Frequency of PSA-mRNA-bearing cells in the peripheral blood of patients after prostate biopsy

Transrectal ultrasound (TRUS) guided prostate biopsy is standard diagnostic procedure for prostate cancer (PCa). However, possibility of dissemination of cancer cells by biopsy is not negligible. To investigate this possibility, we examined prostate specific antigen (PSA)-bearing cells in peripheral blood of the 108 patients before and after prostate biopsy. Peripheral blood samples were obtained from 108 patients with elevated serum PSA (sPSA) levels, who had undergone sextant prostate biopsy using TRUS. The presence of PSA-mRNA bearing cells was examined using the nested RT-PCR method enabling detection of one LNCaP cell diluted in 1 ml of whole blood. Among 108 patients, 62 and 46 were diagnosed with benign prostatic hyperplasia (BPH) and PCa, respectively. PSA-mRNA was detected in 3 PCa cases but in no BPH patients before and after biopsy, and in 16 BPH (25.8%) and in 21 PCa (45.7%) patients only after biopsy (P< 0.01). The patients with positive mRNA before biopsy had higher sPSA (P< 0.001), and those after biopsy had higher sPSA and PSA density (PSAD) levels (P< 0.05). Positive PSA-mRNA cases had more cancer involved biopsy cores than the negative PSA-mRNA cases (P< 0.001). Although further investigations are needed, the present findings suggest that prostate biopsy might scatter prostate cells in the blood stream especially in cases with high sPSA and, thus, might contribute to tumour spreading in the cases of prostate cancer.     

Expression of soluble urokinase plasminogen activator receptor may be related to outcome in prostate cancer patients

The urokinase-type plasminogen activator receptor (uPAR) exists as a GPI anchored glycoprotein (Mr=50-60 kDa) on the surface of various cell types. This receptor can be bound by or cleaved by urokinase. The cleaved receptor, soluble urokinase-type plasminogen activator receptor (suPAR), with an Mr=35 kDa has no known physiological function and can be identified circulating in the blood of normal individuals. Although no function has been characterized, the soluble receptor has been reported to be of clinical significance. The objective of this study is to characterize novel serum markers that can be used for the early detection of prostate cancer and to predict patient prognosis. Thirty-nine patients at the University of Yaounde I, Yaounde, Cameroon, West Africa were examined for prostatic disorders. Of these, 46% were diagnosed with benign prostate hyperplasia (BPH), while 44% of the patients were diagnosed via biopsy with prostate cancer and graded accordingly. Here we show that serum from patients with BPH or prostate cancer contains elevated levels of suPAR. To examine the significance of suPAR as a diagnostic factor, we used a suPAR ELISA kit and compared these results with serum levels of prostate specific antigen (PSA), the current diagnostic marker for prostate cancer. PSA and serum suPAR levels in BPH and cancer patients were greatly elevated in the majority of patients, while others had undetectable levels of either. Serum levels of suPAR were high in cancer patients as well as, although to a lesser degree, in patients with BPH. Cancer patients who died during the follow-up period were found to have consistently higher serum suPAR levels than correlating serum PSA levels. These preliminary findings are the first evaluating serum suPAR levels as a possible diagnostic marker for the early detection of prostate cancer and for the prediction of patient prognosis.     

Frequency of Unnecessarily Biopsies among Patients with Suspicion of Prostate Cancer in Syrian Men

Background: The prevalence of prostate cancer is considered high in many countries, and screening tests arevery important in order to detect prostate cancer in its early stages; however false positivity with these screeningtests means that a lot of patients undergo unnecessary biopsy, which is an invasive procedure, for the confirmatorytest. The purpose of this study was to estimate the frequency of unnecessary biopsy cases in patients referredfor prostate biopsy in one of the most important and overload cancer centers in Syria. Materials and Methods:Retrospective data for a period of four years between January 2009 and December 2012 were collected in Al-Bayrouni University Medical hospital in Damascus, Syria. The patients from whom data were collected werereferred to our histopathological department because of elevated prostate specific antigen (PSA) serum or anabnormal digital rectal examination (DRE). All patients underwent prostatic TRUS-guided biopsies. Diagnosisof prostate cancer (PCa) or benign prostatic hyperplasia (BPH) was based on histopathological examinationand prostate cancers cases were graded and scored according to the Gleason score system. Results: For the 406patients referred to biopsy, the mean±SD age was 58.4 ±23.3 years. The mean ± SD PSA level was 49.2±21.5 ng/ml. Of the total we found 237 patients diagnosed with PCa (58. 4%), 166 patients with BPH (40.9%) and 3 caseswere unable to be diagnosed (0.7%) because of biopsy collection errors. Conclusions: Our study shows that ahigh percentage of patients are undergoing unnecessary biopsy, which suggests that the performed screeningtests had a high level of false positive and may need re-evaluation.     

Measurement of intracellular versus extracellular prostate-specific antigen levels in peripheral macrophages: a new approach to noninvasive diagnosis of prostate cancer

Although prostate-specific antigen (PSA) is a useful screening marker in prostate cancer, it has limited specificity. Previously it was shown that the amount of surface-bound PSA present on circulating macrophages was different between patients with localized prostate cancer and those with metastatic prostate cancer. It was recently demonstrated that intracellular PSA in macrophages can be measured by flow cytometry. In the context of searching for a noninvasive, highly reliable method for prostate cancer diagnosis, we assessed the extent to which extracellular (ie, surface-bound) and intracellular PSA-positive macrophages might differentiate patients with benign versus malignant prostatic disease. In a pilot study, the levels of complexed, surface-bound, and intracellular PSA were measured in 25 patients with elevated serum PSA values and histologically confirmed disease. In this group, no significant differences for serum PSA and complexed PSA levels, respectively, could be detected among patients with benign prostatic hyperplasia, prostatitis, and prostate cancer. Significant differences, however, were detected in intracellular PSA, although not in surface-bound PSA, among the 3 groups of patients. Intracellular PSA was measured prospectively in a second cohort of 189 patients who had a transrectal biopsy because of a serum PSA constellation suspicious for prostate cancer. In the expanded cohort, highly significant differences in intracellular PSA were observed between benign and malignant disease of the prostate, even in patients with serum PSA level<4 ng/mL. Screening of serum PSA alone or in combination with complexed PSA does not clearly distinguish patients with prostate cancer from those with prostatitis or benign prostatic hyperplasia. Macrophage intracellular PSA might represent a more.     

Preoperative serum caveolin-1 as a prognostic marker for recurrence in a radical prostatectomy cohort.

PURPOSE: Up-regulation of caveolin-1 (cav-1) is associated with virulent prostate cancer, and serum cav-1 levels are elevated in prostate cancer patients but not in benign prostatic hyperplasia. In this study, we evaluated the potential of high preoperative serum cav-1 levels to predict biochemical progression of prostate cancer. The value of the combined preoperative markers, prostate-specific antigen (PSA), biopsy Gleason score, and serum cav-1 for predicting biochemical recurrence was also investigated. EXPERIMENTAL DESIGN: Serum samples taken from 419 prostate cancer patients before radical prostatectomy were selected from our Specialized Programs of Research Excellence prostate cancer serum and tissue bank. Serum samples were obtained 0 to 180 days before surgery and all patients had complete data on age, sex, race, stage at enrollment, and follow-up for biochemical recurrence. Serum cav-1 levels were measured according to our previously reported ELISA protocol. RESULTS: Cav-1 levels were measured in the sera of 419 prostate cancer patients; the mean serum level was 4.52 ng/mL (median 1.01 ng/mL). Patients with high serum cav-1 levels had a 2.7-fold (P = 0.0493) greater risk of developing biochemical recurrence compared with those with low serum cav-1 levels. Importantly, patients with serum PSA >/= 10 ng/mL and elevated levels of serum cav-1 had 2.44 times higher risk (P = 0.0256) of developing biochemical recurrence compared with patients with low levels of cav-1. In addition, high serum cav-1 levels combined with increasing biopsy Gleason score predicted much shorter recurrence-free survival in the group of patients with PSA >/= 10 ng/mL (P = 0.0353). Cav-1 was also able to distinguish between high- and low- risk patients with biopsy Gleason score of seven, after adjusting, for patients PSA levels (P = 0.0429). CONCLUSIONS: Overall, elevated preoperative levels of serum cav-1 predict decreased time to cancer recurrence. In the subset of patients with serum PSA of >/=10 ng/mL, the combination of serum cav-1 and biopsy Gleason score has the capacity to predict time to biochemical recurrence.     

Serum matrix metalloproteinase-2 and its density in men with prostate cancer as a new predictor of disease extension

We examined whether the serum matrix metalloproteinase-2 (MMP-2) level and MMP-2 density could be predictors of the development and extension of prostate cancer. Serum samples were collected before any clinical treatment from 98 patients with prostate cancer and from 76 patients with benign prostatic hyperplasia (BPH). Control sera were obtained from 70 healthy men. The serum level of MMP-2 was determined by 1-step enzyme immunoassay. A newly defined MMP-2 density parameter was determined by dividing the serum level of MMP-2 by the prostate volume, which was measured by ultrasonography. The mean serum level of MMP-2 in prostate cancer patients was significantly higher than in the control and BPH groups. Furthermore, the serum MMP-2 levels in prostate cancer patients with metastasis were highly elevated compared with those without metastases. The MMP-2 density in pathologically organ-confined prostate cancer was significantly higher than that in BPH. There was a statistically significant difference in the MMP-2 density between pT2N0M0 and pT1N0M0 prostate cancers. Moreover, the serum MMP-2 level correlated well with the clinical course of prostate cancer with bone metastasis. Our results suggest that MMP-2 plays an important role in the development and extension of prostate cancer and that the serum level of MMP-2 and the MMP-2 density indicate prostate cancer extension and are, therefore, useful for the followup of prostate cancer patients. Int. J. Cancer (Pred. Oncol.) 79:96–101, 1998. © 1998 Wiley-Liss, Inc.     

Prostate-specific antigen

Prostate specific antigen (PSA) is serine protease produced at high concentrations by normal and malignant prostatic epithelium. It is mainly secreted into seminal fluid, where it digests the gel forming after ejaculation. Only minor amounts of PSA leak out into circulation from the normal prostate, but the release of PSA is increased in prostatic disease. Thus PSA is a sensitive serum marker for prostate cancer but its specificity is limited by a high frequency of falsely elevated values in men with benign prostatic hyperplasia (BPH). Approximately two-thirds of all elevated values (>4 microg/l) in men over 50 years of age are due to BPH. In serum, most of the PSA immunoreactivity consists of a complex between PSA and alpha1-antichymotrypsin (PSA-ACT) whereas approximately 5-40% are free. The proportion of PSA-ACT is larger and the free fraction is smaller in prostate cancer than in benign prostatic hyperplasia (BPH). Determination of the proportion of free PSA has become widely used to improve the cancer specificity of PSA especially in men with PSA values in the 'grey zone' (4-10 microg/l). PSA also occurs in complexes with other protease inhibitors and determination of these and other markers may further improve the diagnostic accuracy for prostate cancer. Interpretation of the results for many different markers is complicated, but this can be simplified by using statistical methods. The diagnostic accuracy can be further improved by using logistic regression or neural networks to estimate the combined impact of marker results and other findings like digital rectal examination (DRE), transrectal ultrasound (TRUS) and heredity.     

Detection of prostatic carcinoma: the role of TRUS, TRUS guided biopsy, digital rectal examination, PSA and PSA density

The purpose of this study was to evaluate the efficacy of various diagnostic tests including transrectal ultrasound (TRUS), TRUS guided biopsy, digital rectal examination (DRE), prostate specific antigen (PSA), and prostate specific antigen density (PSAD) in detecting prostatic carcinomas. One hundred and thirty-four men underwent TRUS guided random, or directed and random sonographic biopsies of the prostate. The mean age was 64.67 (range, 31- 88) years. Indications for biopsy were abnormal findings suggesting prostatic carcinoma on DRE or increased levels of PSA, defined as 4.0 ng/ml or greater in a monoclonal antibody assay. PSAD was calculated by dividing the serum PSA in ng/ml to the volume of the entire prostate in cm3. The biopsy results were grouped as benign, malign and, prostatitis. The patients were also divided into three groups according to their PSA values. Of the 134 patients evaluated, 31 (23.1%) had prostate adenocarcinoma, 89 (66.4%) had benign prostatic tissue, hyperplasia or prostatic intraepithelial neoplasia, and 14 (10.4%) had prostatitis. The mean PSA and PSAD of the carcinoma group were significantly higher than those of the noncancer group. In the group of patients with PSA levels between 4 and 10 ng/ml, abnormal TRUS or DRE increased cancer detection rate, where neither PSA nor PSAD was capable of discriminating the patients with and without cancer. PSAD did not prove to be superior to the other diagnostic tests in this study. We recommend biopsy when either TRUS or DRE is abnormal in patients with PSA levels between 4 and 10 ng/ml. In the patients with PSA levels greater than 10 ng/ml, biopsy is indicated whatever the findings on TRUS or DRE are, since cancer detection rate is high.     

海南地区Gleason评分≥7分的前列腺癌患者血清PSA和睾酮水平与预后相关性探讨

目的:分析海南地区Gleason评分≥7分的前列腺癌（prostatic cancer,PCa）患者血清前列腺特异性抗原(prostate specific antigen,PSA)和总睾酮（total testosterone,TT）水平与5年总生存率的相关性。方法:回顾性分析2009年01月至2019年12月我院收治的前列腺癌患者106例作为PCa组,选取同期良性前列腺增生症（benign prostatic hyperplasia,BPH）患者120例作为BPH组,比较两组患者临床资料、血清PSA、TT水平;再根据PCa组患者5年生存情况分为生存组（n=81）和死亡组（n=25）,比较两组患者临床资料、Gleason评分、血清PSA、TT水平;采用多因素COX回归分析影响前列腺癌患者预后的独立危险因素;绘制受试者工作特征曲线（receiver operating characteristic curve,ROC）,分析血清PSA、TT水平早期评估前列腺癌患者预后的预测价值;采用Spearman相关性模型分析血清PSA、TT水平与病理Gleason评分的相关性。结果:PCa组患者年龄、前列腺体积、血清PSA水平高于BPH组,血清TT水平低于BPH组,差异具有统计学意义（P＜0.05）;生存组患者Gleason评分、血清PSA水平、骨转移发生率、TNM分期低于死亡组,血清TT水平高于死亡组,差异具有统计学意义（P＜0.05）;Spearman相关性分析显示,血清PSA水平与病理Gleason评分呈正相关（r=0.634,P＜0.05）,血清TT水平与病理Gleason评分呈负相关（r=-0.755,P＜0.05）;多因素COX回归分析显示,高PSA水平（HR=1.352）、高Gleason评分（HR=4.576）、高TNM分期(HR=2.937)和骨转移（HR=1.258）是前列腺癌患者预后的独立危险因素（P＜0.05）,高TT水平（HR=0.063）是前列腺癌患者预后的保护因素（P＜0.05）;ROC曲线显示,血清PSA、TT水平及两者联合早期预测前列腺癌患者预后的曲线下面积（area under curve,AUC）为0.811、0.887和0.934,敏感度为88.00%、96.00%和92.00%,特异度为68.73%、72.84%和82.72%,截点值分别为21.51 ng/mL和3.74 ng/mL。结论:前列腺癌患者血清PSA、TT水平可作为早期评估患者预后的重要指标,其与病理Gleason评分存在高度相关性。     

The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels.

Prostate cancer is a disease associated with androgens. It has been hypothesized that reducing the conversion of testosterone (T) to dihydrotestosterone (DHT) in the prostate by the use of the drug finasteride, a 5alpha-reductase inhibitor, will reduce the incidence of prostate cancer. We investigated the chemopreventive potential of finasteride by evaluating its effect on the prostate gland of men with elevated serum prostate-specific antigen (PSA). Fifty-two men with elevated PSA and prostate sextant biopsies negative for cancer were randomized to receive finasteride 5 mg day(-1) (27 patients) or no medication (25 patients) for 12 months and were rebiopsied at 12 months. The biopsies were evaluated for the presence of cancer, the proportion of glandular and hyperplastic tissue, and the presence of high-grade prostatic intraepithelial neoplasia (PIN). Epithelial proliferation was assessed in the prestudy and 12-month biopsies by immunohistochemistry using antibody to proliferating cell nuclear antigen (PCNA). Serum blood samples were drawn at baseline and after 1, 3, 6 and 12 months of study. In the control group, serum levels of PSA and T were unchanged throughout the 12 months. In the finasteride group, PSA decreased 48% (P < 0.001), DHT decreased 67% (P < 0.001) and T increased 21% (P < 0.001). Histological evaluation of prestudy and 12-month biopsy specimens revealed that the finasteride group had a 30% reduction in the percentage of hyperplastic epithelial tissue (P = 0.002), although this decrease was not statistically significantly different between the finasteride and control groups (P = 0.11). In patients with PIN on prestudy biopsy, no change occurred in the PIN lesions with finasteride treatment. Finasteride also had no effect on the proliferation index of prostatic epithelial cells. Of the 27 patients treated with finasteride, eight (30%) had adenocarcinoma of the prostate detected on the 12-month biopsy, compared with one (4%) of the control patients (P = 0.025). In the treatment group, six cancers occurred in the eight patients with PIN on the prestudy biopsy; in the observation group no cancers were detected in the five patients with PIN on the prestudy biopsy (P = 0.021). Two cancers occurred in the 19 men in the treatment group with no evidence of PIN on the prestudy biopsy, compared with one cancer in the 20 men in the observation group with no evidence of PIN on the prestudy biopsy (P = 0.60). This study, using a novel model for evaluating short-term efficacy of chemopreventive or therapeutic agents in men at high risk of prostate cancer, provides little evidence that finasteride is an effective chemopreventive agent for prostate cancer in men with elevated PSA.     

Effects of chronic bacterial prostatitis on changes in concentration and free and total prostatic specific antigen in the serum and urine from patients with benign prostatic hyperplasia and prostatic cancer

A comprehensive urological examination was performed in 145 men with benign prostatic hyperplasia (BPH). Concentrations of total prostatic specific antigen (TPSA) suggested prostatic cancer (PC) in 38 patients while finger rectal examination and transrectal ultrasonic investigation gave no evidence for this diagnosis. All the patients have symptoms of chronic prostatitis (CP). All the patients with chronic bacterial prostatitis have undergone a course of antibacterial treatment after which the levels of TPSA and free prostatic specific antigen (FPSA) were evaluated. A polyposition biopsy of the prostate was also made. By its results two groups of patients were formed: 20 patients with BPH and CP (group 1) and 12 patients with CP and PC or prostatic ultraepithelial neoplasia. Low blood concentrations of TPSA high FPSA/TPSA, low urinary concentrations of TPSA and FPSA were registered after antibacterial and antiinflammatory treatment of CP combined with BPH. It is inferred that chronic bacterial prostatitis has a significant effect on PSA expression in BPH. This fact should be considered in interpretation of PSA values.     

血清PSA及超声引导穿刺活检对前列腺癌病理分期预测价值研究

目的 研究血清前列腺特异性抗原(PSA)及超声引导穿刺活检对前列腺癌病理分期的预测价值.方法 选取200例经直肠超声引导前列腺穿刺活检确诊为前列腺癌的患者的临床资料进行研究.分析患者的血清PSA、穿刺活检阳性百分数及Gleason评分3个参数与前列腺癌病理分期的相关性;同时对比性分析以上3个参数在不同病理分期前列腺癌患者中的差异情况.结果 血清PSA、穿刺活检阳性百分数及Gleason评分均与前列腺癌患者的病理分期呈正相关(P﹤0.001);D期前列腺癌患者的血清PSA水平明显高于A期、B期、C期前列腺癌患者(P﹤0.05),而A期、B期、C期前列腺癌患者的血清PSA水平两两之间比较,差异均无统计学意义(P﹥0.05);C期与D期前列腺癌患者的穿刺活检阳性百分数比较,差异无统计学意义(P﹥0.05),而其他各分期间穿刺活检阳性百分数两两比较,差异均有统计学意义(P﹤0.05);A期与C期、B期与C期、A期与D期、B期与D期前列腺癌患者的Gleason评分比较,差异均有统计学意义(P﹤0.05),而A期与B期、C期与D期前列腺癌患者的Gleason评分比较,差异无统计学意义(P﹥0.05).结论 血清PSA、穿刺活检阳性百分数及Gleason评分均可单独用于前列腺期病理分期的预测,同时该3个参数在区分前列腺癌病理分期方面也发挥一定辅助作用.     

Cumulative Probability of Prostate Cancer Detection Using the International Prostate Symptom Score in a Prostate-specific Antigen-based Population Screening Program in Japan

The International Prostate Symptom Score (IPSS) is often used as an interview sheet for assessing lower urinary tract symptoms (LUTS) at the time of prostate-specific antigen (PSA) testing during population-based screening for prostate cancer. However, the relationship between prostate cancer detection and LUTS status remains controversial. To elucidate this relationship, the cumulative probability of prostate cancer detection using IPSS in biopsy samples from patients categorized by serum PSA levels was investigated. The clinical characteristics of prostate cancer detected using IPSS during screening were also investigated. A total of 1,739 men aged 54-75 years with elevated serum PSA levels who completed the IPSS questionnaire during the initial population screening in Kanazawa City, Japan and underwent systematic transrectal ultrasonography-guided prostate biopsy between 2000 and 2013 were enrolled in the present study. Of the 1,739 men, 544 (31.3%) were diagnosed with prostate cancer during the observation period. The probability of cancer detection at 3 years in the entire study population was 27.4% and 32.7% for men with IPSS≤7 and those with IPSS≥8, respectively; there was no statistically significant difference between groups. In men with serum PSA levels of 6.1 to 12.0ng/mL at initial screening, the probability of cancer detection was significantly higher in men with IPSS≤7 than in those with IPSS≥8. There were no significant differences in clinical characteristics between groups of patients stratified by IPSS. These findings indicate that the use of IPSS for LUTS status evaluation may be useful for prostate cancer detection in the limited range of serum PSA levels.     

Progression of prostate cancer: diagnostic and prognostic utility of prostate-specific antigen, alpha2-macroglobulin, and their complexes

We previously reported cases of advanced prostate cancer (PCa) in which serum alpha2-macroglobulin (alpha2M) levels were markedly decreased to less than approximately 50 mg/dl whereas serum prostate-specific antigen (PSA) levels were remarkably increased. These cases were not complicated with disseminated intravascular coagulation (DIC). In this study, we measured serum PSA and alpha2M in 108 patients with either benign prostatic hyperplasia (BPH) or PCa to elucidate the relationship between PSA, i.e. the serum protease derived from the prostatic tissue, and alpha2M, i.e. the protease inhibitor that was the most abundantly contained in serum. alpha2M was determined by ELISA, total PSA and PSA-alpha1-antichymotrypsin (PSA-ACT) by EIA, and free-PSA by RIA in 44 patients with untreated BPH and 64 patients with untreated PCa. The ready association of alpha2M and PSA was assessed using Western blotting to identify complexes of the two. Levels of total serum PSA correlated positively with those of PSA-ACT in PCa (r = 0.99, p < 0.001), and both levels increased with advancing stage of disease. In contrast, the serum-free PSA/total PSA ratio (free/total PSA) and alpha2M levels decreased as the disease progressed. However, only the free/total PSA ratio attained significant difference for localized cancer in stage T1,2 versus BPH (p < 0.05). In stage M1b PCa, in which serum PSA levels were very high, there was a negative correlation between the total PSA and alpha2M values (r = -0.57, p < 0.05). In addition, serum alpha2M levels tended to decrease with progression of PCa. Serum total PSA levels correlated tightly with serum PSA-ACT levels. It is suggested that PSA is usually complexed with ACT in the serum. Free/total PSA was useful for differential diagnosis between early cancer and BPH. Levels of serum alpha2M of less than 50 mg/dl in PCa patients may indicate a possibility of bone metastases.     

The Relationship Between Prostate Biopsy Results and PSA and Free PSA Ratio Changes in Elevated Serum PSA Patients with and without Antibiotherapy

Objectives: To evaluate the impact of antibiotic treatment on total prostate specific antigen (PSA) levels and free/total (f/t) PSA ratio and the relevance of these changes to prostate biopsy results. Methods: We retrospectively evaluated 1,062 patients with elevated age-adjusted serum PSA levels who underwent prostate biopsy between 2004 and 2016. A total of 303 cases with followup PSA levels and f/t PSA ratio before and after antibiotherapy were included into this study. There were 214 patients with persistent elevated serum PSA levels after antibiotic treatment followed by prostate biopsy (treatment group) and 89 patients who had prostate biopsy after a mean followup of 1 month without antibiotherapy (control group). The groups were compared with regard to both 5% and 10% cut off changes in serum PSA levels and f/t PSA ratios. Results: Antibiotic treatment had no impact on the relation between serum PSA levels and biopsy results at both cut off values. On the other hand, f/t PSA ratio changes at both cut off values with relevance to antibiotic treatment were found to be related with histopathologic results. While increase in f/t PSA ratio was more related with benign biopsies, decrease in f/t PSA ratio was more related with cancer (for 5% cut off value p= 0.014, p= 0.004; for 10% cut off value p= 0.026, p= 0.014). Conclusion: Changes at f/t PSA ratio rather than total PSA only, particularly in antibiotic treated cases appear to be more useful in decision making for biopsy.     

超声引导下前列腺10点加定点穿刺活检术诊断前列腺癌

目的 探讨经直肠彩色多普勒超声引导下前列腺穿刺活组织检查在前列腺癌诊断中的应用.方法 181例疑诊前列腺癌的患者进行血清总前列腺特异性抗原(T-PSA)检测,采用10点加前列腺癌可疑灶定点穿刺活检术.结果 181例中检出前列腺癌80例(44.2%),前列腺增生63例(34.8%).前列腺炎36例(19.9%),前列腺结核1例(0.6%),前列腺平滑肌瘤1例(0.6%).T-PSA水平＞20μg/L组的前列腺癌发生率高于其他各组.随着T-PSA水平的升高,Gleason评分增加(P＜0.001).结论 超声引导下10点加定点穿刺活检术诊断前列腺癌的阳性率高,对T-PSA＞20μg/L的疑诊前列腺癌患者活检意义较大.     

Rationale for using serum prostate-specific antigen (PSA) level and PSA density (PSAD) to detect prostatic malignancy in a country with low prostate cancer incidence

Prostate-specific antigen (PSA) and PSA density (PSAD) values in Indonesia had been found uniquely much higher than the normal accepted values in western countries. However, PSA more than 10 ng/ml and PSAD above 0.15 in intermediate PSA of 4-10 ng/ml are still indicative of a prostate biopsy. This condition had led to unnecessary biopsies in view of the low incidence of prostatic carcinoma in our country. Our objective is to find alternative serum PSA levels and PSAD cutoff points that enhance the specificity and sensitivity of prostate cancer detection. This retrospective cross-sectional study included 805 consecutive patients from 40 to 95 years old in Sumber Waras Hospital (SWH) and Cipto Mangunkusumo Hospital (CMH) from 1994 to 1997. All patients underwent digital rectal examination (DRE) and transrectal ultrasonography (TRUS) to measure prostate volume. After the serum PSA level was determined and PSAD was calculated, prostate biopsies were performed if the PSA level was greater than 10 ng/ml or PSAD more than 0.15 at intermediate PSA levels of 4-10 ng/ml. The ability of PSA, intermediate PSA level, and PSAD to improve the accuracy of prostate cancer detection was evaluated using univariate analysis. Among 805 patients, 240 patients had PSA level < 4 ng/ml, 230 patients had PSA level 4-10 ng/ml, and 335 had PSA level > 10 ng/ml. Of the 230 patients with intermediate PSA level, 108 had PSAD > 0.15. Thirty-five patients had histologically confirmed prostatic carcinoma, i.e., 3 of 108 patients with PSA 4-10 ng/ml and PSAD > 0.15, and 32 of 335 patients with PSA > 10 ng/ml. There were 105 and 303 unnecessary biopsies in those groups. With a PSA cutoff level of > or = 8 ng/ml, we found 100% sensitivity to prostate cancer. PSAD > or = 0.20 within a PSA level of 8-30 ng/ml gave 100% sensitivity to prostate cancer. Using these new cutoffs there would be 148 biopsies (33.4%) saved. We concluded from this study that the commonly accepted values of serum PSA level and PSAD resulted in many unnecessary biopsies in our patients. Instead, the most sensitive cutoff points to perform prostate biopsy are serum PSA level greater than 8.0 ng/ml, and PSAD of more than 0.20 at an intermediate serum PSA level of 8-30 ng/ml.     

血清缓激肽与前列腺癌的相关性研究

目的 探讨血清缓激肽在前列腺癌的诊断及鉴别诊断中的临床应用价值.方法 收集68例前列腺癌患者和32例前列腺增生患者,以同期体检的健康男性32例为对照组,收集其血清,酶联免疫吸附试验(enzymelinked immuno sorbent assay,ELISA)法检测血清中的缓激肽水平,比较各组血清缓激肽水平的差异以及前列腺癌患者在不同年龄、临床分期、病理分期(Gleason评分)、前列腺特异抗原(prostate specific antigen,PSA)水平、肿瘤体积以及骨转移、淋巴结转移、局部侵犯与否状态下血清缓激肽水平的差异.比较血清缓激肽与PSA联合诊断前列腺癌和PSA独立诊断前列腺癌的敏感度差异.结果 前列腺癌组血清缓激肽水平[(16.44 ±0.91) μg/L]低于对照组[(19.72±1.10) μg/L]和前列腺增生组[(20.93±1.80) μg/L],差异均具有统计学意义(均P＜0.05).在肿瘤体积较大的前列腺癌患者血清缓激肽水平较低(P＜0.05),而血清缓激肽水平在年龄、肿瘤临床分期、病理分期(Gleason评分)、PSA水平及骨转移、淋巴结转移、局部侵犯与否方面比较差异均无统计学意义(均P＞0.05).血清缓激肽与PSA联合诊断前列腺癌较单独诊断敏感度提高(P＜0.05).结论 前列腺癌患者血清缓激肽表达水平较低,且与肿瘤体积相关.血清缓激肽与PSA联合诊断前列腺癌敏感度较单独诊断高.     

The clinical utility of measuring total PSA, PSA density, gamma-seminoprotein and gamma-seminoprotein/total PSA in prostate cancer prediction

BACKGROUND: To evaluate whether serum total prostate-specific antigen (PSA), PSA density (serum total PSA level divided by prostate volume), gamma-seminoprotein and gamma-seminoprotein/total PSA ratio could predict prostate cancer (PCa) prior to biopsy. METHODS: A total of 316 consecutive patients who had undergone transrectal prostate biopsy and/or transurethral resection were examined. The prostate volume was determined by transrectal ultrasonography (TRUS) and the ability of the above-mentioned four variables to distinguish PCa from benign prostatic hyperplasia (BPH) was evaluated. RESULTS: PCa was detected in 61 cases. Receiver-operating characteristic (ROC) analysis revealed that both the PSA density and serum total PSA were the most useful predictors of PCa among the four variables. For the patients with a serum total PSA level of 4.1-10.0 ng/ml, PSA density was significantly more accurate than total PSA (p < 0.005). An optimum PSA density value of 0.18 was chosen as a cutoff because it showed the highest sum of sensitivity and specificity, 92 and 54%, respectively. Using this PSA density cutoff, the number of biopsies could have been reduced to 57 from 63% when compared with a PSA density of 0.15. CONCLUSIONS: PSA density was significantly more accurate than other variables in predicting PCa. To avoid unnecessary biopsies, the PSA density cutoff value of 0.18 would be recommendable for determining a prostate biopsy for Japanese males with a serum total PSA level of 4.1-10.0 ng/ml.     

Value of free-to-total prostate-specific antigen ratio for detection and staging of prostate cancer

Background. We aimed to evaluate the clinical usefulness of measurement of the free-to-total (F/T) ratio of prostate-specific antigen (PSA) for the differentiation of prostate cancer from benign prostate hyperplasia (BPH) and for the staging of prostate cancer. Values for PSA density (PSAD) and PSAD adjusted to the transition zone volume (PSAD-T) were also evaluated in patients with mildly elevated PSA levels (4.1–10 ng/ml). Methods. Total and free PSA and the F/T ratio were determined in 80 men with prostate cancer and 48 men BPH before treatment. PSA levels were measured with a chemiluminescent enzyme immunoassay. Results. Patients with prostate cancer had a significantly lower F/T ratio than those with BPH. A cut-off value of 14% for the F/T ratio provided a positive predictive value of 81.6% and a negative predictive value of 65.4%. The F/T ratio did not differ between patients with clinically localized and metastatic prostate cancer. In patients with a PSA value of 4.1–10 ng/ml, a cut-off value of 14% for the F/T ratio provided a sensitivity of 66.7% and a specificity of 76.2%. Sixty percent of the missed cancer in patients with an F/T value of 14% or more could be rescued using the PSAD value. Conclusion. Measurement of the F/T PSA ratio has good sensitivity and specificity in distinguishing prostate cancer from BPH, especially in patients with a PSA level of 4.1–10 ng/ml. However, compared with serum PSA level, the F/T PSA ratio is not valuable for the clinical staging of prostate cancer. Received: June 23, 1999 / Accepted: September 22, 1999