Skip to main content
Erschienen in: Targeted Oncology 2/2019

29.03.2019 | Original Research Article

Prognostic Markers for Refined Stratification of IMDC Intermediate-Risk Metastatic Clear Cell Renal Cell Carcinoma Treated with First-Line Tyrosine Kinase Inhibitor Therapy

verfasst von: Toshio Takagi, Hironori Fukuda, Tsunenori Kondo, Hiroki Ishihara, Kazuhiko Yoshida, Hirohito Kobayashi, Junpei Iizuka, Masayoshi Okumi, Hideki Ishida, Kazunari Tanabe

Erschienen in: Targeted Oncology | Ausgabe 2/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

Patients in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate-risk group have heterogeneous prognoses and thus may benefit from improved risk stratification.

Objective

The aim of this study was to analyze inflammatory parameters such as C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) as prognostic markers for IMDC intermediate-risk patients.

Methods

Patients with metastatic clear cell renal cell carcinoma (n = 71) with IMDC intermediate risk who received tyrosine kinase inhibitors as first-line therapy were included in this retrospective study. Multivariate Cox regression analyses were performed to identify prognostic factors for overall survival (OS).

Results

As first-line systemic therapy, 46 (65%), 19 (27%), and 6 (8%) patients received sunitinib, sorafenib, and pazopanib, respectively. An IMDC prognostic score of 1 and 2 were observed in 34 (48%) and 37 (52%) patients, respectively. Mean CRP level was 1.06 mg/dL, and mean NLR was 3.0. Multivariate Cox regression revealed several factors significantly associated with poor OS, including NLR ≥ 3 (vs NLR < 3; hazard ratio [HR] 2.57; p = 0.0228), CRP level ≥ 1 mg/dL (vs CRP < 1 mg/dL; HR 2.89; p = 0.0279), and two or more metastatic organs (vs one organ; HR 3.77; p = 0.0008). Using these risk factors, patients were stratified into the following three risk categories: F0 (no prognostic factors; n = 20), in which the median OS (mOS) was not achieved; F1 (1 prognostic factor; n = 31), in which the mOS was 31 months; and F2–3 (2 or 3 prognostic factors; n = 20) in which the mOS was 13 months (log-rank p < 0.0001).

Conclusion

CRP, NLR, and the number of metastatic organs were independent prognostic factors in IMDC intermediate-risk patients.
Literatur
1.
Zurück zum Zitat Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase ii trial. J Clin Oncol. 2015;33(13):1430–7.CrossRefPubMed Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase ii trial. J Clin Oncol. 2015;33(13):1430–7.CrossRefPubMed
2.
Zurück zum Zitat Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–90.CrossRefPubMedPubMedCentral Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–90.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Powles T, Albiges L, Staehler M, et al. Updated European Association of Urology guidelines recommendations for the treatment of first-line metastatic clear cell renal cancer. Eur Urol. 2018;73(3):311–5.CrossRefPubMed Powles T, Albiges L, Staehler M, et al. Updated European Association of Urology guidelines recommendations for the treatment of first-line metastatic clear cell renal cancer. Eur Urol. 2018;73(3):311–5.CrossRefPubMed
6.
Zurück zum Zitat Takamatsu K, Mizuno R, Omura M, et al. Prognostic value of baseline serum c-reactive protein level in intermediate-risk group patients with metastatic renal-cell carcinoma treated by first-line vascular endothelial growth factor-targeted therapy. Clin Genitourin Cancer. 2018;16(4):e927–33.CrossRefPubMed Takamatsu K, Mizuno R, Omura M, et al. Prognostic value of baseline serum c-reactive protein level in intermediate-risk group patients with metastatic renal-cell carcinoma treated by first-line vascular endothelial growth factor-targeted therapy. Clin Genitourin Cancer. 2018;16(4):e927–33.CrossRefPubMed
7.
Zurück zum Zitat Sella A, Michaelson MD, Matczak E, Simantov R, Lin X, Figlin RA. Heterogeneity of patients with intermediate-prognosis metastatic renal cell carcinoma treated with sunitinib. Clin Genitourin Cancer. 2017;15(2):291.e291–299.e291.CrossRef Sella A, Michaelson MD, Matczak E, Simantov R, Lin X, Figlin RA. Heterogeneity of patients with intermediate-prognosis metastatic renal cell carcinoma treated with sunitinib. Clin Genitourin Cancer. 2017;15(2):291.e291–299.e291.CrossRef
8.
Zurück zum Zitat Semeniuk Wojtaś A, Lubas A, Stec R, Syryło T, Niemczyk S, Szczylik C. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and C-reactive protein as new and simple prognostic factors in patients with metastatic renal cell cancer treated with tyrosine kinase inhibitors: a systemic review and meta-analysis. Clin Genitourin Cancer. 2018;16(3):e685–93.CrossRefPubMed Semeniuk Wojtaś A, Lubas A, Stec R, Syryło T, Niemczyk S, Szczylik C. Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and C-reactive protein as new and simple prognostic factors in patients with metastatic renal cell cancer treated with tyrosine kinase inhibitors: a systemic review and meta-analysis. Clin Genitourin Cancer. 2018;16(3):e685–93.CrossRefPubMed
9.
Zurück zum Zitat Sobin LH, Compton CC. TNM seventh edition: what’s new, what’s changed: communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer. 2010;116(22):5336–9.CrossRefPubMed Sobin LH, Compton CC. TNM seventh edition: what’s new, what’s changed: communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer. 2010;116(22):5336–9.CrossRefPubMed
10.
Zurück zum Zitat Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982;6(7):655–63.CrossRefPubMed Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982;6(7):655–63.CrossRefPubMed
11.
Zurück zum Zitat Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular tumours. Eur Urol. 2016;70(1):93–105.CrossRefPubMed Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM. The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular tumours. Eur Urol. 2016;70(1):93–105.CrossRefPubMed
12.
Zurück zum Zitat Heng DY, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol. 2009;27(34):5794–9.CrossRefPubMed Heng DY, Xie W, Regan MM, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol. 2009;27(34):5794–9.CrossRefPubMed
13.
Zurück zum Zitat Bilen MA, Martini DJ, Liu Y, et al. The prognostic and predictive impact of inflammatory biomarkers in patients who have advanced-stage cancer treated with immunotherapy. Cancer. 2019;125(1):127–34.CrossRefPubMed Bilen MA, Martini DJ, Liu Y, et al. The prognostic and predictive impact of inflammatory biomarkers in patients who have advanced-stage cancer treated with immunotherapy. Cancer. 2019;125(1):127–34.CrossRefPubMed
14.
Zurück zum Zitat Sacdalan DB, Lucero JA. Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis. Oncotargets Ther. 2018;11:955–65.CrossRef Sacdalan DB, Lucero JA. Prognostic utility of baseline neutrophil-to-lymphocyte ratio in patients receiving immune checkpoint inhibitors: a review and meta-analysis. Oncotargets Ther. 2018;11:955–65.CrossRef
15.
Zurück zum Zitat Zahoor H, Barata PC, Jia X, et al. Patterns, predictors and subsequent outcomes of disease progression in metastatic renal cell carcinoma patients treated with nivolumab. J Immunother Cancer. 2018;6(1):107.CrossRefPubMedPubMedCentral Zahoor H, Barata PC, Jia X, et al. Patterns, predictors and subsequent outcomes of disease progression in metastatic renal cell carcinoma patients treated with nivolumab. J Immunother Cancer. 2018;6(1):107.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Bilen MA, Dutcher GMA, Liu Y, et al. Association between pretreatment neutrophil-to-lymphocyte ratio and outcome of patients with metastatic renal-cell carcinoma treated with nivolumab. Clin Genitourin Cancer. 2018;16(3):e563–75.CrossRefPubMedPubMedCentral Bilen MA, Dutcher GMA, Liu Y, et al. Association between pretreatment neutrophil-to-lymphocyte ratio and outcome of patients with metastatic renal-cell carcinoma treated with nivolumab. Clin Genitourin Cancer. 2018;16(3):e563–75.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Lalani A-KA, Xie W, Martini DJ, et al. Change in neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma. J Immunother Cancer. 2018;6(1):5.CrossRefPubMedPubMedCentral Lalani A-KA, Xie W, Martini DJ, et al. Change in neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma. J Immunother Cancer. 2018;6(1):5.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Rini BI, Hutson TE, Figlin RA, et al. Sunitinib in patients with metastatic renal cell carcinoma: clinical outcome according to International Metastatic Renal Cell Carcinoma Database Consortium risk group. Clin Genitourin Cancer. 2018;16(4):298–304.CrossRefPubMedPubMedCentral Rini BI, Hutson TE, Figlin RA, et al. Sunitinib in patients with metastatic renal cell carcinoma: clinical outcome according to International Metastatic Renal Cell Carcinoma Database Consortium risk group. Clin Genitourin Cancer. 2018;16(4):298–304.CrossRefPubMedPubMedCentral
Metadaten
Titel
Prognostic Markers for Refined Stratification of IMDC Intermediate-Risk Metastatic Clear Cell Renal Cell Carcinoma Treated with First-Line Tyrosine Kinase Inhibitor Therapy
verfasst von
Toshio Takagi
Hironori Fukuda
Tsunenori Kondo
Hiroki Ishihara
Kazuhiko Yoshida
Hirohito Kobayashi
Junpei Iizuka
Masayoshi Okumi
Hideki Ishida
Kazunari Tanabe
Publikationsdatum
29.03.2019
Verlag
Springer International Publishing
Erschienen in
Targeted Oncology / Ausgabe 2/2019
Print ISSN: 1776-2596
Elektronische ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-019-00634-8

Weitere Artikel der Ausgabe 2/2019

Targeted Oncology 2/2019 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.