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Quality of Life: It’s Never Too Late

Guy's Hospital, London, United Kingdom

David Khayat

Salpetriere Hospital, Paris, France

THE IMPORTANCE of quality of life (QOL) as an end point in clinical trials is well established. The use of validated multidimensional instruments that systematically ask patients with cancer how they feel has yielded several important and, at times, unexpected results. Such measurements in trials will evaluate the overall clinical benefit a particular treatment has to a patient.¹ By these means, researchers can ascertain whether interventions are truly worthwhile.

At diagnosis, the patient’s perception of his or her QOL can be a powerful, independent prognostic indicator.² When assessed during and after treatment, QOL data provide invaluable clinical information. The assessment of the effect of treatment on QOL is important at all stages of the patient’s cancer journey; however, it has been most widely studied in patients undergoing treatment for advanced or metastatic disease. With the development of new agents, there are now many options for second-, third-, and fourth-line chemotherapy. Although these seldom achieve significant or durable objective responses as individual lines of treatment, clinicians and patients are certain that overall they are of benefit. Even if documented, such improvements in response rate or survival are no longer the only goals of cancer therapy. In this situation, QOL may be more informative and useful for both clinician and patient.

QOL issues are of paramount importance to patients. In a study by Silvestri et al,³ 81 patients with non–small-cell lung cancer (NSCLC) who had experienced cisplatin-based chemotherapy were asked to indicate the minimum survival benefit required to accept the side effects of chemotherapy for advanced disease. For a realistic survival benefit of 3 months, only 22% chose chemotherapy over supportive care alone. However, 68% chose such chemotherapy if it substantially reduced symptoms, even without prolonging life.

There has been a gradual shift from the dependence on objective response rates and survival as sole measures of efficacy, toward reliance on QOL assessment in trials of palliative chemotherapy in patients with advanced NSCLC.^4,5 We can now confirm that, even when palliative chemotherapy does not prolong survival in these patients, it can significantly ameliorate symptoms leading to improvements in QOL.

The issues of QOL in long-term survivors of cancer are quite different from the problems faced by patients at the time of diagnosis or during treatment. Although the number of studies exploring the QOL of cancer survivors is increasing, data from patients after curative therapy for NSCLC have been lacking.⁶

In this edition of the Journal of Clinical Oncology, Sarna et al⁷ report the first study of QOL in long-term survivors of NSCLC. This study required the use of validated instruments that focus on survivorship issues specific to this patient group, rather than those relating to the acute toxicity or initial hopes of therapy.⁸ The long-term consequences of treatment, comorbidity, second cancers, and effects on the patient’s family and caregivers are all issues that should be addressed in such studies. Generic, non–cancer-specific instruments and scales that screen for anxiety and depression also play a role in the comprehensive assessment of QOL issues in this population.

The study reported is retrospective. As such, it is prone to considerable selection bias, with a low rate of response to the initial invitation to participate. However, the study still yields clinically meaningful findings. Using tumor registry data, the authors identified 995 patients who had survived more than 5 years after the diagnosis of NSCLC. Only 142 patients (16%) responded and were eligible to take part. The reasons for this low rate of response are unclear. Were only the fit able and willing to respond, or was it that patients did not want to remember what they had been through? Each respondee provided data via a self-reporting questionnaire and a formal interview. Patient-derived data were obtained in conjunction with information regarding the patient’s initial diagnosis and treatment, physical and mental health status, several clinical variables, and history of tobacco use. These data were compared with generic QOL data in patients of similar demographics, including elderly patients and those with chronic airway disease.

Methodologic issues aside, this report gives clinicians a view of life from the perspective of lung cancer survivors. It confirms our knowledge that they are a heterogeneous group with different needs for support and follow-up. By collecting data on both physical and mental health, the authors are able to report on factors that seem to influence overall QOL. The factor with the most significant adverse effect was the presence of depression or anxiety. It is therefore possible that an appropriate intervention may, even at this late stage, improve QOL. Because of the cross-sectional nature of the study, it is not known whether such symptoms were present before the development of cancer or whether they became apparent at a later stage. However, recognition of depression or anxiety lends weight to the need for continued follow-up of cancer survivors in cancer clinics with multidisciplinary support.

Survivorship issues are likely to be dependent on the time since diagnosis. More than 50% of the patients who responded to this questionnaire had survived for greater than 10 years, so conclusions from this article may be applicable only to this specific patient group. The retrospective nature and limited population would not permit reliable evaluation or stratification of data according to duration of survival. Nevertheless, this is an important issue and is only likely to be reliably studied in a prospective manner. Despite modest progress in the treatment of early-stage, locally advanced, and metastatic NSCLC in recent years, these issues regarding long-term survivorship are likely to become more important. Should the mass screening programs currently being studied yield positive results, the number of early-stage patients being cured of their disease will no doubt increase.

As lung cancer most commonly occurs after the sixth decade of life, the study of long-term survivors will inevitably involve an elderly population. In this study, the mean age of respondents was 70 years and 80% were aged more than 65 years. Seventy percent reported one or more comorbid conditions, including the diagnosis of a second cancer in 24%. The study of QOL in the elderly is currently poorly understood, and few instruments have been designed with the older population in mind. Potential difficulties in assessment may be related to either the test or the patient. These include inadequate representation of issues of interest for the aged, possible excess of questions of minimal relevance, and excessive length and complexity of the test in conjunction with potential visual, hearing, or cognitive impairment.⁹ Sarna et al⁷ attempted to control for these factors by comparing the QOL outcomes with results from a study in which the same tests were used in a similar population without NSCLC. It is difficult in such a retrospective review to control for all confounding variables. Prospective trials in this population are urgently needed. A global network of physicians with an interest in cancer in the elderly, known as the International Society of Geriatric Oncology (SIOG), is now working to redress this imbalance. With formal, prospective evaluation of tools such as the Comprehensive Geriatric Assessment (CGA),¹⁰ our knowledge of this large, yet heterogeneous, patient group should improve. The CGA takes into account the multidimensional nature of the problems associated with aging. Using validated instruments, it provides information on the global physical and mental health of the patient in conjunction with assessment of comorbidity, functional dependence, socioeconomic status, and cognitive function. With the appropriate mechanisms in place to act on the problems identified, the CGA is a potential intervention in itself and future studies should be designed to assess the impact of this instrument on the QOL of elderly patients.

Although instruments specific to the QOL concerns of adult-onset cancer survivors have been developed,^8,11 certain methodologic questions remain. Is there a need for instruments specific to tumor type? Are we able to compare cancer survivors with normal controls? Indeed, whether QOL is best assessed in this population by using a general QOL questionnaire or a cancer-specific instrument also seems unresolved.⁶

How important to our clinical practice is QOL in long-term survivors of lung cancer? At this stage we do not really know, as this was the first study that has attempted to evaluate this question. Is it an issue that at this stage is worth pursuing? From a patient perspective, it is likely to be important in that reproducible, reliable, and relevant data are likely to influence patient decisions regarding treatment options. We have learned from other situations that QOL evaluation has achieved this goal. Prospective evaluation using validated and population-appropriate models is required to assess adequately the QOL issues in long-term survivors of NSCLC. The study of QOL during treatment gives clinicians information about the patient beyond the disease. Study of the long-term effects of curative therapy on QOL can only add to this knowledge and guide future developments in patient management.

REFERENCES

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3. Silvestri G, Pritchard R, Welch HG: Preferences for chemotherapy in patients with advanced non-small cell lung cancer: Descriptive study based on scripted interviews. BMJ 317: 771-775, 1998[Abstract/Free Full Text]

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7. Sarna L, Padilla G, Holmes C, et al: Quality of life of long-term survivors of non–small-cell lung cancer. J Clin Oncol 20: 2920-2929, 2002[Abstract/Free Full Text]

8. Ferrell BR, Dow KH, Grant M: Measurement of the quality of life in cancer survivors. Qual Life Res 4: 523-531, 1995[CrossRef][Medline]

9. Balducci L: Perspectives on quality of life of older patients with cancer. Drugs Aging 4: 313-324, 1994[Medline]

10. Repetto L, Fratino L, Audisio RA, et al: Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: An Italian Group for Geriatric Oncology study. J Clin Oncol 20: 494-502, 2002[Abstract/Free Full Text]

11. Wyatt G, Friedman LL: Long-term female cancer survivors: Quality of life issues and clinical implications. Cancer Nurs 19: 1-7, 1996[CrossRef][Medline]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Steer, C. B. Articles by Khayat, D. Search for Related Content PubMed PubMed Citation Articles by Steer, C. B. Articles by Khayat, D. Social Bookmarking                            What's this?