Impact of Patient- and Clinician-Reported Cumulative Toxicity on Quality of Life in Patients With Metastatic Castration-Naïve Prostate Cancer

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  • a Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands; Department of Psychiatry, Cancer Center Amsterdam, and Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, the Netherlands; Inserm, UMR 912 ‘Economic and Social Sciences, Health Systems and Societies (SESSTIM)’, Aix-Marseille Université, IRD, Marseille, France; Department of Medical Psychology, Academic Medical Center Amsterdam, Cancer Center Amsterdam, the Netherlands; Department of Epidemiology and Biostatistics Amsterdam Public Health Research Institute, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, the Netherlands; Medical Oncology, Centre François Baclesse - CHU Côte de Nacre, Caen, France; Department of Cancer Medicine, Institut Gustave Roussy, University of Paris Sud, Villejuif, France; UNICANCER, Paris, France; Department of Biostatistic, Institut Paoli-Calmettes, Marseille, France; Aix Marseille Université, INSERM, IRD, SESSTIM, Marseille, France; Centre Hospitalier Universitaire Rangueil, Toulouse, France; Hôpital Européen Georges Pompidou, Paris, France; and Institut Paoli-Calmettes, Aix-Marseille University, Centre de Recherche en Cancerologie de Marseille (CRCM), Marseille, France.
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Background: Current toxicity evaluation is primarily focused on high-grade adverse events (AEs) reported by clinicians. However, the cumulative effect of multiple lower-grade AEs may also impact patients' quality of life (QoL). Further, patient-reported toxicity may be more representative of patients' treatment experiences. This study aimed to determine whether cumulative toxicity comprising all-grade AEs is more associated with QoL than cumulative toxicity comprising high-grade AEs only, and whether patient-reported cumulative toxicity is more associated with QoL than clinician-reported cumulative toxicity. Methods: Patients with metastatic castration-naïve prostate cancer participating in the phase III GETUG-AFU 15 trial completed questionnaires on AEs (at 3 and 6 months) and QoL (at baseline and 3 and 6 months). Clinicians reported AEs during clinical visits. Cumulative toxicity scores were calculated for clinicians and patients in 3 ways: total number of high-grade AEs, total number of all-grade AEs, and total number of all AEs multiplied by their grade (severity score). Relationships between cumulative toxicity scores and QoL were studied using longitudinal regression analyses; unstandardized (B) and standardized regression coefficients (β) are reported. Results: Of 385 patients, 184 with complete QoL and toxicity data were included. Clinician-reported all-grade AEs (B, −2.2; 95% CI, −3.3 to −1.1; P<.01) and severity score (B, −1.4; 95% CI, −2.2 to −0.7; P<.01) were associated with deteriorated physical QoL, whereas the total number of high-grade AEs was not. All patient-reported scores were significantly (P<.01 for all) associated with deteriorated physical and global QoL. Standardized regression coefficients indicated that patient-reported toxicity scores were more associated with QoL outcomes than clinician-reported scores, with the strongest association found for the all-grade AEs and severity cumulative toxicity scores. Conclusions: Patient- and clinician-based cumulative toxicity scores comprising all-grade AEs better reflect impact on patient QoL than toxicity scores comprising high-grade AEs only. To assess the effect of toxicity on QoL, patient-reported cumulative toxicity scores are preferred.

Correspondence: Henk M.W. Verheul, MD, PhD, Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, P.O. Box 7057, 1081 HV, Amsterdam, the Netherlands. Email: h.verheul@vumc.nl
  • 1.

    Friese CR, Harrison JM, Janz NK. Treatment-associated toxicities reported by patients with early-stage invasive breast cancer. Cancer 2017;123:19251934.

    • Search Google Scholar
    • Export Citation
  • 2.

    Davis C, Naci H, Gurpinar E. Availability of evidence of benefits on overall survival and quality of life of cancer drugs approved by European Medicines Agency: retrospective cohort study of drug approvals 2009-13. BMJ 2017;359:j4530.

    • Search Google Scholar
    • Export Citation
  • 3.

    Gravis G, Marino P, Joly F. Patients' self-assessment versus investigators' evaluation in a phase III trial in non-castrate metastatic prostate cancer (GETUG-AFU 15). Eur J Cancer 2014;50:953962.

    • Search Google Scholar
    • Export Citation
  • 4.

    Weeks JC, Catalano PJ, Cronin A. Patients' expectations about effects of chemotherapy for advanced cancer. N Engl J Med 2012;367:16161625.

  • 5.

    Maillet D, Blay JY, You B. The reporting of adverse events in oncology phase III trials: a comparison of the current status versus the expectations of the EORTC members. Ann Oncol 2016;27:192198.

    • Search Google Scholar
    • Export Citation
  • 6.

    U.S. Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0. Available at: http://www.hrc.govt.nz/sites/default/files/CTCAE%20manual%20-%20DMCC.pdf. Accessed November 20, 2018.

    • Search Google Scholar
    • Export Citation
  • 7.

    Thanarajasingam G, Hubbard JM, Sloan JA, Grothey A. The imperative for a new approach to toxicity analysis in oncology clinical trials. J Natl Cancer Inst 2015;107:pii: djv216.

    • Search Google Scholar
    • Export Citation
  • 8.

    Schuurhuizen C, Konings I, Braamse A. The predictive value of cumulative toxicity for quality of life in patients with metastatic colorectal cancer during first-line palliative chemotherapy. Cancer Manag Res 2018;10:30153021.

    • Search Google Scholar
    • Export Citation
  • 9.

    Fromme EK, Eilers KM, Mori M. How accurate is clinician reporting of chemotherapy adverse effects? A comparison with patient-reported symptoms from the Quality-of-Life Questionnaire C30. J Clin Oncol 2004;22:34853490.

    • Search Google Scholar
    • Export Citation
  • 10.

    Di Maio M, Basch E, Bryce J. Patient-reported outcomes in the evaluation of toxicity of anticancer treatments. Nat Rev Clin Oncol 2016;13:319325.

    • Search Google Scholar
    • Export Citation
  • 11.

    Dueck AC, Mendoza TR, Mitchell SA. Validity and reliability of the US National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). JAMA Oncol 2015;1:10511059.

    • Search Google Scholar
    • Export Citation
  • 12.

    Gravis G, Fizazi K, Joly F. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol 2013;14:149158.

    • Search Google Scholar
    • Export Citation
  • 13.

    Aaronson NK, Ahmedzai S, Bergman B. 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;85:365376.

    • Search Google Scholar
    • Export Citation
  • 14.

    Macquart-Moulin G, Viens P, Bouscary ML. Discordance between physicians' estimations and breast cancer patients' self-assessment of side-effects of chemotherapy: an issue for quality of care. Br J Cancer 1997;76:16401645.

    • Search Google Scholar
    • Export Citation
  • 15.

    Ringash J, O'Sullivan B, Bezjak A. Interpreting clinically significant changes in patient-reported outcomes. Cancer 2007;110:196202.

  • 16.

    Osoba D, Rodrigues G, Myles J. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol 1998;16:139144.

    • Search Google Scholar
    • Export Citation
  • 17.

    Koo TK, Li MY. A guideline of selecting and reporting intraclass correlation coefficients for reliability research. J Chiropr Med 2016;15:155163.

    • Search Google Scholar
    • Export Citation
  • 18.

    Twisk JW. Applied Longitudinal Data Analysis for Epidemiology: A Practical Guide, 2nd ed. Amsterdam, the Netherlands: Cambridge University Press; 2013.

    • Search Google Scholar
    • Export Citation
  • 19.

    Gravis G, Boher JM, Joly F. Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial. Eur Urol 2016;70:256262.

    • Search Google Scholar
    • Export Citation
  • 20.

    Colan SD. The why and how of Z scores. J Am Soc Echocardiogr 2013;26:3840.

  • 21.

    Di Maio M, Gallo C, Leighl NB. Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials. J Clin Oncol 2015;33:910915.

    • Search Google Scholar
    • Export Citation
  • 22.

    Basch E. New frontiers in patient-reported outcomes: adverse event reporting, comparative effectiveness, and quality assessment. Annu Rev Med 2014;65:307317.

    • Search Google Scholar
    • Export Citation
  • 23.

    Basch E, Deal AM, Dueck AC. Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. JAMA 2017;318:197198.

    • Search Google Scholar
    • Export Citation
  • 24.

    Christodoulou M, McCloskey P, Stones N. Investigation of a patient reported outcome tool to assess radiotherapy-related toxicity prospectively in patients with lung cancer. Radiother Oncol 2014;112:244249.

    • Search Google Scholar
    • Export Citation
  • 25.

    Basch E, Jia X, Heller G. Adverse symptom event reporting by patients vs clinicians: relationships with clinical outcomes. J Natl Cancer Inst 2009;101:16241632.

    • Search Google Scholar
    • Export Citation
  • 26.

    Mercieca-Bebber R, Palmer MJ, Brundage M. Design, implementation and reporting strategies to reduce the instance and impact of missing patient-reported outcome (PRO) data: a systematic review. BMJ Open 2016;6:e010938.

    • Search Google Scholar
    • Export Citation
  • 27.

    Ganz PA, Gotay CC. Use of patient-reported outcomes in phase III cancer treatment trials: lessons learned and future directions. J Clin Oncol 2007;25:50635069.

    • Search Google Scholar
    • Export Citation
  • 28.

    Marino P, Sfumato P, Joly F. Q-TWiST analysis of patients with metastatic castrate naive prostate cancer treated by androgen deprivation therapy with or without docetaxel in the randomised phase III GETUG-AFU 15 trial. Eur J Cancer 2017;84:2733.

    • Search Google Scholar
    • Export Citation
  • 29.

    Movsas B, Hunt D, Watkins-Bruner D. Can electronic web-based technology improve quality of life data collection? Analysis of Radiation Therapy Oncology Group 0828. Pract Radiat Oncol 2014;4:187191.

    • Search Google Scholar
    • Export Citation
  • 30.

    Basch E, Pugh SL, Dueck AC. Feasibility of patient reporting of symptomatic adverse events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a chemoradiotherapy cooperative group multicenter clinical trial. Int J Radiat Oncol Biol Phys 2017;98:409418.

    • Search Google Scholar
    • Export Citation
  • 31.

    Barata A, Martino R, Gich I. Do patients and physicians agree when they assess quality of life? Biol Blood Marrow Transplant 2017;23:10051010.

    • Search Google Scholar
    • Export Citation
  • 32.

    Jensen K, Bonde Jensen A, Grau C. The relationship between observer-based toxicity scoring and patient assessed symptom severity after treatment for head and neck cancer. A correlative cross sectional study of the DAHANCA toxicity scoring system and the EORTC quality of life questionnaires. Radiother Oncol 2006;78:298305.

    • Search Google Scholar
    • Export Citation
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