Trends in prostate cancer mortality among black men and white men in the United States

BACKGROUND: Prostate cancer mortality rates in the United States declined sharply after 1991 in white men and declined after 1992 in black men. The current study was conducted to investigate possible mechanisms for the declining prostate cancer mortality rates in the United States. METHODS: The authors examined and compared patterns of prostate cancer incidence, survival rates, and mortality rates among black men and white men in the United States using the 1969-1999 U.S. prostate cancer mortality rates and the 1975-1999 prostate cancer incidence, survival, and incidence-based mortality rates from the Surveillance, Epidemiology, and End Results (SEER) Program for the U.S. population. The SEER data represent approximately 10% of the U.S. population. RESULTS: Prostate cancer incidence and mortality rates showed transient increases after 1986, when the U.S. Food and Drug Administration approved the use of prostate specific antigen (PSA) testing. The age-adjusted prostate cancer mortality rates for men age 50-84 years, however, have dropped below the rate in 1986 since 1995 for white men and since 1997 for black men. In fact, for white men ages 50-79 years, the 1998 and 1999 rates were the lowest observed since 1950. Incidence-based mortality rates by disease stage revealed that the recent declines were due to declines in distant disease mortality. Moreover, the decrease in distant disease mortality was due to a decline in distant disease incidence, and not to improved survival of patients with distant disease. CONCLUSIONS: Similar incidence, survival, and mortality rate patterns are seen in black men and white men in the United States, although with differences in the timing and magnitude of recent rate decreases. Increased detection of prostate cancer before it becomes metastatic, possibly reflecting increased use of PSA testing after 1986, may explain much of the recent mortality decrease in both white men and black men.     

Cancer surveillance using registry data: Results and recommendations for the Lithuanian national prostate cancer early detection programme

IntroductionWe describe long term trends in prostate cancer epidemiology in Lithuania, where a national prostate specific antigen (PSA) test based early detection programme has been running since 2006.MethodsWe used population-based cancer registry data, supplemented by information on PSA testing, life expectancy and mortality from Lithuania to examine age-specific prostate cancer incidence, mortality and survival trends among men aged 40+ between 1978 and 2009, as well as life expectancy of screening-eligible men, and the proportion of men with a first PSA test per year since the programme started.ResultsThe number of prostate cancer patients rose from 2.237 in 1990–1994 to 15.294 in 2005–2009. By 2010, around 70% of the eligible population was tested, on average around two times. The early detection programme brought about the highest prostate cancer incidence peaks ever seen in a country to date. Recent incidence and survival rises in the age groups 75–84 suggest PSA testing in the elderly non-eligible population. Life expectancy of men aged 70–74 indicates that less than 30% of patients will live for 15 years and may have a chance to benefit from early detection.ConclusionsEarly detection among men aged 70–74, and particularly among the elderly (75+) may have to be reconsidered. Life expectancy assessment before testing, avoiding a second test among men with low PSA values and increasing the threshold for further evaluation and the screening interval may help reducing harm. Publishing information on treatment modalities, side-effects and patient reported quality of life is recommended.     

Prostate cancer incidence in 43 populations worldwide: An analysis of time trends overall and by age group

Prostate cancer is a significant public health burden and a major cause of morbidity and mortality among men worldwide. Analyzing geographic patterns and temporal trends may help identify high‐risk populations, suggest the degree of PSA testing, and provide clues to etiology. We used incidence data available from the International Agency for Research on Cancer (IARC) and certain cancer registries for 43 populations across five continents during a median period of 24 years. Trends in overall prostate cancer rates showed five distinct patterns ranging from generally monotonic increases to peaking of rates followed by declines, which coincide somewhat with changes in the prevalence of PSA testing. Trends in age‐specific rates generally mirrored those in the overall rates, with several notable exceptions. For populations where overall rates increased rapidly and then peaked, exemplified in North America and Oceania, the highest incidence tended to be most pronounced and occurred during earlier calendar years among older men compared with younger ones. For populations with almost continual increases in overall rates, exemplified in Eastern Europe and Asia, peaks were evident among men aged ≥75 years in many instances. Rates for ages 45–54 years did not clearly stabilize or decline in the majority of studied populations. Global geographic variation remained substantial for both overall and age‐specific incidence rates regardless of levels of PSA testing, with the lowest rates consistently in Asia. Explanations for the persistent geographic differences and the continuing increases of especially early‐onset prostate cancer remain unclear.     

Uptake of prostate-specific antigen testing for early prostate cancer detection in Sweden

The aim of our study was to estimate uptake of prostate-specific antigen (PSA) testing in an entire country, including time trends and geographical differences. Data from the Swedish Cancer Register on prostate cancer incidence between 1980 and 2007 and published data from the Gothenburg branch of the European randomized study of screening for prostate cancer (ERSPC), a population-based PSA screening study, were used in two models of changes in incidence of prostate cancer as a proxy for uptake of PSA testing in all 24 Swedish counties. The estimated annual PSA testing, irrespective of previous years' exposure, reached a peak of 12% of all men in 2004 and decreased thereafter to 6% in 2007 and varied from less than 5 to 20% between counties. Under the assumption that men who underwent annual PSA testing were previously unexposed to PSA testing, the cumulated uptake of PSA testing in men aged 55-69 years in Sweden increased from zero in 1997 to 56% in 2007. Our study shows that it is possible to estimate uptake of PSA testing in the population from the prostate cancer incidence pattern. There were large geographical variations in uptake of PSA testing despite a uniform health care system in Sweden and there was a substantial increase in the uptake of PSA testing during the study period, despite that there were no national recommendations for PSA-based prostate cancer screening.     

Epilogue: Different approaches for prostate cancer screening in the EU?

Individual approaches to prostate cancer screening in European countries could occur as a result of individual decision taking, public health policies or the relevance of the prostate cancer problem determined by incidence and mortality in individual countries.MethodsAn attempt is made to analyse current literature with respect to factors that could influence the individual or country-wide preference for or against the use of PSA driven screening.To obtain background information the incidence and mortality of prostate cancer in the EU countries participating in the ERSPC study, as well as the results of a recent join-point analysis of prostate cancer mortality for the same countries are reviewed. In addition, the question whether geographic differences in incidence and mortality could influence the value of screening tests in the different countries is evaluated.ResultsOur literature review shows large regional differences in incidence and mortality of prostate. Proportions of men testing positive with PSA values ?4.0 ng/ml and PPVs do not reflect these regional differences. Also, regional differences are not in line with negative outcomes for any ERSPC center in an exploratory analysis of prostate cancer mortality. In all centers a decrease of prostate cancer mortality at various degrees was seen. Differences in attitude may be visible in the join-point regression analysis which shows differences in mortality trends for some countries. Detection of T1c cancers in the control group is a measure of opportunistic screening (limitations addressed in the text). The differences reported may best reflect regional decision patterns. As far as the validity of PSA driven testing in countries with a different incidence and mortality is concerned, it seems that neither the levels nor the predictive value of PSA is influenced by such differences.ConclusionsA number of factors are identified which may explain the different individual decisions and different levels of use of opportunistic screening in the different EU countries.     

Prostate cancer: Trends in incidence,survival and mortality in the Netherlands, 1989–2006

BackgroundProstate cancer occurrence and stage distribution changed dramatically during the end of the 20th century. This study aimed to quantify and explain trends in incidence, stage distribution, survival and mortality in the Netherlands between 1989 and 2006.MethodsPopulation-based data from the nationwide Netherlands Cancer Registry and Causes of Death Registry were used. Annual incidence and mortality rates were calculated and age-adjusted to the European Standard Population. Trends in rates were evaluated by age, clinical stage and differentiation grade.Results120,965 men were newly diagnosed with prostate cancer between 1989 and 2006. Age-adjusted incidence rates increased from 63 to 104 per 100,000 person-years in this period. Two periods of increasing incidence rates could be distinguished with increases predominantly in cT2-tumours between 1989 and 1995 and predominantly in cT1c-tumours since 2001. cT4/N+/M+-tumour incidence rates decreased from 23 in 1993 to 18 in 2006. The trend towards earlier detection was accompanied by a lower mean age at diagnosis (from 74 in 1989 to 70 in 2006), increased frequency of treatment with curative intent and improved 5-year relative survival. Mortality rates decreased from 34 in 1996 to 26 in 2007.ConclusionsThe increase of prostate cancer incidence in the early 1990s was probably caused by increased prostate cancer awareness combined with diagnostic improvements (transrectal ultrasound, (thin) needle biopsies), but not PSA testing. The subsequent peak since 2001 is probably attributable to PSA testing. The decline in prostate cancer mortality from 1996 onwards may be the consequence of increased detection of cT2-tumours between 1989 and 1995. Unfortunately, data on the use of PSA tests and other prostate cancer diagnostics to support these conclusions are lacking.     

Active surveillance versus radical treatment for favorable-risk localized prostate cancer

Opinion statement Widespread prostate-specific antigen (PSA) screening in North America has resulted in a profound stage migration and a marked increase in incidence. One in six men is now diagnosed, many with small-volume, low-grade cancer. This incidence is dramatically higher than the 3% lifetime risk of prostate cancer death that characterized the prescreening era. This article summarizes the case for active surveillance for “favorable-risk” prostate cancer with selective delayed intervention for rapid biochemical progression, assessed by increasing PSA levels, or grade progression. The results of a large phase II trial using this approach are reviewed. To date, this study has shown that virtually all men with favorable-risk prostate cancer managed in this fashion will die of unrelated causes. Based on the Swedish randomized trial of radical prostatectomy versus watchful waiting, the Connecticut observation series, and the Toronto active surveillance experience, a number needed to treat analysis of the benefit of radical treatment of all newly diagnosed favorable-risk prostate cancer patients, compared with a strategy of active surveillance with selective delayed intervention, is presented. This suggests that approximately 73 patients will require radical treatment for each prostate cancer death averted. This translates into a 3- to 4-week survival benefit, unadjusted for quality of life. This figure is confirmed based on an analysis of the 2004 D'Amico et al. PSA velocity data in favorable-risk disease. The approach of active surveillance with selective delayed intervention based on PSA doubling time and repeat biopsy represents a practical compromise between radical therapy for all patients (which results in overtreatment for patients with indolent disease) and watchful waiting with palliative therapy only (which results in undertreatment for those with aggressive disease).     

Recent trends in prostate cancer mortality show a continuous decrease in several countries

Prostate specific antigen (PSA) screening was introduced to detect prostate cancer at an early stage and to reduce prostate cancer-specific mortality. Until results from clinical trials are available, the efficacy of PSA screening in reducing prostate cancer mortality can be estimated by surveillance of prostate cancer mortality trends. Our study analyzes recent trends in prostate cancer mortality in 38 countries. We used the IARC-WHO cancer mortality database and performed joinpoint analysis to examine prostate cancer mortality trends and identified 3 patterns. In USA, and to a lesser extent in Germany, Switzerland, Canada, France, Italy and Spain, prostate cancer-specific mortality decreased to a level lower than before the introduction of PSA screening. In Australia, New Zealand, Austria, Finland, The Netherlands, Norway, United Kingdom, Hungary, Slovakia, Israel, Singapore, Sweden and Portugal, mortality from prostate cancer decreased but rates remain higher than before the introduction of PSA screening. Prostate cancer mortality continued to increase in Belgium, Denmark, Greece, Ireland, Bulgaria, Czech Republic, Belarus, Ukraine, Russian Federation, Romania, Poland, Argentina, Chile, Cuba, Mexico, Japan, China Hong Kong and the Republic of Korea. The trends in prostate cancer mortality rates in examined countries suggest that PSA screening may be effective in reducing mortality from prostate cancer.     

Prostate-specific antigen in clinical practice

Currently, in the United States (US), most prostate cancers are diagnosed through screening with digital rectal examination (DRE) and measurement of serum prostate-specific antigen (PSA). The serum PSA level correlates directly with prostate cancer risk and aggressiveness, as well as the outcomes after treatment. PSA testing is also useful in monitoring patients for tumor recurrence after treatment. PSA testing has limited specificity for prostate cancer detection, and its appropriate clinical application has been the topic of debate. Accordingly, several variations on the PSA measurement have emerged as useful adjuncts for prostate cancer screening. These take into consideration additional factors, such as the proportion of different PSA isoforms (free PSA, complexed PSA, pro-PSA and B PSA), the prostate volume (PSA density), and the rate of change in PSA levels over time (PSA velocity or PSA doubling time). Widespread PSA screening is associated with a 75% reduction in the proportion of men who present with metastatic disease since 1985-89 in the US and a 32.5% reduction in the age-adjusted prostate cancer mortality rate through 2003. The history and evidence underlying each of these parameters are reviewed in the following article.     

Unanswered questions in screening for prostate cancer

Prostate cancer fulfils some of the conditions required of a disease that might be managed by population screening. In a cohort of 50- to 60-year-old men, carrying out a rectal examination and prostate specific antigen (PSA) test will detect clinically suspicious areas within the prostate in approximately 5%, and approximately 10% will have a raised PSA. We are however unsure which of the prostate cancers that are known to be present in approximately 30-40% of men aged over 60 years will be detected. Eventually after such screening, around 4% of men with an otherwise normal prostate will be found to have prostate cancers. The use of rectal examination may increase the number of tumours found, but will reduce compliance. The use of free/total PSA ratios will reduce the number of unnecessary biopsies at the expense of missing some tumours. Of more concern, we remain uncertain how effective aggressive local treatment is in altering the natural history of the disease. The risk of a 50-year-old man with a 25 year life expectancy of having microscopic cancer is 42%, of having clinically evident cancer is 9.5%, and of dying of prostate cancer 2.9%. Only a small proportion of cancers known to be present become clinically evident: more men die with prostate cancer than of it. Screening will identify some men with cancer who will not benefit from treatment. It is unclear whether screening would be followed by a reduction in morbidity and mortality. Recent data suggest a screening effect has been observed in the USA with: an increase in incidence, a decrease in men with distant metastases. The small decrease in mortality recently observed (many times smaller than the increase in incidence) may be confounded by inappropriate 'attribution' of cause of death, the detection of men with better prognosis distant metastatic disease responsive to hormonal ablation and changes in social factors such as diet. Future changes may incorporate molecular markers that might aid identification of men best treated aggressively because of a risk of progression. Tests to identify genetic pre-disposition may also allow targeted screening. New treatments and early chemoprevention or dietary strategies will again shift the ground on which these arguments are being rehearsed. The most urgent evidence required concerns the effectiveness of treatment strategies.     

Cancer surveillance series: interpreting trends in prostate cancer--part III: Quantifying the link between population prostate-specific antigen testing and recent declines in prostate cancer mortality.

BACKGROUND: The objective of this study was to investigate the circumstances under which dissemination of prostate-specific antigen (PSA) testing, beginning in 1988, could plausibly explain the declines in prostate cancer mortality observed from 1992 through 1994. METHODS: We developed a computer simulation model by use of information on population-based PSA testing patterns, cancer detection rates, average lead time (the time by which diagnosis is advanced by screening), and projected decreased risk of death associated with early diagnosis of prostate cancer through PSA testing. The model provides estimates of the number of deaths prevented by PSA testing for the 7-year period from 1988 through 1994 and projects what prostate cancer mortality for these years would have been in the absence of PSA testing. RESULTS: Results were generated by assuming a level of screening efficacy similar to that hypothesized for the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Under this assumption, the projected mortality in the absence of PSA testing continued the increasing trend observed before 1991 only when it was assumed that the mean lead time was 3 years or less. Projected mortality trends in the absence of PSA screening were not consistent with pre-1991 increasing trends for lead times of 5 years and 7 years. CONCLUSIONS: When screening is assumed to be at least as efficacious as hypothesized in the PLCO trial, it is unlikely that the entire decline in prostate cancer mortality can be explained by PSA testing based on current beliefs concerning lead time. Only very short lead times would produce a decline in mortality of the magnitude that has been observed.     

The role of prostate-specific antigen (PSA) testing patterns in the recent prostate cancer incidence declinein the United States

Objectives: Trends in first-time and later PSA procedure rates are ascertained using longitudinal data from a population-based cohort. These trends are compared to trends in prostate cancer incidence to determine the role of PSA in the recent decline in prostate cancer incidence.Methods: Medicare data were linked with tumor registry data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. A 5 percent random sample (n=39985) of Medicare beneficiaries from the SEER areas without a previous diagnosis of prostate cancer as of January 1, 1988 was followed through 1994. Trends in first-time PSA use were distinguished from those of second or later for men without diagnosed prostate cancer.Results: Trends in the rate of first-time PSA procedures track closely with trends in prostate cancer incidence rates, increasing until 1992 and decreasing thereafter. Similar patterns were observed by race and age group. Geographic variability in the dissemination of PSA screening was observed, yet the association between testing and incidence remained. Men in the cohort had a 4.7 percent chance of being diagnosed within three months of an initial PSA test, with the percentage falling for subsequent tests.Conclusions: It is informative to distinguish first from later tests when assessing the effect of the diffusion of a test in a population. Taking this approach was useful in illuminating the role of PSA testing in a reversal of a long-term increase in prostate cancer incidence rates.     

Overdiagnosis due to prostate-specific antigen screening: lessons from U.S. prostate cancer incidence trends

BACKGROUND: Overdiagnosis of clinically insignificant prostate cancer is considered a major potential drawback of prostate-specific antigen (PSA) screening. Quantitative estimates of the magnitude of this problem are, however, lacking. We estimated rates of prostate cancer overdiagnosis due to PSA testing that are consistent with the observed incidence of prostate cancer in the United States from 1988 through 1998. Overdiagnosis was defined as the detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. METHODS: We developed a computer simulation model of PSA testing and subsequent prostate cancer diagnosis and death from prostate cancer among a hypothetical cohort of two million men who were 60-84 years old in 1988. Given values for the expected lead time--that is, the time by which the test advanced diagnosis--and the expected incidence of prostate cancer in the absence of PSA testing, the model projected the increase in population incidence of prostate cancer associated with PSA testing. By comparing the model-projected incidence with the observed incidence derived from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry data, we determined the lead times and corresponding overdiagnosis rates that were consistent with the observed data. RESULTS: SEER data on prostate cancer incidence from 1988 through 1998 were consistent with overdiagnosis rates of approximately 29% for whites and 44% for blacks among men with prostate cancers detected by PSA screening. CONCLUSIONS: Among men with prostate cancer that would be detected only at autopsy, these rates correspond to overdiagnosis rates of, at most, 15% in whites and 37% in blacks. The observed trends in prostate cancer incidence are consistent with considerable overdiagnosis among PSA-detected cases. However, the results suggest that the majority of screen-detected cancers diagnosed between 1988 and 1998 would have presented clinically and that only a minority of cases found at autopsy would have been detected by PSA testing.     

Prostate cancer incidence and survival in relation to education (United States)

IntroductionThere are few data on prostate cancer incidence and survival in relation to socioeconomic status in the 1990s, after the introduction of prostate specific Antigen (PSA) testing. Materials and methods: We studied the relation of education to prostate cancer incidence and survival in the Cancer Prevention Study II (CPS-II) Nutrition Cohort. Participants provided questionnaire data on diet, medical history, education, and PSA testing. We followed 72,449 men from 1992–1999 for cancer incidence (4279 incident cases), and through 2000 for survival (158 prostate cancer deaths among incident cases). Results: Multivariate-adjusted rate ratios (RRs) were calculated using Cox proportional hazards models. Self-reported (PSA) tests were more common among the more highly educated. Men with at least a college education had a 15–19 higher prostate cancer incidence than those with a high school education or less, but this association was limited to localized cancers and was attenuated by adjustment for PSA testing. Survival analysis among incident prostate cancer cases adjusted for stage and grade at diagnosis showed much lower prostate cancer mortality for men with at least a high school education compared to those with less than a high school education (RR= 0.49, 95 CI=0.32–0.76). Conclusions: This study suggests that higher education is associated with slightly increased incidence of prostate cancer, at least partly due to greater use of PSA screening and a greater detection of localized tumors among more highly educated men. The much lower survival rates from prostate cancer among those with less than a high school education cannot be explained by available data and may reflect disparities in treatment. In 1999, 27 of US males over age 55 and older had less than a high school education.     

Prostate cancer incidence, mortality, and survival trends in the United States: 1981-2001

The increased use of prostate-specific antigen (PSA) in screening for preclinical disease after 1985 is thought to be a major determinant of the changing patterns in prostate cancer incidence; however, the long-term effect of screening on future trends in mortality and survival is uncertain. This article reviews the temporal trends (1981-1998) for prostate cancer incidence, mortality, and survival, and projects prostate cancer incidence and mortality rates for 1999 to 2001. Autoregressive, quadratic, time-series models were used to describe prostate cancer mortality rates in the US population and prostate cancer incidence rates derived from the National Cancer Institute's (NCI) Surveillance, Epidemiology and End Results (SEER) program. These models were based on data collected from 1979 through 1998, with forecasts produced for 1999 to 2001. Prostate cancer incidence increased steadily from 1981 to 1989, with a steep increase in the early 1990s, followed by a decline. Incidence rates were forecasted to remain stable through the year 2001. Mortality rates decreased steadily and were forecasted to continue to decrease concurrently with increasing 5- and 10-year relative survival rates. The incidence, mortality, and survival trends were comparable in US blacks, who exhibited on average 2-fold higher mortality and 50% higher incidence than whites. Decreasing prostate cancer mortality and increasing relative survival trends in the United States were described after the introduction of PSA screening. However, the exaggerated rate of increase in the early 1990s in prostate cancer incidence was transient and likely a result of increased detection of preclinical disease that was prevalent in the general population.     

Changing relationship between socioeconomic status and prostate cancer incidence

BACKGROUND: Understanding the relationship between socioeconomic status (SES) and prostate cancer incidence could identify populations that should be targeted for intervention and prevention programs. We examined this relationship within the major racial/ethnic groups during the period 1972 through 1997, which spans the introduction of prostate-specific antigen (PSA) testing. METHODS: We used data from the population-based Los Angeles Cancer Surveillance Program to examine age-adjusted prostate cancer incidence rates in five SES groups over three specific calendar periods by racial/ethnic subpopulation (white, black, Asian, and Hispanic) and by stage of disease at diagnosis. Linear regression analysis was used to test for trends in the age-adjusted incidence rates that were associated with increasing levels of SES. All P values were two-sided. RESULTS: For men diagnosed with prostate cancer before 1987, when the test for PSA was not widely available, we found no association between SES and the incidence of prostate cancer in any of four racial/ethnic subpopulations or between SES and the stage of disease at diagnosis. In contrast, among men who were diagnosed with prostate cancer after 1987, SES was statistically significantly and positively associated with prostate cancer incidence in men from all racial/ethnic subpopulations except Asians (P =.01 for white men, P =.001 for black men, P =.02 for Hispanic men, P =.06 for Asian men, and P =.01 for all men combined). Higher SES was statistically significantly associated with cancers of earlier stage (P =.01 for localized cancer and P =.00 for regional cancer) for men who were diagnosed with prostate cancer after 1987. CONCLUSIONS: The association between SES and prostate cancer incidence after 1987 may reflect more prevalent PSA screening in populations with higher SES due to their greater access to health care. SES should, therefore, be considered an important factor in interpreting variations and time trends in prostate cancer incidence.     

An open-label phase II study of low-dose thalidomide in androgen-independent prostate cancer

The antiangiogenic effects of thalidomide have been assessed in clinical trials in patients with various solid and haematological malignancies. Thalidomide blocks the activity of angiogenic agents including bFGF, VEGF and IL-6. We undertook an open-label study using thalidomide 100 mg once daily for up to 6 months in 20 men with androgen-independent prostate cancer. The mean time of study was 109 days (median 107, range 4-184 days). Patients underwent regular measurement of prostate-specific antigen (PSA), urea and electrolytes, serum bFGF and VEGF. Three men (15%) showed a decline in serum PSA of at least 50%, sustained throughout treatment. Of 16 men treated for at least 2 months, six (37.5%) showed a fall in absolute PSA by a median of 48%. Increasing levels of serum bFGF and VEGF were associated with progressive disease; five of six men who demonstrated a fall in PSA also showed a decline in bFGF and VEGF levels, and three of four men with a rising PSA showed an increase in both growth factors. Adverse effects included constipation, morning drowsiness, dizziness and rash, and resulted in withdrawal from the study by three men. Evidence of peripheral sensory neuropathy was found in nine of 13 men before treatment. In the seven men who completed six months on thalidomide, subclinical evidence of peripheral neuropathy was found in four before treatment, but in all seven at repeat testing. The findings indicate that thalidomide may be an option for patients who have failed other forms of therapy, provided close follow-up is maintained for development of peripheral neuropathy.     

Prostate-specific antigen levels in 1695 men without evidence of prostate cancer. Findings of the American Cancer Society National Prostate Cancer Detection Project.

The American Cancer Society National Prostate Cancer Detection Project is a prospective, multidisciplinary, and multicenter trial to assess the potential for early detection of prostate cancer by transrectal ultrasonography (TRUS), digital rectal examination (DRE), and serum prostate-specific antigen assay (PSA). By November 1990, 2805 men between the ages of 55 and 70 years with no known signs or symptoms of prostate cancer were enrolled in the study, which is planned to run for 5 years. Annual TRUS, DRE, and PSA tests were done on these subjects, and biopsies were recommended for suspicious lesions when detected. To study the performance of PSA testing in presumed normal subjects, all men were eliminated who had (1) prostate cancer detected on their initial examinations and proven by biopsy or (2) cancer detected during the year or subsequent examinations. Additionally, all men with TRUS or DRE findings that were interpreted as suspicious for cancer but who are being followed and have not yet had biopsies done were removed from this series. This left a unique, extensively screened group of 1695 men who were free of prostate cancer, as far as could be determined. Analyses of the PSA levels in this large population in the appropriate age range for increasing risk of prostate cancer revealed several important findings. First, there was a direct relationship between serum PSA levels and estimated prostate volume for both the currently available monoclonal and polyclonal PSA assays. Individuals with benign prostatic hyperplasia and larger gland volume have a higher normal limit of PSA than men with normal gland volume. Second, analyses showed no relationship between age and PSA levels or between symptoms of prostatism and PSA levels independent of gland enlargement. It was concluded that volume-adjusted upper limits of normal PSA can be determined for different levels of specificity desired. This information may be applicable to the use of PSA in men not already suspected of having prostate cancer and may increase its effectiveness as a tool for early detection.     

Is screening for prostate cancer with prostate specific antigen an appropriate public health measure?

Screening and treatment for prostate cancer is controversial. In the absence of randomized trials, several prominent medical organizations in the United States and Europe have formulated policies that range from enthusiastic support to significant skepticism concerning the efficacy of screening and subsequent treatment for prostate cancer. Sharp rises in the incidence of prostate cancer have occurred whenever PSA testing has been introduced on a wide scale. Unfortunately, it is unclear whether declines in prostate cancer mortality can be attributed to PSA testing. Other explanations include the early use of anti-androgen therapy or changes in environmental factors such as diet. Repeated testing for serum PSA has produced significant shifts in the types of cases being identified and has raised the possibility of significant over-diagnosis of this disease. The European screening trial and the PLCO trial in the US will hopefully provide some insights into the value of population-based testing.     

Excess cases of prostate cancer and estimated overdiagnosis associated with PSA testing in East Anglia

This study aimed to estimate the extent of 'overdiagnosis' of prostate cancer attributable to prostate-specific antigen (PSA) testing in the Cambridge area between 1996 and 2002. Overdiagnosis was defined conceptually as detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. Records of PSA tests in Addenbrookes Hospital were linked to prostate cancer registrations by NHS number. Differences in prostate cancer registration rates between those receiving and not receiving prediagnosis PSA tests were calculated. The proportion of men aged 40 years or over with a prediagnosis PSA test increased from 1.4 to 5.2% from 1996 to 2002. The rate of diagnosis of prostate cancer was 45% higher (rate ratios (RR)=1.45, 95% confidence intervals (CI) 1.02-2.07) in men with a history of prediagnosis PSA testing. Assuming average lead times of 5-10 years, 40-98% [corrected] of the PSA-detected cases were estimated to be overdiagnosed. In East Anglia, from 1996 to 2000, a 1.6% excess of cases was associated with PSA testing (around a quarter of the 5.3% excess incidence cases observed in East Anglia from 1996 to 2000). Further quantification of the overdiagnosis will result from continued surveillance and from linkage of incidence to testing in other hospitals.