Outcomes Research Helps Patients Choose Therapy

CHICAGO—Much of cancer treatment rightly relies on evidence from randomized clinical trials. However, definitive clinical trials have not been done on some problem diagnoses, such as ductal carcinoma in situ (DCIS).

Many major clinical investigations also fail to gather information about such aspects of treatment as trade-offs, for example, between potentially improved survival and breast preservation for women with DCIS, or the degree to which patients are willing to tolerate chemotherapy toxicities in exchange for possibly improved survival, for example, in ovarian carcinoma.

Outcomes researchers consequently are developing tools or study approaches to fill in these knowledge gaps. Two such researchers described their efforts at a symposium on quality of life and outcomes sponsored by Northwestern University and Evanston Northwestern Healthcare.

Bruce E. Hillner, MD, professor of medicine, Virginia Commonwealth University, Richmond, has been applying decision modeling using the Markov process to compare treatment strategies for DCIS. The disease is a relatively new enigma for oncology, he said, because it is being diagnosed more frequently (now accounting for between 10% and 15% of all new cases of breast cancer), and its natural history is poorly understood.

Women are not necessarily offered a choice of treatment, however. Nor do they have solid clinical data on which to base an informed decision. No randomized clinical trial has been conducted to evaluate mastectomy vs breast-conserving surgery in this setting, and there has been only one trial comparing breast-conserving surgery alone and breast-conserving surgery plus radiotherapy, he said.

Although two ongoing trials are investigating breast-conserving surgery in combination with radiotherapy or with tamoxifen (NSABP-24), results from these trials are at least a year away.

Dr. Hillner used decision modeling to compare actuarial, average, and discounted survival for mastectomy, breast-conserving surgery, and breast-conserving surgery plus radiotherapy. He then factored in the quality of life for women who had both breasts preserved.

According to this modeling plan, women who opted for mastectomy would not die from breast cancer at 10 and 20 years after treatment for DCIS. (Women could die from other causes.) Although actuarial survival at 20 years dropped off significantly for the two other treatment alternatives, average survival was similar in all groups: 17.94 years for mastectomy, 17.73 years for breast-conserving surgery plus radiotherapy, and 17.38 years for breast-conserving surgery alone.

In terms of discounted survival, which takes into account the value of being alive today vs survival sometime in the future, the differences were minimal. When compared with women who had mastectomy, women who had breast-conserving surgery plus radiotherapy would sacrifice only 38 days of survival, and women who had breast-conserving surgery alone would sacrifice 103 days. Thus, for a compromise of only about 1 to 3 months in survival, women could retain both breasts for 50% to 66% of the 20-year interval.

Although this decision-modeling plan does not provide treatment answers, it does “lay the groundwork for making informed choices,” he said.

Elizabeth Calhoun, PhD, assistant professor, Northwestern University Medical School, has been developing health state utilities that consider the effect of chemotherapy toxicity on quality of life. She has used utility assessments to assess the preferences or attitudes of women with ovarian cancer, women at risk of the disease (such as the daughters of women under treatment for ovarian cancer), and healthy women and physicians.

These utilities evaluate a set of hypothetical scenarios related to the severity of ototoxic, nephrotoxic, and neurotoxic side effects of chemotherapy on a scale of 0 (death) to 1 (perfect health). The objective was to determine the lowest amount of full-quality life a woman would accept as being equal to living one full year in the defined health state.

Women in essence answered the question: How many months of life would you give up to avoid a mild, moderate, or severe side effect?

The utilities were tested in 39 women with ovarian cancer, 15 women at risk of developing the disease, 30 healthy women at baseline risk, and 11 physicians.

Overall, healthy women were the most willing to give up more time in a poorer state of health for less time in perfect health. Women with ovarian cancer and women at high risk for the disease did not differ on any of the health states while physicians underestimated their patients’ willingness to sacrifice quantity of time for quality of time.

It is important to assess how health state utilities or other instruments that assess patients’ preferences can be used in making treatment decisions, she said. She added that these and other types of instruments are needed to learn how far patients are willing to go with treatments that affect overall quality of life.