New Insights Into the Cost-Effectiveness of Lung Cancer Treatment

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(Drug information on 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(Drug information on bleomycin) (Blenoxane), etoposide(Drug information on 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(Drug information on 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]