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Original Investigation
December 2018

Evaluating Progression-Free Survival as a Surrogate Outcome for Health-Related Quality of Life in Oncology: A Systematic Review and Quantitative Analysis

Author Affiliations
  • 1Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
  • 2Alberta PROMs & EQ-5D Research & Support Unit, School of Public Health, University of Alberta, Li Ka Shing Centre for Health Research Innovation, Edmonton, Alberta, Canada
  • 3Department of Diagnostic Radiology, University of Toronto, Toronto, Ontario, Canada
  • 4Department of General Surgery, Université de Sherbrooke, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada
  • 52nd Department of General Surgery, Jagiellonian University Medical College, Krakow, Poland
  • 6Centre for Research, Training and Innovation in Surgery (CERTAIN Surgery), Krakow, Poland
  • 7Department of General Medicine, Kurashiki Central Hospital, Miwa Kurashiki Okayama, Japan
  • 8High Institute of Public Health, Alexandria University, Al Ibrahimeyah Qebli WA Al Hadrah Bahri Qesm Bab Sharqi, Alexandria Governorate, Egypt
  • 9Drug Information Center, Tanta Chest Hospital, Ministry of Health, Tanta, Egypt
  • 10Department of Medicine, McMaster University, Hamilton, Ontario, Canada
  • 11Department of Surgery, Okinawa Prefectural Nanbu Medical Center & Children’s Medical Center, Haebaru-cho, Shimajiri-gun, Okinawa, Japan
  • 12Department of Clinical Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Yoshida Konoe-cho, Sakyo-ku, Kyoto, Japan
  • 13Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
  • 14Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
  • 15Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
  • 16Department of Family Medicine, McMaster University, Hamilton, Ontario, Canada
  • 17Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Huangpu District, Shanghai, People’s Republic of China
  • 18Accident and Emergency Department, Queen Mary Hospital, High West, Hong Kong
  • 19Research Ethics in Medicine Study Group (REMEDY), Department of Philosophy and Bioethics, Jagiellonian University Medical College, Krakow, Poland
  • 20Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, India
  • 21Health Sciences Library, McMaster University, Hamilton, Ontario, Canada
  • 22Biostatistics Unit/FSORC, St Joseph’s Healthcare Hamilton, Hamilton, Ontario, Canada
  • 23Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada
  • 24Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
  • 25Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada
  • 26Kingston Health Sciences Centre, Cancer Centre of Southeastern Ontario, Kingston General Hospital, Kingston, Ontario, Canada
  • 27Cancer Research Institute, Queen’s University at Kingston, Kingston, Ontario, Canada
  • 28Centre for Health Economics and Policy Analysis, McMaster University, Hamilton, Ontario, Canada
  • 29Programs for Health Economics and Outcome Measures, Hamilton, Ontario, Canada
JAMA Intern Med. 2018;178(12):1586-1596. doi:10.1001/jamainternmed.2018.4710
Key Points

Question  How strongly is progression-free survival (PFS) associated with health-related quality of life (HRQoL) in studies of cancer treatments?

Findings  This systematic review and quantitative analysis of 52 articles reporting on 38 randomized clinical cancer trials did not find a significant association between PFS and HRQoL.

Meaning  These findings raise questions about the assumption that interventions prolonging PFS also improve HRQoL in patients with cancer and suggest that HRQoL should be measured directly and accurately, with adequate follow-up time, in future studies.

Abstract

Importance  Progression-free survival (PFS) has become a commonly used outcome to assess the efficacy of new cancer drugs. However, it is not clear if delay in progression leads to improved quality of life with or without overall survival benefit.

Objective  To evaluate the association between PFS and health-related quality of life (HRQoL) in oncology through a systematic review and quantitative analysis of published randomized clinical trials. Eligible trials addressed oral, intravenous, intraperitoneal, or intrapleural chemotherapy or biological treatments, and reported PFS or health-related quality of life.

Data Sources  For this systematic review and quantitative analysis of randomized clinical trials of patients with cancer, we searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 2000, through May 4, 2016.

Study Selection  Paired reviewers independently screened citations, extracted data, and assessed risk of bias of included studies.

Data Extraction and Synthesis  We examined the association of difference in median PFS duration (in months) between treatment groups with difference in global, physical, and emotional HRQoL scores between groups (standardized to a range of 0-100, with higher scores representing better HRQoL) using weighted simple regressions.

Main Outcome and Measure  The association between PFS duration and HRQoL.

Results  Of 35 960 records screened, 52 articles reporting on 38 randomized clinical trials involving 13 979 patients across 12 cancer types using 6 different HRQoL instruments were included. The mean (SD) difference in median PFS between the intervention and the control arms was 1.91 (3.35) months. The mean (SD) differences in change of HRQoL adjusted to per-month values were −0.39 (3.59) for the global domain, 0.26 (5.56) for the physical domain, and 1.08 (3.49) for the emotional domain. The slope of the association between the difference in median PFS and the difference in change for global HRQoL (n = 30 trials) was 0.12 (95% CI, −0.27 to 0.52); for physical HRQoL (n = 20 trials) it was −0.20 (95% CI, −0.62 to 0.23); and for emotional HRQoL (n = 13 trials) it was 0.78 (95% CI, −0.05 to 1.60).

Conclusions and Relevance  We failed to find a significant association between PFS and HRQoL in cancer clinical trials. These findings raise questions regarding the assumption that interventions prolonging PFS also improve HRQoL in patients with cancer. Therefore, to ensure that patients are truly obtaining important benefit from cancer therapies, clinical trial investigators should measure HRQoL directly and accurately, ensuring adequate duration and follow-up.

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    1 Comment for this article
    No wonder
    Tzvi Zur, MD | Physician. Hematology
    If the benefit of PFS was only 1.9 months, which is nothing to be proud about.. and probably has no clinical relevance, then.. no wonder that there was no correlation with QoL..

    Besides.. "CANCER" is too global issue and the QoL so different with different cancers..
    My opinion is that you cannot compare QoL of patients with so many CANCERS. This is just a statistic game with no actual relevance to medicine.
    CONFLICT OF INTEREST: None Reported
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