independent prognostic factor in patients with mUC. Our work is clinically useful for anticipation of outcomes, risks stratification in clinical studies as well as patients counseling.
Collapse
Affiliation(s)
- Meng-Che Hsieh
- Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taiwan
| | - Kun-Ming Rau
- Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taiwan
| | - Po-Hui Chiang
- Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taiwan
| | - Ming-Tse Sung
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taiwan
| | - Jui Lan
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taiwan
| | - Hao-Lun Luo
- Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taiwan
| | - Chun-Chieh Huang
- Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taiwan
| | - Cheng-Hua Huang
- Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taiwan
| | - Harvey Yu-Li Su
- Division of Hematology Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taiwan.,Clinical Trial Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan
| |
Collapse
|
25
|
Yip SM, Kaiser J, Li H, North S, Heng DY, Alimohamed NS. Real-world Outcomes in Advanced Urothelial Cancer and the Role of Neutrophil to Lymphocyte Ratio. Clin Genitourin Cancer 2018; 16:e637-e644. [DOI: 10.1016/j.clgc.2017.12.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2017] [Revised: 11/30/2017] [Accepted: 12/15/2017] [Indexed: 12/15/2022]
|
26
|
Vano YA, Oudard S, By MA, Têtu P, Thibault C, Aboudagga H, Scotté F, Elaidi R. Optimal cut-off for neutrophil-to-lymphocyte ratio: Fact or Fantasy? A prospective cohort study in metastatic cancer patients. PLoS One 2018; 13:e0195042. [PMID: 29624591 PMCID: PMC5889159 DOI: 10.1371/journal.pone.0195042] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 03/08/2018] [Indexed: 01/04/2023] Open
Abstract
This study assessed the prognostic value of pre-treatment neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic solid tumors. Clinical and biological data for patients with metastatic solid tumors treated in an oncology outpatient department and prospectively followed by a call center (PROCHE program) between January 2008 and December 2011 were analyzed. All patients with an NLR value within 28 days before the first cycle of first-line of chemotherapy were included (cohort 1). To assess influence of chemotherapy line on NLR prognostic value, data from patients treated with later chemotherapy lines were also analyzed (cohort 2). Adjusted multivariate Cox regressions with or without non-linear and time-dependent effects were performed. Optimal NLR cut-off was investigated by time-dependent sensitivity analysis using several indices. There were 317 and 134 patients in cohorts 1 and 2, respectively. Elevated NLR was associated with worse survival (hazard ratio [HR] for death, 1.35 [95% confidence interval 1.19-1.54]; p<0.0001). The optimal NLR cut-off in cohort 1 was dependent on index used and time of assessment: HR values were non-significant at a cut-off of 3.0 (1.34 [0.99-1.32], but significant when the cut-off was 4.0 (1.53 [1.11-2.10]). NLR was linearly related to mortality risk; in subgroup analysis, no significant interaction was found with co-variables or tumor localization overall (cohorts 1+2). Pre-treatment NLR is a useful prognostic tool in patients with metastatic solid tumors, irrespective of primary tumor site, chemotherapy line, age, gender and performance status. However, using an NLR cut-off value for clinical decision-making requires extreme caution.
Collapse
Affiliation(s)
- Yann-Alexandre Vano
- Department of Oncology, Hôpital Européen Georges Pompidou, Paris, France
- University of Paris 5 Descartes, Paris, France
- Cancer Immune control and Escape, UMRS1138, Cordeliers Research Center, Paris, France
- * E-mail:
| | - Stéphane Oudard
- Department of Oncology, Hôpital Européen Georges Pompidou, Paris, France
- University of Paris 5 Descartes, Paris, France
- Angiogenesis and Immunotherapy laboratory, PARCC, INSERM U970, team 10, Paris, France
| | - Marie-Agnès By
- Department of Oncology, Centre Hospitalier Universitaire Bretonneau, Tours, France
| | - Pauline Têtu
- Department of Oncology, Hôpital Européen Georges Pompidou, Paris, France
- University of Paris 5 Descartes, Paris, France
| | - Constance Thibault
- Department of Oncology, Hôpital Européen Georges Pompidou, Paris, France
- University of Paris 5 Descartes, Paris, France
| | - Hail Aboudagga
- University of Paris 5 Descartes, Paris, France
- Department of Pharmacy, Hôpital Européen Georges Pompidou, Paris, France
| | - Florian Scotté
- Department of Oncology, Hôpital Européen Georges Pompidou, Paris, France
- University of Paris 5 Descartes, Paris, France
| | - Reza Elaidi
- Association pour la Recherche de Thérapeutiques Innovantes en Cancérologie, Department of Oncology, Hôpital Européen Georges Pompidou, Paris, France
| |
Collapse
|
27
|
Murata H, Koyama K, Takezawa Y, Nishigaki Y. Baseline neutrophil-to-lymphocyte ratio predicts the prognosis of castration-resistant prostate cancer treated with abiraterone acetate. Mol Clin Oncol 2018; 8:592-594. [PMID: 29541468 DOI: 10.3892/mco.2018.1562] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2017] [Accepted: 12/28/2017] [Indexed: 02/03/2023] Open
Abstract
Abiraterone acetate (AA), a CYP17 inhibitor, now has a crucial role in the treatment of castration-resistant prostate cancer (CRPC), and previous studies have reported several prognostic clinical factors for AA treatment. The neutrophil-to-lymphocyte ratio (NLR) has also been investigated for a CRPC treatments in a few reports, however it has not been identified to be a prognostic factor for AA treatment in Japanese patients. The present study aimed to assess the association of the baseline NLR with the overall survival (OS) in CPRC patients treated by AA. The present study retrospectively reviewed a total of 90 consecutive patients with CRPC treated with AA from 2011 to 2016 at Yokohama City University Medical Center and National Cancer Center Hospital East. The primary endpoint of the study was the OS, which was defined as the survival from the start of AA administration. The secondary endpoint was the prostate-specific antigen (PSA) response. PSA response was defined as a reduction in antigen levels of >50%. Complete blood cell counts were performed, and the NLR was calculated using the neutrophil and lymphocyte counts obtained on the same day or a few days prior to the initiation of AA therapy. The NLR cut-off point was determined to be 3.76 for the OS, and divided into the high NLR group of 34 patients and the low NLR group of 56 patients. A PSA response was obtained in 8 patients (23.5%) in the high NLR group and in 24 (42.9%) in the low NLR group. The difference of PSA response between the two groups was significant (P=0.037). Kaplan-Meier curves demonstrated that a high NLR [NLR ≥3.76; median OS: 8.4 months; 95% confidence interval (CI): 6.325-10.475 months] was correlated with a risk of mortality compared with a low NLR (NLR <3.76; median OS not reached). A multivariate analysis demonstrated that the NLR was an independent predictor for the OS (hazard ratio: 2.682; 95% CI: 1.143-6.293; P=0.023). The findings suggest that the NLR may be a useful novel biomarker for predicting the prognosis of CRPC patients treated with AA.
Collapse
Affiliation(s)
- Hiroaki Murata
- Department Orthopaedics, Matsushita Memorial Hospital, Moriguchi, Osaka 570-8540, Japan
| | - Kenzou Koyama
- Department Orthopaedics, Matsushita Memorial Hospital, Moriguchi, Osaka 570-8540, Japan
| | - Yasunobu Takezawa
- Department Orthopaedics, Matsushita Memorial Hospital, Moriguchi, Osaka 570-8540, Japan
| | - Yasunori Nishigaki
- Department Orthopaedics, Matsushita Memorial Hospital, Moriguchi, Osaka 570-8540, Japan
| |
Collapse
|
28
|
Tan YG, Eu EWC, Huang HH, Lau WKO. High neutrophil-to-lymphocyte ratio predicts worse overall survival in patients with advanced/metastatic urothelial bladder cancer. Int J Urol 2017; 25:232-238. [DOI: 10.1111/iju.13480] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Accepted: 09/15/2017] [Indexed: 01/04/2023]
Affiliation(s)
- Yu Guang Tan
- Department of Urology; Singapore General Hospital; Singapore
| | | | - Hong Hong Huang
- Department of Urology; Singapore General Hospital; Singapore
| | | |
Collapse
|
29
|
The clinical use of neutrophil-to-lymphocyte ratio in bladder cancer patients: a systematic review and meta-analysis. Int J Clin Oncol 2017; 22:817-825. [PMID: 28752351 DOI: 10.1007/s10147-017-1171-5] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 07/20/2017] [Indexed: 01/10/2023]
Abstract
The aim of this study was to evaluate the evidence regarding the neutrophil-to-lymphocyte ratio (NLR) as a factor predictive of survival in bladder cancer patients. A search of PubMed and Embase for relevant studies between January 1, 1966 and November 10, 2016 was performed with the terms [NLR OR (neutrophil lymphocyte ratio)] AND [(bladder cancer) OR BCa OR NMIBC OR MIBC]. Inclusion required studies published in English containing bladder cancer patients and evaluating NLR as a predictive factor. Endpoints of NLR and survival data were extracted for pooled analysis. The pooled results showed that an elevated NLR was a predictor for poor overall survival (OS) [hazard ratio (HR) = 1.19, 95% confidence interval (CI) 1.07-1.31], cancer-specific survival (CSS) (HR = 1.40, 95% CI 1.17-1.69), recurrence-free survival (RFS) (HR = 1.58, 95% CI 1.24-2.03) and progression-free survival (PFS) (HR = 1.33, 95% CI 1.19-1.49) in patients with bladder cancer. Heterogeneity between studies was observed for OS, CSS and RFS, but not for PFS. Publication bias was detected for all these outcomes. Our results showed that elevated NLR might be valuable as a predictive factor of survival in bladder cancer patients.
Collapse
|
30
|
Mei Z, Shi L, Wang B, Yang J, Xiao Z, Du P, Wang Q, Yang W. Prognostic role of pretreatment blood neutrophil-to-lymphocyte ratio in advanced cancer survivors: A systematic review and meta-analysis of 66 cohort studies. Cancer Treat Rev 2017; 58:1-13. [PMID: 28602879 DOI: 10.1016/j.ctrv.2017.05.005] [Citation(s) in RCA: 196] [Impact Index Per Article: 24.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 05/15/2017] [Accepted: 05/18/2017] [Indexed: 12/13/2022]
|
31
|
Prognostic Value of Baseline Neutrophil-to-Lymphocyte Ratio in Metastatic Urothelial Carcinoma Patients Treated With First-line Chemotherapy: A Large Multicenter Study. Clin Genitourin Cancer 2017; 15:e469-e476. [DOI: 10.1016/j.clgc.2016.10.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Revised: 10/20/2016] [Accepted: 10/29/2016] [Indexed: 01/04/2023]
|
32
|
Yoshida T, Kinoshita H, Yoshida K, Mishima T, Yanishi M, Komai Y, Sugi M, Murota T, Kawa G, Matsuda T. Perioperative change in neutrophil–lymphocyte ratio predicts the overall survival of patients with bladder cancer undergoing radical cystectomy. Jpn J Clin Oncol 2016; 46:1162-1167. [DOI: 10.1093/jjco/hyw129] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 08/16/2016] [Accepted: 08/17/2016] [Indexed: 12/13/2022] Open
|
33
|
Marchioni M, Primiceri G, Ingrosso M, Filograna R, Castellan P, De Francesco P, Schips L. The Clinical Use of the Neutrophil to Lymphocyte Ratio (NLR) in Urothelial Cancer: A Systematic Review. Clin Genitourin Cancer 2016; 14:473-484. [DOI: 10.1016/j.clgc.2016.04.008] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 04/09/2016] [Accepted: 04/11/2016] [Indexed: 02/07/2023]
|
34
|
Ojerholm E, Smith A, Hwang WT, Baumann BC, Tucker KN, Lerner SP, Mamtani R, Boursi B, Christodouleas JP. Neutrophil-to-lymphocyte ratio as a bladder cancer biomarker: Assessing prognostic and predictive value in SWOG 8710. Cancer 2016; 123:794-801. [PMID: 27787873 DOI: 10.1002/cncr.30422] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Revised: 09/12/2016] [Accepted: 10/03/2016] [Indexed: 12/18/2022]
Abstract
BACKGROUND Risk stratification is a major challenge in bladder cancer (BC), and a biomarker is needed. Multiple studies have reported the neutrophil-to-lymphocyte ratio (NLR) as a promising candidate; however, these analyses have methodological limitations. Therefore, the authors performed a category B biomarker study to test whether NLR is prognostic for overall survival (OS) after curative treatment or is predictive for the survival benefit from neoadjuvant chemotherapy (NAC). METHODS This study is an unplanned secondary analysis of SWOG 8710, a randomized phase 3 trial that assessed cystectomy with or without NAC in 317 patients with muscle-invasive BC. NLR was calculated from prospectively collected complete blood counts. For the prognostic analysis, 230 patients were identified; for the predictive analysis, 263 were identified. NLR was evaluated with proportional hazards models including prespecified factors (age, sex, T-stage, lymphovascular invasion, and treatment arm). RESULTS With a median follow-up of 18.6 years, there were 172 and 205 deaths in the prognostic and predictive cohorts, respectively. In a multivariable analysis, NLR was not prognostic for OS (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.98-1.11; P = .24). Furthermore, NLR did not predict for the OS benefit from NAC (HR, 1.01; 95% CI, 0.90-1.14; P = .86). Factors associated with worse OS were older age (HR, 1.05; 95% CI, 1.04-1.07; P < .001) and surgery without NAC (HR, 1.39; 95% CI, 1.03-1.88; P = .03). CONCLUSIONS This is the first analysis of NLR in BC to use prospectively collected clinical trial data. In contrast to previous studies, it suggests that NLR is neither a prognostic nor predictive biomarker for OS in muscle-invasive BC. Cancer 2017;123:794-801. © 2016 American Cancer Society.
Collapse
Affiliation(s)
- Eric Ojerholm
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Andrew Smith
- Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Wei-Ting Hwang
- Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Brian C Baumann
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Kai N Tucker
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | | | - Ronac Mamtani
- Medical Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Ben Boursi
- Medical Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - John P Christodouleas
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| |
Collapse
|
35
|
Yoshida M, Taguchi A, Kawana K, Adachi K, Kawata A, Ogishima J, Nakamura H, Fujimoto A, Sato M, Inoue T, Nishida H, Furuya H, Tomio K, Arimoto T, Koga K, Wada-Hiraike O, Oda K, Nagamatsu T, Kiyono T, Osuga Y, Fujii T. Modification of the Tumor Microenvironment in KRAS or c-MYC-Induced Ovarian Cancer-Associated Peritonitis. PLoS One 2016; 11:e0160330. [PMID: 27483433 PMCID: PMC4970724 DOI: 10.1371/journal.pone.0160330] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Accepted: 07/18/2016] [Indexed: 12/15/2022] Open
Abstract
The most common properties of oncogenes are cell proliferation and the prevention of apoptosis in malignant cells, which, as a consequence, induce tumor formation and dissemination. However, the effects of oncogenes on the tumor microenvironment (TME) have not yet been examined in detail. The accumulation of ascites accompanied by chronic inflammation and elevated concentrations of VEGF is a hallmark of the progression of ovarian cancer. We herein demonstrated the mechanisms by which oncogenes contribute to modulating the ovarian cancer microenvironment. c-MYC and KRAS were transduced into the mouse ovarian cancer cell line ID8. ID8, ID8-c-MYC, or ID8-KRAS cells were then injected into the peritoneal cavities of C57/BL6 mice and the production of ascites was assessed. ID8-c-MYC and ID8-KRAS both markedly accelerated ovarian cancer progression in vivo, whereas no significant differences were observed in proliferative activity in vitro. ID8-KRAS in particular induced the production of ascites, which accumulated between approximately two to three weeks after the injection, more rapidly than ID8 and ID8-c-MYC (between nine and ten weeks and between six and seven weeks, respectively). VEGF concentrations in ascites significantly increased in c-MYC-induced ovarian cancer, whereas the concentrations of inflammatory cytokines in ascites were significantly high in KRAS-induced ovarian cancer and were accompanied by an increased number of neutrophils in ascites. A cytokine array revealed that KRAS markedly induced the expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in ID8 cells. These results suggest that oncogenes promote cancer progression by modulating the TME in favor of cancer progression.
Collapse
Affiliation(s)
- Mitsuyo Yoshida
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Ayumi Taguchi
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Kei Kawana
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
- * E-mail:
| | - Katsuyuki Adachi
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Akira Kawata
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Juri Ogishima
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Hiroe Nakamura
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Asaha Fujimoto
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Masakazu Sato
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Tomoko Inoue
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Haruka Nishida
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Hitomi Furuya
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Kensuke Tomio
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Takahide Arimoto
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Kaori Koga
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Osamu Wada-Hiraike
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Katsutoshi Oda
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Takeshi Nagamatsu
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Tohru Kiyono
- Division of Virology, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104–0045, Japan
| | - Yutaka Osuga
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| | - Tomoyuki Fujii
- Department of Obstetrics and Gynecology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113–8655, Japan
| |
Collapse
|
36
|
Hsieh MC, Huang CH, Chiang PH, Chen YY, Tang Y, Su YL. Tailored Selection of First-Line Cisplatin-Based Chemotherapy in Patients with Metastatic Urothelial Carcinoma of Bladder. J Cancer 2016; 7:1347-52. [PMID: 27390610 PMCID: PMC4934043 DOI: 10.7150/jca.15213] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2016] [Accepted: 05/24/2016] [Indexed: 01/04/2023] Open
Abstract
Purpose: Methotrexate, vinblastine, doxorubicin plus cisplatin (MVAC) and gemcitabine plus cisplatin (GC) are both effective first-line chemotherapy. We explore the responsive variables of MVAC and GC for patients with metastatic urothelial carcinoma of bladder (mUCB). Materials and Methods: Patients who were initially diagnosed to have mUCB and received MVAC or GC as metastatic first-line chemotherapy between 2000 and 2014 at Kaohsiung Chang Gung Memorial Hospital were reviewed. Totally, 130 patients were enrolled into our study. Univariable Cox proportional hazard models were constructed for OS. Hazard ratio (HR) and 95% confidence intervals (CIs) was also presented. Results: There were 50 patients (38%) in the MVAC group and 80 patients (62%) in the GC group. The median OS was insignificantly different between MVAC and GC groups, accounting for 17.0 and 14.4 months (P = 0.214), respectively. OS of MVAC group was significantly longer with regard to age ≦ 60 years (HR: 0.38, 95% CI: 0.12-0.97, P = 0.036), pure urothelial carcinoma (HR: 0.56, 95% CI: 0.34-0.90, P = 0.015), > 1 metastatic sites (HR: 0.19, 95% CI: 0.08-0.44, P = < 0.001), and neutrophil to lymphocyte ratio > 3(HR: 0.45, 95% CI: 0.25-0.81, P = 0.006), while OS with GC group was significantly longer with regard to variant urothelial carcinoma (HR: 0.56, 95% CI: 0.34-0.90, P = 0.015). Conclusions: Our study disclosed the predictive factors of different regimen for mUCB. These results have clinical implication for physicians who treat patients with mUCB.
Collapse
Affiliation(s)
- Meng-Che Hsieh
- 1. Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Cheng-Hua Huang
- 1. Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Po-Hui Chiang
- 2. Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yen-Yang Chen
- 1. Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yeh Tang
- 3. Division of Hematology-Oncology, Department of Internal Medicine, E-Da hospital, Kaohsiung, Taiwan
| | - Yu-Li Su
- 1. Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| |
Collapse
|
37
|
Li X, Ma X, Tang L, Wang B, Chen L, Zhang F, Zhang X. Prognostic value of neutrophil-to-lymphocyte ratio in urothelial carcinoma of the upper urinary tract and bladder: a systematic review and meta-analysis. Oncotarget 2016; 8:62681-62692. [PMID: 28977980 PMCID: PMC5617540 DOI: 10.18632/oncotarget.17467] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 02/20/2017] [Indexed: 12/11/2022] Open
Abstract
The neutrophil-to-lymphocyte ratio (NLR) is an inflammation marker that has prognostic value for various tumors, but its prognostic value in urothelial carcinoma (UC) remains controversial. This meta-analysis investigated the prognostic value of NLR in UC. A systematic search was performed on PubMed, ISI Web of Science, and Embase for studies focusing on the association between NLR and clinical features or prognosis of UC and published until November 2016. Prognostic outcomes and clinical features were collected and analyzed. A total of 11,538 patients from 32 studies were included in the meta-analysis. Increased pretreatment NLR predicted poor overall survival (hazard ratio [HR] = 1.72, 95% confidence interval [CI] = 1.45–2.05), progression free survival (HR = 1.68, 95% CI = 1.44–1.96), and cancer specific survival (HR = 1.64, 95% CI = 1.39–1.93) in all the patients. The increased pretreatment NLR was correlated with increased lymphovascular invasion (HR = 1.29, 95% CI = 1.17–1.43), high tumor T stage (HR = 1.25, 95% CI = 1.12–1.39), and tumor grade (HR = 1.07, 95% CI = 1.01–1.14) but not with lymph node involvement, carcinoma in situ, multifocality, or positive margin. Our meta-analysis indicated that NLR could predict the prognosis for UC and was associated with UC progression in terms of lymphovascular invasion, tumor T stage, and tumor grade.
Collapse
Affiliation(s)
- Xintao Li
- Department of Urology, State Key Laboratory of Kidney Disease, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Xin Ma
- Department of Urology, State Key Laboratory of Kidney Disease, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Lu Tang
- Department of Urology, State Key Laboratory of Kidney Disease, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Baojun Wang
- Department of Urology, State Key Laboratory of Kidney Disease, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Luyao Chen
- Department of Urology, State Key Laboratory of Kidney Disease, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Fan Zhang
- Department of Urology, State Key Laboratory of Kidney Disease, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Xu Zhang
- Department of Urology, State Key Laboratory of Kidney Disease, Chinese PLA Medical Academy, Chinese People's Liberation Army General Hospital, Beijing, China
| |
Collapse
|
38
|
Morizawa Y, Miyake M, Shimada K, Hori S, Tatsumi Y, Nakai Y, Anai S, Tanaka N, Konishi N, Fujimoto K. Neutrophil-to-lymphocyte ratio as a detection marker of tumor recurrence in patients with muscle-invasive bladder cancer after radical cystectomy. Urol Oncol 2016; 34:257.e11-7. [PMID: 27038696 DOI: 10.1016/j.urolonc.2016.02.012] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Revised: 01/28/2016] [Accepted: 02/06/2016] [Indexed: 12/20/2022]
Abstract
PURPOSE High-neutrophil to lymphocyte ratio (NLR) values have been shown to be associated with a poor prognosis in many human malignant tumors. We evaluated the correlation of the NLR with other variables in patients with muscle-invasive bladder cancer after radical cystectomy (RC); in particular, we evaluated chronological changes in the postoperative NLR. METHODS We included the data from a total of 110 patients who underwent RC for muscle-invasive bladder cancer. The NLR was calculated using complete blood counts determined before RC. Kaplan-Meier and Cox proportional regression analyses of recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were performed to identify significant prognostic variables. RESULTS The median patient age was 72 years (41-91 years). In univariate analysis, the pretreatment NLR (≥2.6 vs.<2.6) was associated with RFS (hazard ratio [HR] = 2.41, P = 0.008), CSS (HR = 2.89, P = 0.006), and OS (HR = 2.73, P = 0.002). In multivariate analysis, an NLR≥2.6 and an infiltrative growth pattern at the tumor invasion front were significantly associated with RFS (HR = 2.61, P = 0.023), CSS (HR = 2.58, P = 0.08), and OS (HR = 2.77, P = 0.004). Postoperative chronological analysis revealed that the NLR of 68 patients without recurrence remained low during follow-up, whereas the NLR of the remaining 42 patients with recurrence increased significantly in the last visit before recurrence was detected radiographically (P< 0.01). CONCLUSIONS The NLR and tumor growth pattern were strong predictors of prognosis for patients undergoing RC. Our results suggest that an increase in the NLR during follow-up after RC is a potential marker for the early detection of recurrence.
Collapse
Affiliation(s)
| | - Makito Miyake
- Department of Urology, Nara Medical University, Nara, Japan
| | - Keiji Shimada
- Department of Pathology, Nara Medical University, Nara, Japan
| | - Shunta Hori
- Department of Urology, Nara Medical University, Nara, Japan
| | - Yoshihiro Tatsumi
- Department of Urology, Nara Medical University, Nara, Japan; Department of Pathology, Nara Medical University, Nara, Japan
| | - Yasushi Nakai
- Department of Urology, Nara Medical University, Nara, Japan
| | - Satoshi Anai
- Department of Urology, Nara Medical University, Nara, Japan
| | | | - Noboru Konishi
- Department of Pathology, Nara Medical University, Nara, Japan
| | | |
Collapse
|
39
|
Taguchi S, Akamatsu N, Nakagawa T, Gonoi W, Kanatani A, Miyazaki H, Fujimura T, Fukuhara H, Kume H, Homma Y. Sarcopenia Evaluated Using the Skeletal Muscle Index Is a Significant Prognostic Factor for Metastatic Urothelial Carcinoma. Clin Genitourin Cancer 2015; 14:237-43. [PMID: 26337653 DOI: 10.1016/j.clgc.2015.07.015] [Citation(s) in RCA: 67] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Accepted: 07/30/2015] [Indexed: 01/04/2023]
Abstract
BACKGROUND The purpose of the study was to evaluate the prognostic value of sarcopenia (muscle loss) in patients with metastatic urothelial carcinoma (UC), in a comparison of several methods of computed tomography (CT)-based evaluation of sarcopenia. PATIENTS AND METHODS We retrospectively reviewed 100 patients with metastatic UC who underwent first-line systemic chemotherapy between 2003 and 2014. Sarcopenia was assessed by the following CT-based methods: skeletal muscle index (SMI), total psoas area (TPA), axial and/or transversal psoas thickness at the level of the third lumbar vertebrae, and axial and/or transversal psoas thickness at the umbilicus level (U-TPT). All parameters were standardized by either height or height squared. Cutoff points were SMI: < 55 cm(2)/m(2) (men), < 39 cm(2)/m(2) (women); others: lowest sex-specific quartiles. Predictive values for cancer-specific survival (CSS) were assessed using the Cox proportional hazards regression model. RESULTS Sixty-four patients met the eligibility criterion for analysis: those who underwent CT scans within 30 days before chemotherapy. Of them, 52 (81%) died of UC during the follow-up, with a median survival time of 13 months. Univariate analysis associated decreased SMI, TPA, and U-TPT with poor CSS. Multivariate analysis together with other pretreatment clinicopathologic parameters showed decreased SMI to be an independent predictor of poor CSS. CONCLUSION Evaluation using SMI showed sarcopenia was an independent predictor of poor prognosis for patients with metastatic UC who underwent first-line systemic chemotherapy. Our results might improve stratification of patients and help optimize evaluation of sarcopenia.
Collapse
Affiliation(s)
- Satoru Taguchi
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Nobuhiko Akamatsu
- Department of Radiology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Tohru Nakagawa
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
| | - Wataru Gonoi
- Department of Radiology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Atsushi Kanatani
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Hideyo Miyazaki
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Tetsuya Fujimura
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Hiroshi Fukuhara
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Haruki Kume
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| | - Yukio Homma
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
| |
Collapse
|
40
|
Taguchi S, Nakagawa T, Uemura Y, Matsumoto A, Nagase Y, Kawai T, Tanaka Y, Yoshida K, Yamamoto S, Enomoto Y, Nose Y, Sato T, Ishikawa A, Fujimura T, Fukuhara H, Kume H, Homma Y. Validation of major prognostic models for metastatic urothelial carcinoma using a multi-institutional cohort of the real world. World J Urol 2015; 34:163-71. [PMID: 26135306 DOI: 10.1007/s00345-015-1631-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Accepted: 06/23/2015] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Several prognostic models predicting survival of patients with metastatic urothelial carcinoma (UC) have been developed; however, of them, the first model by Bajorin in 1999 is still the most representative and widely used, and validations of newer models are lacking. This study aimed to validate three major prognostic models for metastatic UC constructed based on clinical trials. METHODS We reviewed 200 patients with metastatic UC who received first-line chemotherapy at our five affiliate institutions between 2003 and 2011. Using this multi-institutional cohort, we validated the following models: the "Bajorin model," a model consisting of visceral metastasis and performance status; the "Apolo model," a nomogram including visceral metastasis, performance status, albumin and hemoglobin; and the "Galsky model," a nomogram including leukocyte count, number of sites of visceral metastases, site of primary tumor, performance status and lymph node metastasis. Harrell's c-index was calculated for each model. Cox proportional hazards regression model was used for multivariate analysis. RESULTS Among 200 patients, 171 (85.5%) died during the follow-up, with a median survival of 12.0 months. Multivariate analysis demonstrated ECOG performance status, visceral metastasis and leukocyte count to be independent predictors of overall survival. C-index results (95% confidence interval) were Bajorin: 0.86 (0.74-0.95); Apolo: 0.89 (0.78-0.98); and Galsky: 0.82 (0.69-0.93). CONCLUSIONS All models were demonstrated to have high external validities in real-world patients, and of them, the "Apolo model" achieved the highest c-index in the present population. Further studies with larger populations are needed for establishment of the next standard model.
Collapse
Affiliation(s)
- Satoru Taguchi
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Tohru Nakagawa
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Yukari Uemura
- Central Coordinating Unit, Biostatistics Division, Clinical Research Support Center, The University of Tokyo Hospital, Tokyo, Japan
| | - Akihiko Matsumoto
- Department of Urology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan
| | - Yasushi Nagase
- Department of Urology, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan
| | - Taketo Kawai
- Department of Urology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Yoshinori Tanaka
- Department of Urology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Kanae Yoshida
- Division of Urology, Mitsui Memorial Hospital, Tokyo, Japan
| | - Sachi Yamamoto
- Division of Urology, Mitsui Memorial Hospital, Tokyo, Japan
| | - Yutaka Enomoto
- Division of Urology, Mitsui Memorial Hospital, Tokyo, Japan
| | - Yorito Nose
- Department of Urology, Tokyo Teishin Hospital, Tokyo, Japan
| | - Toshikazu Sato
- Department of Urology, Tokyo Teishin Hospital, Tokyo, Japan
| | - Akira Ishikawa
- Department of Urology, Tokyo Teishin Hospital, Tokyo, Japan
| | - Tetsuya Fujimura
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hiroshi Fukuhara
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Haruki Kume
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Yukio Homma
- Department of Urology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| |
Collapse
|
41
|
Mitsui Y. Editorial Comment to Pretreatment neutrophil-to-lymphocyte ratio as an independent predictor of survival in patients with metastatic urothelial carcinoma: A multi-institutional study. Int J Urol 2015; 22:643-4. [PMID: 25903446 DOI: 10.1111/iju.12772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Accepted: 02/26/2015] [Indexed: 11/30/2022]
Affiliation(s)
- Yozo Mitsui
- Department of Urology, Shimane University Faculty of Medicine, Izumo, Japan.
| |
Collapse
|