QOL Research Helps Physicians Tailor Cancer Treatment

May 1, 1997

Concerns over the rising costs of health care in the United States have recently focused attention on the young discipline of health services research.

Concerns over the rising costs of health care in the United States haverecently focused attention on the young discipline of health services research.

By measuring health outcomes, such as consumer satisfaction, evaluatedhealth status, and perceived health status, health services researchersare helping to assist physicians in determining appropriate treatment strategiesthat are tailored to individuals. Perceived health status, or quality oflife (QOL), is particularly important in determining efficacious treatmentprotocols.

Quality of life is a multidimensional construct, affected by both treatmentand disease, that includes somatic symptoms, functional ability, emotionalwell-being, social functioning, sexuality and body image, treatment satisfaction,and global quality of life.[1-4]

While other measures, such as pain scales, mood scales, measures ofability to fulfill the activities of daily living, and toxicity ratings,provide useful information, they are often unidimensional in nature.

QOL measures emphasize the impact of symptoms on patients' functionalstatus and well-being, providing a more comprehensive evaluation of theimpact of illness and its treatment on patients than does a unidimensionalmeasure.

The application of QOL studies to the clinical practice of oncologybegins with the identification of baseline patient characteristics thatare predictive of prognosis, response to treatment, and the likelihoodof experiencing treatment-related toxicities.

This, in turn, allows oncologists to advise patients on the differingeffects on QOL of different treatments with comparable survival benefits,as well as assist patients in choosing between palliative therapies thatinvolve tradeoffs between survival and QOL.

The ability of QOL assessment to predict patient prognosis and responseto treatment has been demonstrated by Ganz et al[5], who observed a significantrelationship between QOL at diagnosis and subsequent survival in patientswith metastatic non-small-cell lung cancer.

Using the Functional Living Index-Cancer (FLIC), a validated cancer-specificmeasure of QOL, Ganz et al found that patients scoring high on the FLICat baseline (prior to any treatment) had a median survival of 24 weeks,compared with 11.9 weeks for patients who scored low. This finding suggeststhat patients with metastatic non-small-cell lung cancer and low QOL atdiagnosis are likely to have a worse outcome regardless of treatment.

In less severely ill patients, such as newly diagnosed breast cancerpatients, baseline QOL assessment may assist in the identification of patientsat high risk for difficulties coping with treatment and later on with "cancersurvivorship."[6]

Localized Prostate Cancer

The treatment of localized prostate cancer is another area in whichthe results of QOL research can be used to help guide medical decisionmaking. Nonran-domized studies of patients with localized prostate cancerhave demonstrated similar 10-year disease-specific survival rates and overallsurvival rates (approximately 85% and 60%, respectively) for patients treatedwith radical prostatectomy or radiation therapy.[7] Thus, QOL is an extremelyimportant tool for patients deciding which therapy to pursue.

In a descriptive study, Lim et al[8] asked all patients with localizedprostate cancer who underwent either radical prostatectomy or radiationtherapy to complete several QOL measures, including the FLIC and the Profileof Mood States.

Patients treated with radical prostatec-tomy had significantly worsesymptoms of urinary incontinence and worse sexual function scores, whilepatients treated with radiation therapy were more likely to report problemswith loose stools.

In both groups, problems with incontinence, sexual functioning, andbowel functioning were significantly associated with higher scores fordepression, tension, and fatigue on the Profile of Mood States, so theseproblems do appear to impact QOL.

In a similar study, Litwin et al[9] compared QOL outcomes in men treatedwith radical prostatectomy, radiation therapy, or observation, as wellas with a randomly selected, age-matched control group of men without prostatecancer.

The researchers found no significant differences in overall QOL betweenthe treatment groups or between men with prostate cancer and the age-matchedcontrols. However, men with prostate cancer did report more problems withsexual functioning than men without prostate cancer. And problems withurinary function were reported more often in patients treated with surgery,while patients undergoing radiation therapy experienced more problems withbowel function.

Tradeoffs: Survival vs QOL

Making decisions that involve tradeoffs between survival and QOL isa frequent part of oncology practice. For many patients, treatment decisionsare based exclusively upon a desire to prolong survival, while for otherpatients preserving QOL, even at the expense of length of life, is of paramountimportance.

Randomized clinical trials that compare the effects of palliative treatmentson survival and QOL can provide important information to physicians andto their patients when it is necessary to make a very difficult and personalchoice regarding various possible treatments.

One trial by Chodak et al[10] examines the differences in survival andQOL, measured every three months for one year, for men with advanced prostatecancer treated with antiandrogen therapy (bicalutamide, Casodex) or castration.

All patients reported increased physical capacity and vitality, lesslimitation of activity, less time in bed, and less pain, regardless oftreatment. However, bical-utamide-treated patients maintained baselinesexual interest and functioning throughout treatment while patients treatedwith castration did not. The trade-off is that disease progression andsurvival analysis both favored castration.

The Measurement Tools

The measurement of QOL is a complex task that draws on the fields ofsocial science research and psychometrics.[11,12] The tools used to measureQOL, in general, are self-administered questionnaires that have undergoneextensive reliability and validity testing.

The tools currently available for clinical research include measuresof general health status that can be applied to a variety of clinical situations,cancer-specific instruments, and symptom-oriented scales .

Instruments Used to Measure Quality of Life in Cancer Patients

General health status instruments

Cancer-specific instruments

Cancer site-specific instruments

Symptom-oriented scales

In developing or selecting a QOL instrument for use in a research orclinical setting, several methodological considerations need to be addressedto ensure the validity of the data obtained, as well as its clinical relevance.

Problem of Missing Data

Many of the cancer-specific QOL instruments have been tested primarilyin research settings with adequate staff to ensure completion of the questionnaires.Use of these same QOL measures in clinical treatment trials has presentedfrequent problems with missing data, especially in patients with deterioratingphysical status for whom there is the greatest interest in measuring QOL.[13]

In a study by Ganz et al[5] of QOL in lung cancer patients, the KarnofskyPerformance Status, an expert rating of patients' functional status, showedthat patients with the lowest performance status had a disproportionatelylow rate of self-administration of the QOL questionnaire, with 30% of thequestionnaires being completed by the interviewer.

As patients' functional status deteriorated during the course of theirdisease, self-administration rates declined, and missing data was an evengreater problem. Because of missing data, these investigators were unableto perform their intended comparison of quality of life between two treatmentarms (supportive care alone and supportive care with combination chemotherapy).

This difficulty in obtaining complete data on quality of life has beennoted in a number of trials, and stems from a combination of patient andstaff-related problems.[13-15]

In July 1996, the major international cooperative clinical trials groupsmet at a workshop in Switzerland, with representation of methodologistsand statisticians, and a forthcoming supplement to Statistics in Medicinebased on the workshop will address in more detail the problem of missingQOL data in clinical trials.

Another meth-odologic concern in QOL research lies in the interpretationof differences in scores over time. In clinical trials, differences betweengroups of patients can be statistically significant over time. These differences,however, are not always applicable to an individual patient's scores inclinical practice.[16] What does a two-point change in emotional well-beingon a particular QOL instrument mean in an individual patient assessed fourweeks apart?

Clinically Important Differences

While work has been done in trying to ascertain the minimal clinicallyimportant difference on a QOL scale for patients with other chronic illnesses,such as congestive heart failure, it remains to be established for QOLinstruments commonly used in oncology.[17]

One additional concern of QOL instruments is that they are languageand culture specific. Patients' responses to illness are culturally mediated[18,19],and their perception of illness and its effect on a QOL dimension are alsosubject to culture-specific constructs.

Validity must therefore be established in each new patient population,which presents an important challenge in linguistically and culturallydiverse cities like Los Angeles.

Important Issues Remain

The time is not too far off when oncologists will be able to order a"QOL Test" to help them evaluate a patient, much in the way theyorder bone scans or chest x-rays today.

Using QOL instruments in clinical practice will allow oncologists toobtain baseline information about patients and, by applying the resultsof QOL research as we described earlier, to help predict prognosis, plantreatment, and anticipate patients' needs for social or psychological support.

Although QOL assessment is on the verge of becoming available for usein clinical practice, further testing in the clinical setting is required,and several issues need to be addressed.

First, QOL instruments need to be reliable for individual subjects,which is particularly challenging due to the focus on group outcomes inthe clinical research setting.

Quality of life instruments must also be sensitive enough to detectchanges over time in an individual patient. To be applicable in clinicalpractice, QOL instruments must be capable of determining and interpretinga clinically significant change, while maintaining "user-friendly"characteristics.

Improving oncology outcomes requires a comprehensive, multidimensionalapproach, of which QOL assessment is proving to be a valuable asset.

References:

1. Cella DF, Bonomi AE: Measuring QOL: 1995 Update (suppl). Oncology9(11):47-60, 1995.

2. National Cancer Institute, Division of Cancer Prevention and ControlResearch: QOL assessment in cancer clinical trials: Report of the workshopon QOL research, 1990.

3. Cella DF, Tulsky, DS: QOL in cancer: Definition, purpose and methodof measurement. Cancer Invest 11(3):327-336, 1993.

4. Aronson NK: QOL: What is it? How should it be measured? Oncology2(5):69-74, 1988.

5. Ganz PA, Lee JJ, Siau J: Quality of life assessment: An independentprognostic variable for survival in lung cancer. Cancer 67:3131-3135, 1991.

6. Coscarelli Schag AC, Ganz PA, Polinsky ML, et al: Characteristicsof women at risk for psychosocial distress in the year after breast cancer.J Clin Oncol 11:783-793, 1993.

7. Garnick MB: Prostate cancer: Screening, diagnosis and management.Ann Intern Med 118:849-855, 1993.

8. Lim AJ, Brandon AH, Fiedler J, et al: Quality of life: Radical prostatectomyversus radiation therapy for prostate cancer. Journal of Urology 154:1420-1425,1995.

9. Litwin MS, Hays RD, Fink A, et al: Quality-of-life outcomes in mentreated for localized prostate cancer. JAMA 273:129-135, 1995.

10. Chodak G, Sharifi R, Kasimis B, et al: Single-agent therapy withbicalutamide: A comparison with medical or surgical castration in the treatmentof advanced prostate carcinoma. Urology 46:849-855, 1995.

11. Ware JE: Standards for validating health measures: Definition andcontent. J Chronic Dis 40:473-480, 1987.

12. Tulsky DS: An Introduction to test theory. Oncology 4(5):43-48,1990.

13. Coats A, Gebski V, Bishop JF, et al: Improving the quality of lifeduring the chemotherapy for advanced breast cancer: A comparison of intermittentand continuous treatment strategies. N Engl J Med 317:1490-1495, 1987.

14. Finkelstein DM, Cassileth BR, Bonomi PD, et al: A pilot study ofthe functional living index-cancer (FLIC) scale for the assessment of qualityof life for metastatic lung cancer patients and Eastern Cooperative OncologyGroup Study. Am J Clin Oncol 11:630-633, 1988.

15. Hayden KA, Moinpour CM, Metch B, et al: Pitfalls in quality of lifeassessment: Lessons from a Southwest Oncology Group Breast Cancer ClinicTrial. Oncol Nurs Forum 20:1415-1419, 1993.

16. Guyatt G, Walter S, Norman G: Measuring change over time: Assessingthe usefulness of evaluative instruments. J Chronic Dis 40(2):171-178,1987.

17. Jaeschke R, Singer J, Guyatt GH: Measurement of health status: Ascertainingthe minimal clinically important differences. Control Clin Trial 10:407-415,1989.

18. Angel R, Thoits P: The impact of culture on the cognitive structureof illness. Culture Medicine and Psychiatry 11(4):465-494, 1987.

19. Kagawa-Singer M: Socio-economic and cultural influences on the cancercare of women. Semin Oncol Nurs 11(2):109-119, 1995.