The prognostic power of inflammatory indices and clinical factors in metastatic castration-resistant prostate cancer patients treated with radium-223 (BIO-Ra study)

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Abstract

Purpose

To combine peripheral blood indices and clinical factors in a prognostic score for metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223 dichloride ([ ²²³Ra]RaCl ₂).

Patients and methods

Baseline neutrophil-to-lymphocyte ratio (NLR), derived NLR (donor), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason score (GS) group, number of bone metastases, prostate-specific antigen (PSA), alkaline phosphatase (ALP), line of therapy, previous chemotherapy, and the presence of lymphadenopathies were collected from seven Italian centers between 2013 and 2020. Lab and clinical data were assessed in correlation with the overall survival (OS). Inflammatory indices were then included separately in the multivariable analyses with the prognostic clinical factors. The model with the highest discriminative ability (c-index) was chosen to develop the BIO-Ra score.

Results

Five hundred and nineteen mCRPC patients (median OS: 19.9 months) were enrolled. Higher NLR, dNLR, PLR, and SII and lower LMR predicted worse OS (all with a p < 0.001). The multivariable model including NLR, ECOG PS, number of bone metastases, ALP, and PSA (c-index: 0.724) was chosen to develop the BIO-Ra score. Using the Schneeweiss scoring system, the BIO-Ra score identified three prognostic groups (36%, 27.3%, and 36.6% patients, respectively) with distinct median OS (31, 26.6, and 9.6 months, respectively; hazard ratio: 1.62, p = 0.008 for group 2 vs. 1 and 5.77, p < 0.001 for group 3 vs. 1).

Conclusions

The BIO-Ra score represents an easy and widely applicable tool for the prognostic stratification of mCRPC patients treated with [ ²²³Ra]RaCl ₂ with no additional costs.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00259-021-05550-6.

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Most cited references 52

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Hallmarks of Cancer: The Next Generation

Douglas Hanahan, Robert A. Weinberg (2011)

The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

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Nonparametric Estimation from Incomplete Observations

E. Kaplan, Paul Meier (1958)

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Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis.

Arnoud Templeton, Mairéad McNamara, Bostjan Seruga … (2014)

Inflammation may play an important role in cancer progression, and a high neutrophil-to-lymphocyte ratio (NLR) has been reported to be a poor prognostic indicator in several malignancies. Here we quantify the prognostic impact of this biomarker and assess its consistency in solid tumors. A systematic review of electronic databases was conducted to identify publications exploring the association of blood NLR and clinical outcome in solid tumors. Overall survival (OS) was the primary outcome, and cancer-specific survival (CSS), progression-free survival (PFS), and disease-free survival (DFS) were secondary outcomes. Data from studies reporting a hazard ratio and 95% confidence interval (CI) or a P value were pooled in a meta-analysis. Pooled hazard ratios were computed and weighted using generic inverse-variance and random-effect modeling. All statistical tests were two-sided. One hundred studies comprising 40559 patients were included in the analysis, 57 of them published in 2012 or later. Median cutoff for NLR was 4. Overall, NLR greater than the cutoff was associated with a hazard ratio for OS of 1.81 (95% CI = 1.67 to 1.97; P < .001), an effect observed in all disease subgroups, sites, and stages. Hazard ratios for NLR greater than the cutoff for CSS, PFS, and DFS were 1.61, 1.63, and 2.27, respectively (all P < .001). A high NLR is associated with an adverse OS in many solid tumors. The NLR is a readily available and inexpensive biomarker, and its addition to established prognostic scores for clinical decision making warrants further investigation. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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Author and article information

Contributors

Matteo Bauckneht:

ORCID: http://orcid.org/0000-0002-1937-9116

matteo.bauckneht@hsanmartino.it

Journal

Journal ID (nlm-ta): Eur J Nucl Med Mol Imaging

Journal ID (iso-abbrev): Eur J Nucl Med Mol Imaging

Title: European Journal of Nuclear Medicine and Molecular Imaging

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 1619-7070

ISSN (Electronic): 1619-7089

Publication date (Electronic): 6 September 2021

Publication date PMC-release: 6 September 2021

Publication date (Print): 2022

Volume: 49

Issue: 3

Pages: 1063-1074

Affiliations

[1 ]GRID grid.410345.7, ISNI 0000 0004 1756 7871, Nuclear Medicine, , IRCCS Ospedale Policlinico San Martino, ; Genova, Italy

[2 ]GRID grid.5606.5, ISNI 0000 0001 2151 3065, Department of Health Sciences (DISSAL), , University of Genova, ; Genova, Italy

[3 ]GRID grid.410345.7, ISNI 0000 0004 1756 7871, Medical Oncology Unit 1, , IRCCS Ospedale Policlinico San Martino, ; Genova, Italy

[4 ]GRID grid.5606.5, ISNI 0000 0001 2151 3065, Department of Internal Medicine and Medical Specialties, , University of Genova, ; Genova, Italy

[5 ]GRID grid.7841.a, Department of Radiological Sciences, Oncology and Anatomical Pathology, , Sapienza University of Rome, ; Rome, Italy

[6 ]GRID grid.6292.f, ISNI 0000 0004 1757 1758, Radiation Oncology, , IRCCS Azienda Ospedaliero-Universitaria Di Bologna, ; Bologna, Italy

[7 ]GRID grid.461844.b, Unit of Nuclear Medicine, , Spirito Santo Hospital, ; Pescara, Italy

[8 ]GRID grid.7644.1, ISNI 0000 0001 0120 3326, Nuclear Medicine Section, Interdisciplinary Department of Medicine, , University of Bari “Aldo Moro”, ; Bari, Italy

[9 ]GRID grid.11450.31, ISNI 0000 0001 2097 9138, Unit of Nuclear Medicine, Department of Medical, Surgical and Experimental Sciences, , University of Sassari, ; Sassari, Italy

[10 ]GRID grid.10776.37, ISNI 0000 0004 1762 5517, Unit of Nuclear Medicine, Biomedical Department of Internal and Specialist Medicine, , University of Palermo, ; Palermo, Italy

[11 ]GRID grid.6292.f, ISNI 0000 0004 1757 1758, Department of Experimental Diagnostic and Specialty Medicine, , Alma Mater Studiorum Bologna University, ; Bologna, Italy

[12 ]Department of Urology, Villa Stuart Private Hospital, Rome, Italy

[13 ]GRID grid.417007.5, Department of Urology, , Sapienza University of Rome, Policlinico Umberto I, ; Rome, Italy

Author information

Matteo Bauckneht http://orcid.org/0000-0002-1937-9116

Article

Publisher ID: 5550

DOI: 10.1007/s00259-021-05550-6

PMC ID: 8803683

PubMed ID: 34486070

SO-VID: cae2e1c1-663e-4636-84ea-58d8435400fd

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 3 June 2021

Date accepted : 29 August 2021

Funding

Funded by: Università degli Studi di Genova

Open Access :

Open access funding provided by Università degli Studi di Genova within the CRUI-CARE Agreement.

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ScienceOpen disciplines: Radiology & Imaging

Keywords: metastatic castration-resistant prostate cancer,[223ra]racl2,inflammatory indices,neutrophil-to-lymphocyte ratio,clinical factors

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ScienceOpen disciplines: Radiology & Imaging

Keywords: metastatic castration-resistant prostate cancer, [223ra]racl2, inflammatory indices, neutrophil-to-lymphocyte ratio, clinical factors

The prognostic power of inflammatory indices and clinical factors in metastatic castration-resistant prostate cancer patients treated with radium-223 (BIO-Ra study)

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Most cited references 52

Hallmarks of Cancer: The Next Generation

Nonparametric Estimation from Incomplete Observations

Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis.

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