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Journal of Clinical Oncology, Vol 26, No 25 (September 1), 2008: pp. 4215-4216 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.18.4994
Predication of Cancer Patients’ Survival by Pain Interference Items Is Not the Same As Evidence That Pain Intensity Is a Survival PredictorDepartment of Circulation and Medical Imaging, Norwegian University of Science and Technology; Department of Intensive Care Medicine, St Olavs University Hospital, Trondheim, Norway
Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology; Department of Oncology and Radiotherapy, St Olavs Hospital, Trondheim, Norway To the Editor: We read with great interest the recent paper by Halabi et al1 reporting that pain predicts overall survival in men with metastatic prostate cancer. The concept that patient subjective symptoms, such as pain and other adverse effects, influence survival is of general interest and of great clinical importance. The authors are to be complemented for analyzing this relationship. As outlined in the Discussion of the article, other patient-related outcomes (PROs) such as general well-being have been shown to predict survival; however, pain as one of the key symptoms in advanced cancer has previously not been given much attention. PROs are of great importance in clinical practice. When single items are applied to measure subjective symptoms, the intuitive clinical interpretation will often be obvious. If more complex questions are asked, such as how one subjective symptom may interfere with others, the content validity of the outcome may be considerably more complex. This complexity may further increase when summary scores of various dimensions are applied. An important question for this study is whether pain intensity itself influences survival or whether pain is simply a marker for more advanced disease. In this respect, we would like to take part in the discussion of the findings by Halabi et al.1 First, in the survival analyses, the authors used the Brief Pain Inventory (BPI) pain interference scores and not the BPI pain intensity scores as an indicator of pain perception. The BPI pain interference scores ask patients to interpret how much their function is limited by pain. One key clinical question is: What is the clinical meaning of these interference items? In a recent study, we reported that it is difficult for cancer patients to decipher loss of function caused by pain from loss of function as a result of other causes.2 In fact, we observed similar scores when the BPI interference items were rephrased from pain interference on functions to an overall assessment of each of the seven functions in the BPI. These observations suggest that the patients are not able to report the true pain-related component of interference on functions, and therefore, the pain interference will also reflect the loss of function caused by progressive disease and anticancer treatments. In the report by Halabi et al,1 all seven items of pain interference predicted overall survival almost equally. These finding may be interpreted to mean that all seven items measure one general dimension, which may be named general illness or lack of well-being. Such an interpretation is in concordance with the article cited earlier by Stenseth et al.2 Given these questions, we are curious about whether the relationship between pain interference and survival observed in the study by Halabi et al1 is also present if any of the pain intensity items of the BPI are analyzed. Second, the point presented in this letter suggesting that the BPI pain interference items are influenced by more than pain is underlined by the fact that several markers reflecting disease (performance status, hemoglobin, prostate-specific antigen, alkaline phosphatase, lactate dehydrogenase, and morphine doses) were different between patients with high versus low BPI interference scores. Given these uncertainties, we fully agree with Halabi et al1 that the possible link between patients’ experiences of subjective symptoms and biologic outcomes such as survival is a research field that should be pursued vigorously. Furthermore, when applying PROs in research, we will argue for careful examination of the content validity of any outcomes that is used in clinical research. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: None Stock Ownership: None Honoraria: Pål Klepstad, GlaxoSmithKline, Mundipharma; Stein Kaasa, Nycomed, Mundipharma Research Funding: Stein Kaasa, Nycomed Expert Testimony: None Other Remuneration: None REFERENCES
1. Halabi S, Vogelzang NJ, Kornblith AB, et al: Pain predicts overall survival in men with metastatic castration-refractory prostate cancer. J Clin Oncol 26:2544-2549, 2008 2. Stenseth G, Bjørnnes M, Klepstad P, et al: Can cancer patients assess the influence of pain on functions? A randomised, controlled study of the pain interference items in the Brief Pain Inventory. BMC Palliat Care 6:2, 2007[CrossRef][Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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