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Palliative Chemotherapy or Watchful Waiting? A Vignettes Study Among Oncologists

From the Department of Medical Psychology, Internal Medicine, Clinical Epidemiology, and Biostatistics, Academic Medical Center, University of Amsterdam, and Department of Internal Medicine, University Medical Center, Amsterdam, the Netherlands.

Address reprint requests to CG Koedoot, MA, Academic Medical Center, Department of Medical Psychology, PO Box 22700, 1100 DE Amsterdam, the Netherlands; email: c.g.koedoot{at}amc.uva.nl

	ABSTRACT

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PURPOSE: To determine the preferences of oncologists for palliative chemotherapy or watchful waiting and the factors considered important to that preference.

METHODS: Sixteen vignettes (paper case descriptions), varying on eight patient and treatment characteristics, were designed to assess the oncologists’ preferences. Their strength of preference was rated on a 7-point scale. An orthogonal main effects design provided a subset of all possible combinations of the characteristics, allowing estimations of the relative weights of the presented characteristics. A written questionnaire was sent to a random sample of oncologists (N = 1,235).

RESULTS: The response rate was 67%, and 697 questionnaires were available for analysis. Eighty-one percent of the respondents were male. The mean age was 46 years. We found considerable variation among the oncologists. No major associations between physician characteristics and preferences were found. Of the patient and treatment characteristics affecting treatment preference, age was the strongest predictor, followed by the patient’s wish to be treated and the expected survival gain. Other patient and treatment characteristics had a limited effect on preferences, except for psychologic distress, which had no independent impact.

CONCLUSION: Patients will encounter different decisions depending on their oncologists’ preferences and their own personal background. Therefore, to ensure adequate information for decision-making processes, decision aids are proposed.

	INTRODUCTION

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DURING THE PAST decade, there has been little improvement in survival for the most common types of cancer. As a result, approximately half of all cancer patients will become eligible for palliative treatment at some point in time.¹ Many patients will receive palliative chemotherapy, endocrine treatment, surgery, or radiation therapy, not with curative intention, but primarily to ensure an optimal quality of life and/or sometimes increase their length of survival.^2,3 In palliative oncology, chemotherapy and watchful waiting are often equivalent options.

Palliative chemotherapy not only has limited efficacy but side effects as well. The efficacy of palliative chemotherapy in clinical trials is often evaluated by its ability to induce a tumor response. However, tumor shrinkage does not necessarily imply a benefit to patients.⁴ There have been optimistic expectations about the success of chemotherapy in the treatment of metastatic tumors of adults. However, "pessimists have been right and the optimists wrong"⁴ about the subsequent achievements of chemotherapy as a treatment for metastatic solid tumors of adults. The effect of palliative chemotherapy on survival is modest.² With regard to the effect of treatment on quality of life, researchers have found different outcomes. In some studies, palliative chemotherapy seemed to enhance a patient’s quality of life significantly.^5-9 However, Ramirez et al¹⁰ reported that after palliative chemotherapy, only 26% of breast cancer patients felt better. Finally, there are also studies that reported no improvement or deterioration of quality of life as an effect of palliative chemotherapy.^11-14 Thus, physicians may have a dilemma when proposing palliative chemotherapy, and patients may have a dilemma about whether to accept it.^3,15 Still, such treatment is offered to many patients and often accepted by them.¹⁶

The other, alternative option is watchful waiting. Such a wait-and-see policy focuses on the quality of life of patients by providing symptomatic treatments, thus minimizing their physical complaints. However, although equivalent to a certain extent to palliative chemotherapy, in medical practice, watchful waiting is not often explicitly discussed with patients.¹⁶

Data on patient preferences for palliative chemotherapy or watchful waiting are sparse.¹⁷ Whereas this might be considered unfortunate, patients with a life-threatening disease often want to leave important decisions to their physician.^18-21 Consequently, the preference of physicians is weighty in actual decision making. However, we know even less about the preferences of physicians in palliative oncology.

Generally accepted guidelines about offering palliative chemotherapy are usually lacking. Little is known about the magnitude of practice variation and about considerations that play a role in attitudes towards palliative chemotherapy. Variation among oncologists is usually found when no option is evidently preferable²² and may be thus expected.

We studied the strength of preference for palliative chemotherapy versus watchful waiting for treating patients with incurable cancer among a large random sample of oncologists. We approached the clinical reality by using vignettes to enable us to confront all the specialists with the same "paper patient." Additionally, the impact of physician, patient, and treatment characteristics on their preferences was assessed. The study was carried out between July and November 1999 in the Netherlands. Medical specialists who treat cancer patients indicated their strength of preference for palliative chemotherapy versus watchful waiting by evaluating 16 vignettes of patients with incurable cancer.

	METHODS

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Participants
All members of the Society of Medical Oncology (n = 262), the Society of Pulmonologists and Tuberculosis (n = 346), the Society of Surgical Oncology (n = 332), the Society of Radiotherapy and Oncology (n = 150), the Society of Gynecological Oncology (n = 108), and the Head and Neck Cancer Society (head and neck surgeons, n = 37) were eligible for the study. All clinicians (N = 1,235) were sent a questionnaire.

Questionnaire
The questionnaire contained items on physician characteristics, including specialty (medical oncology, pulmonology, surgery, radiation oncology, gynecology, or head and neck surgery), sex, age, employment status, and type of hospital (academic teaching, nonacademic teaching, or nonteaching). Additionally, we asked what percentage of their patients was being treated for malignancies. After 6 weeks, a reminder was sent to nonresponders.

We used a set of vignettes to assess the strength of preference for palliative chemotherapy versus watchful waiting and to establish the influence of physician, patient, and treatment characteristics on these preferences. A vignette is a paper case description in which patient, disease, and treatment characteristics are given (Table 1). The selection of relevant factors and the wording of the vignettes were based on in-depth interviews with three medical oncologists and on the outcomes of a pilot study. Eight patient background and outcome parameters were selected. All factors varied at two or three levels: (1) age (40, 60, or 80 years), (2) physical condition (World Health Organization [WHO]-0, WHO-1, or WHO-2), (3) psychologic distress (little anxiety and/or depression v severe anxiety and/or depression), (4) patient’s wish to be treated (no v outspoken wish to be treated), (5) expected toxicity of chemotherapy (mild v severe toxicity), (6) disease-related complaints expected in the future (few v many complaints), (7) chance of tumor response (15%, 25%, or 50%), and (8) possible chemotherapy-related survival gain (no survival gain v survival gain of 3 months or more). The case descriptions could thus be cancer-specific because relevant considerations in the decision-making process were covered by the factors included. For each vignette, the respondents rated their strength of preference for palliative treatment versus watchful waiting on an anchored 7-point scale ranging from a strong preference for watchful waiting (1) via a neutral position, implying no preference for either alternative (4), to a strong preference for palliative chemotherapy (7).

To avoid order effects, the vignettes were randomly presented to respondents in three different orders. The anchoring points, preference for watchful waiting (1) and preference for palliative chemotherapy (7), were randomly reversed as well.

Statistical Analyses
The characteristics of the sample were summarized using descriptive statistics. Differences between proportions were analyzed with the ² statistic. After recoding, higher preference scores systematically indicated a stronger preference for palliative chemotherapy. The strength of preference for each vignette was analyzed using a mixed linear model with a null model case as a fixed factor and individual respondents as a random factor. The physician, patient, and treatment characteristics were added as main effects afterwards. In the model-building phase, the Akaike Information Criterion²³ in combination with the maximum likelihood estimation was used. The final models were estimated using restricted maximum likelihood to obtain appropriate SE. Finally, the least-square-mean and corresponding SE were estimated from the model, whereby cases were split into their characteristics and corrected for the neutral preference value. The analyses were performed in S-plus for Windows using the function linear mixed effects model (LME, version 8.0; MathSoft Inc, Cambridge, MA), whereas computation of least-square-mean was performed with a S-plus function designed for this study. Statistical uncertainty was expressed in 95% confidence intervals (CIs).

	RESULTS

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Participants
Of the 1,235 questionnaires that were sent to the physicians, 826 (67%) were returned. Of those, 101 were from specialists stating that they did not treat cancer patients (any longer), 12 had not been delivered, and 16 were incompletely returned. Thus, 697 questionnaires were used in the analyses. There was no significant difference in response rate between the different specialties (P = .12; ² statistic). The characteristics of the 697 respondents are listed in Table 2. The majority of the responding physicians were male (81%), with a mean age (SD) of 46 (7.9) years. Almost all specialists working in an academic hospital were employed by the hospital, whereas specialists in nonacademic hospitals usually worked in a solo or group practice.

Strength of Preference for Palliative Chemotherapy
The mean overall preference for palliative chemotherapy for the 16 case descriptions combined was 3.70 (95% CI, 3.59 to 3.81), indicating a slightly stronger preference for watchful waiting. On average, as is presented in Fig 1, the respondents favored palliative chemotherapy in seven cases (especially in case 3) and opted for watchful waiting in eight cases (especially in case 2). There was no clear preference for either alternative in case 12. In one of 16 cases (case 2), more than 90% of the physicians strongly preferred watchful waiting (score 1 or 2). In three other cases (cases 4, 5, and 11), 66% reported a strong preference for watchful waiting (score 1 or 2). In other cases, there was more variation among the physicians.

View larger version (27K): [in this window] [in a new window]   Fig 1. Mean preference score (95% CI) for palliative chemotherapy or watchful waiting.

Impact of Patient and Treatment Characteristics on Treatment Preference
Figure 2 shows the independent impact of the case (patient and treatment) characteristics on the preference of the respondents. As compared with the reference group of patients of 60 years of age, being 80 years old had the strongest independent impact on the oncologists’ preferences, with a mean increase of preference score in favor of watchful waiting of -1.25 points (95% CI, 1.01 to 1.49). In contrast, when the patients were 40 years old, there was a significant shift of the preference towards palliative chemotherapy (mean increase of 0.68 points; 95% CI, 0.44 to 0.91).

View larger version (23K): [in this window] [in a new window]   Fig 2. Independent impact of patient and treatment characteristics on the preference score for palliative chemotherapy or watchful waiting of the respondents.

As compared with the situation in which no survival gain was expected, a survival gain of 3 months was strongly associated with the preference for palliative chemotherapy (mean increase of 1.13; 95% CI, 0.91 to 1.35).

All but one of the remaining case characteristics had a significant, albeit smaller, independent impact on the preference scores. Mild toxicity of the treatment led to a stronger preference for palliative chemotherapy as compared with severe toxicity. When patients were suffering from a worse physical condition or when an increase of disease-related complaints was expected, a stronger preference for palliative chemotherapy was reported. If there was 50% chance of tumor response, the preference for palliative chemotherapy was stronger than in cases with a smaller chance of tumor response. Psychologic distress was found to have no independent influence on treatment preferences.

	DISCUSSION

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Diversity in patterns of practice and considerations that play a role in deciding about palliative chemotherapy may be expected, but little is known about them. We therefore studied the strength of preference for palliative chemotherapy versus watchful waiting, two alternative options for patients with incurable cancer, among a large random sample of oncologists. To sum up the dilemma with these two alternative options, physicians chose palliative chemotherapy in a situation with a possible survival gain of 3 months with existing physical complaints and when future complaints are expected. Watchful waiting was preferred in cases where they expect severe toxicity of chemotherapy, where there is no explicit wish of the patients to be treated, and when patients are of older age.

It is difficult to assess the influence of different considerations of specialists on their actual palliative treatment preferences. Therefore, we approached the clinical reality by using vignettes, ie, paper case descriptions. This approach enabled us to confront all specialists with the same "patients." It has proven useful in earlier studies among oncologists and provides insight into their treatment preferences.^24-27 Peabody et al²⁸ recently compared vignettes, standard patients, and chart abstractions and concluded that actual clinical practice can be measured in a valid manner by using such vignettes.

The physicians’ preference scores were well distributed. This result indicates that we succeeded in eliciting preferences for both palliative chemotherapy and watchful waiting. The small CIs reveal a considerable consensus among physicians with regard to individual patient profiles. However, in only 25% of the cases, an agreement percentage of 66% was achieved. In a comparable study, Lind et al²⁹ found a higher level of agreement, but they nevertheless interpreted this as considerable heterogeneity. According to these authors, personal values might be at stake. On the other hand, practice variation, especially when equivalent options are available, is often seen.³⁰

With the exception of specialty, physician characteristics such as sex, age, employment status, type of hospital, and number of cancer patients treated did not influence preference scores. To some extent, these findings are in contrast with the outcomes of a smaller study performed by Tannock et al²⁶ in which both sex and age had an impact on the preference of physicians for chemotherapy. Their results might be explained by the fact that their physicians were younger and were more often female. Additionally, their scenarios referred to adjuvant rather than palliative chemotherapy. Our only significant finding regarding physician characteristics is that radiation oncologists have, on average, a stronger preference for watchful waiting. This might be explained by the fact that radiotherapy is usually intended to relieve symptoms in the short term with a minimum of side effects, whereas palliative chemotherapy may induce tumor shrinkage in the long term only and may result in substantially more severe side effects.

It is important to understand which patient-, disease-, or treatment-related characteristics are relevant for the oncologists’ preference for palliative chemotherapy. Palliative care means striving to achieve or maintain an acceptable quality of life as long as possible. Palliative chemotherapy tries to relieve or postpone symptom distress, and thus enhance quality of life, by reducing tumor size. Watchful waiting tries to maintain the quality of life by using treatments directed against specific symptoms only when they occur. In line with its objective, it can be expected that palliative chemotherapy is preferred when a patient has (tumor-related) physical complaints or if major physical complaints are expected in the near future. Present or future physical complaints were indeed found to be indicative for a stronger preference for palliative chemotherapy in our study.

The rate of response to chemotherapy and the possible survival gain associated with it are also expected to influence preferences for palliative chemotherapy. This expectation was supported by our results. Palliative chemotherapy was more strongly preferred when there was a survival gain of 3 months or more and a tumor response of 50% rather than 25% or 15%. However, the toxicity of the chemotherapy cannot be ignored, and a trade-off between burden and benefits of the therapy is unavoidable. Our results show that severe toxicity of the chemotherapy was indeed associated with a stronger preference for watchful waiting.

In the trade-off process, the wish of the patient to be treated also plays a role. In cases where patients did not have an outspoken wish to be treated, the preference for watchful waiting among physicians increased significantly. This result is fortunate in times when shared decision making becomes increasingly important.^31-33

Interestingly, older age had the strongest impact on the preference scores towards watchful waiting. It is questionable whether this preference is rational or whether age discrimination was a factor. The literature on the effects of palliative chemotherapy in the elderly is sparse.^34-38 Some studies indicate that in lung cancer patients, the elderly in particular benefited from chemotherapy.^35,37 Another study found that elderly patients tolerated chemotherapy as well as younger patients.³⁸ Although one should bear in mind that in these studies a selection bias could be present based on performance status or other factors, it nevertheless seems unjustified to withhold palliative chemotherapy on the basis of age alone.

The presence of psychologic distress did not influence the oncologists’ preference for either palliative chemotherapy or watchful waiting. This result can be considered as positive because no evidence can be found in the literature that indicates an effect of such distress on the effectiveness of chemotherapy. Even though depressive patients seem to be less willing to undergo chemotherapy,³⁹ Kramer et al⁴⁰ recently showed that emotional function does not influence response to palliative chemotherapy.

Some limitations of our study merit discussion. Not all characteristics that might influence the physicians’ preferences could be included in the vignettes. For example, cost-effectiveness of the therapy or social circumstances of the patient were disregarded, even though these aspects might have an impact on the decision-making process.^41,42 Also, because of the orthogonal study design, only main effects could be measured. Therefore, possible interactions between the different case characteristics are unknown, eg, the effect of older age and the wish to be treated⁴² or the co-occurrence of physical complaints and emotional distress.

We found that the preferences for treatment among oncologists vary from a strong preference for palliative chemotherapy to a strong preference for watchful waiting. However, in daily clinical practice, watchful waiting is offered less frequently.¹⁶ Different explanations might account for this discrepancy between our findings and clinical reality. First, referral bias may be at stake. In daily practice, medical oncologists see mostly patients who are referred to them for chemotherapy and, thus, expect such treatment. It may then be less obvious to propose watchful waiting as an alternative. Second, there may be a difference between preferences expressed in a paper case and the decisions made in daily clinical practice. The wish of the patient to be treated is an important factor, which was confirmed by our results. It is interesting to note that in our study, when there was no explicit preference of the patient to be treated, the preference towards watchful waiting became stronger. Slevin et al⁴³ found that cancer patients often wish to be treated for small chances of response. In fact, cancer patients were found to be reluctant to "do nothing."⁴⁴ Therefore, physicians may anticipate a strong wish to be treated and propose chemotherapy to patients, even if they would prefer watchful waiting themselves.^44,45

Given the patient’s wish to be treated, one might wonder how well patients are being informed about the alternative treatment option of watchful waiting. Silvestri et al⁴⁶ found that patients are willing to choose supportive care, watchful waiting, when they knew that the survival gain would only be 3 months. The question arises of how physicians can inform their patients adequately with regard to such treatment and their own preferences. Given the uncertainty of the side effects of palliative chemotherapy and the possibilities of watchful waiting, a systematic counseling procedure may be needed to prepare patients for decision making.^31,47,48 In such procedure, information on the present health condition, probabilities of certain health outcomes with or without palliative chemotherapy, side effects, and the opinion of others can be discussed. The use of a decision aid, such as decision boards, interactive videodiscs and CD-ROMs, or group presentations, may then be supportive for both the patient and the physician.

	ACKNOWLEDGMENTS

 
Supported by grant no. AMC 97-1620 from the Dutch Cancer Foundation, Amsterdam, the Netherlands. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, and writing and publishing articles.

We thank Rien de Vos, PhD, for his support with conceiving the article.

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Submitted December 13, 2001; accepted May 23, 2002.

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