Introduction Of Prostate-specific Antigen Testing Research Articles

Trends in Prostate Specific Antigen (PSA) testing and prostate cancer incidence and mortality in Australia: A critical analysis

BackgroundPopulation trends in PSA testing and prostate cancer incidence do not perfectly correspond. We aimed to better understand relationships between trends in PSA testing, prostate cancer incidence and mortality in Australia and factors that influence them. MethodsWe calculated and described standardised time trends in PSA tests, prostate biopsies, treatment of benign prostatic hypertrophy (BPH) and prostate cancer incidence and mortality in Australia in men aged 45–74, 75–84, and 85 + years. ResultsPSA testing increased from its introduction in 1989 to a peak in 2008 before declining in men aged 45–84 years. Prostate biopsies and cancer incidence fell from 1995 to 2000 in parallel with decrease in trans-urethral resections of the prostate (TURP) and, latterly, changes in pharmaceutical management of BPH. After 2000, changes in biopsies and incidence paralleled changes in PSA screening in men 45–84 years, while in men ≥85 years biopsy rates stabilised, and incidence fell. Prostate cancer mortality in men aged 45–74 years remained low throughout. Mortality in men 75–84 years gradually increased until mid 1990s, then gradually decreased. Mortality in men ≥ 85 years increased until mid 1990s, then stabilised. ConclusionAge specific prostate cancer incidence largely mirrors PSA testing rates. Most deviation from this pattern may be explained by less use of TURP in management of BPH and consequent less incidental cancer detection in TURP tissue specimens. Mortality from prostate cancer initially rose and then fell below what it was when PSA testing began. Its initial rise and fall may be explained by a possible initial tendency to over-attribute deaths of uncertain cause in older men with a diagnosis of prostate cancer to prostate cancer. Decreases in mortality rates were many fold smaller than the increases in incidence, suggesting substantial overdiagnosis of prostate cancer after introduction of PSA testing.

Potentiometric Sensors Based on Molecularly Imprinted Polymers for the Detection of Sarcosine

Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. Prostate cancer (PCa) is the second most diagnosed cancer and the sixth leading cause of death in men worldwide. PCa incidence is 2 to 5 times higher in developed countries as a result of variations in risk factors and diagnostic practices. PCa new cases represent between 6-14% of all global cancer deaths in 2008. In 2013, malignant tumors were ranked in third place as the cause of death in men (10.5%) in Mexico and the most frequent was PCa (16.3%). PCa mortality increased steadily by 2% per year from 1980 to 2011. The incidence varies due to the practice of prostate-specific antigen (PSA) screening and prostate biopsy. In Latin America, the early detection of PCa is very low and it gets frequently detected in advanced stages. Since the introduction of PSA test in 1986, detection and prevention had been improved, but it is still common to found false positive and false negative results. For PCa detection, it is commonly used ELISA test for PSA screening, digital rectal exam for physical inspection of the prostate and the biopsy to confirm or discard the presence of cancer cells. ELISA test is highly sensitive and specific but also its cost is expensive due to the need for natural specific antibodies, their handling and storage and their low chemical stability. Digital rectal exam (DRE) and biopsy are invasive methods and their main disadvantages are several health risks after the biopsy and the incapacity of PCa detection in areas out of the tumor. Hence, there is a need to develop new technologies with high sensibility and lower response time for the detection of prostate cancer biomarkers during the early stage of the disease. Chemical sensors and biosensors have emerged in recent years as particular interest inside the field of analytical chemistry due to their versatility in clinical assays, drugs detection, food and environmental analysis. An essential part of every sensor is the recognition element, which it gives selectivity towards the analyte in a complex matrix. Biosensors used biological components for recognition such as enzymes, receptors, and antibodies. These allowed a high selectivity but due to their low physical and chemical stability, they cannot be used in rough environments. As an alternative, it can be used biomimetics components, which mimic and selectively bind to a natural molecule. Molecularly imprinted technology is based on the “key-lock” principle, which used a template molecule to create a specific recognition site for it through a polymeric matrix. This molecularly imprinted polymer can be used as a recognition element in chemical sensors for detecting cancer biomarkers. For processing signal, a transducer must be used. Epoxy resins constitute a versatile class characterized by excellent chemical and corrosion resistance, good adhesion to various materials, electrically insulating and easy to fabricate. The addition of powdered fillers like carbonaceous material increases the electrical and heat conductivities of epoxies, providing composite materials that combine a high conductivity. These materials can be used as an all solid-contact electrode and can be used in sensors as a transducer. The present work proposes the construction of selective potentiometric electrodes for the detection of biomarkers related to prostate cancer in early stages of the disease. For that, the use of molecularly imprinted polymers as an element of recognition in a liquid membrane, coupled with a conductive support was investigated. All of this will provide a better response time, limits of detection below concentrations from blood and urine, high selectivity, sensitivity, and reproducibility. Transducers were constructed by using 3 types of carbonaceous materials (graphite, graphene and carbon nanotubes) and epoxy resin. They were characterized by cyclic voltammetry, electrochemical impedance spectroscopy, and four-point probe technique to obtain electrical properties of the materials. A molecularly imprinted polymer was synthesized non-covalent via and analytically characterized. The constructed potentiometric sensor employed an all solid-state electrode for sensing and the effect of pH, selectivity, response time and its potentiometric features were evaluated.

The use of transrectal ultrasound-guided biopsy following the introduction of prostate-specific antigen testing in Denmark: a population-based analysis

Objective: Incidence rates of prostate cancer in Denmark resemble those of countries that endorse prostate-specific antigen (PSA) screening. So far, no studies have described the consequences of PSA testing on diagnostic activity on a population level. The aim of this study was to describe the frequency of systematic transrectal ultrasound-guided biopsy (TRUS-gb) activity, including rebiopsy rates, in Denmark between 1995 and 2011.Materials and methods: All men who underwent TRUS-gb during the period were identified in the Danish Prostate Cancer Registry. In total, 83,041 biopsy sets from 64,430 individuals were identified. The diagnostic rate and the frequency of rebiopsy were analyzed. Age, histology and PSA were compared at the time of biopsy.Results: The number of TRUS-gb per 100,000 men per year increased 4.6-fold. The mean number of TRUS-gb procedures per individual increased from 1.08 in 1995 to 1.46 in 2011 (p = .0001), and the proportion of men with negative initial biopsy sets who underwent rebiopsy increased from 22% in 1995 to 41% in 2004, later decreasing to 31% in 2009.Conclusions: The diagnostic activity in Denmark and the rebiopsy rates in men with initial negative TRUS-gb have increased substantially, and guidelines for the management of men with a negative initial biopsy are highly warranted.

The treatment of metastatic prostate cancer

Prostate cancer is the second most common cancer in men worldwide. The incidence of prostate cancer is increasing with an ageing population. Since the introduction of prostate-specific antigen testing in Western countries, prostate cancers are now being diagnosed earlier. The treatment of metastatic prostate cancer has progressed dramatically in the past decade and includes advances in chemotherapy, androgen receptor-targeted agents, immunotherapy, radiopharmaceuticals and bone-targeted agents. These new treatments bring a new range of side effects, which must be managed promptly and effectively. An understanding of potential treatment toxicities and their management is essential for nursing staff in order to provide a high standard of care for men with prostate cancer.

Trends in the Incidence of Fatal Prostate Cancer in the United States by Race

BackgroundProstate-specific antigen (PSA) testing has dramatically changed the composition of prostate cancer (PCa), making it difficult to interpret incidence trends. New methods are needed to examine temporal trends in the incidence of clinically significant PCa and whether trends vary by race. ObjectiveTo conduct an in-depth analysis of incidence trends in clinically significant PCa, defined as cases in which PCa was the underlying cause of death within 10 yr of diagnosis. Design, setting, and participantsWe extracted incident PCa cases during the period 1975–2002 and associated causes of death and survival through 2012 from nine cancer registries in the population-based Surveillance Epidemiology and End Results program database. Outcome measurements and statistical analysisWe applied joinpoint regression analysis to identify when significant changes in trends occurred and age–period–cohort models to examine longitudinal and cross-sectional trends in the incidence of fatal PCa. Results and limitationsAmong 51 680 fatal PCa cases, incidence increased 1% per year prior to 1992, declined 15% per year from 1992 to 1995, and further declined by 5% per year through 2002. Age-specific incidence rates of fatal disease decreased >2% per year among men aged ≥60 yr, yet rates remained relatively stable among men aged ≤55 yr. Fatal disease rates were >2-fold higher in black men compared with white men, a racial disparity that increased to 4.2-fold among younger men. ConclusionsThe incidence of fatal PCa substantially declined after widespread PSA screening and treatment advances. Nevertheless, rates of fatal disease among younger men have remained relatively stable, suggesting the need for additional attention to early onset PCa, especially among black men. The persistent black-to-white racial disparity observed in fatal PCa underscores the need for greater understanding of the causes of this difference so that strategies can be implemented to eliminate racial disparities. Patient summaryWe assessed how the incidence of ultimately fatal prostate cancer (PCa) changed over time. We found that the incidence of fatal PCa declined by >50% since the introduction of prostate-specific antigen testing and advances in treatment options; however, incidence rates among younger men remained relatively stable, and younger black men exhibited a 4.2-fold higher risk for fatal disease compared with white men.

Patterns of changing cancer risks with time since diagnosis of a sibling.

Family history is a well-known risk factor for many cancers. However, it is important to know if/how the familial risk of cancer changes over time. For each of four major cancers (colorectal, breast, prostate and melanoma), we identified siblings of cancer patients (case siblings) and siblings of matched cancer-free controls sampled from Swedish population-based registers. Effects of age and time since diagnosis on sibling risks were examined using Poisson regression and presented graphically as smoothed hazard ratios (HRs). Screening effects were investigated by comparing hazards before/after the introduction of mammography for breast cancer and prostate-specific antigen (PSA) testing for prostate cancer. Case siblings had higher cancer incidence than control siblings for all cancers at all ages, with overall incidence rate ratios (IRRs) of 2.41 (95% confidence interval 2.14-2.71) for colorectal cancer, 2.37 (2.24-2.52) for breast cancer, 3.69 (3.46-3.93) for prostate cancer and 3.20 (2.72-3.76) for melanoma. Risks were highest in siblings who were young when the first cancer was diagnosed in the family, with siblings aged 30-40 having IRR 9.05 (3.03-27.00) for colorectal cancer and 4.30 (2.87-6.45) for breast cancer. Smoothed HRs remained fairly constant for up to 20 years except for prostate cancer, where the HR decreased steeply during the first few years. After introduction of PSA testing, men had higher incidence of prostate cancer shortly after diagnosis in a brother, but no such screening effect was found for breast cancer. Our findings can help inform the screening and counseling of family members of cancer patients.

Prostate specific antigen. Current clinical application and future prospects.

Prostate-specific antigen (PSA) is a glycoprotein produced by the prostate gland and its production can be enhanced in benign and malignant diseases. The introduction of PSA testing has greatly increased the detection of prostate cancer. However there is continuing controversy and confusion over the most appropriate application of the PSA test. PubMed and Web of Science databases were used to search original and review articles on the historical aspects, clinical utilization and possible future directions in PSA. After its discovery, PSA was quickly established as an exquisitely sensitive tumor marker for prostate cancer detection, assessment of treatment responses and follow-up among patients with prostate cancer. Nevertheless, controversy exists about the proper threshold for recommending prostate biopsy. If this limit is lowered to improve the sensitivity even more, patients with low-risk prostate cancer would be subsequently detected. Post-treatment PSA levels can certainly provide valuable information about the effectiveness of the therapy given. Recently introduced ultrasensitive PSA detection techniques are offering new insight into the changes in serum PSA at very low concentrations. This has resulted in identification of valuable postoperative prognostic variables together with the possibility of earlier cancer relapse detection. The development of assays that may show superior sensitivity and specificity in prostate cancer diagnosis is focused on proteins possibly complexed with PSA and other potential markers detectable both in serum and urine. The goal of newly discovered prostate cancer biomarkers is greater cancer specificity in order to reduce the overdiagnosis, overtreatment and financial cost.

The prostate cancer conundrum revisited: Further insights

Prostate cancer incidence and mortality trends in the United States continue to perplex researchers. The rise and subsequent decline in prostate cancer incidence can clearly be traced to the introduction of prostate-specific antigen testing. However, prostate cancer mortality rates have fallen sooner and faster than can be attributed to the impact of surgery and radiotherapy. Computer modeling by the National Cancer Institute's Cancer Intervention and Surveillance Modeling Network (CISNET) research teams provides insights into these complex relationships.

Prostate-specific antigen (PSA) velocity: a test of controversial benefit in the era of increased prostate cancer screening

Prostate-specific antigen (PSA) velocity: a test of controversial benefit in the era of increased prostate cancer screening

Promoter Methylation in APC, RUNX3, and GSTP1 and Mortality in Prostate Cancer Patients

PURPOSE There is a need to better understand prostate cancer progression and identify new prognostic markers for this tumor. We investigated the association between promoter methylation in a priori selected genes and survival in two independent large series of prostate cancer patients. METHODS We followed up with two cohorts of patients (216 patients diagnosed in 1982 to 1988 and 243 patients diagnosed in 1993 to 1996) diagnosed at one hospital pathology ward in Turin, Italy. DNA was obtained from paraffin-embedded tumor tissues and evaluated for promoter methylation status in glutathione S-transferase (GSTP1), adenomatous polyposis coli (APC), and runt-related transcription factor 3 (RUNX3). Results The two cohorts had different prevalences of methylation in APC (P = .047), GSTP1 (P = .002), and RUNX3 (P < .001). Methylation in APC was associated with an increased risk of prostate cancer-specific mortality (hazard ratio [HR] = 1.42; 95% CI, 0.98 to 2.07 in the 1980s cohort; HR = 1.57; 95% CI, 0.95 to 2.62 in the 1990s cohort; HR = 1.49; 95% CI, 1.11 to 2.00 in the two cohorts combined). In subgroup analyses, the HRs were higher among patients with a Gleason score less than 8 (HR = 1.52; 95% CI, 0.85 to 2.73 in the 1980s cohort; HR = 2.09; 95% CI, 1.02 to 4.28 in the 1990s cohort). Methylation in RUNX3 was associated with prostate cancer mortality only in the 1990s cohort, and methylation in GSTP1 did not predict mortality in either cohort. CONCLUSION The pattern of hypermethylation may have changed after the introduction of prostate-specific antigen testing in the beginning of the 1990s. Promoter methylation in APC was identified as a marker for prostate cancer progression.

Screening for Prostate Cancer — The Controversy That Refuses to Die

In the United States, most men over the age of 50 years have had a prostate-specific–antigen (PSA) test,1 despite the absence of evidence from large, randomized trials of a net benefit. Moreover, about 95% of male urologists and 78% of primary care physicians who are 50 years of age or older report that they have had a PSA test themselves,2 a finding that suggests they are practicing what they preach. And indeed, U.S. death rates from prostate cancer have fallen about 4% per year since 1992, five years after the introduction of PSA testing.3 Perhaps the answer to the PSA . . .

Changes in case mix and treatment patterns in prostate cancer in Saskatchewan during the prostate specific antigen testing era

The prostate specific antigen (PSA) test became available in Saskatchewan in 1990 as a part of the provincial health plan. The purpose of this population-based study was to describe the changes in case mix and treatment patterns for prostate cancer following its introduction. The Saskatchewan Cancer Registry was used to identify all new cases of prostate cancer for the period 1985-2001. We reviewed over 10,000 charts to collect information on tumor characteristics, diagnostic methods, and first choice of treatment. This information was linked to the demographic and mortality data from the registry. The age-adjusted incidence of prostate cancer was influenced greatly by PSA testing volumes. Overall, the rate increased from 90.3 per 100,000 in 1985 to 151.3 per 100,000 in 2001. The increase was mostly organ-confined moderately differentiated cases. The incidence rate of metastatic disease dropped about 50% but only in the 70-79 and 80+ age groups. In 1985, 34% of cases were diagnosed by needle biopsy and 60.4% by TURP. In 2001, the values were 76.1% and 19.7%, respectively. More men now choose radical therapy as the first course of treatment, 81% during 1997-2001 compared to only 63.2% in the 1985-1989 period. Mortality rates remained stable in all age groups over these years. There have been dramatic changes in the case mix of prostate cancers diagnosed since the introduction of PSA testing in the population and significant changes in clinical management of this disease. Thus far, no changes have occurred in mortality rates in the population.

Chemical Exposures: Prostate Cancer and Early BPA Exposure

In animal models, estrogens can drive carcinogenesis of the prostate and have long been suspected of playing a role in human prostate cancer. Scientists have hypothesized that prenatal exposure to estrogen-like compounds, including monomeric bisphenol A (BPA), may account for recent increases in rates of prostate cancer. Now a rat study by Gail Prins of the University of Illinois at Chicago Department of Urology, Shuk-Mei Ho of the University of Cincinnati Department of Environmental Health, and their colleagues provides the first evidence of a direct link between low-dose BPA exposure during development and later prostate cancer. BPA initially was synthesized for use in also is used as a cross-linking compound in the manufacture of polycarbonate plastics and epoxy resins. It leaches from food and beverage containers and from dental sealants, although the latter currently are not thought to be a major source of exposure. Today, this hormonally active chemical is widespread in the environment, with detectable serum levels present in approximately 90% of humans in the United States and other industrialized countries, by Prins’s estimate. BPA concentrations measured in placental and fetal tissues may be fivefold higher than maternal serum levels, with higher levels found in male fetuses compared to females, according to Prins. BPA has been in use for about 50 years in the industrialized world. Some investigators have proposed that widespread ingestion of monomeric BPA from polycarbonate food and drink containers might partially explain recent increases in prostate cancer rates. According to the American Cancer Society, rates have been on the rise since 1975. With the 1987 introduction of prostate-specific antigen testing, the newly enhanced ability to diagnose the disease caused incidence to spike to 240 age-adjusted cases per 100,000 men by 1992. After this “catch-up” period, rates dropped for three years, but are now back on the rise. In the study, described in the 1 June 2006 issue of Cancer Research, groups of newborn rats were given high or low doses of estradiol or an environmentally relevant dose of BPA. The findings provide a molecular underpinning for potential long-term effects by showing changes in methyl groups on DNA that are responsible for turning genes on or off. For example, one key prostate gene that normally fuels cell growth during development stayed turned on in the prostates of male rats exposed to BPA or elevated estradiol from birth, says Prins. Such epigenetic alterations may leave a permanent impression on genes, possibly sensitizing the animal to developing diseases later in life. One must exercise caution, however, in extrapolating the current rat findings to humans. How might one conduct an analogous program of research on men? The researchers consider such a program virtually impossible because 50 years or more typically would be required for results of early exposure to BPA to show up as prostate cancer. Indeed, Rebecca Sokol, a professor of medicine at the University of Southern California, cautions against extrapolating human effects from rat studies. She does, however, note that unlike strong carcinogens that damage DNA profoundly, BPA appears to cause subtle changes that may pass from one generation to the next. She asks whether something is happening to alter genes seemingly without changing the genetic code itself. Says Prins, “Our evidence shows that in an animal model, some genes are altered by the addition or removal of methyl groups on the DNA, which changes the ability of those genes to be transcribed and translated to proteins. It is possible that these effects may pass through generations as has been shown recently for sperm cells.” However, she adds, that analysis awaits future studies.

Reduction of Prostate Cancer Mortality in Tyrol, Austria, after Introduction of Prostate-specific Antigen Testing

The objective of this study was to analyze in detail the time trend in prostate cancer mortality in the population of Tyrol, Austria. In Tyrol, prostate-specific antigen tests were introduced in 1988-1989 and, since 1993, have been offered to all men aged 45-74 years free of charge. More than three quarters of all men in this age group had at least one such test in the last decade. The authors applied the age-period-cohort model by Poisson regression to mortality data covering more than three decades, from 1970 to 2003. For Tyrol, the full model with age and period and cohort terms fit fairly well. Period terms showed a significant reduction in prostate cancer mortality in the last 5 years, with a risk ratio of 0.81 (95% confidence interval: 0.68, 0.98) for Tyrol; for Austria without Tyrol, no effect was seen, with a risk ratio of 1.00 (95% confidence interval: 0.95, 1.05). Each was compared with the mortality rate in the period 1989-1993. Although the results of randomized screening trials are not expected until 2008-2010, these findings support the evidence that prostate-specific antigen testing offered to a population free of charge can reduce prostate cancer mortality.

The increased rate of prostate specific antigen testing has not affected prostate cancer presentation in an inner city population in the UK

To assess whether the increased use of prostate-specific antigen (PSA) testing over the last 15 years has changed the way prostate cancer presents in an inner city UK population, where PSA screening rates might be expected to be lower than in epidemiological studies based in North America, where there is a significant tendency to a localized stage and earlier age at diagnosis. The study comprised a 5-year retrospective and 5-year prospective analysis of data on 704 men diagnosed with prostate cancer over the 10-year period since the introduction of PSA testing (1994-2003). The median (range) age at presentation remained unchanged, at 72 (45-94) years; the PSA level at diagnosis was 20-46 microg/L, with a steady decline after 1997. There was no significant change in stage at diagnosis; overall, 38 (20-44)% presented with clinically localized disease, 37 (31-48)% with locally advanced and 25 (18-29)% with metastatic disease. The Gleason grade changed significantly, with more moderately differentiated tumours and a decline in well-differentiated cancers. Closer examination showed this to have been due to a change in diagnostic practice rather than a true population trend. PSA testing increased over the 10 years of the study (2.35 times), with requests from general practitioners rising seven times, compared with urologists or other hospital doctors (1.25 and 2.3 times, respectively). Community PSA testing remained lower than in other reported UK series, which may be explained in part by the lower socio-economic status of the population assessed. There was no apparent change in patient age or tumour stage in men presenting with prostate cancer over a 10-year period after the introduction of PSA testing. While there was an increase in PSA testing during the study period, the testing rate remains much lower than in other reported series from the UK.

Prostate Cancer and the Will Rogers Phenomenon

Information on tumor stage and grade are used to assess cancer prognosis and to produce standardized comparisons of end results over time. Changes in the interpretation of classification schemes can alter the apparent distribution of cancer stage or grade in the absence of a true biologic change. Since the introduction of prostate-specific antigen testing, the reported incidence of low-grade prostate cancer has declined. To determine whether this decline is in part a result of Gleason score reclassification during the same time period, we documented the potential impact of reclassification between 1992 and 2002 on clinical outcomes. A population-based cohort of 1858 men who were < or = 75 years of age at diagnosis of prostate cancer in 1990-1992 was assembled retrospectively from the Connecticut Tumor Registry. Histology slides of the diagnostic prostate tissue were retrieved and reread in 2002-2004 by an experienced pathologist blinded to the original Gleason score readings. Prostate cancer mortality rates for the cohort calculated using the original Gleason score readings were compared with those calculated using the contemporary Gleason score readings. Statistical tests were two sided. The contemporary Gleason score readings were statistically significantly higher than the original readings (mean score increased from 5.95 to 6.8; difference = 0.85, 95% confidence interval = 0.79 to 0.91; P < .001). Consequently, the Gleason score-standardized contemporary prostate cancer mortality rate (1.50 deaths per 100 person-years) appeared to be 28% lower than standardized historical rates (2.08 deaths per 100 person-years), even though the overall outcome was unchanged. This apparent improvement in mortality held for all Gleason score categories. In this population, a decline in the reported incidence of low-grade prostate cancers appears to be the result of Gleason score reclassification over the past decade. This reclassification resulted in apparent improvement in clinical outcomes. This finding reflects a statistical artifact known as the Will Rogers phenomenon.

Prostate cancer and prostate-specific antigen (PSA) screening in Austria

The possible effect of prostate-specific antigen (PSA) testing on prostate cancer mortality has remained controversial, despite the test's widespread application. We examined age-specific mortality trends for prostate cancer in Austria before and after the introduction of (opportunistic) PSA testing, to ask whether PSA screening reduces prostate cancer mortality in a uniform cohort of men with equal access to health care. Prostate cancer mortality data covering all 9 federal states of Austria were analysed from 1970 to 2002. PSA testing became widely available in Austria not before 1989. Tyrol, one of the nine federal states of Austria, independently launched a mass prostate cancer prevention project in 1993. We applied join-point regression models to identify changes in the slope of age-specific mortality trends in selected age groups (50-59, 60-69, 70-79, and 80-89 years) and calculated the annual percent change (APC) in mortality between 1970 and 2002 for Tyrol and the rest of Austria separately. After 12 years of follow-up, we were not able to observe a significant reduction in prostate cancer mortality since the introduction of the PSA test in the age groups of 50-59, 60-69, and 80-89 years. A significant decrease was found in the age group of 70-79 (Austria without Tyrol 1989 through 2002: APC, -2.36; 95% CI, -3.38 to -1.34; Tyrol 1991 through 2002: APC, -6.42; 95% CI, -8.92 to -3.86). In this age group the join points 1989 and 1991 cannot be related to PSA testing. PSA screening does not appear to reduce prostate cancer mortality in a uniform cohort of men with equal access to health care. However, given the long lead-time for prostate cancer, even longer follow-up may still be needed to detect any important trends.

Risk of prostate cancer associated with a family history in an era of rapid increase in prostate cancer diagnosis (Australia).

We conducted a case-control study of prostate cancer and familial risk of the disease in Australia between 1994 and 1998, a period during which the incidence of prostate cancer increased dramatically with widespread use of prostate-specific antigen (PSA) testing. 1475 cases and 1405 controls were asked about prostate cancer in their first-degree relatives. Odds ratios (OR) were calculated using logistic regression. Cases were more likely to report a family history of prostate cancer than controls (OR 3.0; 95% confidence interval (CI) 2.3-3.9) and cases reporting an affected relative were younger (58.8 versus 60.9 years, p < 0.0001). The OR for an affected first-degree relative increased with increasing number of affected relatives and decreased with increasing age of the case. The OR for more than one affected first-degree relative was 6.9 (95% CI 2.7-18). The OR for an affected brother was 3.9 (95% CI 2.5-6.1) and for an affected father was 2.9 (95% CI 2.1-3.9) but these were not significantly different (p = 0.2). When analyses were repeated including only diagnoses made in relatives prior to 1992, the risks were generally similar except that the OR for an affected brother decreased to 3.1 (95% CI 1.2-3.9). When only relatives' diagnoses made after 1991 were included results were again similar to those for all relatives, although the effect for brothers was greater and the attenuation with age at diagnosis dissipated. The recent introduction of PSA testing that has resulted in a greater prevalence of apparent prostate cancer, does not appear to have substantially altered familial risks of disease, although effects associated with brothers may be inflated.

Cancer surveillance series: interpreting trends in prostate cancer--part II: Cause of death misclassification and the recent rise and fall in prostate cancer mortality.

The rise and fall of prostate cancer mortality correspond closely to the rise and fall of newly diagnosed cases. To understand this phenomenon, we explored the role that screening, treatment, iatrogenic (i.e., treatment-induced) deaths, and attribution bias (incorrect labeling of death from other causes as death from prostate cancer) have played in recent mortality trends. Join point regression is utilized to assess the recent rise and fall in mortality and the relationship of total U.S. trends to those areas served by the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Cancer Registry Program. Incidence-based mortality (IBM) is estimated with the use of prostate cancer data from the SEER Program to partition (from overall prostate cancer mortality trends) the contribution of cases diagnosed since the widespread use of prostate-specific antigen (PSA) testing starting in 1987. IBM is also used to examine the contribution of stage at diagnosis to the recent prostate cancer mortality trends. IBM for cases diagnosed since 1987 rose above the pre-1987 secular (i.e., background) trend, peaked in the early 1990s, and almost returned to the secular trend by 1994. This rise and fall of IBM track with the pool of prevalent cases diagnosed within the prior 2 years. IBM for cases diagnosed with metastatic disease fell starting in 1991, while IBM for those diagnosed with localized/regional disease was relatively flat. The rise and fall in prostate cancer mortality observed since the introduction of PSA testing in the general population are consistent with a hypothesis that a fixed percent of the rising and falling pool of recently diagnosed patients who die of other causes may be mislabeled as dying of prostate cancer. The decline in IBM for distant stage disease and flat IBM trends for localized/regional disease provide some evidence of improved prognosis for screen-detected cases, although alternative interpretations are possible.

Trends in survival of prostate cancer in southeastern Netherlands, 1971-1989.

The increase in the incidence of prostate cancer observed over the past 2 decades is suggested to be largely due to increased detection of insignificant tumors. To explore this assumption, we investigated trends in survival of prostate cancer patients in southeastern Netherlands, an area with almost 1 million inhabitants, where the age-adjusted incidence of prostate cancer increased by 53% between 1971 and 1989, i.e., before the introduction of prostate-specific antigen testing. Survival was calculated for all patients registered in the Eindhoven Cancer Registry between 1971 and 1989 (n = 2,562). In spite of earlier diagnosis, survival barely changed during this time period. Five-year relative survival improved slightly from 53% [95% confidence interval (CI) 47%, 59%] in 1975-1979 to 56% (CI 51%, 61%) in 1985-1989. Stratified analyses suggested an improvement since 1980 for patients below 75 years with localized tumors but, despite possible stage migration, decreased survival for those with metastasized and/or poorly differentiated tumors. Patients below 75 years whose tumors were diagnosed unexpectedly during transurethral resection of the prostate (TURP) exhibited a relative survival of 85% 5 years and 68% 10 years after diagnosis. Less extensive application of TURP in The Netherlands might explain why our findings do not agree with those in Sweden and the United States. Inference from country-specific trends in survival appears not to be necessarily generalizable to other countries with a similar increase in the incidence of prostate cancer. We conclude from our results that earlier diagnosis of prostate cancer between 1971 and 1989 may be accompanied by an increased incidence of an aggressive variant.