Finasteride For Prevention Of Prostate Cancer Research Articles

Serum markers, obesity and prostate cancer risk: results from the prostate cancer prevention trial.

Molecular mechanisms linking obesity to prostate cancer involve steroid hormone and insulin/insulin-like growth factor 1 (IGF1) pathways. We investigated the association of circulating serum markers (e.g. androgens and IGFs/IGFBPs) with BMI and in modifying the association of obesity with prostate cancer risk. Data and specimens for this nested case-control study are from the Prostate Cancer Prevention Trial, a randomized, placebo-controlled trial of finasteride for prostate cancer prevention. Presence or absence of cancer was determined by prostate biopsy. Serum samples were assayed for sex steroid hormone concentrations and IGF1 axis analytes. Logistic regression estimated odds ratio and 95% CIs for risk of overall, low-grade (Gleason 2-6), and high-grade (Gleason 7-10) cancers. We found significant associations between BMI with serum steroids and IGFs/IGFBPs; the IGF1 axis was significantly associated with several serum steroids. Serum steroid levels did not affect the association of BMI with prostate cancer risk; however, IGFBP2 and IGFs modified the association of obesity with low- and high-grade disease. While serum steroids and IGFs/IGFBPs are associated with BMI, only the IGF1 axis contributed to obesity-related prostate cancer risk. Understanding the biological mechanisms linking obesity to prostate cancer risk as it relates to circulating serum markers will aid in developing effective prostate cancer prevention strategies and treatments.

Insulin-like growth factors and insulin-like growth factor-binding proteins and prostate cancer risk: results from the prostate cancer prevention trial.

The role of the insulin-like growth factor (IGF) axis and whether IGFs interact with androgen-suppressing agents in relation to prostate carcinogenesis is unclear. This nested case-control study (n = 1,652 cases/1,543 controls) examined whether serum IGF1, IGF2, IGFBP2, IGFBP3, and the IGF1:IGFBP3 ratio were associated with prostate cancer in the Prostate Cancer Prevention Trial (PCPT), a randomized, placebo-controlled trial of finasteride for prostate cancer prevention. Presence or absence of cancer was determined by prostate biopsy. Baseline serum was assayed for IGF-axis analytes using ELISA. Logistic regression estimated ORs and 95% confidence intervals for risk of total, low-grade (Gleason 2-6) and high-grade (Gleason 7-10) cancers. Results were stratified by intervention assignment. In both the placebo and finasteride arms, serum IGF1, IGF2, IGFBP3, and the IGF1:IGFBP3 ratio were not associated with prostate cancer. However, men in the highest versus lowest quartile of serum IGFBP2 had a 48% (P(trend) = 0.02) and 55% (P(trend) = 0.01) increased risk for total and low-grade cancers, respectively. These IGFBP2 associations were attenuated and no longer statistically significant in the finasteride arm. Our results suggest that in general, serum IGF-axis analytes were not associated with prostate cancer risk in the PCPT in which presence or absence of all cancers was biopsy-determined. The exception was the finding that high serum IGFBP2 is a risk factor for low-grade disease, which was attenuated for men on finasteride. Further research is needed to understand better the risk incurred by high IGFBP2 and whether androgen-suppressing agents such as finasteride influence aspects of IGFBP2 physiology relevant to prostate carcinogenesis.

PCPT, MTOPS and the use of 5ARIs: a Canadian consensus regarding implications for clinical practice

Two large, recently published, definitive trials evaluated the benefits of 5-alpha reductase inhibitors (5ARIs). The Prostate Cancer Prevention Trial (PCPT) tested the effect of finasteride for prostate cancer prevention and the Medical Therapy of Prostatic Symptoms (MTOPS) tested its effect in benign prostatic hyperplasia (BPH). Both trials were strongly positive. However, the role of 5ARIs in the clinical management of patients remains controversial. The consensus conference, which forms the basis for this report, attempted to develop an expert opinion, based on these studies, as to the optimal use of 5ARIs in patient management. The Canadian Consensus Meeting, organized by the Canadian Urology Research Consortium and the Canadian Urologic Oncology Group, held in Toronto on May 7, 2006, focused on the new data from the PCPT and the MTOPS study. Internationally recognized experts and clinicians discussed the implications of these data on clinical practice and issued a recommendation on the optimal management of patients with BPH. The Consensus meeting agreed on the following recommendations: The overall results from the PCPT and MTOPS studies are of importance to the urologic, as well as to the greater medical, community.Prostate management guidelines should be updated to include the results from both the MTOPS and the PCPT studies.In the PCPT, the incidence of high-grade cancer was higher in the finasteride-treated group (6.4%), compared with the placebo group (5.1%). Subsequent analyses strongly suggest that this increased prevalence was owing to a detection bias caused by the reduction in prostate volume in patients taking finasteride, compared with patients taking placebo. This resulted in an improved detection at biopsy of high-grade cancer in the finasteride group.In men who have large prostates and lower urinary tract symptoms (LUTS), 5ARIs( section sign) should be considered, both for the treatment of BPH and for prostate cancer risk reduction.For men who are concerned about prostate cancer, it is appropriate to discuss chemoprevention with finasteride.Urologists are encouraged to disseminate these recommendations among other healthcare professionals.

Does variation in either age at start of therapy or duration of therapy make chemoprevention with finasteride cost-effective?

Incremental cost-effectiveness ratios (ICERs) of finasteride for prostate cancer prevention are consistent with estimates beyond $100 000 per quality-adjusted life-year (QALY). The majority of these analyses are based on chemoprevention starting in men aged 50-55 years. We sought to evaluate the impact of varying both age at commencement of therapy and length of therapy on the cost-effectiveness of finasteride. A probabilistic Markov model was designed to estimate lifetime prostate health-related costs and quality-adjusted survival for men receiving or not receiving chemoprevention with finasteride. ICERs across scenarios varying age at start of therapy and duration of chemoprevention were compared. The ICER for men starting chemoprevention at age 50 and continuing to age 75 was $88 800 per QALY when assuming finasteride causes a constant risk reduction across all tumor grades (base case 1) and $142 300 per QALY when assuming a differential treatment effect according to Gleason score (base case 2). When starting age is increased, the ICERs trend downward and nadir at 65 years to $64 700 per QALY (base case 1) and $118 600 per QALY (base case 2). Altering duration of therapy had minimal impact. Patient-level experiences with finasteride and BPH significantly influenced the cost-effectiveness of chemoprevention. Initiating chemoprevention at ages when prostate cancer incidence is higher improves its cost-effectiveness profile. Only when assuming a constant risk reduction for all tumor grades, did finasteride fall below $100 000 per QALY, but this finding was not upheld when accounting for side effects associated with the drug.

Highlights of This Issue

Metastases from men with castration resistant prostate cancer (CRPC) express increased levels of androgens, compared to untreated prostate cancers (PCa). Wright and colleagues examined whether the sequence and expression of SLCO genes, which encode proteins that mediate androgen transport into PCa cells, were associated with risk of PCa metastases. SLCO gene sequence and expression were analyzed in untreated PCa and metastatic CRPC tumors. The authors found that CRPC metastases had increased expression of six SLCO genes, and carriers of certain variant alleles of SLCO2B1 and SLCO1B3 had an increased risk of PCa-specific mortality. This study suggests that SLCO genes are potential biomarkers for assessing risk of PCa-specific mortality.There is racial/ethnic variation in mammography use patterns before and after age 40. To explore this, Kapp and colleagues investigated racial/ethnic differences in future mammography behavior among women who had received a baseline screening mammogram before age 40. Using data from the Breast Cancer Surveillance Consortium (BCSC), the authors identified and followed women for two outcomes: (1) future BCSC mammography and (2) delay in screening mammography until ages 43-45 compared to 40-42. The authors report that Hispanic women had an increased risk of no future BCSC mammography, relative to non-Hispanic white women. Among women with future BCSC screening mammography, African American women were more likely to delay the timing. This work indicates that race/ethnicity is differentially associated with obtaining future BCSC mammography and the timing of that screening.Whether or not lycopene reduces the risk of prostate cancer remains controversial. In a nested case-control study, Kristal and colleagues examined the association of serum lycopene with prostate cancer risk among participants in the Prostate Cancer Prevention Trial (PCPT), a placebo-controlled trial of finasteride for prostate cancer prevention. The authors found no associations of lycopene with prostate cancer risk. This study does not support a role for lycopene in prostate cancer prevention.Healthy lifestyle behaviors could have a role in ameliorating some of the adverse-effects of androgen suppression therapy (AST) in men with prostate cancer. Bourke and colleagues assessed the feasibility of a tapered supervised exercise program in combination with dietary advice, in men with advanced prostate cancer receiving AST. The authors found that, compared with standard care controls, the lifestyle intervention group demonstrated improvements in many health outcomes including exercise behavior, dietary fat intake, and muscle strength. This study provides evidence that pragmatic lifestyle interventions have potential to evoke improvements in important health outcomes in men with advanced prostate cancer receiving AST.

Serum lycopene concentration and prostate cancer risk: results from the Prostate Cancer Prevention Trial.

Lycopene has been promoted for prostate cancer prevention, despite the inconsistency of scientific evidence. This nested case-control study examined whether serum lycopene was associated with prostate cancer risk among participants in the Prostate Cancer Prevention Trial, a placebo-controlled trial of finasteride for prostate cancer prevention. Presence or absence of cancer was determined by prostate biopsy, recommended during the trial due to elevated prostate specific antigen (PSA) level or abnormal digital rectal examination (DRE) and offered to all men at the trial end. There were 1,683 cases (461 Gleason score ≥ 7, 125 Gleason score ≥ 8) and 1,751 controls. There were no associations of lycopene with prostate cancer risk. The odds ratios for a linear increase in lycopene (per 10 μg/dL) were 0.99 (95% CI: 0.94-1.04), 1.01 (0.94-1.08), and 1.02 (0.90-1.15) for Gleason 2 to 6, 7 to 10, and 8 to 10, respectively. In the placebo arm, a 10 μg/dL increase in lycopene was associated with a 7% (95% CI: 14-0) reduced risk of cancer diagnosed following an elevated PSA or abnormal DRE, which are cancers that best match those detected in screened populations. However, a 10 μg/dL increase in lycopene was also associated with an 8% (95% CI: 1-16) increased risk of cancer diagnosed without a biopsy prompt, which are cancers generally not detected. These findings were similar for low- and high-grade cancer. This study does not support a role for lycopene in prostate cancer prevention. Scientists and the public should understand that early studies supporting an association of dietary lycopene with reduced prostate cancer risk have not been replicated in studies using serum biomarkers of lycopene intake. Recommendations of professional societies to the public should be modified to reflect the likelihood that increasing lycopene intake will not affect prostate cancer risk.

309 DOES VARIATION IN EITHER AGE AT START OF THERAPY OR DURATION OF THERAPY MAKE CHEMOPREVENTION WITH FINASTERIDE COST-EFFECTIVE?

You have accessJournal of UrologyGeneral & Epidemiological Trends & Socioeconomics: Practice Patterns, Cost Effectiveness1 Apr 2011309 DOES VARIATION IN EITHER AGE AT START OF THERAPY OR DURATION OF THERAPY MAKE CHEMOPREVENTION WITH FINASTERIDE COST-EFFECTIVE? Suzanne Biehn Stewart, Charles Scales, Judd Moul, and Shelby Reed Suzanne Biehn StewartSuzanne Biehn Stewart Durham, NC More articles by this author , Charles ScalesCharles Scales Durham, NC More articles by this author , Judd MoulJudd Moul Durham, NC More articles by this author , and Shelby ReedShelby Reed Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2628AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Finasteride is an effective chemoprevention therapy for prostate cancer. However, previous studies have shown that widespread utilization of finasteride for prostate cancer prevention is likely not a cost−effective strategy. The majority of these analyses are based on a model where chemoprevention is started in men aged 50−55 years. The influence of varying age at start of therapy and duration of chemoprevention on the cost−effectiveness of finasteride has not been investigated. We sought to evaluate the impact of varying both age at commencement of therapy and length of therapy on the cost−effectiveness of finasteride. METHODS A Markov model with probabilistic sensitivity analysis was designed to estimate lifetime prostate health related costs, survival, and quality−adjusted survival for men receiving or not receiving chemoprevention with finasteride. Model assumptions were based on PCPT, SEER, national cancer registries, and medical literature. The model was continued to age 85, as the average remaining life expectancy at age 75 in the US is 10 years. Incremental cost−effective ratios (ICER) of models varying in age at start of therapy and duration of chemoprevention were compared. RESULTS In the base case analysis, the ICER for men starting chemoprevention with finasteride at age 50 years was $86,600 per quality adjusted life year (QALY) (95% CI: $57,900−$147,300) when assuming finasteride reduces all grades of prostate cancer by 24.8%. When age at start of therapy is increased, the ICERs initially trend downward, nadir at an age of 65 years, ICER $65,600 per QALY (95% CI: $45,500−$112,100), and then subsequently rise to where commencing therapy at age 80, the ICER is $78,300 per QALY (95% CI: $49,600−$139,000). At each age of therapy commencement, sensitivity analysis of duration of chemoprevention showed that stopping use at age 80 was most cost−effective. CONCLUSIONS Assuming equal effectiveness at all ages and across years of treatment, the cost−effectiveness of chemoprevention with finasteride is optimized when initiated at age 65 and continued until age 80 years. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e126 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Suzanne Biehn Stewart Durham, NC More articles by this author Charles Scales Durham, NC More articles by this author Judd Moul Durham, NC More articles by this author Shelby Reed Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Finasteride Decreases the Risk of Prostatic Intraepithelial Neoplasia

High grade prostatic intraepithelial neoplasia is likely a premalignant lesion of the prostate. Decreasing the frequency of high grade PIN may decrease the risk of prostate cancer. In the Prostate Cancer Prevention Trial we evaluated the impact of finasteride on the risk of a needle biopsy diagnosis of high grade prostatic intraepithelial neoplasia. The Prostate Cancer Prevention Trial was a randomized, placebo controlled clinical trial that enrolled 18,882 men without evidence of prostate cancer, prostate specific antigen less than 3.0 ng/ml and normal digital rectal examination, and randomized them to 5 mg finasteride daily or placebo. Subjects were followed for 7 years with biopsy recommended for prostate specific antigen greater than 4.0 ng/ml, adjusted in the finasteride group to achieve an equal number of biopsy recommendations or for abnormal digital rectal examination. All cancer-free subjects were recommended to undergo biopsy after 7 years on study. We evaluated the diagnosis of high grade prostatic intraepithelial neoplasia with or without concomitant prostate cancer in these 2 study groups. The number of men evaluable for high grade prostatic intraepithelial neoplasia was 4,568 in the finasteride group and 4,886 in the placebo group. High grade prostatic intraepithelial neoplasia alone was diagnosed in 276 men (6.0%) in the finasteride group vs 347 (7.1%) in the placebo group (RR 0.85, 95% CI 0.73-0.99, p=0.04). High grade prostatic intraepithelial neoplasia accompanied by prostate cancer was diagnosed in 144 men (3.2%) in the finasteride group vs 223 (4.6%) in the placebo group (RR 0.69, 95% CI 0.56-0.85, p=0.0004). Finasteride significantly decreased the overall risk of high grade prostatic intraepithelial neoplasia (alone and with cancer) from 570 cases (11.7%) in the placebo group to 420 (9.2%) in the finasteride group (HR 0.79, 95% CI 0.70-0.89, p<0.001). Finasteride significantly decreased the risk of high grade PIN. This observation may explain how finasteride decreased prostate cancer in the Prostate Cancer Prevention Trial, supporting the notion that high grade prostatic intraepithelial neoplasia is a premalignant lesion of the prostate, and it provides new information relevant to the consideration of finasteride for prostate cancer prevention.