A National Multicenter Study on overall survival in elderly metastatic castrate-resistant prostate cancer patients treated with Radium-223.
Elderly
Overall survival
Prostate cancer
Radium-223
mCRPC
Journal
Aging clinical and experimental research
ISSN: 1720-8319
Titre abrégé: Aging Clin Exp Res
Pays: Germany
ID NLM: 101132995
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
21
02
2020
accepted:
17
04
2020
pubmed:
3
5
2020
medline:
12
3
2021
entrez:
3
5
2020
Statut:
ppublish
Résumé
Radium-223 prolongs overall survival (OS) and delays time to the first symptomatic skeletal events in patients with symptomatic metastatic castration-resistant prostate cancer (mCRPC). There is a lack of evidence on the safety and efficacy of Radium-223 treatment in the very elderly population. Aim of this multicentre study is to analyze mCRPC patients treated with Radium-223 in terms of OS and to assess whether there are differences between young and elderly, as well as to verify efficacy and safety in patients ≥ 75 years of age. 430 mCRPC patients of six Italian Centres were analyzed in this multicenter retrospective study. At baseline and after each cycle were collected clinical and diagnostic patients' parameters. The whole cohort was divided into two groups based on the age of the patients (< 75 years old and ≥ 75 years old). 47% of the patients were < 75 years old and 53% were ≥ 75 years old. The primary outcome, OS, does not show significant differences between the two subgroups if other basal parameters are considered. Considering clinical covariates in univariate models (p < 0.05) several clinical aspects have an impact on OS, except for age (p = 0.072). Age continues to have no significant impact on the OS (p = 0.274) even in multivariate models in the two groups. The toxic effects are similar in the two groups. Radium-223 prolongs survival in both younger and older patients at the same baseline condition and is a good option in the symptomatic mCRPC setting compared to other agents.
Sections du résumé
BACKGROUND
BACKGROUND
Radium-223 prolongs overall survival (OS) and delays time to the first symptomatic skeletal events in patients with symptomatic metastatic castration-resistant prostate cancer (mCRPC). There is a lack of evidence on the safety and efficacy of Radium-223 treatment in the very elderly population.
AIMS
OBJECTIVE
Aim of this multicentre study is to analyze mCRPC patients treated with Radium-223 in terms of OS and to assess whether there are differences between young and elderly, as well as to verify efficacy and safety in patients ≥ 75 years of age.
METHODS
METHODS
430 mCRPC patients of six Italian Centres were analyzed in this multicenter retrospective study. At baseline and after each cycle were collected clinical and diagnostic patients' parameters. The whole cohort was divided into two groups based on the age of the patients (< 75 years old and ≥ 75 years old).
RESULTS
RESULTS
47% of the patients were < 75 years old and 53% were ≥ 75 years old. The primary outcome, OS, does not show significant differences between the two subgroups if other basal parameters are considered. Considering clinical covariates in univariate models (p < 0.05) several clinical aspects have an impact on OS, except for age (p = 0.072). Age continues to have no significant impact on the OS (p = 0.274) even in multivariate models in the two groups. The toxic effects are similar in the two groups.
CONCLUSIONS
CONCLUSIONS
Radium-223 prolongs survival in both younger and older patients at the same baseline condition and is a good option in the symptomatic mCRPC setting compared to other agents.
Identifiants
pubmed: 32358729
doi: 10.1007/s40520-020-01573-5
pii: 10.1007/s40520-020-01573-5
doi:
Substances chimiques
Radium-223
8BR2SOL3L1
Radium
W90AYD6R3Q
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
651-658Références
Siegel RL, Miller KD, Jemal A (2018) Cancer statistics. CA Cancer J Clin 68:7–30. https://doi.org/10.3322/caac.21442
doi: 10.3322/caac.21442
Sciarra A, Gentilucci A, Silvestri I et al (2019) Androgen receptor variant 7 (AR-V7) in sequencing therapeutic agents for castratrion resistant prostate cancer: a critical review. Medicine 98:e15608. https://doi.org/10.1097/md.0000000000015608
doi: 10.1097/md.0000000000015608
pubmed: 31083254
pmcid: 6531263
Ricci M, Frantellizzi V, Bulzonetti N et al (2018) Reversibility of castration resistance status after Radium-223 dichloride treatment: clinical evidence and review of the literature. Int J Radiat Biol. https://doi.org/10.1080/09553002.2019.1558301
doi: 10.1080/09553002.2019.1558301
Mohler JL, Antonarakis ES, Armstrong AJ et al (2019) Prostate Cancer, Version 2. 2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw 17:479–505. https://doi.org/10.6004/jnccn.2019.0023
doi: 10.6004/jnccn.2019.0023
Sciarra A, Gentilucci A, Salciccia S et al (2018) Psychological and functional effect of different primary treatments for prostate cancer: a comparative prospective analysis. Urol Oncol 36:340. https://doi.org/10.1016/j.urolonc.2018.03.022
doi: 10.1016/j.urolonc.2018.03.022
pubmed: 29706458
Jiang W, Ulmert D, Simons BW et al (2018) The impact of age on radium-223 distribution and an evaluation of molecular imaging surrogates. Nucl Med Biol 62–63:1–8. https://doi.org/10.1016/j.nucmedbio.2018.05.003
doi: 10.1016/j.nucmedbio.2018.05.003
pubmed: 29800797
pmcid: 6054814
Costa RP, Bordonaro S, Cappuccio F et al (2019) Hematologic toxicity of radium-223 in elderly patients with metastatic Castration Resistant Prostate Cancer: a real-life experience. Prostate Int 7:25–29. https://doi.org/10.1016/j.prnil.2018.08.001
doi: 10.1016/j.prnil.2018.08.001
pubmed: 30937295
Parker C, Heidenreich A, Nilsson S et al (2018) Current approaches to incorporation of radium-223 in clinical practice. Prostate Cancer Prostatic Dis 21:37–47. https://doi.org/10.1038/s41391-017-0020-y
doi: 10.1038/s41391-017-0020-y
pubmed: 29298991
pmcid: 5895600
Lutz S, Balboni T, Jones J et al (2017) Palliative radiation therapy for bone metastases: update of an ASTRO Evidence-Based Guideline. Pract Radiat Oncol 7:4–12. https://doi.org/10.1016/j.prro.2016.08.001
doi: 10.1016/j.prro.2016.08.001
pubmed: 27663933
Shulman RM, Meyer JE, Li T et al (2019) External beam radiation therapy (EBRT) for asymptomatic bone metastases in patients with solid tumors reduces the risk of skeletal-related events (SREs). Ann Palliat Med 8:159–167. https://doi.org/10.21037/apm.2018.10.04
doi: 10.21037/apm.2018.10.04
pubmed: 30525770
Berg RS, Yilmaz MK, Hoyer M et al (2009) Half body irradiation of patients with multiple bone metastases: a phase II trial. Acta Oncol 48:556–561. https://doi.org/10.1080/02841860802488128
doi: 10.1080/02841860802488128
pubmed: 18979285
Lowrance WT, Murad MH, Oh WK et al (2018) Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2018. J Urol 200:1264–1272. https://doi.org/10.1016/j.juro.2018.07.090
doi: 10.1016/j.juro.2018.07.090
pubmed: 30086276
Sartor O, Coleman R, Nilsson S et al (2014) Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol 15:738–746. https://doi.org/10.1016/s1470-2045(14)70183-4
doi: 10.1016/s1470-2045(14)70183-4
pubmed: 24836273
Parker C, Nilsson S, Heinrich D et al (2013) Alpha emitter Radium-223 and survival in metastatic prostate cancer. N Engl J Med 369:213–223. https://doi.org/10.1056/nejmoa1213755
doi: 10.1056/nejmoa1213755
Roviello G, Gallicchio R, Bozza G et al (2019) Pain predicts overall survival in men with metastatic castration-resistant prostate cancer treated with radium-223. Onco Targets Ther 12:9–13. https://doi.org/10.2147/ott.S174206
doi: 10.2147/ott.S174206
pubmed: 30588025
Wilson JM, Parker C (2016) The safety and efficacy of radium-223 dichloride for the treatment of advanced prostate cancer. Expert Rev Anticancer Ther 16:911–918. https://doi.org/10.1080/14737140.2016.1222273
doi: 10.1080/14737140.2016.1222273
pubmed: 27501059
Prior JO, Gillessen S, Wirth M et al (2017) Radiopharmaceuticals in the elderly cancer patient: practical considerations, with a focus on prostate cancer therapy: a position paper from the International Society of Geriatric Oncology Task Force. Eur J Cancer 77:127–139. https://doi.org/10.1016/j.ejca.2017.01.030
doi: 10.1016/j.ejca.2017.01.030
pubmed: 28391026
De Vincentis G, Follacchio GA, Frantellizzi V et al (2017) 223Ra-dichloride therapy in an elderly bone metastatic castration-resistant prostate cancer patient: a case report presentation and comparison with existing literature. Aging Clin Exp Res 30:677–680. https://doi.org/10.1007/s40520-017-0826-4
doi: 10.1007/s40520-017-0826-4
pubmed: 28856577
Castellucci P, Nanni C, Ambrosini V (2018) Nuclear Medicine Imaging of Prostate Cancer in the Elderly. Semin Nucl Med 48:541–547. https://doi.org/10.1053/j.semnuclmed.2018.07.004
doi: 10.1053/j.semnuclmed.2018.07.004
pubmed: 30322480
Zuo W, Jiang S, Guo Z, Feldman MW et al (2018) Advancing front of old-age human survival. Proc Natl Acad Sci USA 115:11209–11214. https://doi.org/10.1073/pnas.1812337115
doi: 10.1073/pnas.1812337115
pubmed: 30327342
Droz JP, Albrand G, Gillessen S et al (2017) Management of prostate cancer in elderly patients: recommendations of a task force of the international society of geriatric oncology. Eur Urol 72:521–531. https://doi.org/10.1016/j.eururo.2016.12.025
doi: 10.1016/j.eururo.2016.12.025
pubmed: 28089304
Baldari S, Boni G, Bortolus R et al (2017) Management of metastatic castration-resistant prostate cancer: a focus on radium-223: Opinions and suggestions from an expert multidisciplinary panel. Crit Rev Oncol Hematol 113:43–51. https://doi.org/10.1016/j.critrevonc.2017.03.001
doi: 10.1016/j.critrevonc.2017.03.001
pubmed: 28427521
Prelaj A, Rebuzzi SE, Buzzacchino F et al (2019) Radium-223 in patients with metastatic castration-resistant prostate cancer: efficacy and safety in clinical practice. Oncol Lett 17:1467–1476. https://doi.org/10.3892/ol.2018.9785
doi: 10.3892/ol.2018.9785
pubmed: 30675201
De Vincentis G, Frantellizzi V, Follacchio GA et al (2019) No evidence of association between psychological distress and pain relief in patients with bone metastases from castration-resistant prostate cancer treated with 223 Radium. Eur J Cancer Care. https://doi.org/10.1111/ecc.13112
doi: 10.1111/ecc.13112
De Vincentis G, Monari F, Baldari S et al (2018) Narrative medicine in metastatic prostate cancer reveals ways to improve patient awareness & quality of care. Fut Oncol 14:2821–2832. https://doi.org/10.2217/fon-2018-0318
doi: 10.2217/fon-2018-0318
Tucci M, Caffo O, Buttigliero C et al (2019) Therapeutic options for first-line metastatic castration-resistant prostate cancer: suggestions for clinical practise in the CHAARTED and LATITUDE era. Cancer Treat Rev 74:35–42. https://doi.org/10.1016/j.ctrv.2019.01.002
doi: 10.1016/j.ctrv.2019.01.002
pubmed: 30738364
Nakazawa M, Paller C, Kyprianou N (2017) Mechanisms of Therapeutic Resistance in Prostate Cancer. Curr Oncol Rep 19:13. https://doi.org/10.1007/s11912-017-0568-7
doi: 10.1007/s11912-017-0568-7
pubmed: 28229393
pmcid: 5812366
Miller K, Gschwend J, Wolff JM (2016) Strategies for first-line treatment of mCRPC. Aktuelle Urol 47:395–401. https://doi.org/10.1055/s-0042-108533
doi: 10.1055/s-0042-108533
pubmed: 27680191
Etchebehere EC, Milton DR, Araujo JC et al (2016) Factors affecting (223)Ra therapy: clinical experience after 532 cycles from a single institution. Eur J Nucl Med Mol Imaging 43:8–20. https://doi.org/10.1007/s00259-015-3185-4
doi: 10.1007/s00259-015-3185-4
pubmed: 26416392
Frantellizzi V, Costa R, Mascia M et al (2019) Primary radical prostatectomy or ablative radiotherapy (RP/EBRT) are protective factors in mCRPC patients treated with 223 Radium-dichloride: an Italian Multicenter Study. Clin Genitourin Cancer. https://doi.org/10.1016/j.clgc.2019.10.009
doi: 10.1016/j.clgc.2019.10.009
pubmed: 32173355
De Vincentis G, Follacchio GA, Frantellizzi V et al (2016) Prostate-specific antigen flare phenomenon during 223 Ra-dichloride treatment for bone metastatic castration-resistant prostate cancer: a case report. Clin Genitourin Cancer 14:e529–e533. https://doi.org/10.1016/j.clgc.2016.04.014
doi: 10.1016/j.clgc.2016.04.014
pubmed: 27212044
Som A, Tu SM, Liu J et al (2012) Response in bone turnover markers during therapy predicts overall survival in patients with metastatic prostate cancer: analysis of three clinical trials. Br J Cancer 107:1547–1553. https://doi.org/10.1038/bjc.2012.436
doi: 10.1038/bjc.2012.436
pubmed: 23033003
pmcid: 3493771
Heinrich D, Bruland O, Guise TA et al (2018) Alkaline phosphatase in metastatic castration-resistant prostate cancer: reassessment of an older biomarker. Fut Oncol 14:2543–2556. https://doi.org/10.2217/fon-2018-0087
doi: 10.2217/fon-2018-0087
Sabbatini P, Larson SM, Kremer A et al (1999) Prognostic significance of extent of disease in bone in patients with androgen-independent prostate cancer. J Clin Oncol 17:948–957
doi: 10.1200/JCO.1999.17.3.948
Frantellizzi V, Farcomeni A, Follacchio GA et al (2017) A 3-variable prognostic score (3-PS) for overall survival prediction in metastatic castration-resistant prostate cancer treated with 223 Radium-dichloride. Ann Nucl Med 32:142–148. https://doi.org/10.1007/s12149-017-1228-6
doi: 10.1007/s12149-017-1228-6
pubmed: 29285670
Graff JN, Beer TM (2014) Pharmacotherapeutic management of metastatic, castration-resistant prostate cancer in the elderly: focus on non-chemotherapy agents. Drugs Aging 31:873–882. https://doi.org/10.1007/s40266-014-0224-y
doi: 10.1007/s40266-014-0224-y
pubmed: 25387443
pmcid: 4418948
Tanaka H, Nakashima Y, Ito M et al (2019) Intensity-modulated radiation therapy for elderly patients (aged ≥ 75 years) with localized prostate cancer: comparison with younger patients (aged < 75 years). Mol Clin Oncol 10:476–480. https://doi.org/10.3892/mco.2019.1810
doi: 10.3892/mco.2019.1810
pubmed: 30931121
pmcid: 6425511
Tay KJ, Moul JW, Armstrong AJ (2016) Management of Prostate Cancer in the Elderly. Clin Geriatr Med 32:113–132. https://doi.org/10.1016/j.cger.2015.08.001
doi: 10.1016/j.cger.2015.08.001
pubmed: 26614864