Lead time associated with screening for prostate cancer

Screening serum levels of prostate-specific antigen (PSA) is now a major strategy for early detection of prostate cancer (PC). Quantification of the lead time thus obtained is important both for understanding the development of PC and for evaluating the advantages and disadvantages of widespread screening. In our study, 1,233 randomly selected men living in Stockholm in 1988 were invited to participate in an early detection (ED) program, in which suspicious findings provided by digital rectal examination (DRE), transrectal ultrasonography (TRUS) and/or a PSA value >/=10.0 ng/mL were followed up by biopsy. The cumulative incidence (Kaplan-Meier) of PC in the 946 participants (ED) during 12 years of follow-up was compared to that of an age-matched, randomly selected reference population (RP) of 657 men for whom PSA values (from frozen serum samples) could also be obtained. The PC incidence in men in the RP with PSA values >/=3.0 ng/mL reached the corresponding level for the ED group after 10.6 years (the "catch-up" point). After 12 years of follow-up, the estimated median lead time for men with PSA values in this interval was 4.5 years in the ED population, compared to 7.8 years in the RP. With 20 years of follow-up, the estimated median lead time of the RP was enhanced to 10.7 years. The lead time in connection with PC was influenced by the initial PSA level (although with large variations), length of follow-up and sensitivity of the ED procedure employed. The ED program described here was not associated with major overdetection.     

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。     

血清铁蛋白联合前列腺特异性抗原检测对前列腺癌的诊断价值

目的探讨血清铁蛋白(Ferr)、总前列腺特异性抗原(tPSA)、游离前列腺特异性抗原(f PSA)、fPSA/tPSA联合检测对前列腺癌(PCa)的诊断价值。方法选择90例PCa患者、84例前列腺良性病变患者和50例健康男性体检者分别作为PCa组、良性组和对照组,检测3组研究对象的血清Ferr、tPSA、fPSA水平并计算fPSA/tPSA,分析Ferr、tPSA、fPSA、fPSA/tPSA联合检测对PCa的诊断价值。结果PCa组患者的血清Ferr、tPSA、fPSA水平均高于良性组和对照组,fPSA/tPSA低于良性组和对照组,差异均有统计学意义(P﹤0.05)。良性组患者的血清Ferr、tPSA、fPSA水平均高于对照组,fPSA/tPSA低于对照组,差异均有统计学意义(P﹤0.05)。PCa患者的血清Ferr与tPSA、fPSA均呈正相关,tPSA与f PSA呈正相关,tPSA与fPSA/tPSA呈负相关(P﹤0.05)。血清Ferr、tPSA、fPSA、fPSA/tPSA联合检测诊断PCa的灵敏度、特异度、曲线下面积均高于四个指标的三联、两联、单独检测。结论PCa患者的血清Ferr、t PSA、fPSA水平均高于前列腺良性病变患者,fPSA/tPSA低于前列腺良性病变患者。血清Ferr、tPSA、f PSA、f PSA/tPSA联合检测对PCa具有较高的诊断价值,值得在临床中推广应用。     

Negative influence of changing biopsy practice patterns on the predictive value of prostate-specific antigen for cancer detection on prostate biopsy

BACKGROUND: A correlation between prostate specific antigen (PSA) level and positive prostate biopsy rate was established in an era when biopsy practice patterns were different from what they are today. We evaluated if changes in biopsy practice patterns have affected the ability of PSA to predict cancer detection on prostate biopsy in the current era. METHODS: Of 3634 prostate biopsies performed from 1993-2005, 1607 met criteria for analysis. Biopsy data were divided into 3 time-cohorts (1993-1997, 1998-2001, and 2002-2005) to assess for practice patterns shifts and correlation between PSA and biopsy results. RESULTS: Significant changes in biopsy practice patterns included an increase in biopsy cores and more frequent use of PSA 2.5-3.99 ng/mL as a biopsy indication. In men with normal DRE, a moderate correlation between PSA and positive biopsy rate did exist from 1993-1997, but was subsequently lost. On multivariate analysis, PSA was not a significant predictor of biopsy result in men with normal DRE. CONCLUSIONS: Early in the PSA era, the predictive power of PSA depended on multiple factors: high prevalence of disease, higher prevalence of high-grade disease, and low likelihood of prostate cancer diagnosis in men with low PSA. Now, beyond the culling effect of increased biopsy incidence and with shifted biopsy practice patterns, the correlation between PSA and biopsy result is lost in men with normal DRE. Diagnosing a higher proportion of tumors in men with a PSA between 2.0-4.0 ng/mL has negatively influenced the predictive value of PSA for cancer detection.     

The Relationship of PSA, PSAD and Clinicopathological Stage in Patients with Prostate Cancer

OBJECTIVE To investigate the relationship between the clinicopatho- logical stage and serum prostate specific antigen(PSA)concentration and PSAdensity(PSAD)in patients with prostate cancer. METHODS The clinicopathological stage was determined on the basis of a pathological examination and clinical data in 65 prostate cancer patients treated by radical prostatectomy.PSA and PSAD were measured before the operation.The Spearman rank correlation was applied to evaluate the relationship between the clinicopathological stage,serum PSAconcentration and PSAD. RESULTS Patients with higher PSA and PSAD were significantly more likely to have higher clinical stages,a higher Gleason score,positive surgical margins,capsular penetration,and seminal vesicle invasion(each P<0.05). But there was no significant association between PSA and lymph node metastasis(P=0.053).The levels of serum PSA concentration and PSAD were significantly correlated with the clinical stage(P<0.05)in the prostate cancer patients. CONCLUSION The level of both PSA and PSAD were significantly correlated with the clinical stage(P<0.05)in the prostate cancer patients.But PSAD may be a more powerful predictor of clinical stage and prognosis than PSA.     

Biological aggressiveness of prostate cancer in the Finnish screening trial

Prostate cancer aggressiveness was evaluated based on pathologic characterization of cases detected in the Finnish prostate cancer screening trial. The trial population consists of 80,458 men aged 55–67 years. A total of 32,000 men were randomized to the screening arm. The remaining 48,000 men formed the control arm. The interval cases and cancers among nonparticipants and in the control arm were identified from the Finnish Cancer Registry. Random samples were selected from screen‐detected cases (126 of 543 in the first and 133 of 508 in the second round) and control arm cancers (133 out of 863), in addition to all 92 interval cancers and 106 cases among nonparticipants. All the biopsies were regraded according to the Gleason system. The expression of the proliferation antigen Ki‐67 was determined in 479 cases (72%). More than half of the tumors diagnosed in the first round of screening were high‐grade cancers (Gleason 7 or higher). In the second round, the proportion of low‐grade cancers increased from 47% to 70%. Cancers in the screening arm were more commonly focal and fewer bilateral cancers were detected. The cancers among nonparticipants were the most aggressive group. The aggressiveness of the interval cancers was between the cancers detected in the first and the second round. Our results indicate that prostate cancers detected through screening are less biologically aggressive. This was most notable after the first screening round. Nonparticipants had more aggressive cancers. © 2008 Wiley‐Liss, Inc.     

TRUS引导下前列腺穿刺活检联合PSA水平变化在诊断前列腺癌中的价值

目的 探讨经直肠内超声(TRUS)引导下前列腺穿刺活检联合血清前列腺特异性抗原(PSA)诊断前列腺癌(PCA)的临床价值.方法 选取怀疑为PCA的患者128例,分别接受TRUS引导下前列腺穿刺活检、血清PSA检测,以最终病理学检查结果作为金标准,探讨二者联合诊断PCA的临床价值.结果 不同PSA水平下TRUS引导下前列腺穿刺活检对PCA的检出率比较,差异有统计学意义(P﹤0.001).血清PSA检测鉴别诊断PCA的灵敏度为72.97%,特异度为61.11%,漏诊率为27.03%,误诊率为38.89%;TRUS引导下前列腺穿刺活检鉴别诊断PCA的灵敏度为70.27%,特异度为61.11%,漏诊率为29.73%,误诊率为38.89%;TRUS引导下前列腺穿刺活检联合血清PSA检测鉴别诊断PCA的灵敏度为98.65%,特异度为87.04%,漏诊率为1.35%,误诊率为12.96%.结论 TRUS引导下前列腺穿刺活检联合血清PSA检测诊断PCA的临床价值高于二者单独应用.     

Primary care providers' perspectives on discontinuing prostate cancer screening

BACKGROUND:

Clinical guidelines recommend against routine prostate‐specific antigen (PSA) screening for older men and for those with lower life expectancies. The authors of this report examined providers' decision‐making regarding discontinuing PSA screening.

METHODS:

A survey of primary providers from a large, university‐affiliated primary care practice was administered. Providers were asked about their current screening practices, factors that influenced their decision to discontinue screening, and barriers to discontinuing screening. Bivariate and multivariable logistic regression analyses were used to examine whether taking age and/or life expectancy into account and barriers to discontinuing were associated with clinician characteristics and practice styles.

RESULTS:

One hundred twenty‐five of 141 providers (88.7%) participated in the survey. Over half (59.3%) took both age and life expectancy into account, whereas 12.2% did not consider either in their decisions to discontinue PSA screening. Providers varied in the age at which they typically stopped screening patients, and the majority (66.4%) reported difficulty in assessing life expectancy. Taking patient age and life expectancy into account was not associated with provider characteristics or practice styles. The most frequently cited barriers to discontinuing PSA screening were patient expectation (74.4%) and time constraints (66.4%). Black providers were significantly less likely than nonblack providers to endorse barriers related to time constraints and clinical uncertainty, although these results were limited by the small sample size of black providers.

CONCLUSIONS:

Although age and life expectancy often figured prominently in decisions to use screening, providers faced multiple barriers to discontinuing routine PSA screening. Cancer 2012. © 2012 American Cancer Society.     

Adherence to a risk-adapted screening strategy for prostate cancer: First results of the PROBASE trial

PROBASE is a population-based, randomized trial of 46 495 German men recruited at age 45 to compare effects of risk-adapted prostate cancer (PCa) screening starting either immediately at age 45, or at a deferred age of 50 years. Based on prostate-specific antigen (PSA) levels, men are classified into risk groups with different screening intervals: low-risk (<1.5 ng/ml, 5-yearly screening), intermediate-risk (1.5-2.99 ng/ml, 2 yearly), and high risk (>3 ng/ml, recommendation for immediate biopsy). Over the first 6 years of study participation, attendance rates to scheduled screening visits varied from 70.5% to 79.4%, depending on the study arm and risk group allocation, in addition 11.2% to 25.4% of men reported self-initiated PSA tests outside the PROBASE protocol. 38.5% of participants had a history of digital rectal examination or PSA testing prior to recruitment to PROBASE, frequently associated with family history of PCa. These men showed higher rates (33% to 57%, depending on subgroups) of self-initiated PSA testing in-between PROBASE screening rounds. In the high-risk groups (both arms), the biopsy acceptance rate was 64% overall, but was higher among men with screening PSA ≥4 ng/ml (>71%) and with PIRADS ≥3 findings upon multiparameter magnetic resonance imaging (mpMRI) (>72%), compared with men with PSA ≥3 to 4 ng/ml (57%) or PIRADS score ≤ 2 (59%). Overall, PROBASE shows good acceptance of a risk-adapted PCa screening strategy in Germany. Implementation of such a strategy should be accompanied by a well-structured communication, to explain not only the benefits but also the harms of PSA screening.     

The influence of serial prostate-specific antigen (PSA) screening on the PSA velocity at diagnosis

BACKGROUND: A prostate-specific antigen (PSA) velocity (PSAV) >2 ng/mL during the year before diagnosis has been associated with an increased risk of prostate cancer-specific mortality (PCSM) after radical prostatectomy (RP) or radiation therapy. The objective of the current study was to examine whether the proportion of men with a PSAV >2 ng/mL per year has changed significantly during the PSA era. METHODS: The authors evaluated 1095 men from a prospective prostate cancer screening study who underwent RP between 1989 and 2002. For the purposes of this analysis, clinicopathologic features were compared between men who were treated during the following 3 periods: before 1995, from 1995 to 1998, and after 1998. Logistic regression analysis was used to evaluate for an association between the year of diagnosis and the proportion of men with a PSAV >2 ng/mL per year. RESULTS: Two hundred sixty-two of 1095 men (24%) had a PSAV >2 ng/mL per year. There was a statistically significant reduction in the proportion of men presenting with a PSAV >2 ng/mL per year over the study period. Specifically, 35% of men presented with a PSAV >2 ng/mL per year in the early period compared with only 22% and 12% in the middle and late periods, respectively (P < .001). Over the studied periods, there also was a significantly greater proportion of men with >2 PSA values obtained before diagnosis (P < .001). CONCLUSIONS: Men who were screened serially with PSA were less likely to present with a PSAV >2 ng/mL per year. This association lends support to the hypothesis that serial PSA-based screening may lead to a decrease in PCSM.     

Assessment of causes of death in a prostate cancer screening trial

Accurate assessment of the causes of death is crucial for a conclusive evaluation of the ongoing prostate cancer screening trials. Here, we report the validity of the official causes of death as compared with an independent expert review in the Finnish prostate cancer screening trial. Because nearly 80,000 men were involved, death-cause evaluation was restricted to men diagnosed for prostate cancer. Medical charts were retrieved and the cause of death was assigned by an expert review panel for all deaths among men with prostate cancer during the study period, 1996-2003. The panel decision was compared with both death certificates and the official causes of death as assigned by Statistics Finland. Of a total of 315 deaths, the review panel attributed 127 (41%) to prostate cancer and 184 (59%) to other causes, the corresponding figures in death certificates being 124 (40%) and 187 (60%). Four cases were excluded because of insufficient information. The death-certificate data were in agreement with the panel's assessment in 305 out of 311 cases (overall agreement 97.7%, kappa = 0.95). The overall agreement between the official causes of death and the panel's decision was 97.4% (304/311, kappa = 0.95). The sensitivity of the certificates in identifying prostate cancer deaths was 96.1% (panel as golden standard). Correspondingly, specificity was 98.9%. The official causes of death thus provide an accurate means for evaluating disease-specific mortality in a large population-based prostate-cancer screening trial in Finland.     

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.     

PSA、ECT骨显像诊断前列腺癌骨转移的临床意义

目的：探讨前列腺特异抗原（PSA）、发射型计算机断层扫描（ECT）99Tc-MDP骨显像诊断前列腺癌骨转移的临床意义。方法：对80例（骨转移组31例,非骨转移组49例）前列腺癌病人的PSA、ECT与骨转移的关系进行回顾性分析。结果：骨转移组与非骨转移组的PSA值差异有显著性（139.36μg/Lvs37.58μg/L,P〈0.01）;PSA与骨转移的程度正相关,PSA〈10μg/L,骨转移率为15.38%;PSA〈20μg/L,骨转移率为19.35%;PSA〉20μg/L,骨转移率为51.02%;PSA〉100μg/L,骨转移率为78.95%。结论：ECT骨显像对前列腺癌骨转移有较高的敏感性,对未经治疗的前列腺癌病人,PSA〈10μg/L,前列腺癌骨转移的可能性极小;PSA〉100μg/L者,骨转移的可能性极大。PSA〉20μg/L,建议行ECT骨扫描。     

PSA、ECT骨显像诊断前列腺癌骨转移的临床意义

目的:探讨前列腺特异抗原(PSA)、发射型计算机断层扫描(ECT)99Tc-MDP骨显像诊断前列腺癌骨转移的临床意义。方法:对80例(骨转移组31例,非骨转移组49例)前列腺癌病人的PSA、ECT与骨转移的关系进行回顾性分析。结果:骨转移组与非骨转移组的PSA值差异有显著性(139.36μg/Lvs37.58μg/L,P<0.01);PSA与骨转移的程度正相关,PSA<10μg/L,骨转移率为15.38%;PSA<20μg/L,骨转移率为19.35%;PSA>20μg/L,骨转移率为51.02%;PSA>100μg/L,骨转移率为78.95%。结论:ECT骨显像对前列腺癌骨转移有较高的敏感性,对未经治疗的前列腺癌病人,PSA<10μg/L,前列腺癌骨转移的可能性极小;PSA>100μg/L者,骨转移的可能性极大。PSA>20μg/L,建议行ECT骨扫描。     

Identifying and characterizing "escapes"-men who develop metastases or die from prostate cancer despite screening (ERSPC, section Rotterdam)

We aim to identify and characterize "escapes," men who developed metastasis and/or died from prostate cancer (PCa) despite screening, in the framework of the novel international ESCAPE-project. With this knowledge, the ultimate goal is to improve screening strategy. In this article, we focus on the study cohort of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam. In all, 21,210 men were randomized to the screening arm of whom 19,950 were actually screened. The screening interval was 4 years. Men with prostate-specific antigen ≥3.0 ng/ml were recommended to undergo lateralized sextant prostate biopsy. The follow-up was complete until January 1, 2009. Of 19,950 screened men, 2,317 were diagnosed with PCa. Of these cancers 1,946 were detected in a screening round and 371 during an interval. The median follow-up was 11.1 years for the whole cohort and 7.3 years for men diagnosed with PCa. In total, we identified 168 escapes among 2,317 cancers (7.3%) within our screening cohort of 19,950 men (0.8%). More than half of these escapes were found in the initial screening round (94 of 168). Possible mechanisms behind escaping are nonattending, inadequate screening tests, the relative long screening interval, the age cut-off at 75 years, and undertreatment. International cooperation is crucial to compare the escapes of our cohort with other study groups participating in the ESCAPE-project which have different, more aggressive screening strategies. Subsequently, we can achieve improvements of the current screening algorithm, which hopefully will further decrease PCa-specific mortality without increasing overdiagnosis and overtreatment.     

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

PURPOSE: To evaluate the natural background of prostate cancer in Iran a large population-based study of screening using total prostate-specific antigen (tPSA) and per cent free PSA (fPSA) as the initial test was performed. MATERIALS AND METHODS: For 9 years (1996 to 2004) in Tehran, Iran, 3670 Iranian men older than 40 years were mass checked by PSA-based screening. They were invited to have a digital rectal examination (DRE), serum PSA assay and transrectal ultrasonography (TRUS)-guided sextant prostate biopsy to see if the DRE was clinically suspicious of malignancy, the serum PSA was > or =2.1 ng/ml or free-to-total PSA (f/tPSA) ratio < or=15%. RESULTS: In 433 (11.8%) of screened males, tPSA levels exceeded the cut-off value of > or =2.1 ng/ml and 128 prostate cancers were diagnosed [positive predictive value (PPV) 29.6%] corresponding to an overall detection rate of 3.5%. Altogether 138 cancers were detected (detection rate 3.8%); none were stage M(1), three were stage N(+) and 4 stage T(3). A threshold tPSA of > or =2.1 ng/ml would have detected 128 cancers in 447 biopsied men (PPV 29%). There were 109 of 138 (79%) men with cancer who had an f/tPSA of < or =15%, while 152 of 305 (49.8%) with benign biopsies had a f/tPSA of < or =15%, which corresponds to a PPV of 30.8%. CONCLUSION: PSA-based screening with low PSA cut-off values increase the detection rate of clinically significant, organ confined and potentially curable prostate cancer. Further studies are warranted in order to determine the incidence and prevalence of prostate cancer in different ethnic groups.     

晚期前列腺癌的外照射治疗

目的：研究晚期前列腺癌的外照射治疗的疗效。方法：１９９３年３月－１９９９年３月共收治晚期前列腺癌４５例,Ｃ期３２例,Ｄ期１３例,对所有病例均予外照射治疗,局部肿瘤量达５５－７０Ｇｙ／５．５－７周。结果：所有病例放疗后排尿困难、骨转移疼痛改善,血尿消失,放疗后血前列腺特异性抗原（ＰＳＡ）均明显下降,为０．０１－２．８ｎｇ／ｍｌ,平均０．３５ｎｇ／ｍｌ,放疗后９个月复查局部肿瘤消失２９例,明显缩小１６