Prostate-specific antigen-based population screening for prostate cancer: current status in Japan and future perspective in Asia

In Western countries, clinical trials on prostate cancer screening demonstrated a limited benefit for patient survival. In the Asia-Pacific region, including Japan, the rate of prostate-specific antigen (PSA) testing remains very low compared with Western countries, and the benefits of population-based screening remain unclear. This review describes the current status of population screening and diagnosis for prostate cancer in Japan and discusses the efficacy of population screening for the Asian population. Since the 1990s, screening systems have been administered by each municipal government in Japan, and decreases in the prostate cancer mortality rate are expected in some regions where the exposure rate to PSA screening has increased markedly. A population-based screening cohort revealed that the proportion of metastatic disease in cancer detected by screening gradually decreased according to the increased exposure rate, and a decreasing trend in the proportion of cancer with high serum PSA levels after population screening was started. The prognosis of the prostate cancer detected by population screening was demonstrated to be more favorable than those diagnosed outside of the population screening. Recent results in screening cohorts demonstrated the efficacy of PSA. These recent evidences regarding population-based screening in Japan may contribute to establishing the optimal prostate cancer screening system in Asian individuals.     

Screening for prostate cancer: History,evidence, controversies and future perspectives toward individualized screening

Differences in the incidence and mortality rate of prostate cancer between the USA and Japan have been decreasing over time, and were only twofold in 2017. Therefore, countermeasures against prostate cancer could be very important not only in Western countries, but also in developed Asian countries. Screening for prostate cancer in the general population using transrectal ultrasonography, digital rectal examination and/or prostate acid phosphatase began in Japan in the early 1980s, and screening with prostate‐specific antigen and digital rectal examination has been widespread in the USA since the late 1980s. Large‐ and mid‐scale randomized controlled trials on screening for prostate cancer began around 1990 in the USA, Canada and Europe. However, most of these studies failed as randomized controlled trials because of high contamination in the control arm, low compliance in the screening arm or insufficient screening setting about screening frequency and/or biopsy indication. The best available level 1 evidence is data from the European Randomized Study of Screening for Prostate Cancer and the Göteborg screening study. However, several non‐urological organizations and lay media around the world have mischaracterized the efficacy of prostate‐specific antigen screening. To avoid long‐term confusion about screening for prostate cancer, leading professional urological organizations, including the Japanese Urological Association, are moving toward the establishment of an optimal screening system that minimizes the drawbacks of overdetection, overtreatment and loss of quality of life due to treatment, and maximizes reductions in the risk of death as a result of prostate cancer and the development of metastatic prostate cancer.     

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.     

Usefulness of prostate-specific antigen velocity in screening for prostate cancer

BACKGROUND: The cut-off value of prostate-specific antigen velocity (PSAV) was investigated in relation to the initial prostate-specific antigen (PSA) value in subjects with initial values of 1.0-4.0 ng/mL, and the usefulness and limitations of PSAV as a screening test for prostate cancer were examined. METHODS: In this study, 4883 men who underwent mass screening for prostate cancer two or more times between 1987 and 1998 and had initial PSA levels of 1.0-4.0 ng/mL were investigated. The subjects ranged in age from 42 to 96 years (mean: 68.0 +/- 6.6 years). The cut-off value of PSAV was set at 0.1-1.5 ng/mL per year, and the sensitivity, specificity, efficiency and positive predictive value (PPV) of PSAV for detecting prostate cancer were determined according to the initial PSA value. A similar examination of the average PSAV was carried out in 2888 subjects with three or more visits for mass screening for prostate cancer. RESULTS: The diagnostic efficiency of PSAV was optimal with cut-off values of 0.3 and 0.75 ng/mL per year in those subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 1.8% in subjects with initial PSA levels of 1.0-1.9 ng/mL. When the cutoff value of PSAV was set at 1.2 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV increased to 7.3% and the sensitivity was 40%. The diagnostic efficiency of the average PSAV was optimal at the cut-off values of 0.2 and 0.4 ng/mL per year in subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 2.2% in the subjects with initial PSA values of 1.0-1.9 ng/mL. When the cut-off value of PSAV was set at 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV was 9.8% and the sensitivity was 46%. CONCLUSION: It is possible to improve the diagnostic accuracy of prostate cancer screening using the cut-off value of PSAV and average PSAV in subjects with initial PSA levels of 1.0-4.0 ng/mL. The cut-off values of PSAV should be set at 1.2 and 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively. The cut-off values of the average PSAV should be set at 0.75 and 0.4 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively.     

Prostate specific antigen testing and digital rectal examination before and during a randomized trial of screening for prostate cancer: European randomized study of screening for prostate cancer, Rotterdam

PURPOSE: Worldwide 2 large-scale randomized screening trials for prostate cancer have been initiated. Determining prostate specific antigen (PSA) involves a simple test that may influence the outcome of these trials if frequently done in the control arm or before study enrollment. We quantified PSA and digital rectal examination before and during the screening trial in Rotterdam, The Netherlands and in the general population. MATERIALS AND METHODS: Trial participants were administered study intake questionnaires on tests done before study participation. Data on PSA from the regional general practice laboratory were correlated with participant data. Various sources were used to quantify PSA tests and digital rectal examinations in the general population. RESULTS: Of men 55 to 74 years old 45% underwent digital rectal examination at 1 time and 13% reported that PSA was tested before trial participation. Each rate increased with age. No statistically significant effect of former PSA testing or digital rectal examination on the cancer detection rate was identified. The rate of PSA determination after initial screening and/or randomization in the control arm was 2-fold that in the screening arm (76 versus 33/1,000 person-years). PSA determination initially decreased in the screening arm but increased rapidly after some time. The number of PSA determinations in the general population was estimated to be 45/1,000 person-years at ages 55 to 69 years. CONCLUSIONS: PSA testing was moderate in the control arm but if different men undergo this test each year, the contamination rate may become rather high. In the final analysis of mortality PSA testing should be considered.     

Evidence of prostate cancer screening in a UK region

OBJECTIVE: To examine the pattern of use of prostate-specific antigen (PSA) testing in a UK region, where National Health Service policy does not recommend screening for prostate cancer. SUBJECTS AND METHODS: Data were collected on all PSA tests in Northern Ireland between 1990 and 1999. Annual rates of PSA testing were calculated by age, GP Practice and year. RESULTS: In all, 165 862 PSA tests were performed on 84 669 men, and over a third of men aged > or = 50 years had at least one PSA test. Men aged < 50 years accounted for 12.9% of first tests. The proportion of tests from primary care increased from 47.2% in 1993 to 67.0% in 1999. The mean age of men tested once decreased from 65.6 to 61.9 years (P trend < 0.001) and the proportion with an elevated PSA level also declined during the period. Repeat testing increased with PSA level (P < 0.001) but 29.4% of men with a PSA level of < or = 4 ng/mL also had repeat testing. Raised PSA values were more common from hospital than primary care (32.4% vs 20.6%, P < 0.001) and in older men. Test rates varied 100-fold across general practices, a finding not explained by sociodemographic factors, but one which reflects differential adherence to national guidelines, suggesting that general practitioners are key targets for attempting to rationalise the use of the PSA test. CONCLUSION: These findings suggest that PSA screening is taking place against evidence-based advice and has resulted in over 20 000 men being designated as having a raised PSA level, creating a need for further assessment.     

Prostate-specific antigen adjusted for the transition zone volume versus free-to-total prostate-specific antigen ratio in predicting prostate cancer

BACKGROUND: We performed this study to assess the efficacy of prostate-specific antigen adjusted for the transition zone volume (PSATZ) and free-to-total prostate-specific antigen (PSA) ratio (F/T ratio) in predicting prostate cancer in men with intermediate PSA levels of 4.1-10.0 ng/mL. METHODS: Between March 1997 and September 1998, PSATZ was obtained from 67 patients who underwent ultrasonography guided systemic sextant biopsies and had a PSA of 4.1-10.0 ng/mL. PSATZ was compared with F/T ratio via receiver operating characteristic (ROC) curves. RESULTS: Of 67 patients, 22 (32.8%) had prostate cancer and 45 (67.2%) had benign prostatic hyperplasia (BPH) on pathologic examination. Mean PSA, PSA density, F/T ratio and PSATZ were 7.96+/-2.01ng/mL, 0.28+/-0.14 ng/mL/cc, 0.10+/-0.06 and 0.70+/-0.28 ng/mL/cc in patients with prostate cancer and 6.39+/-1.68 ng/mL, 0.16+/-0.06 ng/mL/cc, 0.15+/-0.05 and 0.29+/-0.10 ng/mL/cc in patients with BPH, respectively. The ROC curve analysis demonstrated that PSATZ predicted the biopsy outcome significantly better than F/T ratio in all 67 patients (P<0.01) and in a subset of 53 men with normal digital rectal examination (P<0.01). With a cut-off value of 0.35 ng/mL/cc, PSATZ had a sensitivity of 86% and a specificity of 89% for predicting prostate cancer. CONCLUSIONS: These results suggest that PSATZ and F/T ratio may be useful in diagnosing prostate cancer with intermediate levels of PSA. Prostate-specific antigen adjusted for the transition zone volume is more accurate than F/T ratio in distinguishing benign prostatic disease from prostate cancer. But large prospective studies are required to assess the precise role of PSATZ and F/T ratio in early prostate cancer detection.     

Prostate-specific antigen, Gleason sum and clinical T stage for predicting the need for radionuclide bone scan for prostate cancer patients in Japan

AIM: In the present study, we evaluated the relationships between prostate-specific antigen (PSA) level and bone metastasis, between Gleason sum and bone metastasis, and between clinical T stage and bone metastasis in Japanese patients. METHODS: Between November 1998 and June 2004, we performed ultrasound-guided biopsies on 709 patients (mean age: 70.5 years, range: 39-90). Prostate cancer was detected in 339 patients (47.8%), 297 (87.6%) of whom underwent a radionuclide bone scan. In close collaboration with orthopedists, bone computed tomography scans, bone magnetic resonance imaging and/or plain rentogenograms were performed for cases that were difficult to diagnose as bone metastasis through radionuclide bone scans only. RESULTS: We detected 61 (20.6%) bone metastasis cases in 296 patients. A simple linear regression analysis between log[PSA] and bone metastasis (n = 296) produced a significant relationship (P < 0.05). When we set the cut-off PSA value for the indication for a bone scan at 15 ng/mL, the possibility of bone metastasis was 10%. However, from our experience, there was no bone metastasis in the patients whose Gleason sums were less than five, and in the patients whose Gleason sum were five or more, and the PSA levels were less than 15, there was no bone metastasis. The rate of bone metastasis increased with the increase of PSA level. In the clinical T1-T2 stage cases, there were significant higher PSA levels in the cases with bone metastasis. In the T1-T2 patients whose PSA levels were less than 16, there was no bone metastasis. CONCLUSIONS: From the analysis of PSA, Gleason sum and clinical T stage, we suggest that bone scan is unnecessary for patients whose PSA level is less than 15 ng/mL or Gleason sum is less than five.     

Relationship among initial serum prostate specific antigen, prostate specific antigen progression and prostate cancer detection at repeat screening visits

PURPOSE: We evaluated the probability of positive serum PSA (3 ng/ml or greater) and CaP detection at annual followup visits in men with negative initial PSA (less than 3 ng/ml) to optimize the re-screening schedule. MATERIALS AND METHODS: Data on 5,387 men 45 to 80 years old with negative PSA and no CaP diagnosis at the first screening visit were obtained from the Laval University Prostate Cancer Screening Program database. Accelerated failure time regressions were fitted to time from baseline to positive PSA and to time from positive PSA to CaP detection. The models were combined to estimate the cumulative probability of positive PSA followed by CaP detection at re-screening. RESULTS: The 5-year cumulative probability of detecting CaP at annual visits in men with baseline PSA up to 1.5 ng/ml remained below 0.8%, while it was 1.3%, 4.8% and 8.3% in men with PSA 1.5 to less than 2, 2 to less than 2.5 and 2.5 to less than 3 ng/ml, respectively. Time to positive PSA significantly decreased with increasing baseline PSA and age, while the time between positive PSA and CaP detection depended only on age. Men with PSA below 1.0 ng/ml could wait for 4 to 5 years before being re-tested, while men with PSA between 1.0 and 1.5 ng/ml should be screened every second year and men with PSA 1.5 ng/ml or greater should be screened every year. CONCLUSIONS: The proposed retesting schedule using current PSA and age decreases the number of visits by 38.1%, while delaying the detection of only 2.4% of CaPs that would have been detected using annual PSA testing.     

Relationship between initial prostate specific antigen level and subsequent prostate cancer detection in a longitudinal screening study

PURPOSE: Previous studies of archived blood samples from nonscreened populations have shown an association between the prostate specific antigen (PSA) and the subsequent detection of prostate cancer. In the current study we evaluated the relationship between the initial screening PSA and the subsequent risk of prostate cancer detected in a prospective, longitudinal screening study. We also examined the relationship between initial PSA and the clinicopathological features of the cancers detected. MATERIALS AND METHODS: Between May 1991 and November 2001 we enrolled 26,111 volunteers in our PSA and digital rectal examination based prostate cancer screening study. The men were followed biannually or annually depending on the results of previous screening tests. The chi-square and Kruskal-Wallis tests were used to compare the clinical stage, pathological stage and Gleason score of subsequently detected prostate cancers as well as the time to cancer detection in different initial screening PSA strata. RESULTS: The initial screening PSA stratum was strongly associated with the subsequent detection of prostate cancer as well as the clinicopathological stage and grade of the cancers detected. CONCLUSIONS: Even in the lower PSA ranges initial screening serum PSA can help identify men at increased risk for subsequent prostate cancer detected in a longitudinal screening study.     

Effect of body mass index on prostate-specific antigen and percentage free prostate-specific antigen: Results from a prostate cancer screening cohort of 1490 men

Objectives:   Several studies have reported an effect of obesity, defined as elevated body mass index (BMI), on prostate cancer biology. We examined the relationship between BMI and total prostate-specific antigen (tPSA) as well as percent free tPSA (%f/tPSA) in a large prostate cancer screening cohort.
Methods:   Height, weight, tPSA and %f/tPSA were assessed in 1490 consecutively screened Canadian men without known prostate cancer. Continuously coded and categorized BMI were studied. Statistical analyses consisted of anova , linear regression and bivariate correlations, which adjusted for the effect of age.
Results:   Median tPSA was 1.06 ng/mL and median %f/tPSA was 27. Median BMI was 26.17 kg/m². Increasing BMI was weakly, albeit statistically significantly, associated with decreasing %f/tPSA values (correlation coefficient = −0.06, P  = 0.01). However, when the World Health Organization BMI categories were considered, there were no statistically significant differences between %f/tPSA values according to categories ( anova P  = 0.2). tPSA failed to demonstrate any statistically significant association with either continuously coded (correlation coefficient = −0.03, P  = 0.2) or categorized BMI ( anova P  = 0.5).
Conclusions:   Body mass index is not a confounder of either tPSA or %f/tPSA in Canadian men without known prostate cancer.     

总体和自由型前列腺特异抗原指数在日本人群前列腺癌筛选中的价值和局限性(英文)

目的:在日本某单机构中评定前列腺特异抗原指数(f/tPSA)的价值和局限性,重点在于避免无意义的前列腺组织活检。方法:631名年龄在44-93岁之间(平均年龄69.8岁)的男性,在日本新滹中心医院用能量多普勒超声波图像引导的经直肠10-点前列腺组织活检后发现其 PSA 值增加,用总体前列腺特异抗原 (tPSA)和前列腺特异抗原指数(f/tPSA)观察组织学特征。结果:在134名 tPSA 为26 ng/mL 或更高病人中,126人(94.3%)检测到前列腺癌(PCa),tPSA 为21-25 ng/mL 时的 PCa 检出率是59.4%,16-20 ng/mL 时为39.2%,11-15 ng/mL 时为30.0%,4.1-10 ng/mL 时为20.0%,小于等于4.0 ng/mL 时为7.6%。在任何一个 tPSA 值区间,PCa 组的 f/tPSA 值都明显低于非肿瘤组(平均为0.122vs.0.160,P<0.001)。接收器特性法表明,对于 tPSA 值在3.0-10 ng/mL(P<0.01)之间的病人,f/tPSA(AUC:0.664)比 tPSA(AUC:0.559)更有价值。虽然以 f/tPSA 等于0.250为分界点可能产生1.8%的 PCa 漏诊率,但是这样有可能节约9.2%不必要的组织活检。结论:对预测 PCa 发病率,f/tPSA 比单独的 tPSA 更有价值。因此,对于被称为 tPSA 灰色地带的亚洲男性来说,我们推荐在 PCa 筛查中用0.250作为 f/tPSA分界点。     

Prostate-specific antigen cut-off point of 2.5 ng/mL and increasing the number of prostate biopsies results in the detection of curable prostate cancer even in Japanese population

AIM: There is a trend for the cut-off point of Prostate-specific antigen (PSA) to be lower and the number of biopsies to be increased for detecting prostate cancer. I divided patients who visited my institution for prostate biopsy into 3 groups based on the time of examination. The results were evaluated retrospectively. METHODS: The three groups were: group A, PSA cut-off point of 4.0 ng/mL and sextant biopsy; group B, 2.5 ng/mL and 12 core biopsies; and group C, 2.5 ng/mL and saturation biopsy. I evaluated the rates of cancer detection, localized cancer, T1c, high grade cancer, major complications, insignificant cancer and the pain scores, and compared biopsy number and cancer detection rates with PSA range. Only the patients with T1c and PSA 2.6-10.0 ng/mL were evaluated about high grade cancer and insignificant cancer rates. RESULTS: Cancer detection rates, localized cancer rates and T1c rates were significantly high in group C. There were no significant differences in the high grade cancer rates, major complication rates and the insignificant cancer rates. A comparison between biopsy number and cancer detection rates was significantly high in the saturation biopsy group with PSA 4.1-10.0 ng/mL. CONCLUSION: A PSA cut-off point of 2.5 ng/mL and increasing the number of biopsies results in the increased detection of localized prostate cancer. The insignificant cancer rate, the high grade cancer rate and the complication rate were not significantly different among the groups. I recommend a PSA cut-off point of 2.5 ng/mL and an increased number of biopsies, saturation biopsy particularly in cases with PSA 4.1- 10.0 mg/mL.     

Mass screening of prostate cancer in a Chinese population：the relationship between pathological features of prostate cancer and serum prostate specific antigen

Aim: To investigate the pathological features of the prostate biopsy through mass screening for prostate cancer in a Chinese cohort and their association with serum prostate specific antigen (PSA). Methods: A total of 12027 Chinese men in Changchun were screened for prostate cancer by means of the serum total prostate specific antigen tPSA test (by Elisa assay). Transrectal ultrasound-guided systematic six-sextant biopsies were performed on those whose serum tPSA value was > 4.0 ng/mL and those who had obstructive symptoms (despite their tPSA value) and were subject to subsequent pathological analysis with the aid of the statistic software SPSS 10.0 (SPSS. Inc., Chicago. USA). Results: Of the 12027 cases, 158 (including 137 patients whose serum tPSA values were 4.0 ng/mL and 21 patients [serum tPSA < 4.0 ng/mL] who had obstructive symptoms) undertook prostate biopsy. Of the 158 biopsies, 41 cases of prostatic carcinoma were found (25.9 %, 41/158). The moderately differentiated carcinoma and poorly differentiated carcinoma accounted for 61% and 34%, respectively. A significant linear positive correlation between the serum tPSA and the Gleason scores in the 41 cases of prostatic carcinoma (r = 0.312, P < 0.01) was established. A significant linear positive correlation between the serum tPSA value of the 41 prostatic carcinoma and the positive counts of carcinoma in sextant biopsies was established (r = 0.406, P < 0.01), indicating a significant linear relationship between serum tPSA and the size of tumor. Conclusion: This study was the first to conduct mass screening for prostate cancer by testing for serum tPSA values and the first to investigate the pathological features of prostate cancer in a cohort of Chinese men. Our results reveal that the moderately differentiated carcinoma is the most common type of prostate cancer. This study also has shown that the serum tPSA value in prostate cancer is associated with the Gleason score and the size of tumor.     

Relationship between body mass index and prostate cancer screening in the United States

PURPOSE: Obesity is associated with more advanced disease and worse outcomes in men with prostate cancer. To our knowledge the relationship between obesity and prostate cancer screening behavior in men 40 or older is unknown. Thus, we examined associations between body mass index and prostate cancer screening behavior. MATERIALS AND METHODS: We used the 2002 Behavioral Risk Factor Surveillance System to study prostate cancer screening in a representative sample of 57,827 men 40 years or older. Primary outcomes were the proportion of men ever screened and the proportion screened in the last year for prostate cancer. RESULTS: Obese men were more likely than normal weight men to have had a prostate specific antigen test (62.1% vs 56.1%, p <0.001) and to have had a prostate specific antigen test in the last year (44.2% vs 38.2%, p <0.001). After controlling for sociodemographic characteristics obese men remained more likely than normal weight men to have had a prostate specific antigen test (OR 1.46, 95% CI 1.33-1.61) and to have had a prostate specific antigen test in the last year (OR 1.42, 95% CI 1.30-1.55). Respondents reporting an ongoing relationship with a physician (OR 2.88, 95% CI 2.57-3.22) and black nonHispanic men vs white men (OR 1.58, 95% CI 1.38-1.81) were also more likely to have had a prostate specific antigen test in the last year. CONCLUSIONS: Obese men are more likely than normal weight men to be screened for prostate cancer. Associations between advanced stage, worse outcomes and obesity may not be explained by disparities in the screening of obese men for prostate cancer.     

Population screening for prostate cancer: an overview of available studies and meta-analysis

The objective of the present review was to evaluate the effect of population-based screening on the incidence of prostate cancer, prostate cancer tumor stage and grade, prostate cancer mortality, and overall mortality. A systematic review was carried out in April 2011, searching the Medline and Web of Science databases. The records were reviewed to identify comparative and randomized controlled trials evaluating the effect of screening on prostate cancer. Eight trials were identified containing personalized data on a screened versus a non-screened cohort. Prostate-specific antigen and digital rectal examination were the main screening tools. Prostate-specific antigen threshold and screening interval was not uniform among the different trials. Screening was associated with a significant increase in prostate cancer detection (relative risk 1.55; P=0.002), and a significant shift towards more localized (relative risk 1.81; P=0.01) and more low-grade tumors (relative risk 2.32; P=0.001). In overall analysis, no significant effect on prostate cancer mortality (relative risk 0.88; P=0.18) and overall mortality (relative risk 0.90; P=0.27) in favor of screening was observed. An adjusted analysis excluding papers with short follow up, high prostate-specific antigen contamination in the non-screening group and low participation in the screening group was able to show a significant reduction in prostate cancer mortality of 24%. The ideal screening strategy is unclear. Screening is associated with better PC detection and this in a more localized stage and of less aggressive tumors. Excluding the main shortcomings in screening studies (short follow up, high prostate-specific antigen contamination in non-screening group and low participation in screening group), screening is able to reduce prostate cancer mortality.