Health-related quality of life, psychological distress, and fatigue in metastatic castration-resistant prostate cancer patients treated with radium-223 therapy

Maarten J van der Doelen, Irma M Oving, Dirk N J Wyndaele, Jean-Paul van Basten, Frederiek Terheggen, Addy C M van de Luijtgaarden, Wim J G Oyen, W Dick van Schelven, Franchette van den Berkmortel, Niven Mehra, Marcel J R Janssen, Judith B Prins, Winald R Gerritsen, José A E Custers, Inge M van Oort, Maarten J van der Doelen, Irma M Oving, Dirk N J Wyndaele, Jean-Paul van Basten, Frederiek Terheggen, Addy C M van de Luijtgaarden, Wim J G Oyen, W Dick van Schelven, Franchette van den Berkmortel, Niven Mehra, Marcel J R Janssen, Judith B Prins, Winald R Gerritsen, José A E Custers, Inge M van Oort

Abstract

Background: Radium-223 is a registered treatment option for symptomatic bone metastatic castration-resistant prostate cancer (mCRPC). Aim of this multicenter, prospective observational cohort study was to evaluate health-related quality of life (HR-QoL), psychological distress and fatigue in mCRPC patients treated with radium-223.

Methods: Primary endpoint was cancer-specific and bone metastases-related HR-QoL, as measured by the EORTC QLQ-C30 and BM-22 questionnaires. Secondary endpoints were psychological distress and fatigue, evaluated by the HADS and CIS-Fatigue questionnaires. Outcomes were analyzed for the total cohort and between subgroups (1-3 versus 4-5 versus 6 radium-223 injections). A trajectory analysis was performed to explore HR-QoL patterns over time.

Results: In total, 122 patients were included for analysis. Baseline HR-QoL, pain intensity, psychological distress and fatigue were worse in patients who did not complete radium-223 therapy. In patients who completed therapy, stabilization of HR-QoL was perceived and psychological distress and fatigue remained stable, whereas clinically meaningful and statistically significant deterioration of HR-QoL, psychological distress and fatigue over time was observed in patients who discontinued radium-223 therapy. Trajectory analysis revealed that HR-QoL deterioration over time was more likely in patients with baseline opioid use, low hemoglobin and high alkaline phosphatase levels.

Conclusions: Patients who discontinued radium-223 therapy showed worse HR-QoL, psychological distress and fatigue at baseline and more frequent deterioration of HR-QoL, psychological distress and fatigue over time when compared to patients who completed therapy. Specific attention with regard to HR-QoL during follow-up is indicated in patients with opioid use, low hemoglobin and high alkaline phosphatase levels before radium-223 therapy initiation.

Clinical trial registration number: NCT04995614.

Conflict of interest statement

MJvdD discloses research grants from Bayer and Janssen, and received speaker fees from Astellas. ACMvdL received speaker en advisory honorarium from Janssen and financial support for educational program from Astellas, and is a member of the advisory board of the Dutch prostate cancer foundation. WJGO discloses consultancy and speaker fees from Bayer and AAA Novartis. NM reports personal fees from Bayer, Sanofi and MSD and received grants and personal fees from Janssen, Roche and Astellas. WRG is a member of the advisory boards for Bristol-Myers Squibb, Astellas, Janssen, Bayer, Sanofi Genzyme, Amgen, Morphosys and CureVac, received speaker fees from Bayer and MSD, and received research funding from Astellas, Bayer and Janssen. IMvO is a member of the advisory boards for MSD and AstraZeneca and received research grants and personal fees from Astellas, Bayer, Janssen and Sanofi. The other authors indicated no financial relationships.

© 2022. The Author(s).

Figures

Fig. 1. Consort diagram of patient enrollment.
Fig. 1. Consort diagram of patient enrollment.
Enrollment based on completion of the European Organization for Research and Treatment of Cancer (EORTC) core QoL questionnaire (QLQ-C30) and the bone metastases module (BM-22).
Fig. 2. Course of cancer-specific health-related quality…
Fig. 2. Course of cancer-specific health-related quality of life (EORTC QLQ-C30 functional scales and global health status) over time in patients treated with radium-223 for metastatic castration-resistant prostate cancer.
Bars indicate mean scores with 95% confidence intervals.

References

    1. Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res. 2006;12:6243s–6249s. doi: 10.1158/1078-0432.CCR-06-0931.
    1. Saad F, Lipton A, Cook R, Chen YM, Smith M, Coleman R. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer. 2007;110:1860–7. doi: 10.1002/cncr.22991.
    1. Fizazi K, Massard C, Smith M, Rader M, Brown J, Milecki P, et al. Bone-related parameters are the main prognostic factors for overall survival in men with bone metastases from castration-resistant prostate cancer. Eur Urol. 2015;68:42–50. doi: 10.1016/j.eururo.2014.10.001.
    1. Weinfurt KP, Li Y, Castel LD, Saad F, Timbie JW, Glendenning GA, et al. The significance of skeletal-related events for the health-related quality of life of patients with metastatic prostate cancer. Ann Oncol. 2005;16:579–84. doi: 10.1093/annonc/mdi122.
    1. Sullivan PW, Mulani PM, Fishman M, Sleep D. Quality of life findings from a multicenter, multinational, observational study of patients with metastatic hormone-refractory prostate cancer. Qual Life Res. 2007;16:571–5. doi: 10.1007/s11136-006-9156-2.
    1. Nead KT, Sinha S, Yang DD, Nguyen PL. Association of androgen deprivation therapy and depression in the treatment of prostate cancer: a systematic review and meta-analysis. Urol Oncol. 2017;35:664.e661–664.e669. doi: 10.1016/j.urolonc.2017.07.016.
    1. Chipperfield K, Fletcher J, Millar J, Brooker J, Smith R, Frydenberg M, et al. Predictors of depression, anxiety and quality of life in patients with prostate cancer receiving androgen deprivation therapy. Psychooncology. 2013;22:2169–76. doi: 10.1002/pon.3269.
    1. Guan T, Santacroce SJ, Chen DG, Song L. Illness uncertainty, coping, and quality of life among patients with prostate cancer. Psychooncology. 2020;29:1019–25. doi: 10.1002/pon.5372.
    1. Parker C, Nilsson S, Heinrich D, Helle SI, O’Sullivan JM, Fossa SD, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369:213–23. doi: 10.1056/NEJMoa1213755.
    1. Hoskin P, Sartor O, O’Sullivan JM, Johannessen DC, Helle SI, Logue J, et al. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. Lancet Oncol. 2014;15:1397–406. doi: 10.1016/S1470-2045(14)70474-7.
    1. Parker C, Finkelstein SE, Michalski JM, O’Sullivan JM, Bruland O, Vogelzang NJ, et al. Efficacy and safety of radium-223 dichloride in symptomatic castration-resistant prostate cancer patients with or without baseline opioid use from the phase 3 ALSYMPCA trial. Eur Urol. 2016;70:875–83. doi: 10.1016/j.eururo.2016.06.002.
    1. Nilsson S, Cislo P, Sartor O, Vogelzang NJ, Coleman RE, O’Sullivan JM, et al. Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study. Ann Oncol. 2016;27:868–74. doi: 10.1093/annonc/mdw065.
    1. Nilsson S, Larsen RH, Fossa SD, Balteskard L, Borch KW, Westlin JE, et al. First clinical experience with alpha-emitting radium-223 in the treatment of skeletal metastases. Clin Cancer Res. 2005;11:4451–9. doi: 10.1158/1078-0432.CCR-04-2244.
    1. Nilsson S, Strang P, Aksnes AK, Franzen L, Olivier P, Pecking A, et al. A randomized, dose-response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer. Eur J Cancer. 2012;48:678–86. doi: 10.1016/j.ejca.2011.12.023.
    1. Badrising SK, Louhanepessy RD, van der Noort V, Kieffer J, Coenen J, Hamberg P, et al. Integrated analysis of pain, health-related quality of life, and analgesic use in patients with metastatic castration-resistant prostate cancer treated with Radium-223. Prostate Cancer Prostatic Dis. 2022;25:248–55. doi: 10.1038/s41391-021-00412-6.
    1. Parimi S, Bondy S, Tsang E, McKenzie MR, Bachand F, Aparicio M, et al. Pain response in a population-based study of radium-223 (Ra223) for metastatic castration-resistant prostate cancer. Can Urol Assoc J. 2019;13:E311–E316. doi: 10.5489/cuaj.5685.
    1. Morris MJ, Sartor O, Vogelzang NJ, Shore ND, Cislo P, Bangerter K, et al. Effect of radium-223 dichloride (Ra-223) on pain from US EAP. J Clin Oncol. 2015;33:160–160. doi: 10.1200/jco.2015.33.7_suppl.160.
    1. Kuppen MCP, Westgeest HM, van den Eertwegh AJM, Coenen J, van Moorselaar RJA, van den Berg P, et al. Health-related quality of life and pain in a real-world castration-resistant prostate cancer population: results from the PRO-CAPRI study in the Netherlands. Clin Genitourin Cancer. 2020;18:e233–e253. doi: 10.1016/j.clgc.2019.11.015.
    1. Nussbaum N, George DJ, Abernethy AP, Dolan CM, Oestreicher N, Flanders S, et al. Patient experience in the treatment of metastatic castration-resistant prostate cancer: state of the science. Prostate Cancer Prostatic Dis. 2016;19:111–21. doi: 10.1038/pcan.2015.42.
    1. Kretschmer A, Ploussard G, Heidegger I, Tsaur I, Borgmann H, Surcel C, et al. Health-related quality of life in patients with advanced prostate cancer: a systematic review. Eur Urol Focus. 2021;7:742–51. doi: 10.1016/j.euf.2020.01.017.
    1. Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016;34:1402–18. doi: 10.1200/JCO.2015.64.2702.
    1. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85:365–76. doi: 10.1093/jnci/85.5.365.
    1. Chow E, Hird A, Velikova G, Johnson C, Dewolf L, Bezjak A, et al. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for patients with bone metastases: the EORTC QLQ-BM22. Eur J Cancer. 2009;45:1146–52. doi: 10.1016/j.ejca.2008.11.013.
    1. Chow E, Nguyen J, Zhang L, Tseng LM, Hou MF, Fairchild A, et al. International field testing of the reliability and validity of the EORTC QLQ-BM22 module to assess health-related quality of life in patients with bone metastases. Cancer. 2012;118:1457–65. doi: 10.1002/cncr.26410.
    1. Scott NW, Fayers P, Aaronson NK, Bottomley A, de Graeff A, Groenvold M, et al. EORTC QLQ-C30 reference values manual. EORTC Quality of Life Group, Brussels, Belgium 2008.
    1. Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol. 1998;16:139–44. doi: 10.1200/JCO.1998.16.1.139.
    1. Cleeland CS. The measurement of pain from metastatic bone disease: capturing the patient’s experience. Clin Cancer Res. 2006;12:6236s–6242s. doi: 10.1158/1078-0432.CCR-06-0988.
    1. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361–70. doi: 10.1111/j.1600-0447.1983.tb09716.x.
    1. Puhan MA, Frey M, Büchi S, Schünemann HJ. The minimal important difference of the hospital anxiety and depression scale in patients with chronic obstructive pulmonary disease. Health Qual Life Outcomes. 2008;6:46. doi: 10.1186/1477-7525-6-46.
    1. Vercoulen JH, Swanink CM, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G. Dimensional assessment of chronic fatigue syndrome. J Psychosom Res. 1994;38:383–92. doi: 10.1016/0022-3999(94)90099-X.
    1. Worm-Smeitink M, Gielissen M, Bloot L, van Laarhoven HWM, van Engelen BGM, van Riel P, et al. The assessment of fatigue: psychometric qualities and norms for the Checklist individual strength. J Psychosom Res. 2017;98:40–46. doi: 10.1016/j.jpsychores.2017.05.007.
    1. Giesinger JM, Kieffer JM, Fayers PM, Groenvold M, Petersen MA, Scott NW, et al. Replication and validation of higher order models demonstrated that a summary score for the EORTC QLQ-C30 is robust. J Clin Epidemiol. 2016;69:79–88. doi: 10.1016/j.jclinepi.2015.08.007.
    1. Husson O, de Rooij BH, Kieffer J, Oerlemans S, Mols F, Aaronson NK, et al. The EORTC QLQ-C30 summary score as prognostic factor for survival of patients with cancer in the “Real-World”: results from the population-based PROFILES registry. Oncologist. 2020;25:e722–e732. doi: 10.1634/theoncologist.2019-0348.
    1. Westdorp H, Creemers JHA, van Oort IM, Mehra N, Hins-de Bree SM, Figdor CG, et al. High health-related quality of life during dendritic cell vaccination therapy in patients with castration-resistant prostate cancer. Front Oncol. 2020;10:536700. doi: 10.3389/fonc.2020.536700.
    1. Sraieb M, Hirmas N, Conrad R, Marinova M, Essler M, Herrmann K, et al. Assessing the quality of life of patients with metastatic castration-resistant prostate cancer with bone metastases receiving [223Ra]RaCl2 therapy. Medicines. 2020;99:e22287.
    1. Sullivan PW, Nelson JB, Mulani PM, Sleep D. Quality of life as a potential predictor for morbidity and mortality in patients with metastatic hormone-refractory prostate cancer. Qual Life Res. 2006;15:1297–306. doi: 10.1007/s11136-006-0003-2.
    1. Frantellizzi V, De Feo MS, Di Rocco A, Pontico M, Pani A, Farcomeni A, et al. Baseline quality of life predicts overall survival in patients with mCRPC treated with (223)Ra-dichloride. Hell J Nucl Med. 2020;23:12–20.
    1. De Vincentis G, Frantellizzi V, Follacchio GA, Farcomeni A, Pani A, Samaritani R, et al. No evidence of association between psychological distress and pain relief in patients with bone metastases from castration-resistant prostate cancer treated with 223Radium. Eur J Cancer Care. 2019;28:e13112. doi: 10.1111/ecc.13112.
    1. van der Doelen MJ, Mehra N, Hermsen R, Janssen MJR, Gerritsen WR, van Oort IM. Patient selection for radium-223 therapy in patients with bone metastatic castration-resistant prostate cancer: new recommendations and future perspectives. Clin Genitourin Cancer. 2019;17:79–87. doi: 10.1016/j.clgc.2018.11.008.
    1. van der Doelen MJ, Stockhaus A, Ma Y, Mehra N, Yachnin J, Gerritsen WR, et al. Early alkaline phosphatase dynamics as biomarker of survival in metastatic castration-resistant prostate cancer patients treated with radium-223. Eur J Nucl Med Mol Imaging. 2021;48:3325–34. doi: 10.1007/s00259-021-05283-6.
    1. Wintner LM, Sztankay M, Aaronson N, Bottomley A, Giesinger JM, Groenvold M, et al. The use of EORTC measures in daily clinical practice—a synopsis of a newly developed manual. Eur J Cancer. 2016;68:73–81. doi: 10.1016/j.ejca.2016.08.024.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅