Search

What's known on the subject? and What does the study add? The use of a single, elevated PSA level to screen for prostate cancer is controversial given its reported low specificity and the questionable benefits of PSA screening on prostate cancer mortality. Current guidelines in the USA recommend against screening using a single PSA measurement. Previous studies suggest that using changes in PSA level over time, or PSA velocity, may improve the detection of prostate cancer and/or aggressive disease; however, this is also controversial as other studies suggest PSA velocity does not improve detection and may further contribute to the overdetection of indolent prostate cancer. Given the questions that remain regarding the use of the rate of change in PSA as a screening tool for prostate cancer because of previous conflicting studies, which to date have included small, highly selected populations, this study adds to the existing knowledge by assessing this question in general practice settings among a large, diverse population. Objective To determine whether the rate of change in total serum prostate-specific antigen (PSA) levels accurately detects prostate cancer and to evaluate whether it adds any predictive value to a single measurement of serum PSA alone, in general practice settings. Materials and Methods A retrospective cohort of 219 388 community-dwelling men, aged ≥45 years, enrolled in the Kaiser Permanente Southern California health plan, with no history of prostate cancer and at least three PSA measurements, were followed from 1 January 1998 to 31 December 2007, for the development of biopsy-confirmed prostate cancer. Annual percent changes in total serum PSA levels were estimated using linear mixed models. The accuracy of prostate cancer prediction was assessed for prostate cancer overall and for aggressive disease (Gleason score ≥7) and compared with that of a single measure of PSA level using area under the receiver-operating characteristic curves (AUCs). Results The men in this cohort experienced a mean change of 2.9% in PSA levels per year and the rate of change in PSA increased modestly with age (P ≤ 0.001). Annual percent changes in PSA accurately predicted the presence of prostate cancer (AUC = 0.963) and aggressive disease (AUC = 0.955) and had more predictive accuracy for aggressive disease than did a single measurement of PSA alone (AUC = 0.727). Conclusions Longitudinal measures of PSA improve the accuracy of aggressive prostate cancer detection when compared with a single measurement of PSA alone. Findings from this study provide insight into the usefulness of PSA velocity as a detection marker for aggressive prostate cancer.

Study Type – Diagnostic (cost effectiveness) Level of Evidence 2b What's known on the subject? and What does the study add? The Beckman Coulter prostate health index (phi) was developed as a combination of serum prostate specific antigen (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 PSA test 2–10 ng/mL and non-suspicious digital rectal examination. Phi has been shown to improve diagnostic accuracy in prostate cancer detection compared with total and free PSA. An earlier 1-year budget impact analysis revealed it to be a complementary approach to current prostate cancer screening strategies. The current study evaluated the cost-effectiveness of early prostate cancer detection with phi in combination with a PSA test compared with a PSA test alone from the US societal perspective. The model with over 25 annual screening cycles for men aged 50–75 years indicated that PSA plus phi dominated the PSA test alone in prostate cancer detection and consequent treatment. PSA plus phi may be an important strategy 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.

To determine whether the rate of change in total serum prostate-specific antigen (PSA) levels accurately detects prostate cancer and to evaluate whether it adds any predictive value to a single measurement of serum PSA alone, in general practice settings.A retrospective cohort of 219,388 community-dwelling men, aged ≥45 years, enrolled in the Kaiser Permanente Southern California health plan, with no history of prostate cancer and at least three PSA measurements, were followed from 1 January 1998 to 31 December 2007, for the development of biopsy-confirmed prostate cancer. Annual percent changes in total serum PSA levels were estimated using linear mixed models. The accuracy of prostate cancer prediction was assessed for prostate cancer overall and for aggressive disease (Gleason score ≥7) and compared with that of a single measure of PSA level using area under the receiver-operating characteristic curves (AUCs).The men in this cohort experienced a mean change of 2.9% in PSA levels per year and the rate of change in PSA increased modestly with age (P ≤ 0.001). Annual percent changes in PSA accurately predicted the presence of prostate cancer (AUC = 0.963) and aggressive disease (AUC = 0.955) and had more predictive accuracy for aggressive disease than did a single measurement of PSA alone (AUC = 0.727).Longitudinal measures of PSA improve the accuracy of aggressive prostate cancer detection when compared with a single measurement of PSA alone. Findings from this study provide insight into the usefulness of PSA velocity as a detection marker for aggressive prostate cancer.

• 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.• 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.• 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.• 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.

Study Type – Symptom prevalence (prospective cohort) Level of Evidence 1b OBJECTIVE To evaluate patient-reported reasons for discontinuing antimuscarinic prescription medications for overactive bladder (OAB). PATIENTS AND METHODS A phase 1 screening survey was sent to a representative sample of 260 000 households in the USA to identify patients using antimuscarinic agents for OAB. A detailed phase-2 follow-up survey was sent to 6577 respondents with one or more antimuscarinic prescriptions for OAB in the 12 months before the phase 1 survey. The follow-up survey included questions about demographics, clinical characteristics, antimuscarinic use, beliefs about OAB, treatment expectations, OAB symptom bother, and pre-coded reasons for discontinuation. Patients who reported discontinuing one or more OAB medication during the 12 months before phase 2 were grouped by reason, using latent class analysis (LCA); the Lo-Mendell-Rubin likelihood statistical test was used to determine the number of classes. Conditional probabilities of reasons for discontinuation were calculated for each class. Multivariable logistic regression was used to assess the influence of demographic and clinical characteristics on class assignment. RESULTS In all, 162 906 (63%) and 5392 (82%) useable responses were returned in phases 1 and 2, respectively; the demographics were similar in respondents and nonrespondents in both phases. In all, 1322 phase 2 respondents (24.5%) reported discontinuing one or more antimuscarinic drugs during the 12 months before phase 2. LCA identified two classes (Lo-Mendell-Rubin statistic, P = 0.01) based on reasons for discontinuation. Most respondents (89%) reported discontinuing OAB medication primarily due to unmet treatment expectations and/or tolerability; many respondents in this class switched to a new antimuscarinic agent. A smaller group (11%) indicated a general aversion to taking medication. Age, sex, race, income, and history of incontinence were not predictive of class assignment. CONCLUSIONS Expectations about treatment efficacy and side-effects are the most important considerations in discontinuing OAB medications for most patients. Interventions to promote realistic expectations about treatment efficacy and side-effects might enhance adherence.