Prostate cancer incidence in men with prostate-specific antigen below 3 ng/mL: The Finnish Randomized Study of Screening for Prostate Cancer

Prostate-specific antigen (PSA)-based screening for prostate cancer (PCa) can reduce PCa mortality, but also involves overdetection of low-risk disease with potential adverse effects. We evaluated PCa incidence among men with PSA below 3 ng/mL and no PCa diagnosis at the first screening round of the Finnish Randomized Study of Screening for PCa. Follow-up started at the first screening attendance and ended at PCa diagnosis, emigration, death or the common closing date (December 2016), whichever came first. Cox regression analysis was used to estimate hazard ratios and their confidence intervals (CI). Among men with PSA <3 ng/mL, cumulative PCa incidence was 9.1% after 17.6 years median follow-up. Cumulative incidence was 3.6% among men with baseline PSA 0 to 0.99 ng/mL, 11.5% in those with PSA 1.0 to 1.99 ng/mL and 25.7% among men with PSA 2 to 2.99 ng/mL (hazard ratio 9.0, 95% CI: 7.9-10.2 for the latter). The differences by PSA level were most striking for low-risk disease based on Gleason score and EAU risk group. PSA values <1 ng/mL indicate a very low 20-year risk, while at PSA 2 to 2.99 ng/mL risks are materially higher, with 4- to 5-fold risk for aggressive disease. Using risk-stratification and appropriate rescreening intervals will reduce screening intensity and overdetection. Using cumulative incidence of clinically significant PCa (csPCa) as the criterion, rescreening intervals could range from approximately 3 years for men with initial PSA 2 to 2.99 ng/mL, 6 years for men with PSA 1 to 1.99 ng/mL to 10 years for men with PSA <1 ng/mL.     

Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer: analysis of the placebo arm of the SPCG-6 study

BackgroundThe prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients with localised PCa managed on watchful waiting.Patients and methodsPatients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: ≤10, 10.1–25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen-Johansen method.ResultsTwo hundred and sixty-three patients were included of which 116, 76 and 71 had a PSA at consent ≤10, 10.1–25, and >25 ng/ml, respectively. Median follow-up was 13.6 years. For patients with PSA at consent between 10.1 and 25 ng/ml, the 13-year risks of PCa mortality were associated with PSA kinetics: PSAdt ≤3 years: 62.0% versus PSAdt >3 years: 16.3% (Gray's test: P < 0.0001), PSAvel ≥2 ng/ml/year: 48.0% versus PSAvel <2 ng/ml/year: 11.0% (Gray's test: P = 0.0008), and PSAvRC 2: 45.0% versus 0–1: 3.8% (Gray's test: P = 0.001). In contrast, none of the PSA kinetics were significantly associated with changes of 13-year risks of PCa mortality in patients with PSA at consent ≤10 or >25 ng/ml.ConclusionWe found that magnitude changes in 13-year risks of PCa mortality that can be indicated by PSA kinetics depend on PSA level in patients with localised PCa who were managed observationally. Our results question PSA kinetics as surrogate marker for PCa mortality in patients with low and high PSA values.Clinical trial numberNCT00672282.     

Disparities in prostate cancer screening,diagnoses, management,and outcomes between Indigenous and non-Indigenous men in a universal health care system

Background

Indigenous Peoples have higher morbidity rates and lower life expectancies than non-Indigenous Canadians. Identification of disparities between Indigenous and non-Indigenous men regarding prostate cancer (PCa) screening, diagnoses, management, and outcomes was sought.

Methods

An observational cohort of men diagnosed with PCa between June 2014 and October 2022 was studied. Men were prospectively enrolled in the province-wide Alberta Prostate Cancer Research Initiative. The primary outcomes were tumor characteristics (stage, grade, and prostate-specific antigen [PSA]) at diagnosis. Secondary outcomes were PSA testing rates, time from diagnosis to treatment, treatment modality, and metastasis-free, cancer-specific, and overall survivals.

Results

Examination of 1,444,974 men for whom aggregate PSA testing data were available was performed. Men in Indigenous communities were less likely to have PSA testing performed than men outside of Indigenous communities (32 vs. 46 PSA tests per 100 men [aged 50–70 years] within 1 year; p < .001). Among 6049 men diagnosed with PCa, Indigenous men had higher risk disease characteristics: a higher proportion of Indigenous men had PSA ≥ 10 ng/mL (48% vs. 30%; p < .01), TNM stage ≥ T2 (65% vs. 47%; p < .01), and Gleason grade group ≥ 2 (79% vs. 64%; p < .01) compared to non-Indigenous men. With a median follow-up of 40 months (interquartile range, 25–65 months), Indigenous men were at higher risk of developing PCa metastases (hazard ratio, 2.3; 95% CI, 1.2–4.2; p < .01) than non-Indigenous men.

Conclusions

Despite receiving care in a universal health care system, Indigenous men were less likely to receive PSA testing and more likely to be diagnosed with aggressive tumors and develop PCa metastases than non-Indigenous men.     

Baseline prostate-specific antigen measurements and subsequent prostate cancer risk in the Danish Diet,Cancer and Health cohort

AimAlthough prostate-specific antigen (PSA) screening reduces mortality from prostate cancer, substantial over-diagnosis and subsequent overtreatment are concerns. Early screening of men for PSA may serve to stratify the male population by risk of future clinical prostate cancer.Methods and materialCase–control study nested within the Danish ‘Diet, Cancer and Health’ cohort of 27,179 men aged 50–64 at enrolment. PSA measured in serum collected at cohort entry in 1993–1997 was used to evaluate prostate cancer risk diagnosed up to 14 years after. We identified 911 prostate cancer cases in the Danish Cancer Registry through 31st December 2007 1:1 age-matched with cancer-free controls. Aggressive cancer was defined as ?T3 or Gleason score ?7 or N1 or M1. Statistical analyses were based on conditional logistic regression with age as underlying time axis.ResultsTotal PSA and free-to-total PSA ratio at baseline were strongly associated with prostate cancer risk up to 14 years later. PSA was grouped in quintiles and free-to-total PSA ratio divided in three risk groups. The incidence rate ratio for prostate cancer was 150 (95% confidence interval, 72–310) among men with a total PSA in the highest quintile (>5.1 ng/ml) compared to the lowest (<0.80 ng/ml). The risk of aggressive cancer was highly elevated in men with a PSA level in the highest quintile. The results indicate that one-time measurement of PSA could be used in an individualised screening strategy, sparing a large proportion of men from further PSA-based screening.     

Informed decision making on PSA testing for the detection of prostate cancer: An evaluation of a leaflet with risk indicator

BackgroundPopulation-based screening for prostate cancer (PCa) remains controversial. To help men making informed decisions about prostate specific antigen (PSA) screening a risk indicator (www.uroweb.org) was developed. This risk indicator is embedded in a leaflet that informs men about the pros and cons of PCa screening and enables calculation of the individual risk of having a biopsy detectable PCa.AimTo assess the effect of providing a leaflet including individualized risk estimation on informed decision making of men, i.e. knowledge about PCa and PSA screening, attitude towards undergoing a PSA test and intention to have a PSA test.MethodsAn intervention study among 2000 men, aged 55–65 years, randomly selected from the population registry of the city of Dordrecht, the Netherlands, in 2008. Men were sent a questionnaire on knowledge of PCa, attitude and intention to have a PSA test. Men without a history of (screening for) PCa were sent the leaflet and Questionnaire 2 within 2 weeks after returning Questionnaire 1. Validated health and anxiety measures were used.ResultsOne thousand and twenty seven of 2000 men completed Questionnaire 1 (51%), of whom 298 were excluded due to a history of (screening for) PCa. Of the 729 remaining men, 601 completed Questionnaire 2 as well. At the second assessment significantly more men met the requirements of informed decision making (15% versus 33%, p < 0.001), more men had relevant knowledge (284/601, 50% versus 420/601, 77%, p < 0.001) and the intention to have a PSA test had increased (p < 0.001).ConclusionsProviding information on PCa screening combined with individualized risk estimation enhanced informed decision making and may be used for shared decision making on PSA screening of physicians and patients.     

Impact of Multiparametric MRI and PSA Density on the Initial Indication or the Maintaining in Active Surveillance During Follow-Up in low-Risk Prostate Cancer

IntroductionA greater selection of candidates for active surveillance (AS) of prostate cancer (PCa) may decrease the rate of delayed treatment. We aimed to study: 1) the impact of MRI and PSA density (PSAd) at baseline on the final status, and 2) the impact of bio-clinical features during the follow-up on pursuing AS.Materials and MethodsThis retrospective, monocentric study between June 2013 and July 2020, included 99 patients in AS (median follow-up: 19 months [18-92]). All MRI were reviewed by a single radiologist. Lost to follow-up were 17 patients and 6 patients chose treatment by themselves. Treatment was proposed in case of upgrading (≥ GG2) or increasing PCa volume.ResultsImpact of MRI and PSAd at baseline:  Combining PSAd ≤ 0.15 and PIRADS ≤ 3, the probability to remain in AS was 72%. This rate reached 83% when PSAd ≤ 0.10 was associated to normal MRI.  During follow-up:  One hundred fifty-seven prostatic biopsies (PBx) were performed and 38 (24%) found PCa upgrading. The association between negative MRI and PSAd ≤ 0.10, during follow-up, had an excellent NPV to predict treatment (95%). This combination concerned 25% (37/151) of surveillance biopsies that could have been avoided at the cost of delaying upgrading in 3% (1/37). In multivariate analysis, only PIRADS ≥ 4 before PBx was associated to a risk of treatment during follow-up (OR, 10.4 [95% CI, 4.2-25.8]; P < .0001).ConclusionUsing PSAd and MRI at baseline to select patients showed excellent performances to predict the maintenance in AS. During follow-up, MRI PIRADS ≥ 4 was associated to an increased risk of treatment.     

Should men with serum prostate-specific antigen < or =4 ng/ml and normal digital rectal examination undergo a prostate biopsy? A literature review

The clinical significance of a prostate cancer (PCa) cannot be determined solely by tumor volume (< or =0.5 cm(3)), as small tumors of higher Gleason grade and tumors occurring in younger men may become clinically significant even though the initial volume at diagnosis is small. A certain number of these minimal cancers are likely to remain clinically insignificant; however, it is unpredictable how many can progress beyond the curable stage by the time there is a rise in serum prostate-specific antigen (PSA) values. Compared to clinically detected PCa, PCa detected exclusively by PSA screening (clinical stage T1c) are less likely to be advanced but no more likely to be insignificant in terms of volume, pathologic stage, and Gleason pattern. Only 10-15% of PSA-detected cancers have the features of PCa found at autopsy or in cystoprostatectomy specimens. Actually, 25-30% of PCa are detected with PSA values between 2.5 and 4 ng/ml, and most of these cancers are clinically significant. Evidence from both retrospective and longitudinal studies has shown that the risk of a PCa is dependent on the patient's age and the initial serum PSA. This allows an individualized approach to PCa screening programs, and PSA cutoff values for biopsy indication may be lowered in selected patients.     

The Finnish prostate cancer screening trial: Analyses on the screening failures

Prostate cancer (PC) screening with prostate‐specific antigen (PSA) has been shown to decrease PC mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). However, in the Finnish trial, which is the largest component of the ERSPC, no statistically significant mortality reduction was observed. We investigated which had the largest impact on PC deaths in the screening arm: non‐participation, interval cancers or PSA threshold. The screening (SA) and control (CA) arms comprised altogether 80,144 men. Men in the SA were screened at four‐year intervals and referred to biopsy if the PSA concentration was ≥4.0 ng/ml, or 3.0–3.99 ng/ml with a free/total PSA ratio ≤16%. The median follow‐up was 15.0 years. A counterfactual exclusion method was applied to estimate the effect of three subgroups in the SA: the non‐participants, the screen‐negative men with PSA ≥3.0 ng/ml and a subsequent PC diagnosis, and the men with interval PCs. The absolute risk of PC death was 0.76% in the SA and 0.85% in the CA; the observed hazard ratio (HR) was 0.89 (95% confidence interval (CI) 0.76–1.04). After correcting for non‐attendance, the HR was 0.78 (0.64–0.96); predicted effect for a hypothetical PSA threshold of 3.0 ng/ml the HR was 0.88 (0.74–1.04) and after eliminating the effect of interval cancers the HR was 0.88 (0.74–1.04). Non‐participating men in the SA had a high risk of PC death and a large impact on PC mortality. A hypothetical lower PSA threshold and elimination of interval cancers would have had a less pronounced effect on the screening impact.     

Editorial comments

Ninety-nine of 105 consecutive men who underwent transrectal prostatic ultrasound (TRUS) at Highland Park Hospital had the results correlated with digital rectal examination (DRE), serum prostate specific antigen (PSA), and biopsy results. Ninety-six cases had evaluable ultrasound studies. Thirty-two of the 99 who underwent biopsy had primary carcinoma of the prostate. Prostate volume, predicted PSA, a ratio of observed/predicted PSA, and Gleason score were examined. There was no correlation between age and prostate volume, volume and the presence of carcinoma, or PSA and Gleason score. Thirty-one point six percent of the abnormal DREs, 36.6% of the abnormal TRUSs, and 40.6% of the elevated PSAs occurred in men with prostatic carcinoma (PCa). If PSA was normal (less than or equal to 4.0 ng/ml) and either DRE or TRUS was abnormal, then the risk of carcinoma was 2.9%. If PSA was elevated, regardless of the other two tests, the risk of finding PCa was at least 38%. If all three tests were abnormal, the risk of carcinoma was 38% in our series and 68% in a meta-analysis. Many men with PSA values between 4 and 10 ng/ml have benign biopsies. However, close future follow-up with consideration of repeat biopsy should be strongly considered. © 1994 Wiley-Liss, Inc.     

应用前列腺特异抗原筛查诊断前列腺癌的临床意义

目的 探讨应用前列腺特异抗原(PSA)筛查诊断前列腺癌的临床意义.方法 对年龄≥50岁的8562例男性体检者进行PSA筛查,对血清PSA≥4.0 ng/ml者建议进行经直肠前列腺系统活检,活检病理确诊为前列腺癌的患者人选筛查组,记录其临床病理特点,并与同时期临床诊治的82例前列腺癌患者(临床组)进行比较.结果 在8562例进行血清PSA筛查的男性中,有719例血清PSA水平≥4.0 ng/ml,其中295例接受经直肠前列腺系统活检,共检出前列腺癌58例,活检率和活检阳性率分别为41.0%和19.7%.虽然两组患者的年龄分布差异无统计学意义(P=0.176),但筛查组中有41.4%(24/58)的患者年龄＞75岁,明显高于临床组(25.6%,P=0.0491).筛查组中血清PSA水平≥20.0 ng/ml的患者所占的比例为44.8%,明显低于临床组(75.6%,P＜0.0001).筛查组中活检Gleason评分＜7分的患者所占的比例为60.3%,明显高于临床组(34.1%,P=0.0020).筛查组中临床分期为T1和T2期(局限期)患者所占的比例为87.9%,明显高于临床组(26.8%,P＜0.0001).筛查组中接受根治性前列腺切除术的患者所占的比例为50.0%,明显高于临床组(18.3%,P＜0.0001).在年龄≤75岁的患者中,筛查组患者诊断时的血清PSA水平、活检Gleason评分和临床分期均显著低于临床组(均P＜0.05);在年龄＞75岁的患者中,筛查组患者的临床分期也明显低于临床组(P=0.0002),但两组诊断时血清PSA水平和活检Gleason评分的差异并无统计学意义(均P＞0.05).结论 应用血清PSA在我国50岁以上男性中进行前列腺筛查是有效的.筛查出的前列腺癌患者在血清PSA水平、活检Gleason评分、临床分期以及根治性切除的机会等方面均较临床组有明显优势.     

Clinical and pathological characteristics of screen-detected versus clinically diagnosed prostate cancer in Nanjing, China

Previous studies have suggested that implementation of PSA screening in China is of crucial importance. This study compared clinical and pathological characteristics of screen-detected and clinically diagnosed prostate cancers and evaluated the effectiveness of PSA screening for early detection of prostate cancer in Nanjing. Between July 2004 and December 2005, 8,562 men aged ≥50 years were included for PSA screening. Participants with serum PSA ≥4.0 ng/ml were recommended for transrectal ultrasonography (TRUS)-guided prostate needle biopsy (TRNB). During the same period, 82 consecutive clinically diagnosed prostate cancers were included as controls. The clinical and pathological features of the screened versus clinically diagnosed cancers were evaluated. A total of 719 (8.4%) of screened men had PSA levels ≥4.0 ng/ml. Biopsy was performed in 295 men, and 58 prostate cancers were detected. The biopsy rate, positive predictive value (PPV), and detection rate were 41.0, 19.7, and 0.68%, respectively. More screened patients were found with PSA levels <20 ng/ml (55.2 vs. 22.4%, P < 0.001), Gleason scores <7 (60.3 vs. 34.1%, P = 0.002), organ-confined tumors (87.9 vs. 26.8%, P < 0.001), and opportunities for radical prostatectomy (50.0 vs. 18.3%, P < 0.001) than that in clinically diagnosed patients. PSA screening is effective for early detection of prostate cancer in Chinese elderly men. Favorable PSA levels, Gleason scores, clinical stages, and chances for radical prostatectomy are associated with PSA screening. Further studies are needed to evaluate the effect of screening on treatment outcomes and mortality of prostate cancer in Chinese.     

Optimal prostate-specific antigen screening interval for prostate cancer

BackgroundTo identify the optimal interval for repeat prostate-specific antigen (PSA) testing to screen for prostate cancer in healthy adults.Patients and methodsA retrospective cohort study was conducted on 7332 healthy males without prostate cancer at baseline from 2005 to 2008. Participants underwent annual health checkups including PSA testing at the Center for Preventive Medicine in Japan. Participants with high PSA (≥4.0 ng/ml) underwent further examination for prostate cancer. A subgroup analysis was conducted age group (<50 years, ≥50 years).ResultsMean age was 50 years. Mean PSA at baseline was 1.2 ng/ml. In over 50-year group, for those with initial PSA of <1.0, 1.0–1.9, 2.0–2.9, and 3.0–3.9 ng/ml at baseline, the 3-year cumulative incidence of prostate cancer was 0%, 0.1%, 0.3%, and 5.7%, respectively. No prostate cancer was identified in those <50 years, regardless of PSA level.ConclusionsIf PSA screening is recommended, males >50 years with PSA of 3.0–3.9 ng/ml at baseline should undergo rescreening at 2 years. For men with PSA <3.0 ng/ml, PSA rescreening at intervals of ≥3 years is appropriate. PSA screening may not be indicated in males of <50 years of age.     

PSA-gestützte Früherkennung

Background

In the recent European randomized study of screening for prostate cancer (ERSPC), prostate-specific antigen (PSA)-based screening was shown to reduce the relative prostate cancer-specific mortality by up to 32?%. This advantage, however, was at the expense of substantial overdiagnostics and overtreatment. With economic factors also taken into account, a general PSA screening is not considered advisable. Despite this evaluation PSA remains the best tumor marker to meet the needs of the individual patient to reduce the risk of developing prostate cancer.

Results and conclusions

A risk-adapted PSA screening in a well-defined age group could represent a potentially better trade off in this situation. Studies have shown a strong correlation between absolute PSA values relatively early in life and the risk of developing prostate cancer decades later. Thus risk stratification can be performed according to the individual baseline PSA by identifying high-risk patients early while protecting those at lower risk from overtreatment and overtherapy. The prospectively randomized PROBASE study examines the optimal time to assess this baseline PSA level. Furthermore the study evaluates the ideal time schedule for such an intelligent PSA screening.     

Cumulative probability of PSA increase above 4.0 NG/ML in population-based screening for prostate cancer

Routine screening for prostate cancer remains controversial. However, it is very important to show how the optimal rescreening interval should be set for men who want to be screened after informed consent. To solve this issue, the risk of prostate-specific antigen (PSA) increase above 4.0 ng/ml relative to baseline PSA levels and age was investigated. Between 1988 and 2000, 7,757 subjects screened twice or more and also with baseline PSA levels of 4.0 ng/ml or lower were enrolled in our study. All serum PSA levels were measured by E-test Tosoh II PA assay at one center. Interval PSA levels for men undergoing screening with a greater than 1 year interval were calculated on the assumption that PSA levels changed over time in a simple exponential fashion. Then, the cumulative rate of freedom from PSA increase above 4.0 ng/ml was estimated using the Kaplan-Meier technique stratified by baseline PSA ranges of 0.0 to 1.0, 1.1 to 2.0, 2.1 to 3.0 and 3.1 to 4.0 ng/ml and every 10 years of age ranges. Of the 7,757 subjects, 559 (7.2%) were expected to have had PSA levels increase above 4.0 ng/ml within 5 years after the baseline PSA measurements. The cumulative rate of freedom from the PSA increase above 4.0 ng/ml at 5 years was 98.7%, 92.9%, 70.3% and 38.5% in cases of baseline PSA levels of 1.0 ng/ml or lower, 1.1 to 2.0 ng/ml, 2.1 to 3.0 ng/ml and 3.1 to 4.0 ng/ml, respectively. The cumulative rates of freedom from the PSA increase were significantly decreased with the baseline PSA ranges being higher regardless of age range. Re-screening interval should be set stratified by baseline PSA levels, regardless of age and race. Rescreening interval should be set at 1, 1 to 2 and 3 to 5 years for men with baseline PSA ranges of 2.1 to 4.0 ng/ml, 1.1 to 2.0 ng/ml and 0.0 to 1.0 ng/ml, respectively, in individual-based screening. In mass screening system using PSA alone, rescreening interval should be set in the same manner as in individual-based screening, except for men with baseline PSA levels of 1.1 to 2.0 ng/ml, which should be set at 1 year to avoid developing incurable prostate cancer.     

Do the risk factors of age,family history of prostate cancer or a higher prostate specific antigen level raise anxiety at prostate biopsy?

To date, little is known of the impact knowledge of personal risk factors has on anxiety in men undergoing biopsy tests for prostate cancer. This analysis explores anxiety scores of men at higher risk due to age, family history of prostate cancer and a higher prostate specific antigen (PSA) level when proceeding from PSA test to prostate biopsy. A prospective cohort of 4198 men aged 50–69 years with a PSA result of >3 ng/ml was studied, recruited for the Prostate testing for cancer and Treatment study (ProtecT). Anxiety scores at the time of biopsy were lower in older men (p < 0.001). No age group showed an increase in anxiety as the men proceeded from PSA testing to biopsy, although older men did not show the same level of decrease in anxiety as younger men (p = 0.035). There was no difference in anxiety scores at biopsy between men with or without a family history of prostate cancer (p = 0.68), or between those with a raised PSA of 10–<20 ng/ml compared to a PSA result of 3–<10 ng/ml (p = 0.46). Change in scores since the initial PSA test appeared unaffected by family history (p = 0.995) or by PSA result (p = 0.76). Within the context of a research study, the increased risk of prostate cancer through older age, having a family history of prostate cancer, or having a significantly elevated PSA level appears to have no detrimental effect on men’s anxiety level when proceeding to biopsy.     

Maximum Tumor Diameter and the Risk of Prostate-Specific Antigen Recurrence After Radical Prostatectomy

Introduction/BackgroundThe aim of this study was to investigate whether the MTD could identify men at low risk of PSA recurrence after RP who might not benefit from ART despite other adverse features.Patients and MethodsThe study cohort consisted of 354 men with T1c to T2 prostate cancer diagnosed between September 2001 and December 2008 who underwent RP without adjuvant therapy. Multivariable Cox regression was used to assess the effect of MTD on the risk of PSA recurrence (> 0.1 ng/mL and verified), adjusting for known predictors.ResultsAfter a median follow-up of 4.0 years, 34 men (9.6%) experienced PSA failure. In multivariable analysis, increasing MTD was significantly associated with an increased PSA recurrence risk (hazard ratio, 2.74; 95% confidence interval, 1.23-6.10; P = .01) within the interaction model. Estimates of PSA recurrence-free survival stratified around the median MTD value (1.2 cm) were significantly different in men with a pre-RP PSA > 4 ng/mL (P < .001; 5-year estimate: 74.5% vs. 99.0%) but not in men with PSA ≤ 4 ng/mL (P = .59; 5-year estimate: 89.6% vs. 92.6%), consistent with the significant interaction (P = .004) between PSA and MTD. Moreover, in men with a pre-RP PSA > 4 ng/mL these estimates were significantly different if at least 1 adverse feature (pT3, R1, or Gleason score ≥ 8) was present at RP (P = .01; 5-year estimate: 46.6% vs. 100%) versus none (P = .09; 5-year estimate: 93.4% vs. 98.9%).ConclusionMen with a low MTD (≤ 1.2 cm) appear to be at low risk of PSA recurrence despite adverse features at RP and might not benefit from ART.     

Utility of Digital Rectal Examination,Serum Prostate Specific Antigen,and Transrectal Ultrasound in the Detection of Prostate Cancer: A Developing Country Perspective

Purpose: To determine the utility of digital rectal examination (DRE), serum total prostate specific antigen(tPSA) estimation, and transrectal ultrasound (TRUS) for the detection of prostate cancer (PCa) in men withlower urinary tract symptoms (LUTS). Materials and Methods: All patients with abnormal DRE, TRUS, or serumtPSA >4ng/ml, in any combination, underwent TRUS-guided needle biopsy. Eight cores of prostatic tissue wereobtained from different areas of the peripheral prostate and examined histopathologically for the nature of thepathology. Results: PCa was detected in 151 (50.3%) patients, remaining 149 (49.7%) showed benign changeswith or without active prostatitis. PCa was detected in 13 (56.5%), 9 (19.1%), 26 (28.3%), and 103 (74.6%) ofpatients with tPSA <4 ng/ml, 4-10 ng/ml, 10-20 ng/ml and >20 ng/ml respectively. Only 13 patients with PCahad abnormal DRE and TRUS with serum PSA <4 ng/ml. The detection rate was highest in patients with tPSA>20 ng/ml. The association between tPSA level and cancer detection was statistically significant (p<0.01). Among209 patients with abnormal DRE and raised serum PSA, PCa was detected in 128 (61.2%). Conclusions: Theincidence of PCa increases with increasing serum level of tPSA. The overall screening and detection rate can befurther improved by using DRE, TRUS and TRUS-guided prostate needle biopsies.     

PSA-basierte Prostatakarzinom-Früherkennung

Background

Prostate-specific antigen (PSA)-based early detection of prostate cancer has resulted in a reduction of prostate cancer-specific mortality of 27?%; however, population-based PSA screening has been critisized for a relatively high rate of overdiagnosis and overtreatment. New results on the significance of an early PSA baseline value at the age of 40–45 years, clinical risk factors, molecular and new imaging procedures have the potential to individualize and to greatly improve screening for prostate cancer.

Aim, material and methods

This review article presents the currently available data and gives recommendations for the practical approach. A semiquantitative literature search was performed with special emphasis on studies from the last 2 years.

Results

Current data confirm the prognostic value of a baseline PSA value at the age of 45–50 years. This represents one of four possible risk-adapted screening approaches. This strategy is currently being tested in a prospective randomized trial in Germany with 50,000 men (PROBASE). The other modalities of risk-adapted screening have not yet been shown to be applicable in practice but together with clinical parameters, molecular profiles and modern magnetic resonance imaging (MRI), early detection programs will be improved in the future.

Discussion

Even now, a baseline PSA-based risk-adapted screening strategy can reduce the number needed to screen. With active surveillance and modern multiparameter MRI the number needed to treat has also already been decreased.

     

Clinical Significance of Prostate Specific Antigen for Early Stage Prostate Cancer Detection

The characteristics of serum prostate specific antigen (PSA)in normal Japanese men were studied in 1480 subjects examinedby mass screening (MS) for prostate cancer (Pea) in Gunma Prefecturein 1992. The serum PSA concentration was correlated with patientage. The average serum PSA level increased by 0.04 ng/ml/year.The upper normal limits (95 percentiles)of age specific PSAfor normal men are 1.33 ng/ml for those aged 39–49 years,3.65 ng/ml for those aged 50–59 years, 4.06 ng/ml forthose aged 60–69 years, 5.09 ng/ml for those aged 70–79years and 5.66 ng/ml for those aged 80–89 years. Among227 normal men examined by our MS in 1991 and 1992, the PSAvelocity (PSAV) was calculated to be 0.05 ng/ml/year. Among10 Pea patients with normal PSA levels ( < 6 ng/ml) detectedpreviously by our MS, three had an abnormal PSAV. We demonstratedthe possibility that PSA density could distinguish between Peaand benign prostate hypertrophy. The significance of PSA asa Pea screening modality should be evaluated across multipleage ranges and in combination with previous PSA data and/orprostate volume estimated by sonography.     

On the use of prostate-specific antigen for screening of prostate cancer in European Randomised Study for Screening of Prostate Cancer

Prostate-specific antigen (PSA) has been the main drive for early detection of prostate cancer (PCa), including in population-based screening as in the European Randomised Study for Screening of Prostate Cancer (ERSPC). The specificity of PSA to indicate men with biopsy detectable prostate cancer can be improved by adding information obtained by new biomarkers, such as PSA isoforms. This improvement is needed to increase the efficacy of the screening procedure for the population-based as well as the individual screening. Various PSA isoforms, kallikreins and molecular markers have been validated in various cohorts from ERSPC of men with and without PCa in order to design the optimal diagnostic procedure for screening asymptomatic men. So far, most promising results have been obtained from the analysis of free PSA, proPSA, nicked PSA and hK2. The use of free PSA in addition to total PSA reduces the number of negative sextant biopsies at a PSA cut-off level of 3 ng/ml at initial screening with 30%, at the cost of losing 10% of detectable cancers that are predominantly well differentiated on histology. Further addition of PSA isoforms and hK2 only improve ROC curves in selected samples by a maximum of 5%. Molecular markers like PCA3 and TMPRSS2 in urine do not appear to be useful but they have been assessed insufficiently so far. The level of PSA at initial screening is highly predictive for the chance of being diagnosed with PCa later on in life. The changes in PSA over time after initial screening (like PSA-velocity and PSA-doubling time) are statistically different between men with detectable cancers versus those without (PSA-doubling time 5.1 versus 6.1 years), but this does not contribute significantly to population-based screening overall. Changes in specificity need to be related to a cost efficacy evaluation in the final analysis of ERSPC.