Screening by prostate-specific antigen and digital rectal examination in relation to prostate cancer mortality: a case-control study

BACKGROUND: The potential role of prostate cancer screening in reducing mortality is uncertain. To examine whether screening with the prostate-specific antigen (PSA) test or digital rectal examination is associated with reduced prostate cancer mortality, we conducted a population-based case-control study in 4 health maintenance organizations. METHODS: Cases were 769 health plan members who died because of prostate adenocarcinoma during the years 1997-2001. We randomly selected 929 controls from the health plan membership and matched them to cases on health plan, age, race, and membership history. Medical records were used to document all screening tests in the 10 years before and including the date on which prostate cancer was first suspected. RESULTS: Among white participants, 62% of cases and 69% of controls had a least 1 screening PSA test or digital rectal examination (odds ratio = 0.73; 95% confidence interval = 0.55-0.97). The corresponding proportions for blacks were 59% and 61% (1.0; 0.59-1.4). Most screening tests were digital rectal examinations; therefore, in the subgroup with no history of PSA screening, the association between digital rectal screening and prostate cancer mortality was similar to the overall association (0.65 [0.48-0.88] among whites; 0.86 [0.53-1.4] among blacks). Very few men received screening PSA without screening digital rectal examination (6% of cases and 7% of controls among whites). CONCLUSIONS: Digital rectal screening was associated with a reduced risk of death due to prostate cancer in our population. Because of several data limitations, this study could not accurately estimate the effect of PSA screening separate from digital rectal examination.     

The efficacy of screening for carcinoma of the prostate by digital examination

Screening for carcinoma of the prostate by digital examination has been frequently advocated. In the United States prostate cancer is an important health problem for which current treatment is unsatisfactory; most patients with progressive disease die of the condition. While the pattern of spread of prostate cancer is understood, rates of progression of early disease are unknown. There has been no randomized clinical trial of digital examination in screening for prostate cancer; and thus, whether prognosis is definitely improved by early detection is unknown. Measures of test performance--test sensitivity and specificity--are unknown for an asymptomatic screened population. Interpreting the results of treatment for asymptomatic cases diagnosed by screening is difficult because of selection bias, lead time bias, and possible overdiagnosis of nonprogressive cancers. The limited cost-efficacy of routine digital examination of the prostate should be compared with the cost-efficacy of other routine health care in deciding about the use of this procedure.     

The diagnostic value of digital rectal examination in primary care screening for prostate cancer: a meta-analysis

OBJECTIVE: This systematic review examines the diagnostic value of the digital rectal examination (DRE) for the diagnosis of prostate cancer. METHOD: Only studies relating to unselected populations and using either biopsy or surgery as the reference standard were included. The methodological quality of the studies was used in an attempt to explain differences between studies. RESULTS: Fourteen studies were eligible for selection, of which five complied with the predetermined list of 'good-quality' requirements. Between study heterogeneity was high, even within the group of high-quality studies, and could not be explained by the registered indicators of methodological quality. CONCLUSIONS: In this setting, the DRE appears to be a test with a high specificity and negative predictive value, but a low sensitivity and positive predictive value. Neither a positive nor a negative test result is sufficient to enable conclusions without further confirmation.     

#7-S the efficacy of the digital rectal examination,total prostate specific antigen,and prostate specific antigen ratio algorithm in diagnosing prostate cancer

PURPOSE: The primary objective of this study was to determine the efficacy of the algorithm Digital Rectal Examination (DRE), Prostate Specific Antigen (PSA), and free/total Prostate Specific Antigen ratio (PSAr) in diagnosing prostate cancer. A criterion of 1 test, 2 tests and all 3 tests being positive was utilized for the DRE/PSA/PSAr algorithm.METHODS: A sample of 446 males suspected for prostate cancer was referred for transrectal ultrasound and biopsy. All patients consented to participate by allowing venipuncture and DRE prior to sextant biopsy examination. Analysis of PSA and PSAr were performed using Abbott Diagnostics kits. Statistical analysis in determining diagnostic utility for DRE/PSA/PSAr included ROC curve analysis, calculated sensitivity (Sens), specificity (Spec), and likelihood ratio (LR) with corresponding 95% confidence intervals (CI) as well as Kappa statistics.RESULTS: Positivity criteria for PSA and PSAr were identified at >4 and <0.15, respectively. The algorithm of DRE/PSA/PSAr ([Sens = 99%; CI, 1%] [Spec = 3%; CI, 2%], {LR = 1.02; CI, 0.05} demonstrated no significant Kappa agreement (p > 0.05) with the confirmed diagnosis for prostate cancer. The algorithm of DRE/PSA/PSAr with a criterion of one test being positive ([Sens = 99%; CI, 1%] [Spec = 3%; CI, 2%], [LR = 1.02; CI, 0.05] demonstrated no significant Kappa agreement (p > 0.05) with the confirmed diagnosis for prostate cancer. Furthermore, DRE/PSA/PSAr with a criterion of two tests being positive ([Sens = 83%; CI, 5%], [Spec = 61%; CI, 6%], [LR = 2.13; CI, 0.07]) indicated significant Kappa agreement (p < 0.0001).CONCLUSIONS: This study concluded that the algorithm of DRE/PSA/PSAr, with a criterion of one test being positive, failed to enhance specificity compared to the traditional algorithm of DRE/PSA. Furthermore, the algorithm DRE/PSA/PSAr with a criterion of two tests being positive did enhance specificity but sacrificed sensitivity.     

An analysis of digital rectal examination and serum-prostate-specific antigen in the early detection of prostate cancer in general practice

BACKGROUND: Prostate cancer is now the commonest cancer in men and the second commonest cause of death from cancer. However, general-practice-based research on prostate cancer remains scanty. OBJECTIVES: We aimed to examine the acceptability of digital rectal examination (DRE) and serum-prostate-specific antigen (PSA) in the early detection of prostate cancer in a general practice setting. Another aim was to ascertain the incidence of prostate cancer among 50-79-year-old men in the solo practice. METHODS: We conducted an opportunistic, prospective, population-based study involving men with no prior, proven history of prostate cancer. RESULTS: A total of 211 (87.6%) out of 241 targeted patients agreed to take part in the study. Abnormal DREs were found in 9%, while 9.5% of PSA tests were found to be abnormal. One or both tests were abnormal in 29 patients-13.7% of the study population. Eleven biopsies were performed during the study, with cancer detected in three (27.3%)-1.4% of the total population. Eighteen patients were not biopsied either on clinical grounds or by personal choice. CONCLUSIONS: The incidence of abnormal DRE and PSA tests was lower than that detected in previous hospital or specialist-based studies. Both tests were found to be highly acceptable to the population studied. Not all patients with abnormal early detection tests need necessarily proceed to further invasive investigations.     

Retrospective classification of prostate-specific antigen tests: differentiating screening from diagnostic clinical encounters

To assess the validity of retrospective medical chart review as a method of classifying prostate-specific antigen (PSA) tests as screening or diagnostic services, we reviewed PSA tests ordered at a university hospital (n = 95). PSA tests were reviewed by four raters: medicine resident (RES), oncologist (ONC), urologist (UR), medicine attending (GM)-and the physician who ordered the PSA test (ATTEND) using predefined standardized criteria. Agreement rates by individual rater and ATTEND were 0.79 (GM), 0.80 (ONC), 0.74 (UR), 0.83 (RES), for a composite percent agreement of 0.79. ATTEND incorrectly classified seven tests; exclusion of these tests raised agreement rates to 0.86 (GM), 0.86 (ONC), 0.80 (UR), 0.90 (RES), for a group composite percent agreement of 0.86. Of note, two raters had higher agreement rates when evaluating screening PSA tests than when evaluating diagnostic PSA tests. Standardized criteria applied to medical charts provide a valid method of retrospectively classifying PSA tests.     

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.     

Misclassifying the indications for prostate-specific antigen testing may bias case-control studies of the efficacy of prostate cancer screening

BACKGROUND AND OBJECTIVE: In the absence of data from randomized controlled trials, prostate cancer (CaP) screening recommendations may be based on observational studies that contrast exposure to screening between cases and controls. We evaluated the potential bias from mis-classifying indications for PSA testing in observational studies of CaP screening. METHODS: We randomly selected men undergoing PSA testing and obtained data on PSA results and prostate biopsies. Data were linked with a tumor registry to identify incident and prevalent cases of CaP. We abstracted medical records for 45 incident cases with CaP and 118 controls without, recording information on lower urinary tract symptoms (LUTS), constitutional symptoms, and digital rectal examination findings. PSA testing was classified as definitely, likely, or possibly screening, or not screening based on clinical history. RESULTS: Changing the definitions for PSA screening to variably exclude men with LUTS and enlarged prostates differentially lowered the frequency of screening. With more restrictive screening definitions, the odds ratio for screening decreased from 0.47 to 0.07. CONCLUSION: Accurately classifying PSA testing status is difficult because LUTS are common among men targeted for CaP screening. Failing to correctly classify PSA tests may bias study results.     

The search for better markers for prostate cancer than prostate-specific antigen

Prostate-specific antigen (PSA) is currently the most important biochemical marker for the diagnosis of prostate cancer. Because of the limited specificity of PSA, clinically irrelevant tumours and benign abnormalities are also detected that potentially lead to over-treatment and the accompanying physical and emotional burden for the patient. In addition, PSA is used as an indicator of progression or clinical response after treatment for prostate cancer, but the prognostic value of this marker is limited. Current studies are evaluating a number of alternative markers, such as PSA-related parameters, human kallikrein 2, osteoprotegerin and the gene DD3(PCA3), that may improve the specificity of current PSA-based diagnostics and the prognostic value of PSA.     

A reliable coding system to define screening prostate-specific antigen tests was developed in a case-control study

OBJECTIVE: To establish the reliability of a coding system for screening and diagnostic prostate-specific antigen (PSA) testing from patient charts. STUDY DESIGN AND SETTING: Two investigators reviewed 448 chart abstractions from a population-based case-control study of PSA screening in the Toronto area. The tests evaluated for reliability were transrectal ultrasound (TRUS), digital rectal examination (DRE), and prostate-specific antigen (PSA). RESULTS: DRE results were found in 87%, PSA results in 65%, and TRUS results in 12% of the 749 charts. Interobserver agreement was 94% for DRE texture (kappa =.885), 95% for DRE asymmetry (kappa = .868), 85% for DRE physician interpretation (kappa = .698), 97% for final DRE result (kappa = .856), and 87% for TRUS (kappa = .769). Physician interpretation modified the final result in only 6.2% of DREs. Interobserver agreement for PSA coding was 91% (kappa = .787). Of PSA results, pure PSA screening with no symptoms of obstructive urination was found in 19%, symptomatic PSA screening in 46%, and diagnostic PSA testing in 35%. CONCLUSION: We have developed a practical and reliable coding system for TRUS, DRE, and PSA in the context of a case-control study of PSA screening.     

Colorectal cancer screening participation: comparisons with mammography and prostate-specific antigen screening

OBJECTIVES: The relation of personal characteristics, health and lifestyle behaviors, and cancer screening practices to current colorectal cancer (CRC) screening was assessed and compared with those factors' relation to current mammography screening in women and prostate-specific antigen (PSA) screening in men. METHODS: A cross-sectional random-digit-dialed telephone survey of 954 Massachusetts residents aged 50 and older was conducted. RESULTS: The overall prevalence of current CRC screening was 55.3%. Logistic regression results indicated that family history of CRC (odds ratio [OR] = 1.98; 95% confidence interval [CI] = 1.02, 3.86), receiving a regular medical checkup (OR = 3.07; 95% CI = 2.00, 4.71), current screening by mammography in women and PSA in men (OR = 4.40; 95% CI = 2.94, 6.58), and vitamin supplement use (OR = 1.87; 95% CI = 1.27, 2.77) were significant predictors of CRC screening. CONCLUSIONS: Health and lifestyle behaviors were related to increased current CRC, mammography, and PSA screening. Personal factors independently related to CRC screening were not consistent with those related to mammography and PSA screening. This lack of consistency may reflect different stages of adoption of each type of screening by clinicians and the public.     

An ecologic study of prostate-specific antigen screening and prostate cancer mortality in nine geographic areas of the United States

Ecologic studies of cancer screening examine cancer mortality rates in relation to use of population screening. These studies can be confounded by treatment patterns or influenced by choice of outcome and time horizon. Interpretation can be complicated by uncertainty about when mortality differences might be expected. The authors examined these issues in an ecologic analysis of prostate-specific antigen (PSA) screening and prostate cancer mortality across nine cancer registries in the United States. Results suggested a weak trend for areas with greater PSA screening rates to have greater declines in prostate cancer mortality; however, the magnitude of this trend varied considerably with the time horizon and outcome measure. A computer model was used to determine whether divergence of mortality declines would be expected under an assumption of a clinically significant survival benefit due to screening. Given a mean lead time of 5 years, the model projected that differences in mortality between high- and low-use areas should be apparent by 1999 in the absence of other factors affecting mortality. The authors concluded that modest differences in PSA screening rates across areas, together with additional sources of variation, could have produced a negative ecologic result. Ecologic analyses of the effectiveness of PSA testing should be interpreted with caution.     

Does testing for prostate-specific antigen contribute to declining prostate cancer mortality?

Key variables associated with prostate cancer mortality were examined using Canadian province level time-series data over the period 1979–1999 in a multiple regression framework. The key variables driving the prostate cancer mortality rate are per capita income, per capita number of family physicians, rate of prostate cancer incidence, real per capita total health spending, and a time trend. As well, provincial dummy variables show that regional differences exist with higher rates of mortality in eastern Canada. Econometric results show a positive and significant relationship between incidence and mortality, suggesting that the increased amount of prostate-specific antigen (PSA) testing may not have been responsible for mortality declines. However, there is also a downward trend in mortality from prostate cancer when all other factors are controlled for that can be attributed partly to the onset of PSA testing given that the benefits should emerge over time. A 1% increase in incidence is associated with a 0.2% increase in mortality. A 1% increase in real per capita income is associated with a 0.5% increase in mortality when real per capita income is below Canadian $20,054. A 1% increase in the per capita number of family physicians reduces the mortality rate by 0.5%. A 1% increase in real per capita total health expenditures is associated with a 0.7% decline in the mortality rate. Finally, by 1999 there were 4.74 fewer deaths per 100,000 population due to the effect of time after controlling for all other factors—a decrease of approx. 15%.     

PSA testing and digital rectal examination in New Zealand

OBJECTIVE: To investigate the use of digital rectal examination and prostate specific antigen (PSA) testing in a population-based sample of men in New Zealand. METHODS: A random selection of men aged 40-74 years, weighted by age, was chosen from the general electoral roll of New Zealand. Only men with a telephone who had been married at some time were eligible. Telephone interviews were conducted using a standard questionnaire. Crude and age-adjusted proportions were calculated. Logistic regression was used to explore associations between sociodemographic factors and digital rectal examination or PSA testing. RESULTS: Interviews were completed for 85% of the 1,486 eligible men and analyses were confined to the 1,225 European men. Many more men reported having a digital rectal examination (41%; 95% CI 33.8-48.2) than a PSA test (9%; 95% CI 4.2-14.2). Men in the lowest social class were significantly less likely to have had a digital rectal examination (OR 0.30; 95% CI 0.18-0.50) or PSA test (OR 0.25; 95% CI 0.11-0.60) compared with those in the highest social class. Men with vocational training or no post-school qualifications were approximately half as likely to report a digital rectal examination or a PSA test compared with men with degrees or diplomas. CONCLUSIONS: Although current New Zealand recommendations are that population screening for prostate cancer should not be introduced, many men are still having digital rectal examinations and PSA tests in the absence of symptoms. The frequency of PSA testing is considerably lower than in Australia and appears to be largely influenced by a man's social class.     

Prostate-specific antigen as a tumor marker of prostate carcinoma]

Prostate specific antigen (PSA) is currently the tumour marker of choice for prostatic carcinoma. Various indices of PSA have been developed in an attempt to refine its sensitivity and improve its clinical value. These include the ratio of serum PSA level and prostate volume, the rate of change of the PSA level with time, age-referenced PSA, and the proportion of free PSA in serum relative to total PSA (free to total PSA ratio). The free to total PSA ratio is lower in patients with prostate cancer than in those with elevated PSA levels due to benign prostatic hyperplasia.     

Periodic health examination and screening tests in adults

Whenever a patient presents for the annual health examination, clinicians must choose from a plethora of screening tests and conflicting sets of guidelines. A discussion of the underlying issues leads to practical tips on how select and when to abandon screening tests and when to treat or not treat patients with marginally positive test results.     

Avoidance of anticipated regret: the ordering of prostate-specific antigen tests.

OBJECTIVE: When making decisions, people are known to try to minimize the regret that would be provoked by unwanted consequences of these decisions. The authors explored the strength and determinants of such anticipated regret in a study of physicians' decisions to order prostate-specific antigen (PSA) tests. METHODS: 32 US and 33 French primary care physicians indicated the likelihood they would order a PSA for 32 hypothetical men presenting for routine physical exams. They then indicated how much regret they would feel if they found advanced prostate cancer in 12 other patients for whom they had chosen not to order PSAs several years before. The latter patients differed according to age (55, 65, or 75 years), a prior request or not for PSA testing, and no or some irregularity of the prostate on the earlier rectal exam. RESULTS: ANOVA found that regret was higher when the patient had requested a PSA, the prostate was irregular, and the patient was younger. Shape had less effect when the patient had requested a PSA. US physicians had more regret than the French, patient request had a greater impact on the Americans, and increasing patient age reduced regret more among the French. In a 1-way correlation, the regret score was associated with the likelihood of ordering PSAs for both the French (r = 0.64, P < 0.005) and the Americans (r = 0.42, P< 0.02). In a regression analysis too, the regret score was the most important predictor of the likelihood of ordering a PSA (beta = 0.37, P < 0.0001). CONCLUSIONS: Regret over failing to diagnose aggressive prostate cancer is associated with a policy of ordering PSAs. This regret appears to be culturally sensitive.