|
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:
- 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.
- 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.
- 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.
|
|