ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901).

OBJECTIVES: To determine the activity and safety of lutetium-177 (177 Lu)-prostate-specific membrane antigen (PSMA)-617 in men with metastatic castration-resistant prostate cancer (mCRPC) commencing enzalutamide, who are at high risk of early progression, and to identify potential prognostic and predictive biomarkers from imaging, blood and tissue. PARTICIPANTS AND METHODS: ENZA-p (ANZUP 1901) is an open-label, randomized, two-arm, multicentre, phase 2 trial. Participants are randomly assigned (1:1) to treatment with enzalutamide 160 mg daily alone or enzalutamide plus 177 Lu-PSMA-617 7.5 GBq on Days 15 and 57. Two additional 177 Lu-PSMA-617 doses are allowed, informed by Day-92 Gallium-68 (68 Ga)-PSMA positron emission tomography (PET; up to four doses in total). The primary endpoint is prostate-specific antigen (PSA) progression-free survival (PFS). Other major endpoints include radiological PFS, PSA response rate, overall survival, health-related quality of life, adverse events and cost-effectiveness. Key eligibility criteria include: biochemical and/or clinical progression; 68 Ga-PSMA PET-avid disease; no prior androgen signalling inhibitor, excepting abiraterone; no prior chemotherapy for mCRPC; and ≥2 high-risk features for early enzalutamide failure. Assessments are 4 weekly during study treatment, then 6 weekly until radiographic progression. Response Evaluation Criteria in Solid Tumours (RECIST) are used to assess imaging conducted every 12 weeks, 68 Ga-PSMA PET at baseline, Days 15 and 92, and at progression, and 18 F-fluorine deoxyglucose (18 F-FDG) PET at baseline and progression. Translational samples include blood (and optional biopsies) at baseline, Day 92, and first progression. Correlative studies include identification of prognostic and predictive biomarkers from 68 Ga-PSMA and 18 F-FDG PET/CT, circulating tumour cells and circulating tumour DNA. The trial will enrol 160 participants, providing 80% power with a two-sided type-1 error rate of 5% to detect a hazard ratio of 0.625 assuming a median PSA-PFS of 5 months with enzalutamide alone. RESULTS AND CONCLUSION: The combination of 177 Lu-PSMA-617 and enzalutamide may be synergistic. ENZA-p will determine the safety and efficacy of the combination in addition to developing predictive and prognostic biomarkers to better guide treatment decisions.

Cost-Effectiveness Analysis of Prostate-Specific Antigen Screening Among Chinese Men.

OBJECTIVES: To analyze the cost-effectiveness of prostate cancer screening among Chinese men. METHODS: A cost-effectiveness analysis was performed from a societal perspective using a Markov model to compare 2 strategies: the population-based screening strategy and the current clinical diagnostic strategy. Relevant parameters were retrieved from published literature data and surveys, and univariate sensitivity analysis was used to assess the robustness of the model. We simulated the health outcomes for the next 25 years for 100 000 men and calculated the incremental cost-effectiveness ratio (ICER). RESULTS: This study found that the population-based screening strategy, compared with the clinical diagnostic strategy, could save 756.61 quality-adjusted life-years (QALYs) for the hypothetical population. The ICER for the population-based screening strategy was ¥14 747.11/QALY, and this value was less than the willingness-to-pay threshold of ¥64 520. With life-year gains (LYGs) as the model output, the population-based screening strategy yielded an ICER of ¥16 470.45/LYG. The univariate sensitivity analyses showed that the ICER was sensitive to the prostate-specific antigen (PSA) test fee, the proportion diagnosed with low-grade prostate cancer (PC) in the population-based strategy, and the proportion diagnosed with intermediate-grade PC in the population-based strategy. CONCLUSIONS: Prostate cancer screening based on PSA test results appears to be cost-effective for Chinese men who are in good health and have a life expectancy of more than 10 years. Nevertheless, this finding needs to be further studied with more treatment cost parameters (treatment costs related to impotence and urinary incontinence) and using local utility value information.

Optimal Starting Age and Baseline Level for Repeat Tests: Economic Concerns of PSA Screening for Chinese Men - 10-Year Experience of a Single Center.

OBJECTIVE: To investigate the optimal age for the baseline serum prostate-specific antigen (PSA) test and for repeat screening and its economic burden in a single center in China. MATERIALS AND METHODS: 35,533 men with PSA screening were retrospectively enrolled in this study. Follow-ups were conducted in 1,586 men with PSA >4 ng/mL, and receiver-operating characteristic (ROC) curves were employed to investigate the optimal cutoffs. RESULTS: ROC analysis indicated that the optimal age for initial PSA screening was 57.5 years (AUC = 0.84), 62.5 years (AUC = 0.902), 60.5 years (AUC = 0.909), and 61.5 years (AUC = 0.890) for individuals with PSA >4 and >10 ng/mL, a diagnosis of prostate cancer (PCa), and clinically significant PCa defined as the focus events, respectively. For Chinese men aged 50-59, 60-69, and >70 years, the initial PSA levels of 1.305 ng/mL (AUC = 0.699), 1.975 ng/mL (AUC = 0.711), and 2.740 ng/mL (AUC = 0.720) might have a PSA velocity >0.75 ng/mL per year during the follow-up. In addition, the total cost amounts to CNY 13,609,260 in these cases, but only 60 of the 35,533 (0.17%) men gained benefit from PSA screening. CONCLUSION: In our opinion, the optimal starting age for initial PSA testing was 57.5 years. The necessity for repeat screening should be based on the first PSA level depending on age. A cost--benefit analysis should be included in population-based screening.

Cost implications of PSA screening differ by age.

BACKGROUND: Multiple guidelines seek to alter rates of prostate-specific antigen (PSA)-based prostate cancer screening. The costs borne by payers associated with PSA-based screening for men of different age groups-including the costs of screening and subsequent diagnosis, treatment, and adverse events-remain uncertain. We sought to develop a model of PSA costs that could be used by payers and health care systems to inform cost considerations under a range of different scenarios. METHODS: We determined the prevalence of PSA screening among men aged 50 and higher using 2013-2014 data from a large, multispecialty group, obtained reimbursed costs associated with screening, diagnosis, and treatment from a commercial health plan, and identified transition probabilities for biopsy, diagnosis, treatment, and complications from the literature to generate a cost model. We estimated annual total costs for groups of men ages 50-54, 55-69, and 70+ years, and varied annual prostate cancer screening prevalence in each group from 5 to 50% and tested hypothetical examples of different test characteristics (e.g., true/false positive rate). RESULTS: Under the baseline screening patterns, costs of the PSA screening represented 10.1% of the total costs; costs of biopsies and associated complications were 23.3% of total costs; and, although only 0.3% of all screen eligible patients were treated, they accounted for 66.7% of total costs. For each 5-percentage point decrease in PSA screening among men aged 70 and older for a single calendar year, total costs associated with prostate cancer screening decreased by 13.8%. For each 5-percentage point decrease in PSA screening among men 50-54 and 55-69 years old, costs were 2.3% and 7.3% lower respectively. CONCLUSIONS: With constrained financial resources and with national pressure to decrease use of clinically unnecessary PSA-based prostate cancer screening, there is an opportunity for cost savings, especially by focusing on the downstream costs disproportionately associated with screening men 70 and older.

Downstream tests, treatments, and annual direct payments in older men cared for by primary care providers with high or low prostate-specific antigen screening rates using 100 percent Texas U.S. Medicare public insurance claims data: a retrospective cohort study.

BACKGROUND: All authorities recommend against prostate specific antigen (PSA) screening in men 75 years and older. However, some primary care physicians (PCPs) continue to have high rates of PSA, with large variation in testing. We assessed the tests, treatments, and payments for prostate cancer care in men aged 75 or older who have PCPs with high or low PSA testing rates. METHODS: We performed a retrospective cohort study using the 2010 Medicare beneficiaries aged 75 or older in Texas, United States who had no prostate cancer in 2007-2009 and had an identifiable PCP. We first identified high vs. low PSA testing PCPs, and then grouped older men in the two PCP groups. We determined health care visits to any provider and to urologists in office and outpatient settings. We estimated the direct medical payments for prostate cancer care for diagnostics, treatments and visits to providers in 2010-2011 using the generalized gamma model with log link function. RESULTS: In multilevel, multivariable analyses, 25.4% (n = 550) of PCPs had PSA testing rates in men aged 75 or older that were significantly higher than the mean rate of all 2,169 Texas PCPs; 29.4% (n = 638) had rates that were significantly lower. In all, 22,853 vs. 23,929 older men were cared for by PCPs with high vs. low testing rates. Older men cared for by high PSA rate PCPs were more likely to receive a PSA test (OR 3.64, 95% CI 3.48-3.80), a biopsy (OR 1.16, 95% CI 1.02-1.31), an ultrasound (OR 1.19, 95% CI 1.07-1.32) or any radiation treatment (OR 1.31, 95% CI 1.03-1.66) than men cared for by low PSA rate PCPs. Men with high PSA rate PCPs were 1.21 (95% CI 1.05-1.39) times more likely to have such outpatient visits. The average annual adjusted Medicare payments for prostate cancer care was $25.60 higher for patients cared for by PCPs with high PSA test rates. CONCLUSIONS: Older men seeing PCPs with high rates of PSA testing undergo more testing and treatments for prostate cancer, with higher Medicare insurance payments. Future studies are needed to delineate whether men seeing PCPs with low testing rates likely received PSA tests from other providers.

The costs of identifying undiagnosed prostate cancer in asymptomatic men in New Zealand general practice.

BACKGROUND: Screening for prostate cancer (PCa) using the prostate-specific antigen (PSA) test is widespread in New Zealand. Aim. This study estimates the costs of identifying a new case of PCa by screening asymptomatic men. METHODS: Men aged 40+, who had PSA tests in 31 general practices in the Midland Cancer Network region during 2010, were identified. Asymptomatic men without a history of PCa were eligible for this study. A decision tree was constructed to estimate the screening costs. We assumed GPs spent 3 minutes of the initial consultation on informed consent of PCa screening. RESULTS: About 70.7% of the estimated costs were incurred in general practice. The screening costs per cancer detected were NZ$10 777 (€5820; £4817). The estimated costs for men aged 60-69 were NZ$6268 compared to NZ$24 290 for men aged 40-49, NZ$30 022 for 50-59 and NZ$10 957 for those aged 70+. The costs for Maori were NZ$7685 compared to NZ$11 272 for non-Maori. The costs for men without PSA testing history in 2007-09 were NZ$8887 compared to NZ$13 870 if the men had PSA tests in 2007-09. If we assumed a PSA test involved a full 15-minute general practice consultation, the estimated costs increased to NZ$26 877 per PCa identified. CONCLUSIONS: Screening of asymptomatic men for PCa is widely practiced. Most of the costs of screening were incurred in general practice. Calls for men to receive increased information on the harms and benefits of screening will substantially increase the costs. The current costs could be reduced by better targeting of screening.

A literature review of cost-effectiveness analyses of prostate-specific antigen test in prostate cancer screening.

Prostate cancer is the most common non-skin cancer in American men, and prostate-specific antigen (PSA) testing is its common screening procedure. In May 2012, the US Preventive Services Task Force recommended against PSA-based screening. These recommendations contradict the current recommendations of other organizations such as the American Urological Association. The authors conducted a systematic review of PubMed, EMBASE and Cochrane to examine the published literature reporting the cost-effectiveness of PSA-based screening. The authors found ten studies each for US and non-US jurisdiction population. All reviewed studies concluded PSA-based screening to be cost effective in younger men (≤60 years of age) and at higher PSA levels (≥3 ng/ml). Further cost-effectiveness analyses reflecting latest clinical practice and current perspectives regarding adverse outcomes of potentially unnecessary treatment are required, especially from the US government perspective.

[The algorithms of evaluation of economic effectiveness of laboratory technologies].

The article considers several practical situations requiring estimation of economic effectiveness. The protocols of estimation, costs and effectiveness accounting requirements of practical public health are proposed. The necessity of development of correct epidemiological model is demonstrated to estimate profit of innovations of diagnostic stage. The estimation "costs-effectiveness" is made for troponins at diagnostic of cardiac infarction and prostate-specific antigen under screening of prostate cancer.

Cost-effectiveness of Prostate Health Index for prostate cancer detection.

OBJECTIVE: • To evaluate the cost-effectiveness of early prostate cancer detection with the Beckman Coulter Prostate Health Index (phi) (not currently available in the USA) adding to the serum prostate-specific antigen (PSA) test compared with the PSA test alone from the US societal perspective. PATIENTS AND METHODS: • Phi was developed as a combination of PSA, free PSA, and a PSA precursor form [-2]proPSA to calculate the probability of prostate cancer and was used as an aid in distinguishing prostate cancer from benign prostatic conditions for men with a borderline PSA test (e.g. PSA 2-10 ng/mL or 4-10 ng/mL) and non-suspicious digital rectal examination. • We constructed a Markov model with probabilistic sensitivity analysis to estimate expected costs and utilities of prostate cancer detection and consequent treatment for the annual prostate cancer screening in the male population aged 50-75 years old. • The transition probabilities, health state utilities and prostate cancer treatment costs were derived from the published literature. The diagnostic performance of phi was obtained from a multi-centre study. Diagnostic related costs were obtained from the 2009 Medicare Fee Schedule. • Cost-effectiveness was compared between the strategies of PSA test alone and PSA plus phi under two PSA thresholds (≥2 ng/mL and ≥4 ng/mL) to recommend a prostate biopsy. RESULTS: • Over 25 annual screening cycles, the strategy of PSA plus phi dominated the PSA-only strategy using both thresholds of PSA ≥2 ng/mL and PSA ≥4 ng/mL, and was estimated to save $1199 or $443, with an expected gain of 0.08 or 0.03 quality adjusted life years, respectively. • The probabilities of PSA plus phi being cost effective were approximately 77-70% or 78-71% at a range of $0-$200,000 willingness to pay using PSA thresholds ≥2 ng/mL and ≥4 ng/mL, respectively. CONCLUSION: • The strategy PSA plus phi may be an important strategy for prostate cancer detection at both thresholds of PSA ≥2 ng/mL and PSA ≥4 ng/mL to recommend a prostate biopsy compared with using PSA alone.

Overdetection, overtreatment and costs in prostate-specific antigen screening for prostate cancer.

BACKGROUND: Prostate cancer screening with prostate-specific antigen (PSA) has shown to reduce prostate cancer mortality in the European Randomised study of Screening for Prostate Cancer (ERSPC) trial. Overdetection and overtreatment are substantial unfavourable side effects with consequent healthcare costs. In this study the effects of introducing widespread PSA screening is evaluated. METHODS: The MISCAN model was used to simulate prostate cancer growth and detection in a simulated cohort of 100,000 men (European standard population) over 25 years. PSA screening from age 55 to 70 or 75, with 1, 2 and 4-year-intervals is simulated. Number of diagnoses, PSA tests, biopsies, treatments, deaths and corresponding costs for 100,000 men and for United Kingdom and United States are compared. RESULTS: Without screening 2378 men per 100,000 were predicted to be diagnosed with prostate cancer compared with 4956 men after screening at 4-year intervals. By introducing screening, the costs would increase with 100% to 60,695,000 euro. Overdetection is related to 39% of total costs (23,669,000 euro). Screening until age 75 is relatively most expensive because of the costs of overtreatment. CONCLUSION: Introduction of PSA screening will increase total healthcare costs for prostate cancer substantially, of which the actual screening costs will be a small part.

Cost-effectiveness of percent free PSA for prostate cancer detection in men with a total PSA of 4-10 ng/ml.

OBJECTIVE: To assess the cost-effectiveness of two diagnostic strategies for prostate cancer in men with prostate-specific antigen (PSA) levels of 4-10 ng/ml and normal digital rectal examination (DRE). DESIGN: Cost-effectiveness analysis was performed using a decision tree model. Data collection and a systematic review of patients at the Urology Department (Carlos Haya Hospital) were made. 101 patients over the age of 40 with PSA levels of 4-10 ng/ml and normal DRE were selected. Transrectal ultrasound-guided prostate biopsy (TRUS-Bx) and percent free PSA testing prior to TRUS-Bx were performed. The outcome measures used were the incremental cost-effectiveness ratio, and costs were calculated through activity-based costing. The effectiveness was measured by means of the number of detected cases, test utility and actual cases (detected cases minus lost cases). RESULTS: Using base-case analysis, the strategy of percent free PSA + TRUS-Bx was found to be the most cost-effective. The incremental cost-effectiveness ratio for free PSA + TRUS-Bx compared with TRUS-Bx was EUR 2,277.40. Strategy 2 (TRUS-Bx) would be more cost-effective if the cost of percent free PSA increased to EUR 21.64 or if prostate cancer prevalence increased to 26%. CONCLUSIONS: The use of percent free PSA prior to TRUS-Bx is the most cost-effective diagnostic strategy. However, this result is very sensitive and strategy 2 (TRUS-Bx) would be more cost-effective if the cost of the percent free PSA increased to EUR 21.64 or if the prevalence of prostate cancer increased to above 26%.

Screening for prostate cancer: updated experience from the Tyrol study.

The aim of the Tyrol study was to monitor the impact of screening in a natural experiment by comparing prostate cancer mortality in Tyrol, where prostate-specific antigen (PSA) testing was introduced at no charge, with the rest of Austria, where it was not strictly organized and not free of charge. In 1993, PSA testing was made freely available to men between the ages of 45 and 75 years in the Federal State of Tyrol, Austria. At least 70% of all of the men in this age range have been tested at least once during the first 10 years of the study. Initially, only total PSA was measured, but free PSA measurement was added in 1995. Since 2001, complexed PSA also has been measured. Digital rectal examination was not part of the screening examination. Significant migration to lower clinical and pathological stages has been observed since the introduction of this screening program. These findings are consistent with the hypothesis that the policy of making PSA testing freely available, and the wide acceptance by men in the population, is associated with a reduction in prostate cancer mortality in an area in which urology services and radiotherapy are available freely to all patients. It is our opinion that most of this decline is likely a result of aggressive downstaging and successful treatment and that any contribution from detecting and treating early cancers will become apparent in the years to come.

Serum prostate-specific antigen screening for prostate cancer: application of current evidence to model criteria.

Prostatic carcinoma, particularly in younger men, carries a significant possibility of morbidity and mortality, although authoritative diagnosis and treatment itself is not without associated risks. Controversy still looms with respect to the actual implementation of routine serum prostate-specific antigen (PSA) screening for the general public. A brief summary of indications for screening programmes is presented, and these concepts are applied specifically to the body of research surrounding prostate cancer screening with PSA testing. Due to the slowly-progressive natural history of prostate cancer and the high morbidity associated with confirmation biopsy and definitive treatment, periodic general screening with insensitive and nonspecific PSA secrum testing emerges as an inefficient allocation of health care capital. The possible effectiveness of targeted screening practices for selected high-risk individuals, however, is considered.

Annual PSA tests are not necessary for men with a PSA level below 2 ng/mL: findings of the Imari prostate cancer screening program.

BACKGROUND: Annual changes in prostate specific antigen (PSA) levels detected by the Imari prostate cancer screening program were evaluated to establish a more efficient and cost-saving screening system, especially for men with low PSA levels. METHODS: Prostate specific antigen-based annual mass screenings for prostate cancer were conducted for men aged 60-69 in the Imari district, Saga, Japan. Between 1992 and 2000, 1822 men had their PSA levels tested. A total of 4661 PSA tests were conducted. Changes in PSA levels over the following 1 to 5 years were analyzed in men with PSA levels of 3 ng/mL or less, a range in which the detection rate of prostate cancer would seem to be negligibly low. RESULTS: The overall detection rate of prostate cancer between 1992 and 2000 was 0.73%. The detection rate in men with a PSA level between 3.1 and 3.9 ng/mL, and between 4 and 9.9 ng/mL was 1.6% and 8.3%, respectively. Of 4661 determinations of PSA, 2553 (54.8%) were found to be < or = 1 ng/mL, 1273 (27.3%) were between 1.1 and 2 ng/mL, and 401 (8.6%) were between 2.1 and 3 ng/mL. Four hundred and thirty-four men (9.3%) had PSA levels > or = 3.1 ng/mL, with possible indications for prostate biopsy. Of the men tested, 1.4% with an initial PSA level of < or = 2 ng/mL and 22.3% with an initial level between 2.1 and 3 ng/mL had a PSA level of > or = 3.1 ng/mL after 1 year. Almost the same rate of PSA increase was observed between the two PSA tests conducted at 2 to 5-year intervals. Of the men tested, 2.2% with an initial PSA level of < or = 2 ng/mL, and 21.9% with an initial level between 2.1 and 3 ng/mL, had a level of > or = 3.1 ng/mL after 5 years. CONCLUSION: Levels of PSA in men with an initial level below 2 ng/mL remained stable for up to 5 years. Levels of PSA in 97.8- 98.8% of men remained below 3 ng/mL after 1 to 5 years. In contrast, 18-35.3% of men with an initial PSA level between 2.1 and 3 ng/mL showed PSA progression to 3.1 ng/mL or more within 5 years. Our present data suggest that annual PSA testing is not necessary for men with a PSA level below 2 ng/mL. Prostate specific antigen testing could therefore be conducted at longer intervals in such individuals.

Evaluation of the BioSign PSA membrane test for the identification of semen stains in forensic casework.

AIM: To evaluate BioSign prostate specific antigen (PSA), a membrane test device used as a clinical aid in the diagnosis of prostate cancer, to determine whether it can be used in forensic laboratories for identifying semen stains. METHODS: Biological fluids were obtained under ethical approval from anonymous consenting donors. BioSign PSA was evaluated in terms of its specificity, sensitivity and cost to replace an ELISA (enzyme linked immunosorbent assay) method of PSA detection. RESULTS: Semen stain extracts and semen diluted 10(5) tested positive with BioSign PSA. Animal semen, other human body fluids and commonly encountered household products tested negative. Anomalous results were observed with semen-free condoms containing nonoxynol-9. The cause of these false positive results is not known. CONCLUSIONS: These results and the ease of use of the BioSign PSA kit indicate that it is a valuable addition to forensic laboratories and can adequately replace the ELISA method of PSA detection. BioSign PSA was not suitable for testing condoms for semen.

Evaluation of prostatic specific antigen and digital rectal examination as screening tests for prostate cancer.

BACKGROUND: The 11,811 first visits and 46,751 annual follow-up visits performed since 1988 were analyzed in order to assess the efficacy of serum prostatic specific antigen (PSA) and digital rectal examination (DRE) for diagnosis of prostate cancer. METHODS: At first visit, screening included DRE and measurement of PSA using 3.0 ng/ml as upper limit of normal, demonstrated as optimal value in the course of the study. Transrectal echography of the prostate (TRUS) was performed only if PSA and/or DRE was abnormal. For elevated PSA, biopsy was performed only if PSA was above the value predicted from prostatic volume measured by TRUS. At follow-up visits, it was decided during the course of the study to use PSA alone. RESULTS: PSA was above 3.0 ng/ml in 16.6% and 15.6% of men at first and follow-up visits, respectively. Prostate cancer was found in 2.9% of men invited for screening at first visit and in only 0.4% of men at follow-up visits for a 7.1-fold decrease at follow-up visits done up to 11 years. PSA alone allowed to find 90.5% and 90. 0% of cancers at first and follow-up visits, respectively, compared to 41.1% and 25.0% by DRE alone. In the presence of normal PSA, 344 and 1,919 DREs are needed to find one prostate cancer at first and follow-up visits, respectively. A significant improvement in stage of the disease is found at follow-up (215 cancers) compared to first visits (337 cancers). Comparison made between men invited for screening and those who were not invited but screened showed no significant difference in terms of incidence and prevalence of prostate cancer as well as diagnosis of cancer as a function of age or as a function of PSA, DRE, and TRUS data. The cost for finding one case of prostate cancer is estimated at Can $2,420 and Can $7, 105 (first and follow-up visits, respectively, when PSA is used as prescreening). CONCLUSIONS: PSA used as prescreening and followed by DRE and TRUS when PSA is abnormal is highly efficient in detecting prostate cancer at a localized (potentially curable) stage since 99% of the cancers diagnosed were at such a localized stage, thus practically eliminating the diagnosis of metastatic and noncurable prostate cancer. The approach used is highly reliable, sensitive, efficient, and acceptable by the general population. The detection of clinically nonsignificant cancer is an exception.

The socioeconomic implications of prostate-specific antigen screening.

Widespread PSA screening will increase overall health care costs. This increase will not result from the detection of clinically insignificant prostate cancer, but rather from the stage migration caused by prostate cancer screening. This stage migration will result in a larger percentage of men with prostate cancer undergoing early treatment options, which are more expensive than treatment of late disease. More importantly, early detection of prostate cancer will lead to treatment several years earlier than would have occurred otherwise. Because treatment then will be paid for in current rather than future dollars, the opportunity costs of money will make treatment costs resulting from PSA screening greater than treatment costs resulting from traditional detection. The critical question is what benefits will be obtained by the expenditure of these additional health care dollars. If early treatment of clinically localized cancer has little or no effect on cause-specific survival, the additional health care costs will have been spent only to limit eventual treatment of local symptoms in the screened men. If early treatment of prostate cancer can increase survival, the added expense is more worthwhile. Because there are not adequate data available to address this issue, several approaches have been used to develop models to estimate cost-effectiveness. Decision analysis models have been used to evaluate the effectiveness of prostate cancer screening and treatment and have found little or no benefit. The current review has demonstrated how assumptions used in the models can influence the results. Benoit et al also have constructed a model of the effectiveness and cost-effectiveness of prostate cancer, but in this study only concrete parameters such as cost, published complication rates, and survival data were used. This quantitative analysis demonstrated that prostate cancer screening is an effective and cost-effective health care intervention compared with currently accepted medical interventions. Although men aged 50 to 70 years will potentially benefit the most from PSA screening, this benefit will not be realized until these men are in their seventh and eighth decades of life. Society must decide if the years of life saved in these men warrants the use of its limited health care resources. This decision will be easier when randomized, controlled trials are available to quantify the costs and benefits of PSA screening.