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New Insights Into the Cost-Effectiveness of Lung Cancer Treatment

New Insights Into the Cost-Effectiveness of Lung Cancer Treatment

ABSTRACT: Despite growing evidence that patients with advanced non–small-cell lung cancer have improved survival and better symptom control with modern systemic therapy, there is still resistance to the use of chemotherapy because of the perceived modest magnitude of benefit and concern about its cost. An analysis of the economic burden of care for non–small-cell lung cancer in Canada has revealed that the average cost to provide this care over 5 years is approximately $30,400 (1993 Canadian dollars). A large component of this cost, however, is related to initial diagnosis and in-hospital care, and to terminal care costs. Estimates of most of the commonly used chemotherapy regimens demonstrate that they are cost-effective and amount to less than the $20,000 per quality-adjusted life-year gained that is thought to be acceptable for the early adoption of a health-care intervention in Canada. Some chemotherapy regimens actually have the potential to decrease total health-care costs by reducing the use of acute care hospital beds for terminal care. Combined modality therapy for locally advanced non–small-cell lung cancer has also been shown to be cost-effective. The available evidence is that the cost of treating advanced non–small-cell lung cancer is not excessive, and estimates of cost-effectiveness are well within the commonly accepted range for the adoption of a new health-care technology. [ONCOLOGY 13(Suppl 4):16-21, 1999]

Introduction

Even in a universal access health- care system
as exists in Canada, there are barriers to care for patients with
lung cancer. The reasons are undoubtedly multiple; one important
issue is the attitude of those physicians who must decide whether to
refer a patient with advanced lung cancer for consideration of
chemotherapy. Most care providers believe that the prognosis of
patients with advanced non–small-cell lung cancer is poor, and
many would not accept treatment themselves if they had this
disease.[1] The survival of lung cancer patients is related to stage
at diagnosis, and at least one-third of Canadian patients present
with stage IV disease and another 25% to 30% have locally advanced
disease.[2] The median survival for stage III non–small-cell
lung cancer is 9 to 14 months and for stage IV, 17 to 33 weeks.[3] In
reality, even when the stage at presentation is advanced, current
therapies offer potential benefits by relieving cancer-related
symptoms and increasing survival.[4-10]

Multiple studies have shown symptomatic improvement in advanced
disease.[6-10] In addition, one randomized, controlled clinical
trial, incorporating a quality-of-life assessment, demonstrated a
significant improvement in quality of life for those patients who
received chemotherapy relative to those managed by best supportive
care alone.[10,11] These observations all suggest that patients
should at least be referred for consideration of treatment. Sometimes
a patient won’t be referred because there is concern from
physicians, health-care administrators, and insurers about the cost
of treatment for advanced and incurable disease. The following
information summarizes the evidence for the benefit of systemic
therapy in metastatic (stage IV) non–small-cell lung cancer, and
then focuses on the cost and cost-effectiveness of chemotherapy for
stages III and IV disease. The data demonstrate that chemotherapy for
stage IV non–small-cell lung cancer and combined modality
therapy for stage III disease are cost-effective treatments that are
competitive with commonly used health care interventions.

Evidence for Use of Chemotherapy

There are now eight randomized controlled clinical trials of
cisplatin (Platinol)-based chemotherapy in comparison to best
supportive care.[10,12-18] Best supportive care has, in general,
consisted of the judicious use of radiotherapy in patients with
localized cancer-related symptoms, as well as the use of antibiotics
and steroids to control infections, cerebral metastases, and
hypercalcemia. Almost all of the trials have been small, with
approximately 20 to 50 patients per arm. Although the response rate
to chemotherapy in metastatic disease has generally been low (range
20% to 25%), there has been a small but consistent increase in median
survival time. Those patients receiving best supportive care
generally have had a median survival of only 17 weeks, whereas the
median survival of those who received chemotherapy has been
approximately 24 weeks. Several of the trials[10,12, 15,18] have
shown a statistically significant survival advantage. Four
meta-analyses have shown a reduction in the hazard ratio for death in
chemotherapy-treated patients [19-22]. As demonstrated in the
Non–Small-Cell Lung Cancer Collaborative Study, the overall
survival advantage at 1 year is 10% in absolute terms.[20]

Five studies of chemotherapy in advanced non–small-cell lung
cancer have evaluated symptom improvement in patients undergoing
treatment.[6-10] The first of these, reported by Osoba et al in 1985,
used a regimen of bleomycin (Blenoxane), etoposide, and cisplatin and
yielded a 44% response rate, but a higher rate of symptom
improvement.[8] Cough improved in 68% of patients, hemoptysis was
relieved in 78%, pain in 68%, dyspnea in 31%, and anorexia in 44%.
Subsequent studies by Ellis,[6] Fernandez,[7] Kris,[9] Hardy,[10] and
Thatcher[24] have confirmed that chemotherapy yields symptomatic
improvement in 60% to 70% of patients.

Billingham has recently reported the results of a quality-of-life
study undertaken during a randomized comparison of MIC (mitomycin
[Mutamycin], ifosfamide [Ifex], cisplatin), compared to best
supportive care.[12] Patients with metastatic disease completed
quality of life questionnaires using the European Organization for
Research and Treatment of Cancer (EORTC) quality-of- life core
questionnaire, as well as the lung module. There was a statistically
significant benefit in terms of quality-of-life in the
chemotherapy-treated patients over the first 6 weeks of the study.

Estimating the Treatment Cost of NSCLC

With the evidence that chemotherapy produces a survival advantage as
well as symptomatic improvement and even benefit in the quality of
life of patients with advanced non–small-cell lung cancer,
resistance to the idea of offering systemic therapy to medically
appropriate patients has diminished. Nonetheless, there remain those
who believe that we cannot afford such treatment in a fiscally
constrained environment. The fiscal barrier appears to be the last
remaining barrier that needs to be dealt with to enable patients with
lung cancer to access the current best available care. An
understanding of what the costs of care are for patients receiving
lung cancer treatment is needed. In Canada, the Health Analysis
Modeling Group at Statistics Canada has undertaken a cost analysis of
the burden of care for common malignancies, including lung cancer.
These cost models are integrated into a microsimulation model of
Canadian health called the Population Health Model (POHEM).[25]

The lung cancer component of the Population Health Model incorporates
information on histologic cell type (small-cell vs
non–small-cell), age, gender, and stage, coupled with clinical
algorithms of care and the survival appropriate for stage of disease.
It assigns costs according to tumor cell type and treatment options.
Multiple databases were accessed to develop the model including the
Canadian Cancer Registry at Statistics Canada’s Health
Statistics Division. This database provided data on lung cancer
incidence, tumor cell type, and patient demographics.

Because staging information was not available from the Canadian
Cancer Registry, a retrospective staging study was undertaken by the
Alberta Cancer Board and the Ontario Cancer Registry. The stage
distribution of cases diagnosed between 1984 and 1985 was entered
into all Canadian non–small-cell lung cancer cases. The
treatment approaches incorporated into the model of care were those
identified from cancer registry data supplemented by responses from a
questionnaire sent to all Canadian thoracic surgeons and radiation
oncologists. From this information, estimates were made of the
proportion of patients who would be treated by a particular treatment approach.

The questionnaire was also used to estimate the average number of
treatment fractions and the total dose of radiation used on
radiotherapy patients, according to stage of disease. It was assumed
that patients with stage IV disease were managed by best supportive
care, as this has been the usual care provided to most patients in
Canada presenting with metastatic disease. At the time the model was
developed, it was estimated that only about 10% of patients with
stage IV non–small-cell lung cancer received chemotherapy in Canada.[1]

Comparison of Hospitalization

Statistics Canada’s 1992-1994 Person Oriented Hospital Morbidity
Information Database provided the duration of hospitalization for
diagnostic work-up and initial treatment for non–small-cell lung
cancer. Costs for hospital and outpatient chemotherapy treatment were
extracted from an economic analysis of a National Cancer Institute of
Canada Clinical Trial (BR.5), which compared chemotherapy vs best
supportive care in advanced non–small-cell lung cancer.[25]

A record linkage study was performed in the province of Manitoba for
all patients diagnosed with lung cancer in 1990 (approximately 600)
to determine if the hospital utilization data from the BR.5 study
were still relevant. The study confirmed that patients with advanced
non–small-cell lung cancer who received chemotherapy used fewer
hospital bed days than those managed by best supportive care and that
the difference in the length of hospital stay was similar to that
observed in the BR.5 study.[26]

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