Elimination of serum complexed prostate-specific antigen after radical retropubic prostatectomy.

Total prostate-specific antigen (PSA) and complexed PSA were determined in venous blood from 12 patients with prostate cancer before and after radical prostatectomy by using Immuno 1 PSA assays. The elimination kinetics of complexed PSA were compared with that of total PSA. Nearly constant concentrations of complexed PSA were found during the first six hours after surgery, in contrast to the rapid elimination of free PSA and the significant decrease of total PSA. From day one to ten there was a continuous and nearly identical decrease of complexed PSA compared to total PSA. Our findings suggest that the initial rapid decrease of free PSA immediately after operation could be caused by formation of new PSA-complex.     

Comparison of free and total forms of serum human kallikrein 2 and prostate-specific antigen for prediction of locally advanced and recurrent prostate cancer

BACKGROUND: We evaluated the association of total and free forms of serum human kallikrein 2 (hK2) and prostate-specific antigen (PSA) with prostate cancers of unfavorable prognosis. METHODS: We retrospectively measured total PSA (tPSA), free PSA (fPSA), and total hK2 (thK2) in preoperative serum samples from 867 men [and assessed free hK2 (fhK2) measured in 577 of these men] treated with radical prostatectomy for clinically localized prostate cancer. Associations between biomarker concentrations and extracapsular extension, seminal vesicle invasion, and biochemical recurrence (BCR) were evaluated. A subset of patients with PSA < or =10 microg/L, the group most commonly seen in clinical practice in the US, was analyzed. RESULTS: thK2 was the strongest predictor of extracapsular extension and seminal vesicle invasion (areas under the ROC curve [AUC], 0.662 and 0.719, respectively), followed by tPSA (AUC, 0.654 and 0.663). All biomarkers were significant predictors of BCR. hK2 forms, but not PSA forms, remained highly significant for predicting BCR in the low-PSA group. Combining tPSA, fPSA, and thK2 in a multivariable model improved prediction compared with any biomarker used individually (AUC, 0.711, 0.755, and 0.752 for this combination predicting extracapsular extension, seminal vesicle invasion, and BCR, respectively; P <0.001 for all). CONCLUSIONS: Increased concentrations of hK2 in the blood are significantly associated with unfavorable features of prostate cancer, and thK2 is predictive of locally advanced and recurrent cancer in patients with PSA < or =10 microg/L. Independent of tPSA and fPSA, hK2 predicts unfavorable prognosis.     

Correlation between serum prostate-specific antigen and alpha-1-antitrypsin in men without and with prostate cancer

Prostate specific antigen (PSA) is frequently used for prostate cancer (PCa) screening, but serum levels are also increased by prostate inflammation. Elevations in serum levels of alpha1-antitrypsin (ATT), a marker of inflammation, in cancer patients are well documented. However, an association between PSA and ATT has never been investigated. The authors, therefore, measured serum acute phase proteins (APPs) ATT, alpha1-acid glycoprotein, C-reactive protein, and alpha1-antichymotrypsin in 174 men without and 34 with newly diagnosed untreated PCa (38-80 years old). As expected, men with PCa had higher mean PSA levels than those without PCa (P < 0.00001). Men with PCa and those without PCa but with PSA >2 ng/mL (n = 68) had significantly higher ATT concentrations than those without these conditions (n = 106) (mean +/- SEM g/L): 1.94+/-0.083, 1.92+/-0.066, 1.25+/-0.043, respectively; p <0.005). Interestingly, African-American men without PCa (n=111) had higher ATT levels than Caucasian men (n=63) (1.565+/-0.045 g/l versus 1.395+/-0.056 g/l; p <0.005); and differences persisted in men with PSA >2 ng/ml (2.094+/-0.07 g/l versus 1.593 for all0.095 g/l; p<0.0002). There were no differences among groups in the levels of other APP. ATT showed the strongest correlation with PSA (r = 0.346 to 0.395; p <0.001) than any other APP (r < or =0.245). Our data suggest that men with PCa have higher ATT levels than those without PCa; and African-American men without PCa have higher ATT levels than Caucasian men. The possible implications of elevated ATT levels in African-American men on the risk of PCa are discussed.     

Serum ribonuclease activity in the diagnosis of prostate cancer in men with serum prostate-specific antigen levels between 2.5 and 20 ng/mL

Objectives:

To evaluate the diagnostic value of serum ribonuclease activity for prostate cancer detection and to compare its performance with serum PSA.

Design and methods:

111 subjects with serum PSA levels between 2.5 and 20 ng/mL underwent prostate biopsy. The diagnostic performance of serum ribonuclease activity, PSA, free PSA, complex PSA and PSA derivatives was studied in regard to discriminating prostate cancer from BPH.

Results:

Of 111 patients, 27 (24.3%) were positive for prostate cancer. Median serum ribonuclease level in patients with prostate cancer was significantly higher than the non-cancer patients (21.3 U/mL vs. 6.6 U/mL, P < 0.001). Area under curve (AUC) values for ribonuclease activity level, PSA, f/tPSA and cPSA were 0.696, 0.514, 0.617 and 0.662, respectively. Of 27 patients with prostate cancer, radical prostatectomy was performed in 15. Of these 15 cases, four (26.7%) had clinical insignificant tumors; all with undetectable serum ribonuclease activity. When median values of various diagnostic parameters were compared in regard to predicting clinically significant and insignificant cancers, only serum ribonuclease activity was found to be significant.

Conclusions:

Although serum ribonuclease activity had no additional benefit beyond serum PSA in the diagnosis of patients with PSA levels between 2.5 and 20 ng/mL, it may be helpful to discriminate the clinically significant prostate cancers and thus select the proper treatment accordingly.     

Individual quality of life following radical prostatectomy in men with prostate cancer

PURPOSE: The aim of this study was to examine the individual quality of life (QoL) of men following radical prostatectomy for prostate cancer. The following research questions were addressed: (a) What are the most important areas of quality of life for men following radical prostatectomy? (b) How do these men rate their satisfaction in each area and what is the relative importance of each area to their overall quality of life? METHODS: The purposive sample consisted of 11 men with prostate cancer who had undergone a radical prostatectomy 3 to 4 months earlier. QoL was examined using the SEIQoL-DW (Schedule for the Evaluation of Individual QoL: A Direct Weighting Procedure). The data were analyzed by means of qualitative content analysis (five most important QoL areas). FINDINGS: The 11 respondents named a total of 55 QoL areas which they described and labelled. They then rated their current satisfaction in each area, and how important each one was to them. A second analysis of the content was made to identify the main QoL areas. The 55 quality of life areas mentioned by respondents were reduced to the following categories: health, activity, family, relationship with a partner, autonomy, independence, hobby, financial security, and sexuality. Health, family, and relationship with a partner are the thee areas which had the most impact on QoL. Overall, the respondents had a high quality of life value. Impotence and incontinence did not appear to have a very negative impact on quality of life. CONCLUSIONS: SEIQoL-DW was used for the first time in patients with prostate cancer. In a urology department where nurses and patients are confronted daily with the topics of intimacy, sexuality, and sense of embarrassment, more importance should be placed on the topic of sexuality when taking a patient history. Nurses should be trained in communication techniques that enable them to engage patients in a safe and therapeutic dialogue about their sexual concerns related to the diagnosis of prostate cancer. SEIQoL-DW can support the communication with patients.     

Diagnostic and prognostic value of quantitative monitoring of prostate specific antigen in blood serum and urine from patients with prostate cancer after radical prostatectomy

AIM: To study values of prostate-specific antigen (PSA) in the blood serum and urine before and after massage of the prostatic bed in patients with prostatic cancer (PC) after radical prostatectomy. MATERIAL AND METHODS: Changes in serum and urine PSA concentrations were followed up in 17 patients with PC (T2-3N0M0) 14 months (4-24 mon) after radical prostatectomy. Control examinations were made once a month. MRT or CT and osteoscintigraphy were made in suspected recurrence and/or metastases of PC. RESULTS: There were no changes in PSA consentrations in the serum and urine before and after the massage of prostatic bed in 10 of 17 patients. In 3 patients PSA concentrations in blood and serum increased after the massage, in one of them blood levels of PSA after the massage went up 5 months after PSA increase in the urine. In 4 of 17 patients urine PSA levels increased after the massage, the blood levels remaining the same. CONCLUSION: Follow-up measurements of blood and urinary levels in PC patients after radical prostatectomy before and following massage of the prostatic bed allow detection of prostatic PSA-positive cells which were not removed at surgery. We suggest that these cells may be the basis of recurrent disease.     

不同血清前列腺特异抗原水平前列腺癌超声造影微血管成像与常规超声靶向引导穿刺活检的对比

目的 比较不同血清前列腺特异抗原(PSA)水平下超声造影微血管成像(MFI)与常规超声靶向引导前列腺癌穿刺活检的价值.方法 对65例血清PSA升高(≥4 ng/ml)的患者行经直肠前列腺穿刺活检,分为A(4 ng/ml≤PSA＜10 ng/ml)、B(10 ng/ml≤PSA＜20 ng/ml)、C(PSA≥20 ng/ml)三组,活检前行经直肠灰阶、彩色多普勒能量图(CDE)及MFI检查.在超声引导下对每例患者行底、中、尖三切面12点穿刺.以病理结果为金标准,比较不同PSA水平组中MFI与常规超声靶向引导前列腺癌穿刺活检的价值.结果 65例患者有230针穿刺活检病理诊断为前列腺癌.A组、B组中MFI检出恶性病灶的敏感度均高于灰阶及CDE(P＜0.01),C组中MFI的敏感度、准确率及阴性预测值均高于灰阶及CDE(P＜0.01).三组间MFI靶向引导前列腺活检的敏感度和准确率差异无统计学意义(P＞0.05).结论 对不同PSA水平前列腺癌,MFI均较常规超声靶向引导穿刺活检的敏感性高.     

Proenzyme forms of prostate-specific antigen in serum improve the detection of prostate cancer

Introduction: Pro or precursor forms of prostate-specific antigen (PSA) have emerged as potentially important diagnostic serum markers for prostate cancer detection. Immunoassays were developed to measure specific proPSA forms containing propeptides of 2, 4, and 7 amino acids [(-2)proPSA, (-4)proPSA, and (-7)proPSA, respectively]. METHODS: Research-use dual monoclonal antibody immunoassays using europium-labeled detection monoclonal antibodies were developed for each form of proPSA. Sera from patients with prostate cancer or benign prostate disease containing 4-10 microg/L PSA were assayed and analyzed by area under the ROC curve (AUC) for specificity and sensitivity. RESULTS: The proPSA forms had quantification limits of 0.015-0.025 microg/L in serum, with cross-reactivities <1% with PSA. The sum of the proPSA forms divided by free PSA (percentage proPSA) had a higher AUC than did percentage of (-2)proPSA, free PSA, and complexed PSA with AUC (95% confidence intervals) of 0.69 (0.64-0.74), 0.64 (0.58-0.68), 0.63 (0.58-0.68), and 0.57 (0.51-0.62), respectively. The proPSA comprised a median of 33% of the free PSA in cancer and 25% in noncancer sera (P <0.0001). One-third (33%) of cancer samples had >40% proPSA, whereas only 8% of noncancer samples did (P <0.0001). In men with cancer and >25% free PSA, the (-2)proPSA had an AUC of 0.77 (0.66-0.86), with 90% sensitivity and 36% specificity at 0.04 microg/L. CONCLUSIONS: The percentage of proPSA gave better cancer detection in the 4-10 microg/L range than did percentage of free PSA and complexed PSA. (-2)proPSA significantly discriminated cancer in men whose serum had >25% free PSA, for whom there is currently no good marker for cancer detection.     

Rise in prostate-specific antigen in men with untreated low-grade prostate cancer is slower during spring-summer

To test the hypothesis that the rate of rise in prostate-specific antigen (PSA) is slower during the spring-summer than during the rest of the year, we used PSA data from a prospective single-arm cohort study of men who had been followed to characterize a watchful observation protocol with selective delayed intervention for clinically localized, low-to-intermediate grade prostate adenocarcinoma. The rate of PSA increase was calculated as the visit-to-visit slope of log (PSA) against time, from 1 calendar-quarter visit to the next. The nonparametric Friedman test confirmed differences in rate of PSA rise among the calendar quarters (P = 0.041). Post hoc analysis showed the rate of PSA increase during Q2 was significantly slower than in each one of the other calendar quarters (Q1 versus Q2, P = 0.025; Q3 versus Q2, P = 0.002; Q4 versus Q2, P = 0.013), with no differences among quarters Q1, Q3, and Q4. These results are consistent with the vitamin D hypothesis that the higher 25-hydroxyvitamin D levels associated with spring and summer have a desirable effect on prostate biology. The therapeutic implication is that vitamin D supplementation in the range of 2000 IU/d, a dose comparable to the effect of summer, can benefit men monitored for rising PSA.     

Stratification of patient risk based on prostate-specific antigen doubling time after radical retropubic prostatectomy

OBJECTIVE: To assess the risk of local recurrence, systemic progression, and death from cancer among patients who experience biochemical relapse after radical retropubic prostatectomy and to stratify those patients by prostate-specific antigen (PSA) doubling time (DT). PATIENTS AND METHODS: We identified patients who experienced biochemical recurrence (defined as a PSA level < or =0.4 ng/mL) after radical prostatectomy from January 1, 1990, to December 31, 1999, for prostate adenocarcinoma. The PSA-DT was calculated by log linear regression using all PSA values within 2 years of biochemical recurrence. Local recurrence- and systemic progression- free survival and cancer-specific survival were estimated using the Kaplan-Meier method and analyzed by the log-rank test and Cox models. RESULTS: Biochemical recurrence was noted in 1521 (27%) of 5533 men during the follow-up period. Of the 1064 patients with a calculable PSA-DT, 322 (30%) had a PSA-DT of less than 1 year, 357 (34%) had a PSA-DT of 1 to 9.9 years, and 385 (36%) had a PSA-DT of 10 years or more. Patients with a PSA-DT of 10 years or more were less likely to have a higher preoperative PSA level, Gleason score, advanced pathologic stage, and seminal vesicle invasion. Patients with a PSA-DT of 10 years or more were at low risk of local recurrence (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.06-0.14; compared with patients with a PSA-DT of <1 year), systemic progression (HR, 0.05; 95% CI, 0.02-0.13), or death from cancer (HR, 0.15; 95% CI, 0.05-0.43). CONCLUSIONS: Prostate-specific antigen DT is an independent predictor of clinical disease recurrence and mortality after surgical biochemical failure. Risk stratification into high-, intermediate-, and low-risk categories based on the PSA-DT provides helpful clinical information and assists in the development of salvage therapy trials.     

Comparison of prostate-specific antigen adjusted for transition zone volume versus prostate-specific antigen density in predicting prostate cancer by transrectal ultrasonography.

OBJECTIVE: Prostate-specific antigen is an excellent tumor marker, but it is not specific for prostate cancer. We evaluated the efficacy of prostate-specific antigen adjusted for transition zone volume calculated by transrectal ultrasonography in predicting prostate cancer in men with intermediate prostate-specific antigen levels of 4.1 to 10.0 ng/mL compared with prostate-specific antigen density. METHODS: Between June 1998 and December 2001, prostate-specific antigen adjusted for transition zone volume was obtained from 131 patients who underwent ultrasonographically guided biopsies and had prostate-specific antigen of 4.1 to 10.0 ng/mL. Prostate-specific antigen density was calculated by dividing total serum prostate-specific antigen by total prostate volume, and total serum prostate-specific antigen was divided by transition zone volume to yield prostate-specific antigen adjusted for transition zone volume. This was compared with prostate-specific antigen density via receiver operating characteristic curves. RESULTS: Of 131 patients, 34 (26%) had prostate cancer, and 97 (74%) had benign prostatic hyperplasia on pathologic examination. Total prostate volume was correlated with transition zone volume (P < .001). Mean prostate-specific antigen adjusted for transition zone volume and prostate-specific antigen density were 0.71 +/- 0.25 and 0.27 +/- 0.09 ng x mL(-1) x mL(-1) in patients with prostate cancer and 0.32 +/- 0.09 and 0.16 +/- 0.05 ng x ml(-1) x mL(-1) in patients with benign prostatic hyperplasia. With a cutoff value of 0.35 ng mL(-1) x mL(-1), prostate-specific antigen adjusted for transition zone volume had sensitivity of 82% and specificity of 84%. Receiver operating characteristic curve analysis showed that prostate-specific antigen adjusted for transition zone volume predicted biopsy outcome significantly better than prostate-specific antigen density (P < .05). CONCLUSIONS: Prostate-specific antigen adjusted for transition zone volume is more accurate than prostate-specific antigen density in distinguishing prostate cancer from benign prostatic hyperplasia in men with intermediate serum prostate-specific antigen of 4.1 to 10.0 ng/mL. Determination of transition zone volume by transrectal ultrasonography may be helpful for predicting the probability of positive biopsy results.     

Screening for prostate cancer with prostate-specific antigen: beware the biases

BACKGROUND: The evidence relating to the use of prostate-specific antigen (PSA) as a screening test is a highly controversial, as demonstrated by the lack of agreement among experts. There may be biases associated with various studies. ISSUES: The main controversy is the relatively high prevalence of prostate cancer (PC) found at autopsy compared with the relatively low death rate from the disease. The lack of modifiable risk factors has led to early detection as a strategy to reduce mortality, as there is evidence for a significant burden of disease. Important issues are the accuracy of current screening tests, some attempts to improve on them, and whether there are good prognostic markers. The consequences of PSA testing (usually further testing including biopsy) and outcomes of treatment are presented in terms of mortality and morbidity; quality of life (QOL) must also be considered. Also important are the benefits from, and the difficulties associated with the "informed choice" approach to PSA screening. CONCLUSION: There is evidence to suggest that biases can have a significant impact on the utility of PSA as a screening test for PC.     

复合前列腺特异性抗原、总前列腺特异性抗原及其比值在前列腺癌诊断中的应用

目的:研究复合前列腺特异性抗原、总前列腺特异性抗原及其比值在鉴别前列腺癌和良性前列腺增生中的应用价值。方法:采用化学发光法检测30例前列腺癌患者、40例良性前列腺增生患者和30例对照组患者复合前列腺特异性抗原、总前列腺特异性抗原,计算并比较其比值。结果:前列腺癌患者的复合前列腺特异性抗原、总前列腺特异性抗原均高于对照组和良性前列腺增生患者,差异均具有统计学意义(P<0.05);其比值前列腺癌患者高于良性前列腺增生患者,差异有统计学意义(P<0.05);其相关性和共线性均不如前列腺癌组病例。结论:前列腺癌患者总前列腺特异性抗原的升高以复合前列腺特异性抗原升高为主,测定复合前列腺特异性抗原更有意义,结合其比值进行综合分析可以有效区分良性前列腺增生和前列腺癌。     

比卡鲁胺治疗晚期前列腺癌对血清PSA、f-PSA含量影响

目的：探讨前列腺癌患者比卡鲁胺治疗后前列腺特异抗原（PSA）、游离前列腺特异抗原与总前列腺特异抗原比值变化的临床意义。方法：测定前列腺癌患者内分泌治疗前及治疗后1，3，6个月血清前列腺特异抗原、游离前列腺特异抗原变化。结果：治疗后1个月与治疗前相比血清前列腺特异抗原下降明显，治疗后6个月较治疗后1个月血清前列腺特异抗原下降亦有显著意义；治疗后患者血清游离前列腺特异抗原水平明显下降。结论：血清游离前列腺特异抗原等可作为判断前列腺癌内分泌治疗效果的标准，比卡鲁胺治疗晚期前列腺癌有较好疗效。     

Analysis of subforms of free prostate-specific antigen in serum by two-dimensional gel electrophoresis: potential to improve diagnosis of prostate cancer

BACKGROUND: The aim of this study was to develop a method to separate and quantify subforms of free prostate-specific antigen (fPSA) in serum by two-dimensional electrophoresis and to assess the diagnostic accuracy of these subforms for prostate cancer (PCa) diagnosis in comparison with total PSA (tPSA) and the ratio of fPSA to tPSA (%fPSA). METHODS: Sera from 50 patients with and without PCa, respectively, were studied. PSA was isolated by immunoadsorption on streptavidin-coated magnetic beads with biotinylated anti-PSA antibodies and separated by two-dimensional electrophoresis. After semidry blotting, the intensities of the fPSA spots were quantified by chemiluminescence using an imager analyzer. RESULTS: The method detected subforms to a concentration of 0.1 mug/L fPSA with an imprecision (CV) <16%. We detected 15 immunoreactive fPSA spots of different intensities. Spots F2 and F3 were present in all samples. F2 was lower in samples from non-PCa patients (median, 23%) than in samples from PCa patients (49%), whereas F3 behaved inversely (non-PCa, 73%; PCa, 45%). Ratios of F2 to F3 and F2/F3 to %fPSA, respectively, showed improved diagnostic accuracy compared with tPSA and %fPSA. Better differentiation by F2/F3 or by F2/F3 to %fPSA was particularly evident in patients with %fPSA values >15%. There were no associations between the PCa grading scale and fPSA subforms. CONCLUSIONS: fPSA subforms separated by two-dimensional electrophoresis may improve both sensitivity and specificity in prostate cancer diagnostics compared with tPSA and %fPSA. The development of a practicable assay based on the immunologic properties of these different fPSA subforms seems to be promising.     

急性前列腺炎对血PSA及游离PSA百分率的影响

目的:探讨急性前列腺炎患者血前列腺特异性抗原(PSA)水平及游离PSA百分率(freetototalPSAra-tio,F-PSAR)的变化。方法:2003年3月至2004年4月,诊断为急性前列腺的患者19例,在患者发病初始、发病后第3天、第10天、第1个月及第3个月分别抽血查PSA、F-PSAR及C反应蛋白(CRP),分析上述指标的衍变。结果:急性前列腺炎经治疗后,CRP在发病后第10天回复到正常水平;PSA在发病后第3天达到高峰,发病后第1个月逐渐下降至正常;F-PSAR在发病后第10天达到低谷,发病后第3个月渐恢复正常。结论:急性前列腺炎亦是血PSA升高的原因之一,急性前列腺炎对PSA及F-PSAR的影响可迁延1～3个月。