Observation Versus Initial Treatment for Men With Localized, Low-Risk Prostate Cancer: A Cost-Effectiveness Analysis
Publication: Annals of Internal Medicine
Volume 158, Number 12
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Abstract
Background:
Observation is underutilized among men with localized, low-risk prostate cancer.
Objective:
To assess the costs and benefits of observation versus initial treatment.
Design:
Decision analysis simulating treatment or observation.
Data Sources:
Medicare schedules, published literature.
Target Population:
Men aged 65 and 75 years who had newly diagnosed low-risk prostate cancer (prostate-specific antigen level <10 µg/L, stage ≤T2a, Gleason score ≤3 + 3).
Time Horizon:
Lifetime.
Perspective:
Societal.
Intervention:
Treatment (brachytherapy, intensity-modulated radiation therapy, or radical prostatectomy) or observation (active surveillance [AS] or watchful waiting [WW]).
Outcome Measures:
Quality-adjusted life expectancy and costs.
Results of Base-Case Analysis:
Observation was more effective and less costly than initial treatment. Compared with AS, WW provided 2 additional months of quality-adjusted life expectancy (9.02 vs. 8.85 years) at a savings of $15 374 ($24 520 vs. $39 894) in men aged 65 years and 2 additional months (6.14 vs. 5.98 years) at a savings of $11 746 ($18 302 vs. $30 048) in men aged 75 years. Brachytherapy was the most effective and least expensive initial treatment.
Results of Sensitivity Analysis:
Treatment became more effective than observation when it led to more dramatic reductions in prostate cancer death (hazard ratio, 0.47 vs. WW and 0.64 vs. AS). Active surveillance became as effective as WW in men aged 65 years when the probability of progressing to treatment on AS decreased below 63% or when the quality of life with AS versus WW was 4% higher in men aged 65 years or 1% higher in men aged 75 years. Watchful waiting remained least expensive in all analyses.
Limitation:
Results depend on outcomes reported in the published literature, which is limited.
Conclusion:
Among these men, observation is more effective and costs less than initial treatment, and WW is most effective and least expensive under a wide range of clinical scenarios.
Primary Funding Source:
National Cancer Institute, U.S. Department of Defense, Prostate Cancer Foundation, and Institute for Clinical and Economic Review.
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Supplemental Material
Supplement 1. Decision Tree for Observation Versus Initial Treatment
Supplement 2. Costs of 1-Time and Recurrent Treatments of Adverse Effects
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Published In
Annals of Internal Medicine
Volume 158 • Number 12 • 18 June 2013
Pages: 853 - 860
History
Published online: 18 June 2013
Published in issue: 18 June 2013
Keywords
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© 2013 American College of Physicians.
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Observation Versus Initial Treatment for Men With Localized, Low-Risk Prostate Cancer: A Cost-Effectiveness Analysis. Ann Intern Med.2013;158:853-860. [Epub 18 June 2013]. doi:10.7326/0003-4819-158-12-201306180-00002
Observation Versus Initial Treatment for Men With Localized, Low-Risk Prostate Cancer: A Cost-Effectiveness Analysis. Ann Intern Med.2013;158:853-860. [Epub 18 June 2013]. doi:10.7326/0003-4819-158-12-201306180-00002
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Unstable HR estimate used in cost-effectiveness model
Author's Response
We appreciate the concerns articulated by Dr. Pinsky regarding the hazard ratio for prostate cancer specific death for treatment vs. watchful waiting used in the base case of our study1. We chose to use the results from the low-risk subset of men in PIVOT, despite the small number of deaths in both arms, in the absence of other randomized controlled data comparing watchful waiting to treatment in the PSA era2. The dearth of long-term data directing therapeutic choices in this context is one reason to perform decision analysis, which allows assumptions to be made and then varied over a wide range to determine their effect on results. We chose the best available data for our base case, but then varied this hazard ratio over a wide range (HR 0.42, the lower limit of the 95% confidence interval reported in PIVOT, to 2.96, twice the base case hazard ratio) and performed threshold analyses to determine at what HR of prostate cancer-specific death treatment would be favored over watchful waiting in terms of QALE (HR 0.47 in 65 year old men). Watchful waiting remained the least expensive strategy over the entire range tested (Appendix Table 2). Probabilistic sensitivity analysis was also performed to assess the effect of varying all key parameters over a wide range simultaneously, including the hazard ratio of prostate cancer-specific death, and our conclusions did not change.
We recognize the suboptimal nature of the hazard ratio of prostate cancer-specific death for men with low-risk prostate cancer provided by PIVOT. However, we used the best available data and then demonstrated in multiple analyses that our results were impervious to changes in this estimate over a wide range. We hope that with time, better data will be available to us to use in future models.
Hayes JH, Barry MJ, McMahon PM
1. Hayes JH, Ollendorf DA, Pearson SD, et al. Observation versus initial treatment for men with localized, low-risk prostate cancer: a cost-effectiveness analysis. Ann Intern Med. Jun 18 2013;158(12):853-860.
2. Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. The New England journal of medicine. Jul 19 2012;367(3):203-213.