The feasibility and results of a population-based approach to evaluating prostate-specific antigen screening for prostate cancer in men with a raised familial risk

The feasibility of a population-based evaluation of screening for prostate cancer in men with a raised familial risk was investigated by studying reasons for non-participation and uptake rates according to postal recruitment and clinic contact. The levels of prostate-specific antigen (PSA) and the positive predictive values (PPV) for cancer in men referred with a raised PSA and in those biopsied were analysed. First-degree male relatives (FDRs) were identified through index cases (ICs): patients living in two regions of England and diagnosed with prostate cancer at age < or =65 years from 1998 to 2004. First-degree relatives were eligible if they were aged 45-69 years, living in the UK and had no prior diagnosis of prostate cancer. Postal recruitment was low (45 of 1687 ICs agreed to their FDR being contacted: 2.7%) but this was partly due to ICs not having eligible FDRs. A third of ICs in clinic had eligible FDRs and 49% (192 out of 389) agreed to their FDR(s) being contacted. Of 220 eligible FDRs who initially consented, 170 (77.3%) had a new PSA test taken and 32 (14.5%) provided a previous PSA result. Among the 170 PSA tests, 10% (17) were > or =4 ng ml(-1) and 13.5% (23) tests above the age-related cutoffs. In 21 men referred, five were diagnosed with prostate cancer (PPV 24%; 95% CI 8, 47). To study further the effects of screening, patients with a raised familial risk should be counselled in clinic about screening of relatives and data routinely recorded so that the effects of screening on high-risk groups can be studied.     

f/T-PSA比值和PSA密度对TPSA灰区前列腺癌的诊断意义

目的探讨游离前列腺特异抗原/总前列腺特异抗原(fPSA/TPSA,f/T)比值和TPSA灰区前列腺特异抗原密度(PSAD)(4.0~10.0ng/m l)对诊断前列腺癌的临床意义。方法回顾性分析TPSA在灰区的38例前列腺癌和56例良性前列腺增生症血清PSA相关检测结果,将两组患者f/T比值和PSAD值进行对比分析。结果两组患者TPSA值无显著性差异(P=0.337);f/T比值(P=0.001)和PSAD值(P=0.012)有显著性差异。f/T比值在前列腺癌患者中较低,而PSAD值较高。当f/T比值和PSAD分别以0.15和0.16作为临界值时,其诊断前列腺癌的灵敏度和特异度分别为81.6%和75.0%、65.8%和57.1%。结论f/T比值和PSAD对TPSA灰区的前列腺癌的诊断有重要的临床意义。     

Adding free to total prostate-specific antigen levels in trials of prostate cancer screening

We used a nested case-control design on data from men in four prospective studies (from the UK, Maryland in the USA, and two from Finland) with available stored serum samples to determine whether there was an advantage in measuring both free prostate-specific antigen (PSA) and total PSA as a potential screening test for prostate cancer. Of these men, 247 were verified through national vital statistics offices as having died of prostate cancer, or having developed the disease, and 953 men who did not develop prostate cancer (controls) were selected, matched to cases for age, study centre and sample storage duration. Fixing the false-positive rate at 1%, the prostate cancer detection rate (sensitivity) over the 3 years following serum collection (based on 14 cancers) increased from an estimated 95% using total PSA to 97% using free and bound PSA (that is, bound to alpha-antichymotrypsin which together with the free form is total PSA). Over a 6-year period (based on 41 cancers) a similar difference occurred (52% and 56% detection rates respectively). We conclude that there is no material advantage in adding free to total PSA in prostate cancer screening trials.     

Specificity of serum prostate-specific antigen determination in the Finnish prostate cancer screening trial

Specificity constitutes a component of validity for a screening test. The number of false-positive (FP) results has been regarded as one of major shortcomings in prostate cancer screening. We estimated the specificity of serum prostate-specific antigen (PSA) determination in prostate cancer screening using data from a randomised, controlled screening trial conducted in Finland with 32 000 men in the screening arm. We calculated the specificity as the proportion of men with negative findings (screen negatives, SN) relative to those with negative and FP results (SN/(SN+FP)). A SN finding was defined as either PSA相似文献   

PSAT 在前列腺穿刺活检中的意义

目的:探讨前列腺移行带特异性抗原密度(PSAT)在前列腺穿刺活检中的意义。方法:对120例患者行前列腺穿刺活检,其中PSA≥4ng/ml者105例,PSA<4ng/ml且直肠指诊及经直肠B超有阳性发现者15例。对PSA、PSAD和PSAT与前列腺穿刺活检的关系进行分析。结果:120例患者中经前列腺穿刺诊断为前列腺癌(PCa)63例,活检阳性率52.5,其中15例PSA<4ng/ml者中,活检结果为前列腺横纹肌肉瘤1例,前列腺小细胞癌2例,腺癌4例,良性前列腺增生8例;42例>20ng/ml者中32例为PCa,活检阳性率76.2;63例PSA4-20ng/ml者中24例为PCa,活检阳性率38.1;29例PSA4-10ng/ml者中10例为PCa,活检阳性率34.5。血清PSA4-20ng/ml患者,PSAD≥0.13或PSAT≥0.15时,敏感性均为100,特异性为20.5或17.9,阳性预测值为43.6或42.9,可避免12.7(8/63)或11.1(7/63)阴性穿刺结果。血清PSA4-20ng/ml时,前列腺穿刺阳性组和阴性组PSA分别为11.18±4.49和10.05±4.29ng/ml(P=0.318);PSAD分别为0.45±0.33和0.26±0.15(P=0.003);PSAT分别为0.94±0.65和0.43±0.24(P=0.000)。血清PSA、PSAD和PSAT的ROC曲线下面积分别为0.576、0.676和0.77,PSAT的ROC曲线下面积与PSA比较,差异均有统计学意义(P<0.05)。结论:PSA4-20ng/ml时,PSAT对预测患者是否行前列腺穿刺活检有较大帮助。     

The Significance of PSA Modified Parameters （F/T）/ PSAD for Diagnosing Prostatic Cancer in the Grey Zone of 4-10 ng/ml

OBJECTIVE To investigate the diagnostic value of modified prostate specific antigen(PSA)parameters in the diagnosis of prostate cancer(PCA) when the serum PSAis in a grey zone of 4~10 ng/ml. METHODS The results of serum PSA determinations of the patients receiving a transrectal ultrasound-guided multiphase prostatic biopsy,were retrospectively analyzed.In the 88 patients with a serum PSA value of 4-10 ng/ml,the final diagnosis of PCA was made in 21,and that of benign prostate hyperplasia(BPH)in 67 patients.The percentage of the free-serum PSA([FPSA]/total-serum PSA[TPSA],F/T),PSA density(PSAD)and the sensitivity and specificity of the new PSA modified parameter(F/T)/PSAD in diagnosing PCA,within a set threshold value,was compared. RESULTS In the 88 patients with serum PSA in the grey zone of 4.0-10.0 ng/ml,there was no significant difference in comparing the TPSA between the 21 PCA patients and 67 BPH patients(P>0.05).However, there was a significant difference in the value of modified PSA parameters, such as F/T,PSAD and(F/T)/PSAD,between the PCA and the BPH groups (P<0.001).As the cut off point-value of the F/T,PSAD and(F/T)/PSAD was set at 0.16,0.15 and 0.8,the diagnostic sensitivity for PCA was 66.7%, 76.2%and 85.7%,and the specificity was 41.8%,43.3%and 68.7%,respectively.There was no significant difference in the sensitivity comparing the modified parameters for diagnosing PCA(P>0.05),whereas an overt predominance was present in the specificity of(F/T)/PSAD for PCAdiagnosis (P<0.05). CONCLUSION In the serum PSA grey zone of 4-10 ng/ml,a modified PSA parameter can improve the PCA diagnostic accuracy rate.With a considerably high sensitivity,application of the(F/T)/PSAD may effectively enhance the diagnostic specificity,which is superior to the F/T and PSAD, and can be expected to be one of the new indices derived from the PSA.     

Efficiency of ultrasensitive prostate-specific antigen assay in diagnosing biochemical failure after radical prostatectomy

BACKGROUND: Ultrasensitive prostate-specific antigen (PSA) is a significant serum biomarker for identifying the PSA nadir and early biochemical failure after radical prostatectomy (RP). We assessed the efficiency of ultrasensitive PSA assay in the follow-up after RP. METHODS: We generated longitudinal ultrasensitive PSA data using a computer program assuming that patients experienced biochemical failure after RP. The simulation experiments, based on several different scenarios, were performed to assess the sensitivity and specificity in the diagnosis of biochemical failure using ultrasensitive PSA values and to estimate the lead time, which is the time advantage of detecting positivity for biochemical failure using the ultrasensitive PSA values compared with conventional PSA assay. We validated the sensitivity, specificity and lead time using actual follow-up data of 182 patients receiving RP. RESULTS: It was suggested that the sensitivity obtained from the actual data was more similar to that obtained using ultrasensitive PSA with an exponential increase than with a linear increase in the simulation experiments. Diagnosing biochemical failure based on two consecutive increases in the ultrasensitive PSA values was not recommended. Of non-biochemical failure patients, 9.4% showed four consecutive increases in their ultrasensitive PSA values. Average lead time in the actual data was 11.2 months (SD: 10.1). CONCLUSIONS: For an accurate diagnosis of biochemical failure, our findings suggest the importance of a certain duration of follow-up and exclusion of false-positive results afterwards.     

Flow cytometric DNA analysis of fresh prostatic resections: Correlation with conventional prognostic parameters in patients with prostate cancer

Background. DNA ploidy analysis has been investigated as a prognostic indicator in prostate cancer. Most of the data is derived from retrospective studies using paraffin-embedded tissue. This method has drawbacks related to the quality of DNA histograms and uncontrolled data collection. Methods. DNA ploidy analysis of freshly resected prostatic tissue was prospectively compared with conventional prognostic variables in 97 men treated with radical prostatectomy for localized prostate cancer. Results. Regarding the patients, 31.9% were African American and 66% had pathologic Stages C or D1 disease. Only 9.6% of patients with Stages A2 and B had a prostate-specific antigen (PSA) value greater than 10 ng/ml, whereas 97% of patients with PSA values greater than 20 ng/ml had pathologic Stages C and D1. PSA levels correlated with Gleason score (P = < 0.05); 51% and 100% of patients with Gleason score 5–7 and 8–10, respectively, had PSA values greater than 10 ng/ml. Twenty-two patients (23%) had DNA aneuploid tumors. Comparisons of mechanical to enzymatic cell suspensions indicated that DNA aneuploidy was better preserved in mechanical cell preparations. DNA ploidy correlated with pathologic stage (P = < 0.05) and Gleason score (P = < 0.05). Fifteen of 79 patients (18.9%) with Gleason score 5–7 had DNA aneuploid tumors versus 71.4% of patients with Gleason score 8–10. PSA groups correlated with ploidy status (P = 0.01). Although the majority of patients (19 of 22) with DNA aneuploid tumors had elevated preoperative PSA levels, none had a PSA value greater than 50 ng/ml. Conclusions. DNA ploidy analysis correlated with established prognostic indicators in prostate cancer; however, its independent correlation with natural history and treatment outcome must be established for it to have an effect on therapeutic decisions.     

Results of the three rounds of the Finnish Prostate Cancer Screening Trial—The incidence of advanced cancer is decreased by screening

Screening for prostate cancer (PC) remains a controversial issue despite some new evidence on the mortality benefits of PC screening. We conducted a prospective, randomized screening trial in Finland to investigate whether screening decreases PC incidence. Here, we report the incidence results from three screening rounds during a 12‐year period. Of the 80,144 men enrolled, 31,866 men were randomized to the screening arm (SA) and invited for screening with prostate‐specific antigen test (cut‐off 4.0 ng/ml) every 4 years, while the remaining men formed the control arm (CA) that received no interventions. The mean follow‐up time for PC incidence in both arms was over 9 years. The incidence rate of PC (including screen‐detected and interval cancers as well as cases among nonparticipants) was 9.1 per 1,000 person‐years in the SA and 6.2 in the CA, yielding an incidence rate ratio (IRR) 1.5 (95% confidence interval 1.4–1.5). The incidence of advanced PC was 1.1 in the SA and 1.5 in the CA, IRR = 0.7 (0.6–0.8) and the difference emerges after 5–6 years of follow‐up. The incidence of localized PC was 7.5 in the SA and 4.6 in the CA, IRR = 1.6 (1.5–1.7). The results from our large population‐based trial indicate that screening for PC decreases the incidence of advanced PC. When compared with the CA, the PC detected in the SA there were substantially more often localized, low‐grade PCs due to overdiagnosis.