Would prostate cancer detected by screening with prostate-specific antigen develop into clinical cancer if left undiagnosed? A comparison of two population-based studies in Sweden

OBJECTIVE: To assess the risk of over-diagnosing and over-treating prostate cancer if population-based screening with serum prostate-specific antigen (PSA) is instituted. PATIENTS AND METHODS: From a serum bank stored in 1980, PSA was analysed in 658 men with no previously known prostate cancer from a well-defined cohort from G?teborg, Sweden (men born in 1913); the incidence of clinical prostate cancer was registered until 1995. From the same area, and with the same selection criteria, another cohort of 710 men born in 1930-31, who in 1995 accepted an invitation for PSA screening, was also analysed. RESULTS: Of men born in 1913, 18 (2.7%) had died from prostate cancer and the cumulative probability of being diagnosed with clinical prostate cancer was 11.1% (5.0% in those with a PSA level of < 3 ng/mL vs 32.9% in those with a PSA level of > 3 ng/mL, P < 0.01). The mean lead-time from increased PSA (> 3 ng/mL) to clinical diagnosis was 7 years. The prostate cancer detection rate in men born in 1930-31 was 4.4% (22% among those with increased PSA levels) and 30 of 31 detected cancers were clinically localized. CONCLUSIONS: Screening and sextant biopsies resulted in a lower detection rate (22%) than the cumulative risk of having clinical prostate cancer (33%) in men with increased PSA levels, indicating that under-diagnosis rather than over-diagnosis is the case at least with 'one-time' screening. Even if the stage distribution in screening-detected cancers seems promising (and thus may result in reduced mortality) it is notable that screening 67-year-old men will result in treatment a mean of 7 years before clinical symptoms occur and only one in four men anticipated to develop prostate cancer will die from the disease within 15 years. Large randomized screening trials seem mandatory to further explore the benefits and hazards of PSA screening.     

Prostate-specific antigen assay using whole blood samples spotted on filter paper and its application to mass screening for prostate cancer

AIM: The disc assay system for prostate-specific antigen (PSA) is a novel technique using a small amount of whole blood on filter paper. The accuracy of this assay system and its feasibility for use in prostate cancer mass screening were evaluated. METHODS: In the first arm of the study, to evaluate the accuracy of the disc assay system, PSA values were determined by both a disc assay system and a standard serum assay system using the same blood samples obtained from 420 outpatients. In the second arm of the study, the feasibility and reliability of the disc assay system were examined in prostate cancer mass screening. A total of 2475 men were screened by the disc assay (disc group) and 3348 men were screened by the standard serum assay (serum group) in the first step of mass screening. In the second step of the screening in the disc group, 101 men underwent PSA tests by a standard serum assay, then the first PSA values determined by the disc assay were compared with the second PSA values determined by the standard serum assay. In the second step of the screening in the serum group, 94 men underwent additional PSA tests by a serum assay, and then the first PSA values were compared with the second PSA values. Two men in each group were excluded from analysis because the true PSA values of the first step were not available (more than 50 ng/mL). RESULTS: The PSA values determined by the disc assay closely correlated with those obtained by the standard assay (r = 0.987) in 295 outpatients with PSA levels between 1.0 and 20 ng/mL. In the PSA mass screening, the PSA values determined in the first step closely correlated with those in the second step both in the disc group (r = 0.916) and in the serum group (r = 0.845). A significant dissociation of the two PSA values was observed in seven of 99 men in the disc group and in three of 92 men in the serum group. However, there was no statistical significance in the incidence of dissociation in the two PSA values between the disc group and the serum group. CONCLUSIONS: The disc assay system seems to be a sensitive and accurate assay system. The feasibility and reliability of the disc assay system were well demonstrated in the field during prostate cancer mass screening.     

The significance of early detection for prostate cancer in mass screening

PURPOSE: In Mitaka city, mass screening for prostate cancer was conducted for 3 years from 1995 to 1997. Clinical stages were compared between patients found by screening and those diagnosed at our clinic during the same time. The significance of serum-free prostate specific antigen (PSA) in mass screening for prostate cancer was examined. MATERIAL AND METHODS: A prospective clinical trial was conducted on men aged 50 years or older. The primary examination consisted of taking the international prostate symptom score, quality of life score, PSA (Tandem-R) and digital rectal examination (DRE). If PSA was greater than 4.0 ng./ml and/or if DRE suggested cancer, transrectal ultrasound-guided sextant prostate biopsies were indicated. RESULTS: Of the men screened, 23.2% (320/1375) had serum PSA greater than 4.0 ng./ml. and/or suspicious findings on DRE. Biopsy was performed in 199 of 320 (62.1%). Cancer was detected in 21 (1.5%, 21/1375). Prostate cancer was found in one case among 154 males (0.65%, 1/154) who were screened twice or more. The cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic (Wilcoxon's rank-sum test: p = 0.0047). Receiver operating characteristics analysis showed that the optimal free PSA-to-PSA ratio was 12%. Positive predictive value increased from 18% to 50% when free PSA-to-PSA ratio was combined with PSA. CONCLUSION: 1. Cancer detection rate was 1.5% in the mass screening in Mitaka City. 2. Cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic. 3. Free PSA determination might eliminate unnecessary biopsies in men with PSA above 4.0 ng./ml with minimal loss of cancer detection.     

Estimation of prostate cancer risk on the basis of total and free prostate-specific antigen,prostate volume and digital rectal examination

Background and Objective: Approximately 70% of the men with an elevated serum prostate-specific antigen (PSA) identified in prostate cancer screening do not have prostate cancer. Other available diagnostic variables may be utilized to reduce the number of false positive PSA results, but few algorithms for calculation of the combined impact of multiple variables are available. The objective of this study was to establish nomograms showing the probability of detecting prostate cancer at biopsy on the basis of total PSA, and the percentage of free PSA in serum, prostate volume and digital rectal examination (DRE) findings.Methods: In a randomized, population-based prostate cancer screening trial 10 284 men aged 55–67 years were screened during 1996 and 1997 in two metropolitan areas in Finland. Results for men (n=758) with a serum PSA of 4–20 μg/l were used to establish the risk nomograms. Of these 200 (26%) had prostate cancer at biopsy.Results: Prostate cancer probability depended most strongly on the percentage of free PSA. Total PSA, prostate volume, and DRE also contributed to prostate cancer probability, whereas age and family history of prostate cancer did not. More false positive PSA results could be eliminated by using the multivariate risk model rather than the percentage of free PSA (p<0.001) or PSA density (p=0.003) alone.Conclusions: Wide variation in probability of detecting prostate cancer among screened men with a serum PSA of 4–20 μg/l was observed. The nomograms established can be used to avoid or defer biopsy in men with a low prostate cancer probability in spite of a serum PSA level exceeding 4 μg/l.     

Diagnostic value of percent free prostate-specific antigen: retrospective analysis of a population-based screening study with emphasis on men with PSA levels less than 3.0 ng/mL

OBJECTIVES: To retrospectively investigate the use of percent free prostate-specific antigen (PSA) compared with total PSA in serum as predictor of prostate cancer in men selected randomly from the general population who underwent biopsy on the basis of abnormal findings on digital rectal examination (DRE) or transrectal ultrasound (TRUS) and/or serum PSA levels greater than 10 ng/mL. METHODS: A single intervention, population-based screening study was undertaken in 1988 and 1989. Of the 2400 men aged 55 to 70 years invited to participate, 1782 men responded and were examined with DRE, TRUS, and PSA testing (Tandem-Hybritech). In 1995, frozen serum samples from 1748 men were analyzed for percent free PSA (Prostatus, Wallac OY). Five-year follow-up data on new cancers in the screened population were obtained from the Swedish Cancer Registry (SCR). RESULTS: Of the 1748 men, 367 underwent TRUS-guided biopsies because of abnormal findings on either DRE or TRUS or serum PSA levels of greater than 10 ng/mL. This resulted in the diagnosis of 64 cases of prostate cancer (3.7%). PSA levels of 3.0 ng/mL or greater were found in 55 (86%) of 64 cancer cases and in 399 (24%) of the 1684 benign cases. Among the 1294 men with PSA less than 3.0 ng/mL, 9 prostate cancers were diagnosed (14% of all prostate cancers). All 9 patients with cancer and with PSA less than 3.0 ng/mL had a percent free PSA of 18% or less. In the group of 1109 patients with PSA less than 3.0 ng/mL and a percent free PSA greater than 18%, 159 biopsies were performed because of abnormal DRE or TRUS. However, no prostate cancer was diagnosed in this category of patients. Five years after the screening intervention, 7 more cases of prostate cancer were clinically diagnosed in the screened population according to the SCR. CONCLUSIONS: The combination of PSA levels less than 3.0 ng/mL and percent free PSA greater than 18% defines a large part of the population at a very low risk of cancer of the prostate both at the time of screening and during the following 5 years. Men in this group may be spared DRE, and longer screening intervals may be considered. However, the risk of having prostate cancer is not negligible in men with PSA less than 3.0 ng/mL and percent free PSA of 18% or less. The results of this study indicate that biopsy should be recommended to men fulfilling these criteria, although these results should be confirmed in larger prospective studies because of the limited number of patients with prostate cancer in the present series.     

Population-based screening for prostate cancer by measuring total serum prostate-specific antigen in Iran

OBJECTIVE: To report the results from an Iranian large population-based randomized study of screening using prostate-specific antigen (PSA) to detect prostate cancer. MATERIALS AND METHODS: A total of 3758 Iranian men older than 40 years were mass checked by PSA-based screening. Men with an abnormal digital rectal examination (DRE) and serum total PSA level of greater than 4 ng/mL, underwent transrectal ultrasonography (TRUS)-guided extended prostate biopsy. RESULTS: The PSA value (mean +/- standard deviation, SD) in all men without prostate cancer was 1.6 +/- 1.1 ng/mL and in those with cancer 18 +/- 44.8 ng/mL (P = 0.001). PSA values increased with age. In those aged 40-49, 50-59, 60-69 and > or = 70 years, the mean +/- SD PSA values were 1.3 +/- 0.7, 1.4 +/- 0.8, 1.8 +/- 1 and 2.2 +/- 1.6 ng/mL, respectively. Among the screened men, 323 (8.6%) had a serum PSA concentration greater than 4 ng/mL. Of patients who underwent prostate biopsy (230, 71.2%), 129 (positive predictive value, 56.1%) had prostate cancer. Additionally, nine cancers were detected among 16 patients with PSA of less than 4 ng/mL who had a doubtful DRE finding. The overall cancer detection rate was 3.6%; 1.4% at 40-49, 1.6% at 50-59, 4.2% at 60-69 and 12.9% at >/=70 years. Conventional systematic sextant biopsies, which accounted for six of the 10 cores in our biopsy scheme, detected 98 (71%) of the cancers. CONCLUSIONS: The Iranian male population develops prostate cancer quite commonly if their serum PSA levels are greater than 4.0 ng/mL. In this study, 65.9% of the detected cancers were clinically significant. The conventional systematic sextant technique may be inappropriate for detection of all prostate cancers. The results need to be confirmed in other randomized trials.     

Decreasing trend in prostate cancer with high serum prostate-specific antigen levels detected at first prostate-specific antigen-based population screening in Japan

To clarify the recent trends in prostate-specific antigen （PSA） distribution in men in Japan, we analyzed the PSA distributions of men undergoing PSA-based population screening. We summarized the annual individual data of PSA-based population screening in Kanazawa, Japan, from 2000 to 2011, and analyzed baseline serum PSA values of the participants at the first population screening. Serum PSA distributions were estimated in all participants and those excluding prostate cancer patients according to age. From 2000 to 2011, 19 620 men participated aged 54-69 years old in this screening program. Mean baseline serum PSA level of all participants at the first screening was 2.64 ng m1-1 in 2000, and gradually decreased to approximately 1.30 ng ml-I in 2006. That of participants excluding prostate cancer patients was 1.46 ng m1-1 in 2000, and there was no remarkable change during the study period. The 95t＂ percentiles in the participants excluding prostate cancer patients detected at the first population screening of men aged 54-59, 60-64, and 65-69 years old were 2.90, 3.60, and 4.50 ng m1-1, respectively. After the commencement of population screening, the proportion of prostate cancer patients with high serum PSA levels decreased. However, there were no changes in serum PSA levels in men without prostate cancer. Age-specific PSA reference level of men without prostate cancer in Japan was similar to that in China and Korea.     

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

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

Delays in cancer detection using 2 and 4-year screening intervals for prostate cancer screening with initial prostate specific antigen less than 2 ng/ml

Purpose:The American Urological Association and American Cancer Society advocate annual screening with serum prostate specific antigen (PSA) and digital rectal examination starting at age 50 years in the general population and earlier in men at high risk. Some groups have suggested that screening at 2 or 4-year intervals may be sufficient in men with initial PSA 2 ng/ml or less. We reviewed the records of men enrolled in a PSA and digital rectal examination based prostate cancer screening study to determine the extent to which the diagnosis of cancer would have been delayed using a 2 or 4-year screening interval.Materials and Methods:We evaluated 18,140 volunteers in a prostate cancer screening study in whom PSA was less than 2 ng/ml at initial screening and who were screened at 6-month to 1-year intervals for up to 8 years. We evaluated the cancers detected in these intervals to determine the possible delay in cancer diagnosis that would occur using prolonged screening intervals. We report the overall cancer detection rate, clinical and pathological tumor stage, and Gleason grade of the cancers detected.Results:Excluding 70 men in whom prostate cancer was detected at initial evaluation 2.0% had prostate cancer detected during the next 8 years (mean 21.6 cancers per 6 months, median 20, range 12 to 33). Using a hypothetical 2-year screening interval cancer detection 62% would have been delayed by 4 to 20 months. Using a hypothetical 4-year screening interval cancer detection would have been delayed in 77% of men by 4 to 44 months. Of the tumors detected 100% were clinically localized, 77% were pathologically organ confined and 29% had a Gleason score of 7 or greater.Conclusions:The 2 or 4-year PSA screening interval in men with initial serum PSA less than 2 ng/ml would result in substantial delays in prostate cancer detection. To our knowledge the extent to which these delays would affect treatment outcomes is undetermined.     

Mass screening for prostate cancer in patients with end-stage renal disease: a comparative study

OBJECTIVE: To determine the usefulness of prostate-specific antigen (PSA) screening for prostate cancer in patients with end-stage renal disease (ESRD), as although serum PSA is effective in the early detection of this cancer in the general population, there are few reports of its utility in patients with ESRD. PATIENTS AND METHODS: Blood samples were obtained for PSA screening from April 2002 to September 2003; 1250 men with ESRD aged >50 years were compared with 1007 healthy control men aged >55 years, all in Kumamoto Prefecture, Japan. All men with a serum PSA level of >4.0 ng/mL were categorized as PSA-positive and were further assessed, including a prostate biopsy. RESULTS: There was a statistically significantly greater increase in PSA level with age in the ESRD group than in the healthy controls. The rate of cancer detection among men with a PSA level of >10 ng/mL was significantly higher in patients with ESRD than in healthy controls. Thirteen patients with ESRD and five healthy control men were finally diagnosed with prostate cancer. CONCLUSION: The serum PSA level was slightly higher and the incidence of prostate cancer at higher PSA levels appeared to be greater in men with ESRD than in healthy controls. The findings of this large study suggest that PSA screening is useful for the diagnosis of prostate cancer in these patients.     

Mass screening for prostate cancer in Tokushima City: the results of 2001

PURPOSE: Screening with prostate specific antigen (PSA) only to detect prostate cancer was started in Tokushima City from 2001 as one of health check lists. We evaluated the first year result. MATERIALS AND METHODS: Fifty-five years old or elder men living in Tokushima City who wants to measure serum PSA level to screen for prostate cancer were entered to screening program. The men whose PSA levels detected as over normal; range were recommended to visit to urologists for further examination to detect prostate cancer include prostate biopsy. The results of further examination were reported to Tokushima City and evaluated. RESULTS: The population of fifty-five or elder men in Tokushima City was 25,416 and 9,019 (35.5%) men were measured serum PSA levels. In 801 (8.9%) men, PSA levels were over normal range, and recommended further examination to detect prostate cancer. 451 (56.3%) men visited to urologists for further examination, and prostate biopsy was performed in 231 (51.2%) men. Finally, 121 men were diagnosed as prostate cancer, 52.1% of 231 men performed prostate biopsy, 26.7% of 451 men visited to urologist for further examination, 1.34% of 9,019 men measured serum PSA levels. Patient number for each clinical stages were 49 in B0, 16 in B1, 16 in B2, 29 in C, one in D1, and 10 in D2. Patients number in each age range were 3 in 55-59, 11 in 60-64, 22 in 65-69, 37 in 70-74, 33 in 75-79, 15 in 80 or elder. Patient number of Stage B and 74 years old or younger was 48 (39.7%). CONCLUSION: Prostate cancer was detected in 1.34% of 9,019 men who measured serum PSA levels, and early stage B was two thirds. PSA screening to detect prostate cancer as one of health check-lists in Tokushima City was useful to detect early prostate cancer.     

VALIDITY OF THE PROSTATE SPECIFIC ANTIGEN TEST FOR PROSTATE CANCER SCREENING: FOLLOWUP STUDY WITH A BANK OF 21,000 SERA IN FINLAND

PURPOSE: We investigate the validity of prostate specific antigen (PSA) as a screening test for prostate cancer. MATERIALS AND METHODS: A registry of serum samples drawn from 1968 to 1976 from 21,387 men was linked to the Finnish Cancer Registry. During followup from 1968 to 1991, 104 prostate cancers were identified. A matched case control design with incidence density sampling and nested in the serum sample bank was applied, and PSA was assessed. RESULTS: The estimated sensitivity of the test was 44% and specificity 94% at a cutoff of 4.0 microg./l. in the total material. The sensitivity had improved to 86% in patients diagnosed in 5 years after the sample drawing. The test had a better sensitivity (93%) and specificity (96%) in men younger than 65 years at the time of the sample drawing compared to those older. The sensitivity further improved to 100% with a cutoff of 2.5 microg./l. CONCLUSIONS: PSA is a valid screening test for prostate cancer, which compares favorably with mammography for breast cancer. However, until an effect on mortality has been shown, routine screening cannot be recommended.     

Prevalence of undiagnosed prostate cancer in men with erectile dysfunction

OBJECTIVE: To explore the prevalence of prostate cancer in men presenting with erectile dysfunction (ED). PATIENTS AND METHODS: In a prospective study, 127 men with ED of at least 6 months duration underwent screening for prostate cancer using prostate specific antigen (PSA) and a digital rectal examination (DRE). Men with a high PSA level (> 4 ng/mL) had sextant biopsies taken under sedoanalgesia. The serum testosterone level was measured in all the men. RESULTS: Twenty-six men were aged < 50 years and all had a normal PSA level; of 101 men aged > 50 years, 20 had an abnormal PSA. The detection rate for prostate cancer using PSA and DRE was 5%, which was not significantly higher than in the general population. All the detected cancers were clinically significant (> T2a, Gleason grade > 4). Two of the five men diagnosed with prostate cancer were Afro-Caribbean. Of the 127 men, 31% had a low serum testosterone level, but there was no association between testosterone and PSA levels. CONCLUSIONS: Prostate cancer is no more common in men with ED than in the normal male population. Therefore, routine screening for prostate cancer in men with ED is not indicated.     

Is It Necessary to Detect All Prostate Cancers in Men with Serum PSA Levels <3.0 ng/ml? A Comparison of Biopsy Results of PCPT and Outcome-Related Information from ERSPC

CONTEXT: The European Randomized Study of Screening for Prostate Cancer (ERSPC) section Rotterdam was initiated in 1993. Men who initially presented with prostate-specific antigen (PSA) values <3.0 ng/ml were not biopsied (with few exceptions). In the Prostate Cancer Prevention Trial (PCPT) eligible men who initially presented with PSA values <3.0 ng/ml were all biopsied during or at the end of a 7-yr study period. OBJECTIVE: To compare biopsy rates in PCPT and cancer detection rates, interval cancers, and prostate cancer deaths in ERSPC. Report the number of additional biopsies needed to detect these cases using PCPT policy. EVIDENCE ACQUISITION: 21,210 men, aged 55-74 yr, were randomised to screening; 19,970 were actually screened between November 1993 and December 1999. A total of 15,852 initially presented with PSA values of <3.0 ng/ml; after excluding 79 detected at first screens, 15,773 remained as the study population. A second and third screening round followed after 4- and 8-yr intervals. All cancers found in three rounds of screening or as interval cancers during the 12-yr interval were identified and characterised. EVIDENCE SYNTHESIS: Screening for prostate cancer and routine clinical management, comparison of detection rates and outcome data. During the 12-yr observation period, which may be too short, 700 cancers were found, 620 through screening and 80 as interval cancers. None of the screen-detected cases but 6 of the 80 men with interval cancers died of prostate cancer. Applying the positive predictive value of 21.7% of the PCPT trial 3472 cancers would have been detected in ERSPC Rotterdam had all men with PSA values <3.0 ng/ml been biopsied. Assuming 80 interval cancers and 6 deaths from prostate cancer might have been prevented if all 15,773 eligible men had undergone biopsy. CONCLUSIONS: The present data suggest a very much unfavourable "number needed to be biopsied" to find one missed cancer or to detect the deadly interval cancers.     

Ten year trend in prostate cancer screening with high prostate-specific antigen exposure rate in Japan

Background:   The tendency of the results and quality control of prostate cancer screening serially performed for 10 years in an area of Japan were evaluated.
Methods:   A total of 39 213 men over 55 years of age have participated in the mass screening of prostate cancer in the Otokuni District, since 1995. Men whose prostate-specific antigen (PSA) levels were more than 4.1 ng/mL were indicated for the second screening. In the second screening, prostate-specific antigen density (PSAD) was calculated in men whose PSA levels ranged from 4.1 to 10.0 ng/mL.
Results:   Secondary screening was indicated in a total of 2428 subjects, of whom 1633 underwent it. Prostate cancer was diagnosed in 267 men. As a result of the evaluation of the indication of prostate biopsy according to the PSAD in 894 who underwent secondary screening for the first time, the procedure was judged to be unnecessary in 269 (35%) of 765 cases. Of these 269 subjects, 23 (8.5%) were found to have cancer. Clinically localized prostate cancer increased by 17%, and locally advanced and metastatic cancers decreased by 12% in the second compared with the first five years of the ten-year period. The exposure rate of PSA screening in the Otokuni District was 65% with the application for the rate of screenees whose PSA level was 4.1 ng/mL or above.
Conclusions:   The Japanese basic health screening system allows the determination of high-PSA exposure areas. Serial prostate cancer screening showed a tendency of stage migration in the screened cancer patients. The use of PSAD in secondary screening substantially reduces the necessity of prostate biopsy; however, the encouragement of PSA-positive individuals to periodically receive prostate cancer screening is essential to maintain the quality of the screening system.     

Prevalence of elevated serum prostate-specific antigen in rural Nigeria

BACKGROUND: Recent hospital and cancer registry data show increasing prostate cancer incidence in Nigeria, which was previously regarded as a low incidence region. This study investigates the prevalence of prostate cancer risk in a previously unscreened cohort of rural Nigerians. METHODS: Rural Nigerian men, 40 years and older, were screened by serum prostate-specific antigen (PSA) and digital rectal examination (DRE) and those with PSA >/= 4 ng/mL and/or abnormal DRE were referred for prostate biopsy. RESULTS: Of 200 consecutive men invited, 151 (75.5%) presented for screening, the mean age was 56.45 + 15.1 and 95 (61.6%) were >/= 50 years of age. Of the 140 who consented to a blood test, PSA correlated with age (r = 0.3, P < 0.01), 14 (10.0%) had abnormal PSA >/= 4 ng/mL, increasing from 3 (3.6%) in men < 60 years to 4 (50%) in men >/= 80 years. The rate was 13 (15.7%) for men >/= 50 years and there was no evidence of increased incidence of prostatitis in the community. Mean (median) PSA in ng/mL increased from 1.17 (0.60) in the youngest to 13.75 (4.45) in the oldest cohort. Of those who accepted DRE, 38 (29.0%) had an enlarged prostate, including two who had nodular prostate, one-third with symptoms, increasing from 4 (5.4%) in those < 50 years to 6 (75.0%) in men >/= 80 years. The proportion of men with PSA >/= 4 ng/mL among those with enlarged vs normal prostate is 27.0 to 3.4%, P < 0.001, and the pattern was similar for men >/= 60 years and those < 60 years of age. The 40 (32.0%) men referred for prostate biopsy defaulted mainly because they did not fully understand the need for further investigation because they were symptom free or afraid of the possible side-effects of the procedure or diagnosis of cancer. CONCLUSION: The proportion of men with PSA >/= 4 ng/mL is comparable to that of previously unscreened populations with high incidence of prostate cancer such as African-American men. A larger study is required to confirm these findings and intensify efforts to determine the prostate cancer detection rate by biopsy in this population. A prostate cancer awareness and education campaign will be useful in this community.     

The changing pattern of prostate cancer at the time of diagnosis: characteristics of screen detected prostate cancer in a population based screening study

PURPOSE: We describe the clinical and pathological features of prostate cancer diagnosed through serum prostate specific antigen (PSA), digital rectal examination and transrectal ultrasonography in a population based randomized screening study. MATERIALS AND METHODS: Between November 1993 and June 1997, 20,632 volunteers 55 to 76 years old were included in the study. In the screening arm 9,776 men underwent digital rectal examination, transrectal ultrasound and serum PSA determination. Biopsies were taken if the digital rectal examination and/or transrectal ultrasound findings were abnormal or if PSA was 4 ng/ml or greater. A total of 2,262 men underwent biopsy and 474 cases of prostate cancer were diagnosed. RESULTS: The pretreatment data were complete in 459 men, of whom 78% had clinically organ confined disease. Bone or lymph node metastases were seen in 8 cases (1.7%). Of 172 men who underwent radical prostatectomy 2 had lymph node metastases. Overall 66.3% of men treated with radical prostatectomy had organ confined disease. CONCLUSIONS: Comparison of the characteristics of prostate cancer detected through screening of the general population with those in a population based cohort of men in which there was no organized screening revealed stage reduction, primarily with regard to number of metastatic cases. Whether this stage reduction will lead to a decrease in disease specific mortality remains unknown until the study is completed and the end point of prostate cancer specific mortality is evaluated.     

Prostate cancer: Diagnosis and staging

The discovery and the use of serum prostate specific antigen (PSA) has considerably improved the diagnosis of prostate cancer during the past 20 years. Before PSA era, early diagnosis was only based on the digital rectal examination (DRE) of which the Limitations have been evidenced; over half of the tumours diagnosed by such means had already spread out of the prostate and were incurable. Assessment of serum PSA has allowed the diagnosis to be made at an earlier stage of the disease, curable by current treatments. Whichever the diagnostic tools, transrectal ultrasound (TRUS) prostatic biopsies remain necessary for diagnosis ascertainment, taking into account the low specificity of PSA assessment. The feasibility of a diagnosis at an early and curable stage of the disease has logically resulted in screening procedures aimed at reducing the high mortality related to prostate cancer. The numerous publications on prostate cancer screening provide precise information on the accuracy of available diagnostic means (PSA, DRE, TRUS, combined PSA and DRE), on the characteristics of screened tumours (stage and differentiation), and also on the population of men likely to benefit from the screening (age at beginning and end of the screening, frequency of PSA testing, identification of the men with ethnic and/or genetic predisposition). In those early diagnosed prostate cancers, the assessment of loco-regional cancer extension (extracapsular and/or, microscopic nodal involvement), remains unsatisfactory because no imaging technique (ultrasonography, CT scan, MRI,...) allows visualising the tumour itself or microscopic metastases. Nevertheless, the combination of multiple parameters such as DRE data, PSA level, biopsy data and tumour differentiation helps approaching with an increasing precision (nomograms) the true pathologic stage of the disease. Such advances allow distinguishing, among the very heterogeneous group of prostate cancers, tumours that differ from one to another in terms of disease stage, progression and prognosis, which is helpful for the determination of an adapted therapeutic strategy.     

Prostate-specific antigen-based screening for prostate cancer: Evidence, controversies and future perspectives

The most recent epidemiological survey revealed that the mortality rate for prostate cancer in Japan has increased and has been getting very close to that in the USA, where it has decreased since 1992. The low exposure rate of prostate-specific antigen (PSA) screening in Japan and the high exposure rate of PSA screening in the USA may result in completely deferent trends in the mortality rate of prostate cancer between the two countries. The Japanese Urological Association recommends PSA-based screening for men at risk of prostate cancer at age 50 years or older in general and 45 years or older in men with a family history of prostate cancer within first generation relatives. The fact sheet on screening for prostate cancer should indicate the most recent reliable clinical research on screening for prostate cancer and its demerits including false-negative and false-positive PSA test results and prostate biopsy, overdetection and overtreatment. However, it should be explained to the public that the demerits for PSA screening will be clarified step by step during screening, and in general, men having more information on screening results (PSA level, pathological findings of biopsy specimens, clinical stage, etc.) can understand their current situation better than those having no information on screening results, including PSA levels.     

Screening with prostate specific antigen and metastatic prostate cancer risk: a population based case-control study

PURPOSE: Screening of asymptomatic men with prostate specific antigen (PSA) remains a controversial issue. There is limited evidence that screening is effective in reducing mortality from prostate cancer. In the current study we determined if screening with PSA reduces the risk of metastatic prostate cancer. MATERIALS AND METHODS: We conducted a population based case-control study among the residents of Metropolitan Toronto and 5 surrounding counties in Ontario, Canada. Data were obtained from 236 cases of metastatic prostate cancer and 462 controls randomly sampled from the source population and frequency matched to cases for age and area of residence. History of PSA testing, digital rectal examination, symptoms and other data were obtained from medical records and a self-administered questionnaire. The association between PSA screening and metastatic prostate cancer was measured by the Mantel-Haenszel odds ratio stratified by exposure observation time and other potential confounding factors. RESULTS: In asymptomatic men, the frequency of PSA screening as determined from medical records was significantly lower among the cases compared with the controls (odds ratio 0.65, 95% confidence interval 0.45 to 0.93). The odds ratio was 0.52 (0.28 to 0.98) in men 45 to 59 years old and 0.67 (0.41 to 1.09) in those 60 to 84 years old. CONCLUSIONS: In this case-control study screening of asymptomatic men with PSA was associated with a significantly reduced risk of metastatic prostate cancer. The results need to be confirmed in randomized controlled trials.