This study suggests the relative costs and benefits of chemoprevention vary significantly based on risk factors for developing CaP. For select subgroups of men who have multiple risk factors, such as an elevated PSA and a prior negative biopsy, chemoprevention with a 5ARI has been shown in a large randomized trial to be efficacious in reducing the risk of finding CaP on a future biopsy. The current cost–effectiveness study suggests quite a favorable cost–effectiveness profile associated with recommending chemoprevention for these high-risk men.
However, for average-risk men, this study provides less compelling support for 5ARI chemoprevention from a cost–effectiveness perspective. Among men who are at average risk of CaP, the main benefit these authors observed appears to be from avoiding health utility detriments due to BPH symptoms rather than gains associated with preventing CaP. These findings should be interpreted with caution, as the relative benefit of reductions in BPH from 5ARI chemoprevention among nonsymptomatic men is likely to be minimal, as treatment with combined α-adrenoceptor antagonists and 5ARIs can be effectively initiated if men develop BPH symptoms.[5–7]
The authors note that at the time of their study, only preliminary 2-year estimates from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial were available. The REDUCE trial specifically tested the efficacy of 5ARI chemoprevention among high-risk men with a prior negative biopsy and elevated PSA level. The 4-year results of REDUCE have been published recently, observing a 22.8% (95% confidence interval [CI]: 15.2–29.8%) reduction in CaP. The overall reduction in CaP was similar to the Prostate Cancer Prevention Trial (PCPT) findings of 24.8% reduction in CaP. Current guidelines recommend that physicians discuss key issues of chemoprevention with asymptomatic, low-risk men. To date, guidelines have not yet incorporated the REDUCE findings into recommendations for higher-risk men.
One source of controversy of the 5ARI chemoprevention has been the observed increase in high-grade CaP associated with finasteride chemoprevention in the PCPT, despite an overall reduction in CaP. The REDUCE trial also observed slightly higher rates of high-grade CaP among men treated with dutasteride (p = 0.15), although the differences in high-grade disease were only observed in years 3 and 4 (p = 0.003). This increase in high-grade CaP with 5ARI treatment has been attributed to increased sensitivity for detecting high-grade disease-associated lower prostate volumes of treated men.[10,11] Nevertheless, both trials observed the majority of benefit exclusively by preventing low-grade disease.
Deaths due to CaP are relatively rare among men with low-grade disease (Gleason 2–7) compared with high-grade disease (Gleason 8–10). In a long-term study with 20 years of follow-up, mortality rates were 25 deaths per 1000 person-years among those with low-grade disease compared with 121 deaths per 1000 person-years for men with high-grade disease. Prior studies have suggested that reductions in low-grade disease only with 5ARI chemoprevention is unlikely to translate to substantial long-term reductions in CaP deaths. The current study did not model long-term survival separately by grade.
A critical shortcoming of the current study is the lack of detail regarding the cost of 5ARIs. Prior studies have concluded that the cost of 5ARIs is a principal factor in the cost–effectiveness of chemoprevention,[9,13–15] suggesting that population-based chemoprevention may not be cost effective until the 30-day supply price is under US$10. The current model is based on 30-day supply cost of finasteride of US$82 and over the course of 10 years this cost is substantial. Based on the model inputs, the present value cost of treating 1000 average-risk men beginning at 50 years of age for a decade is close to US$8,000,000 to prevent six men from being diagnosed with CaP. The cost of the dutasteride is approximately 50% higher, and the authors do not present findings related to the sensitivity of their estimates on drug prices.
Expert Rev Pharmacoeconomics Outcomes Res. 2010;10(5):505-508. © 2010 Expert Reviews Ltd.
Cite this: Cost–Effectiveness of Prostate Cancer Chemoprevention among High-risk Men - Medscape - Oct 01, 2010.