The economic burden of prostate cancer in Canada: forecasts from the Montreal Prostate Cancer Model

Steven A. Grover, Louis Coupal, Hanna Zowall, Raghu Rajan, John Trachtenberg, Mostafa Elhilali, Michael Chetner, Larry Goldenberg

CMAJ 2000;162(7):987-92

• Abstract
• Introduction
• Methods
• Results
• Interpretation
• References

Background: We developed an economic model of prostate cancer management from diagnosis until death. We have used the Montreal Prostate Cancer Model to estimate the total economic burden of the disease in a cohort of Canadian men.

Methods: Using this Markov state-transition simulation model, we estimated the probability of prostate cancer, annual prostate cancer progression rates and associated direct medical costs according to patient age, tumour stage and grade, and treatment modalities in a 1997 cohort of Canadian men. The estimated lifetime costs of prostate cancer included the costs of clinical staging, initial treatments and complications, follow-up cancer therapies, routine outpatient care, and palliative care following metastatic disease.

Results: The clinical burden of prostate cancer forecasted using the model was similar to the projections of the National Cancer Institute. In the 1997 cohort of 5.8 million Canadian men between 40 and 80 years old, prostate cancer would be diagnosed in an estimated 701 491 men (12.1%) over their lifetime. Direct medical costs would total $9.76 billion, or $3.89 billion when discounted 5% annually.

Interpretation: The Montreal Prostate Cancer Model indicates that the economic burden of prostate cancer to Canada's health care system will be substantial. Further analyses are needed to identify the most efficient means of treating this disease.

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Given the increasing prevalence of prostate cancer and the uncertainty surrounding its treatment, there is growing concern that the future burden of disease may be substantial.² To address these questions, we developed the Montreal Prostate Cancer Model (page 977).³ With this Markov state-transition model we were able to estimate the annual probabilities of prostate cancer being diagnosed, the distribution of the initial therapeutic alternatives and their associated complications, annual progression rates of prostate cancer, choices of follow-up therapies and palliative care. We have used the model to estimate the direct medical costs associated with each treatment modality as a means of forecasting the total lifetime clinical and economic burden of the disease among a cohort of Canadian men aged 40 to 80 years in 1997.

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The Montreal Prostate Cancer Model is a validated Markov simulation model that describes the natural history of the disease.³ For a cohort of men initially free of a prostate cancer, the model estimates the expected age at diagnosis of prostate cancer and the probability of progression to metastatic disease. It estimates overall life expectancy as well as metastasis-free and disease-specific survival. The model has been validated using population cancer statistics and survival data specific to tumour stage and grade.³ The resulting forecasts have been shown to approximate closely the observed outcomes in different patient cohorts followed for up to 15 years.

Estimation of clinical burden

We used Canadian age-specific incidence data to estimate the probabilities of prostate cancer diagnoses.⁴ We then distributed cases by tumour stage and grade using data from the National Cancer Data Base.⁵ The model uses the tumour­node­metastasis (TNM) classification for the staging of prostate cancer.⁶ The model also considers 3 tumour histologic grades, as defined by the Gleason scoring system:⁷ well-differentiated tumours (Gleason score of 2­4), moderately differentiated (Gleason score of 5­7) and poorly differentiated (Gleason score of 8­10).

The choice of initial treatment was derived from the National Cancer Data Base.⁵ Therapies include radical prostatectomy, radiation therapy, hormonal therapies (including orchiectomy or drug treatment, or both), combination therapies and watchful waiting. Radiation therapy refers to external-beam therapy because 94% of patients receiving radiation therapy undergo this procedure.⁸

The complications associated with radical prostatectomy were determined from a sample of Medicare beneficiaries and included age-specific 30-day hospital mortality, cardiopulmonary complications, vascular complications and surgical complications.^9,10,11,12Complications following external-beam radiation were taken from the results of 2 radiation therapy trials.¹³ The complication rates for combination therapies were estimated as the weighted sum of treatment-specific rates.¹⁴ No major complications were considered for hormonal therapies.

We considered treatment options following radical prostatectomy to include radiation therapy and hormonal therapies. We assumed that patients initially followed conservatively (watchful waiting) or undergoing radiation therapy could only receive hormonal therapies as follow-up care. Stage- and grade-specific progression rates were used to derive the annual probabilities of additional curative therapies following prostatectomy.¹⁵ The relative frequency of specific follow-up therapies was derived from data for Medicare patients.^12,16 Following watchful waiting, we assumed that either orchiectomy or pharmacologically induced hormone blockade would occur upon disease progression. Progression rates from localized prostate cancer (T1 or T2) to T3 were taken from published data.¹⁷

Stage- and grade-specific probabilities of progression to metastatic disease following radical prostatectomy, radiation therapy and watchful waiting were estimated from the results of published cohorts.^18,19,20,21

Three types of death were considered by the model: death without prostate cancer, death with but not resulting from prostate cancer and death from prostate cancer. Adjusted Canadian life tables²² were used to estimate the risk of death from causes other than prostate cancer. We estimated the annual probability of death from prostate cancer following progression to metastatic disease using 15-year observed survival data.¹⁷

Estimation of economic burden

The costs of initial and follow-up cancer therapies and complications included the costs of initial hospital services, physician fees and outpatient services. Annual outpatient costs included disease monitoring and palliative care expenditures. All costs were expressed in 1996 Canadian dollars. Because health care costs can be incurred at different times, we weighted each by an annual discount rate of 5% to value them at the same point of time.²³

The utilization rates of diagnostic tests and procedures for staging were taken from US data.^8,24 The unit costs of diagnostic tests, procedures and physicians fees were estimated from the mean of the Quebec and Ontario reimbursement schedules.^25,26,27 We considered this choice representative of Canada because health care expenditures per capita are relatively low in Quebec and relatively high in Ontario. Moreover, over 60% of Canada's total health care dollars are spent in Quebec and Ontario.²⁸ We also used the fully allocated 1994/95 unit costs from the Montreal General Hospital (unpublished data) and translated them into Ontario cost equivalents using the ratios of per-diem hospital costs or laboratory unit charges between Quebec and Ontario.²⁹

We estimated inpatient costs associated with prostate cancer (Table 1) using the methodology of the Canadian Institute for Health Information (CIHI).³⁰ The costs associated with external-beam radiation therapy were taken from estimates provided by the Royal Victoria Hospital, Montreal.³¹ For inpatient physician fees we included anticipated charges for surgeons, assistants, anesthetists, urologists, medical oncologists and radiation oncologists in addition to fees for regular care and the care provided by other specialists.

We identified the costs of various outpatient procedures performed in hospital. These interventions included orchiectomy and the management of complications from initial treatments, such as treatment of urethral strictures, penile prosthesis implantation to treat impotence, urinary sphincter implantation to treat incontinence and treatment of rectal strictures. We calculated the costs of outpatient hospital care using CIHI methodology by assigning each diagnosis to a Day Procedure Group.

We assumed palliative care would be required for men whose prostate cancer progressed to metastatic disease and that it would include more frequent visits to the urologist, routine laboratory tests and radiographic examinations. The mean number of chemotherapy sessions per patient with metastatic disease was taken from published Canadian data.³² The cost of palliative radiation was estimated and updated to current (1996) costs using the relative cost difference between radiation for palliative and curative purposes³³ and recent estimates from the Royal Victoria Hospital.³¹ The frequency and duration of various palliative treatments were estimated from the literature.^34,35,36,37 We also estimated the number of urinary procedures that would be required to alleviate urinary tract obstruction.^34,38

Utilization rates of hormone-blocking drug therapy and orchiectomy were derived from data for 23 214 patients in the United States with newly diagnosed prostate cancer.⁸ We assumed that these rates applied to both initial and follow-up hormonal therapies and that drug therapy would be initiated according to specified indications.³⁹ The selection of hormone-blocking drugs was derived using data from the Ontario Drug Benefit plan.⁴⁰

Drug costs were provided by IMS Canada.⁴¹ Monthly costs were based on the average retail prescription price, including dispensing fees, calculated by the IMS. The proportion of opiates, analgesics and steroids used in palliative care were estimated from the literature.^34,35,36,37

The lifetime costs of caring for Canadians with prostate cancer were estimated for the male population between 40 and 80 years of age based on 1997 population projection data.⁴² A cohort representing the number of 40-year-old Canadian men was first entered into the model, and the annual and lifetime prostate-cancer­specific costs were estimated for them. Next, a cohort of 41-year-old men was entered into the model and the lifetime costs were estimated. This process was repeated until the estimated lifetime costs of every cohort of men aged less than 81 years of age were derived.

[Contents]

Validation of the model is described in detail in the accompanying article (page 977).³ In brief, we compared long-term survival rates among 59 876 men with clinically localized prostate cancer enrolled in a population-based study⁴³ with survival estimates forecasted by the model. For example, the 10-year disease-specific survival rates following prostatectomy for tumour grades 1, 2 and 3 were 98%, 91% and 76% in the study, as compared with the model's estimates of 96%, 92% and 84%, respectively.³ We also compared the model's estimates with observed survival rates from the Connecticut Tumor Registry for patients with conservatively treated localized prostate cancer.⁴⁴ For example, the registry data showed that 65-year-old men with clinically localized grade 1, 2 and 3 tumours had on average 16.1, 11.3 and 7.9 remaining years of life respectively, as compared with 14.2, 11.5 and 7.4 years estimated by the model.³

We compared National Cancer Institute of Canada (NCIC) prostate cancer projections⁴⁵ with those generated using the Montreal Prostate Cancer Model (Table 2 and Table 3). The lifetime probability of prostate cancer was determined to be 12.4% by the NCIC and 12.2% by the model; the lifetime probability of death from prostate cancer was 3.8% according to the NCIC and 3.3% according to the model. The model estimated that 15 248 new cases of prostate cancer would be diagnosed in Canada in 1997, as compared with 19 690 estimated by the NCIC; the potential years of life lost were estimated at 33 030 and 33 000 years respectively.

Using the model, we estimated that, among the 5.8 million Canadian men 40 to 80 years of age in 1997 without a diagnosis of prostate cancer, the disease will eventually be diagnosed in 701 491 (12.1%) and that the lifetime costs of care will be $9.76 billion, or $3.89 billion when discounted at 5% annually) (Table 4). The model estimated that disease staging, prostatectomy, external-beam radiation therapy and hormonal therapies will account for 10.2%, 12.9%, 11.9% and 2.7% of the total lifetime costs of care respectively (Table 5).

The annual costs associated with treating prostate cancer in the 1997 cohort of Canadian men were also estimated for the years 1997 through 2060 (Fig. 1 [not available online]). The number of Canadian men with a diagnosis of prostate cancer in 1997 was estimated to be 15 248 and would incur $111 million in direct medical costs in that year. The model projected a peak in annual treatment costs of $286 million in 2022.

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Prostate cancer is a slowly evolving disease, which makes it difficult to demonstrate the efficacy of alternative treatments on clinically important outcomes such as tumour progression or cancer-related mortality.^46,47 The high costs of completing such trials often limits the opportunity to follow patients over the long term. Randomized clinical trials are essential to prove short-term efficacy for a specific therapy but may be inadequate to estimate the long-term impact over a patient's lifetime.^48,49 We therefore developed and validated the Montreal Prostate Cancer Model to forecast the long-term clinical burden of prostate cancer and to estimate the economic burden of this disease on the Canadian health care system.

Similar models have been published by others.^{50,51,52,53,54} Cowen and colleagues⁵⁰ developed a Markov model of the natural history of prostate cancer; however, the model did not include disease progression rates according to tumour grade and did not consider the direct health care costs associated with specific treatments. Fleming and coworkers⁵¹ developed a detailed decision-analysis model that included grade-specific disease progression; however, the direct health care costs associated with these treatments were not considered. An extensive cost-effectiveness analysis was completed by the US Office of Technology Assessment.⁵⁴ This analysis included a comprehensive literature review on prostate cancer management and included grade-specific disease progression rates and an analysis of direct health care costs. However, the costs of managing recurrent cancer beyond hormonal therapies, including palliative care, were not considered because the primary focus of the analysis was the cost-effectiveness of screening and early detection.

We have tried to build on these earlier disease-simulation models to capture the most important clinical and economic consequences of prostate cancer over the entire course of the disease. We have paid particular attention to studies presenting data stratified by tumour grade because tumour grade has been shown to be one of the strongest predictors of disease progression and survival.^18,20,43,44 We have also validated our model against studies in which data were stratified by patient age, tumour stage and grade, and treatment modalities.^43,44,55

The main limitation of our model is that, because of the paucity of Canadian population-based data, we had to rely often on US data. Moreover, because of the model's complexity we are unable at present to provide the confidence intervals around our estimates using techniques such as Monte Carlo simulations. Despite these limitations, the model has a number of potential uses including forecasting the impact of changes in management on disease progression, life expectancy and health care costs. However, it is impossible to use the model to compare alternative treatment strategies in the absence of data from randomized clinical trials demonstrating clinical efficacy.

The clinical burden of prostate cancer in Canada is substantial and appears to be rising.^1,2 Projections from the National Cancer Institute⁴⁵ and our model suggest that prostate cancer will develop in over 12% of Canadian men over their lifetime and will be fatal in 3% to 4% of cases.

The economic burden of this disease also appears to be substantial.^2,56 Our model estimates that the direct health care costs of treating over 700 000 cases of prostate cancer among Canadian men currently aged 40 to 80 will be $9.76 billion over their lifetime. The present value of these expenditures when discounted 5% annually is $3.89 billion, or about 5% of the $77 billion spent on health care in 1997.⁵⁷ A detailed analysis of these costs indicates that initial therapy, including disease staging, prostatectomy and radiation therapy, accounts for over one-third of these health care costs. Palliative care, including the final hospital admission for terminal care, will acount for a quarter of the costs.

These data underscore the need to define which treatment is the most effective in reducing the morbidity and mortality associated with this common cancer.^58,59,60,61 The costs of treatment per patient are relatively modest, ranging from $16 000 to $23 000 depending on the age of the patient, the tumour stage and selected treatments. These expenditures represent good value for the money, provided we can show that the treatments significantly affect the clinical course of this important disease.

We thank Ms. Nadine Bouchard for preparing the manuscript.

Dr. Grover is a senior research scholar (Chercheur-boursier) supported by the Fonds de la recherche en santé du Québec. Financial support for this study was provided by an investigator-initiated research project supported by an unrestricted grant from Abbott Laboratories, Limited. At no time did Abbott Laboratories staff provide any input into the study analysis, results or conclusions.

Competing interests: None declared.

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[Contents]

Reprint requests to: Dr. Steven A. Grover, Centre for the Analysis of Cost-Effective Care, Montreal General Hospital, 1650 Cedar Ave., Montreal QC H3G 1A4

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