Home: Educational Supplement: Appendix

Assessing Individual Benefit

Alan Coates, M.D., FRACP

Three questions are relevant to the decision to give or withhold any particular treatment, including adjuvant systemic therapy for early breast cancer:

1. Is there a benefit (beyond the play of chance)?
   
   This is essentially a statistical question to be answered by reference to appropriate randomized clinical trials. There have been many trials involving patients with early breast cancer, and the answer is expressed in terms of the standard test of significance. If the answer is yes, the next question arises.
   
   
2. How large is the benefit?
   
   Again, the answer to the question is statistical, but it can be more difficult to answer than the first question. Measures of the size of the benefit include reduction in the odds of death or relapse, differences in the probability of survival to a certain time after treatment, and differences in median survival rates. Estimates of these may be available from clinical trials, but it can be a matter of judgment whether to use average values or values derived from trials involving more specific subgroups. Once that question has been answered, one question remains.
   
   
3. Is it worth it (for this patient with this tumor)?
   
   The answer to this question is not statistical and involves the preference of the patient in light of estimates of the morbidity of a treatment. Individual morbidity is difficult to predict, and after a patient has undergone therapy the question becomes academic. Only such patients, however, can provide value judgments based on actual experience of the therapy.

Several studies have tried to establish benchmarks, based on the experience of one group of patients. Our initial study, conducted between November 1986 and December 1987, involved women who had received then-standard cytotoxic chemotherapy of at least three 28-day cycles of treatment (Coates, Simes, 1992). These patients were interviewed to determine the degree of benefit that, in their view, would make such treatment worthwhile. Of 129 patients considered for participation, 104 patients completed the interview, which was conducted at least 3 months after completion of chemotherapy by two observers with no connection to the treatment. The basic goal was to establish the patients’ opinion of what additional period of survival would be worthwhile to justify the adverse experience of the treatment they had received. Patients were presented with hypothetical scenarios which took a general form along these lines:

“Suppose that without treatment you would live 5 years. Based on your experience of chemotherapy, what period of survival would make 6 months of treatment worthwhile?”

A similar scenario was then used to establish equivalence to an expectation of 15 years of survival without treatment, which perhaps was an appropriate expectation for low-risk, node-negative patients. Survival questions were similar to the time trade-off approach but expressed the outcome of treatment in terms of the percentage chance of remaining alive after 5 years.

The major finding was that a large majority of the patients said that relatively modest improvements in the duration of survival or in the percentage chance of 5-year survival would justify their 6 months of treatment. This was true for both the optimistic scenarios (untreated survival of 15 years or 5-year survival of treatment at 85 percent) and in the less favorable (untreated survival of 5 years or 5-year survival of treatment at 65 percent). Most of the patients were inclined to accept treatment in return for an additional year of survival. This was true for both an extension from 5 years to 6 years (77 percent acceptance) and from 15 years to 16 years (61 percent acceptance). When asked about survival percentages, patients were willing to be treated for a 2 percent improvement in survival probability, either from 85 percent to 87 percent (54 percent acceptance) or from 65 percent to 67 percent (53 percent acceptance). In the light of a recent overview (EBCTCG, 1998), differences of this magnitude appear to be reasonably achievable for many patient groups receiving adjuvant cytotoxic therapy. Discussing the proportion of women with treatment experience who found it acceptable in exchange for a realistically achievable gain in survival may assist an untreated woman in reaching a decision about whether or not to undergo treatment herself.

Similar results have been reported by others. Slevin and colleagues interviewed a group of British patients with a variety of tumor types and found that they were much more ready to accept intensive treatment than controls or health professionals (Slevin, Stubbs, Plant, et al., 1990). Median required benefits for the hypothetical intensive treatment were a 1 percent chance of cure or 12 months prolongation of life, findings rather similar to those expressed by the breast cancer patients. Similarly, Bremnes and colleagues offered a hypothetical toxic regimen to Norwegian patients and found that patients, especially younger patients, were significantly more likely to accept treatment than controls or health professionals (Bremnes, Andersen, Wist, 1995; Coates, 1995). More recently, Lindley and colleagues found that more than 65 percent of the patients in their study who had completed adjuvant therapy for breast cancer would accept 6 months of chemotherapy for a 5 percent increase in likelihood of cure (Lindley, Vasa, Sawyer, et al., 1998). In another study, cisplatin-treated lung cancer patients showed a high percentage willing to accept even toxic therapy for a survival gain of 1 year, though that may be a less realistic hope in such patients (Silvestri, Pritchard, Welch, 1998).

Similar studies are under way in Britain to examine the preferences of patients who have received various endocrine therapies, and we are repeating our initial study to determine the preferences of those exposed to more recent therapies and supportive care in early breast cancer. Overall, these studies clearly show that patients’ views cannot be determined by interviewing surrogates, and that the benefit demanded by most patients to justify therapy is modest and within the capabilities of current adjuvant systemic therapy for early breast cancer.

References

Bremnes RM, Andersen K, Wist EA. Cancer patients, doctors and nurses vary in their willingness to undertake cancer chemotherapy. Eur J Cancer 1995;31A:1955-9. Abstract.

Coates AS, Simes RJ. Patient assessment of adjuvant treatment in operable breast cancer. In: Williams CJ, editor. Introducing new treatments for cancer: practical, ethical and legal problems. Chichester: Wiley, 1992:447-58. No Abstract Available.

Coates A. Who shall decide? Eur J Cancer 1995;31A:1917-8. No Abstract Available.

Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 1998;352:930-42. Abstract.

Lindley C, Vasa S, Sawyer WT, Winer EP. Quality of life and preferences for treatment following systemic adjuvant therapy for early-stage breast cancer. J Clin Oncol 1998;16:1380-7. Abstract.

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 1998;317:771-5. Abstract.

Slevin ML, Stubbs L, Plant HJ, Wilson P, Gregory WM, Armes PJ, et al. Attitudes to chemotherapy: comparing views of patients with cancer with those of doctors, nurses, and general public. BMJ 1990;300:1458-60. Abstract.