游离PSA与总PSA比值在前列腺癌鉴别诊断中的意义

目的　探讨游离前列腺特异性抗原 (fPSA)与总前列腺特异性抗原 (tPSA)比值 (f tPSA)在tPSA为 4～ 10ng ml时对前列腺癌和良性前列腺增生 (BPH)鉴别的意义及其局限性。方法　对1998年 10月至 2 0 0 2年 10月接受诊治的 180例血清tPSA为 4～ 10ng ml的前列腺癌和BPH患者进行回顾性分析。经组织学证实 ,36例 (2 0 % )是前列腺癌 ,14 4例 (80 % )是BPH。血清中tPSA和fPSA通过酶免微粒子捕捉法测定。前列腺体积通过经腹壁超声测定。前列腺癌与BPH组间比较用t检验。采用Pearson相关系数分析前列腺体积与f tPSA之间的相关性。结果　前列腺癌患者的tPSA、f tPSA平均值分别是 6 75ng ml与 0 17;BPH患者则是 6 4 8ng ml和 0 2 5。两组患者的tPSA差异无显著意义 (P >0 0 5 ) ,而前列腺癌患者的f tPSA值显著低于BPH患者 (P <0 0 1)。此外 ,两组患者的前列腺体积与f tPSA均呈显著正相关 (前列腺癌组相关系数r=0 5 0 ,P <0 0 1;BPH组r=0 2 4 ,P <0 0 1)。在前列腺体积小于 4 0cm3,两组患者的f tPSA差异有显著意义 (P <0 0 5 ) ,当体积超过 4 0cm3,则差异无显著意义 (P >0 0 5 )。结论　f tPSA对tPSA在 4～ 10ng ml之间的前列腺癌和BPH的鉴别诊断有重要意义 ,但由于受前列腺体积的影响 ,只有在     

Value of the Free to Total Prostate Specific Antigen Ratio and Prostate Specific Antigen Density for Detecting Prostate Cancer in Japanese Patients

Background : This study evaluated the free to total serum prostate specific antigen (f/t PSA) ratio and prostate specific antigen density (PSAD) in detecting prostate cancer in Japanese males with a PSA level between 2.5 and 20.0 ng/mL in a community-based urology practice.
Methods : Twenty-six patients with clinically localized prostate cancer and 44 patients with histologically-proven benign prostatic hyperplasia (BPH) were studied. The serum levels of free PSA (fPSA) and total (t) PSA were determined using a chemiluminescent enzyme immunoassay. The f/t PSA ratio was calculated by dividing the fPSA value by the total PSA value and was compared with the PSA and PSAD via the receiver operating characteristic (ROC) curves.
Results: Patients with prostate cancer had a significantly lower f/t PSA ratio than patients with BPH. The PSAD was a superior diagnostic tool over PSA (P < 0.01) when analyzed by ROC curves. The f/t PSA ratio was also superior to PSA, but lacked significance (P=0.12), and similarly, the PSAD was superior, but not significant, to the f/t PSA ratio. Using a cut-off value of 0.1 9, the PSAD had a sensitivity of 81% and a specificity of 82%. With a cut-off value of 14.0%, the f/t PSA ratio had a sensitivity of 81% and a specificity of 66%.
Conclusion: This study showed that PSAD alone improved cancer detection significantly better than PSA. However, it is still unclear whether the f/t PSA ratio is superior to PSA or PSAD in the discrimination between BPH and prostate cancer in Japanese male patients.     

Hormonal predictors of prostate cancer

INTRODUCTION: Androgens are necessary for the development and functioning of the prostate gland. The association of serum testosterone and pituitary hormone levels with prostate cancer development is not completely understood. In this clinical study, we evaluated the role of serum testosterone, free testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in predicting prostate cancer risk in patients who had transrectal ultrasonography-guided prostate biopsy with the suspicion of prostate cancer. MATERIAL AND METHODS: A total of 211 patients who were selected to undergo prostatic biopsy due to abnormal digital rectal examination and/or a serum prostate-specific antigen (PSA) level >2.5 ng/ml were included in the study. The patient characteristics of total PSA, free/total PSA ratio, serum total testosterone, free testosterone, free/total testosterone ratio, FSH and LH levels were compared according to the pathological diagnosis. RESULTS: The mean age was 63.91 years (range 44-83) and the mean PSA level was 9.23 ng/ml (range 0.13-50.41) in the whole group. Of 211 patients, 69 (32.7%) were positive for prostate cancer. The patients who were positive for prostate cancer had statistically lower levels of serum total testosterone compared with the patients who were diagnosed as having benign prostatic hyperplasia (BPH; 405 vs. 450.5 ng/dl, respectively; p = 0.013). The serum FSH level was significantly higher in men with prostatic cancer than in men with BPH (7.56 vs. 6.06 mIU/ml, respectively; p = 0.029). No significant differences between men with prostatic cancer and those with BPH were found for serum LH levels. When normal ranges for serum free and total testosterone levels were defined as 9 pg/ml and 300 ng/dl, respectively, patients who had low free testosterone and total testosterone levels had significantly higher cancer detection rates than patients with high serum androgen levels: 40.8% (40/98) versus 25.6% (29/113) (p = 0.021), and 48.6% (18/37) versus 29.3% (51/174), respectively (p = 0.023). After logistic regression analysis, none of the hormones showed a significant difference in predicting the risk of prostate cancer in patients undergoing prostate biopsy with suspicion of the disease. CONCLUSION: Our data suggest that patients diagnosed with prostate cancer have low levels of serum testosterone and high levels of serum FSH compared with the patients with BPH. No support was found for the theory that high levels of testosterone increase prostate cancer risk. Further studies are needed to clarify the relationship between hormones and prostate cancer etiology.     

THE EFFECT OF HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA ON SERUM TOTAL AND PERCENTAGE OF FREE PROSTATE SPECIFIC ANTIGEN LEVELS

PURPOSE: It is established that the percentage of free prostate specific antigen (PSA) in serum is low in patients with prostate cancer. An unanswered question is whether a low percentage of free PSA can be explained by high grade prostatic intraepithelial neoplasia alone. We compared the percentage of free PSA in men with high grade prostatic intraepithelial neoplasia alone, prostate cancer, benign prostatic hyperplasia (BPH) and a normal prostate (that is normal digital rectal examination and PSA less than or equal to 2.5 ng./ml.). MATERIALS AND METHODS: From October 1994 through December 1997, 48 men were diagnosed with high grade prostatic intraepithelial neoplasia without concomitant prostate cancer. Of these men 43 with a mean age plus or minus standard deviation of 67.4 +/- 7.8 years comprised our study group. To date none has been diagnosed with cancer during followup. Serum free and total PSA levels were measured, and the percentage of free PSA was calculated. The percentage of free PSA in the 43 men was compared to that in 50 with prostate cancer (mean age 65.4 +/- 7.8 years), 50 with biopsy proved BPH (67 +/- 7) and 43 with a normal prostate (61 +/- 8). RESULTS: There was no significant difference in mean total serum PSA in patients with high grade prostatic intraepithelial neoplasia, prostate cancer or BPH. The percentage of free PSA was significantly lower in patients with prostate cancer (14.9 +/- 6.5%) than those with high grade prostatic intraepithelial neoplasia (20.8 +/- 7.1%), BPH (20.1 +/- 7.3%) or a normal prostate (27.7 +/- 12.2%). There was also no significant difference in the percentage of free PSA between men with high grade prostatic intraepithelial neoplasia (20.8 +/- 7.1%) and those with BPH (20.1 +/- 7.3%). Additionally, men with a normal prostate had a higher percentage of free PSA (27.7%) than those with BPH (20.1%), high grade prostatic intraepithelial neoplasia (20.8%) or prostate cancer (14.9%). CONCLUSIONS: The percentages of free PSA in men with high grade prostatic intraepithelial neoplasia and BPH are similar, and significantly higher than those found in men with prostate cancer.     

High serum prostate-specific antigen levels in the absence of prostate cancer in Middle-Eastern men: the clinician's dilemma

OBJECTIVE: To investigate the common causes of total serum prostate-specific antigen (PSA) values of> 10 ng/mL in an Arab population, as in the USA and Europe the risk of prostate cancer is considered high in men with such PSA levels. PATIENTS AND METHODS: Serum total PSA was measured in men presenting to our hospital as part of the investigation for prostate cancer screening and/or in elderly men with prostatism. Men with a serum PSA level of> 10 ng/mL were further investigated by transrectal ultrasonography (TRUS) of the prostate and biopsy of suspicious lesions for histological diagnosis. In addition, the percentage of free PSA, PSA velocity and PSA density were determined. All the patients included in this study were men of Arab origin residing in Kuwait. RESULTS: In all, 1700 men (mean age 55.6 years, range 35-94) were assessed; of these, 161 had a serum PSA of> 10 ng/mL, attributable to benign prostatic hyperplasia (BPH) in 110 (68%), BPH with histological features of prostatitis in 33 (21%) and prostate cancer in 18 (11%). TRUS of the prostate in 143 of the 161 men with either BPH or BPH with prostatitis showed varying grades of intraprostatic calcifications in 22 (15%). Both PSA density and percentage free PSA did not contribute to determining the causes of total PSA levels of> 10 ng/mL. There was a progressive decline in PSA in all patients with BPH and prostatitis, except one who at re-biopsy had prostate cancer (T1N0M0, G1). CONCLUSION: Total PSA values of> 10 ng/mL in Arab men may be a result of BPH, BPH with prostatitis or prostate cancer, in that order. A gradual decline in total PSA (decreased PSA velocity) with time to < 4 ng/mL often confirms the diagnosis of BPH with prostatitis. The percentage of free PSA and PSA density may not be helpful in diagnosing prostate cancer with certainty in these patients. Compared with Caucasians in the USA and Europe, BPH and BPH with prostatitis appear to be more frequent causes of serum PSA levels of> 10 ng/mL in Arab men.     

Effect of NIH-IV prostatitis on free and free-to-total PSA

OBJECTIVE: To examine the effect of asymptomatic prostatic inflammation (NIH category IV prostatitis) on total PSA (tPSA), free serum PSA (fPSA) and the ratio of free-to-total prostate specific antigen (%fPSA). The role of free and %fPSA as a diagnostic tool for distinguishing between cancer and non-malignant diseases of the prostate was also investigated. MATERIAL AND METHODS: In a retrospective study 1090 prostate biopsies performed between January 2000 and September 2003 were evaluated and the levels of serum total and free PSA as well as the f/tPSA ratio were determined in samples obtained immediately before biopsy. 404 patients with full clinical and histological records were included in the study. All patients underwent 6 or 8 core primary prostate needle biopsies. RESULTS: A total of 404 patients were included in the analysis. 100 prostate cancer (PCa) (24.8%), 137 NIH-IV prostatitis (33.9%) and 143 patients with benign prostatic hyperplasias (BPH) (35.4%) were identified. 24 (5.9%) patients presented with both PCa and prostatitis on histology and were excluded from further analysis. The mean (median) levels of tPSA, fPSA and %fPSA were 11.94 ng/ml (8.0), 1.31 ng/ml (1.07) and 0.15 (0.14) for NIH-IV prostatitis; 11.94 ng/ml (8.35), 1.54 ng/ml and 0.13 (0.11) for prostate cancer; and 8.19 ng/ml (7.0), 1.48 ng/ml (1.03) and 0.18 (0.15) for BPH. No significant difference was found in tPSA levels between PCa and prostatitis (p = 0.32), while the difference in tPSA levels between PCa and BPH was significant (p = 0.007). Free PSA alone had no diagnostic power in distinguishing PCa from prostatitis (p = 0. 37) and BPH (p = 0. 61). By contrast, the f/tPSA ratio showed significant between-group differences (PCa versus prostatitis (p = 0. 011), PCa versus BPH (p = 0.0001). CONCLUSIONS: Chronic asymptomatic prostatitis NIH category IV has similar effects on total PSA and free PSA levels in serum as PCa. fPSA alone cannot distinguish prostate cancer from non-malignant inflammatory disease of the prostate. The ratio of free-to-total PSA is significantly different in PCa and NIH category IV prostatitis.     

Study of free to total prostate specific antigen ratio in the detection of patients with prostate cancer

BACKGROUND: We investigated the clinical usefulness of free to total serum prostate specific antigen (PSA) ratio (F/T ratio) in order to improve the specificity of total PSA measurement for detecting prostate cancer. METHOD: In this study 129 patients with total PSA level 4-20 ng/ml underwent transrectal ultrasound guided sextant biopsy. Serum samples were assessed for total PSA, free PSA and the F/T ratio calculated. All patients were pathologically diagnosed as benign prostatic hyperplasia or prostate cancer. RESULTS: Of 129 patients 21 had prostate carcinoma (PCa) and 108 had benign prostatic hyperplasia (BPH) from the results of prostate biopsies. The mean of total PSA were not significantly different between men with PCa and with BPH. The mean of free PSA for PCa was significantly lower than that for BPH (p = 0.043). Furthermore, the mean of F/T ratio was significantly different between PCa and BPH group (p = 0.0014). The F/T ratio had a higher specificity than total PSA at all levels of sensitivity in detecting prostate cancers. Sensitivity, specificity and accuracy for cancer detection at a cut off 0.12 was 90.4%, 51.8% and 58.1%, respectively. Also, free PSA was as useful as F/T ratio for cancer detection when analyzed in receiver operating characteristic curves analysis. When determined the cut off number of free PSA at 0.78 ng/ml, the sensitivity, specificity and accuracy for cancer detection were 61.9%, 66.7% and 65.9%, respectively. CONCLUSION: This study indicated that the F/T ratio and free PSA could improve the specificity without impairing the sensitivity for detecting PCa in patients with 4-20 ng/ml of total PSA.     

Changes in molecular forms of prostate-specific antigen during treatment with finasteride

OBJECTIVE: To study the influence of finasteride treatment on the molecular forms of prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Total PSA, free PSA and PSA complexed to alpha1-antichymotrypsin (PSA-alpha1ACT) were measured in plasma and serum from 40 men with BPH and a total PSA of < 20 ng/mL, using in-house and commercial immunoassays, before and during treatment with finasteride (30 men) or placebo (10 men). RESULTS: The baseline values were not significantly different between the groups, with mean (sd) total plasma PSA levels of 3.6 (4.3) and 4.8 (5.9) ng/mL in the finasteride and placebo groups, respectively. Finasteride, but not placebo, induced a significant reduction in total PSA, free PSA and PSA-alpha1ACT levels in plasma and serum (P < 0.001). However, complexed-to-total (c/t) and free-to-total (f/t) PSA ratios remained constant in both groups, both in plasma and serum, during the follow-up. CONCLUSION: The decrease in total PSA after finasteride treatment results from a proportional reduction in its two major molecular forms, free PSA and PSA-alpha1ACT, which explains why the c/t and f/tPSA ratios do not change significantly despite treatment. This suggests that routine analysis of molecular forms of PSA could improve the utility of the change in total PSA associated with finasteride for the early diagnosis of prostate cancer. It also suggests that any subsequent change in both ratios, particularly an increase in c/tPSA or a decrease in f/tPSA ratio, could be considered an early sign of neoplastic degeneration rather than a therapeutic consequence.     

Comparison of the clinical value of complexed PSA and total PSA in the discrimination between benign prostatic hyperplasia and prostate cancer

BACKGROUND: To compare the clinical value of the measurement of complex and total PSA in the discrimination between benign prostatic hyperplasia (BPH) and prostate cancer. METHODS: In serum samples collected from 166 men with histopathologically proven clinically localized prostate cancer and of 97 men with BPH, total prostate-specific antigen (PSA), complexed PSA and the free to total PSA ratio were determined. The statistical analysis was done by the comparison of the receiver operator characteristic (ROC) curves. RESULTS: The areas under the ROC curves were 0.776 for total PSA, 0.799 for complexed PSA (total PSA vs. cPSA: p < 0.0001) and 0.812 for the free to total PSA ratio. With a cut-off of 3.0 ng/ml for complexed PSA, the sensitivity was 90%, the specificity 58%, the positive and the negative predictive values 79 and 78%, respectively. With a cut-off of 4.0 ng/ml for total PSA, the sensitivity was 87%, the specificity 59%, the positive and the negative predictive values were 78 and 72%, respectively. CONCLUSIONS: There was a statistically significant advantage for complexed PSA compared to total PSA in the discrimination between BPH and prostate cancer. The difference was, however, small and its clinical relevance is questionable.     

Circulating tumour-associated plasma DNA represents an independent and informative predictor of prostate cancer

OBJECTIVE: To investigate whether preoperative plasma levels of free DNA can discriminate between men with localized prostate cancer and benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: In all, 161 referred patients suspicious for prostate cancer either by an elevated prostate-specific antigen (PSA) level and/or abnormal digital rectal examination (DRE) were included in this prospective study. Peripheral plasma was taken before prostate biopsy and genomic DNA was extracted from the plasma using the a commercial kit and a vacuum chamber. After controlling for age, PSA level, the percentage free/total (f/t) PSA and prostate volume, the median prostate cancer plasma DNA concentration served as diagnostic threshold in uni- and multivariate logistic regression models. Multivariate models were subjected to 200 bootstraps for internal validation and to reduce over-fit bias. RESULTS: Subgroups consisted of 142 men with clinically localized prostate cancer and 19 with BPH. The median plasma concentration of cell-free DNA was 267 ng/mL in men with BPH vs 709 ng/mL in men with prostate cancer. In univariate analyses, plasma DNA concentration was a statistically significant and informative predictor (P = 0.032 and predictive accuracy 0.643). In multivariate analyses, it remained statistically significant after controlling for age, tPSA, f/tPSA and prostate volume, increasing the predictive accuracy by 5.6%. CONCLUSIONS: Our data suggest that plasma DNA level is a highly accurate and informative predictor in uni- and multivariate models for the presence of prostate cancer on needle biopsy. The predictive accuracy was substantially increased by adding plasma DNA level. However, larger-scale studies are needed to further confirm its clinical impact on prostate cancer detection.     

Dual monoclonal antibody immunoassay for free prostate-specific antigen

Prostate-specific antigen (PSA) is the most important tumor marker for early detection and monitoring of prostate cancer (PCa) patients. PSA is also elevated in many patients with benign prostatic hyperplasia (BPH). The study of the serum PSA forms, free PSA (f-PSA) and PSA complexed with α₁-antichymotrypsin (PSA-ACT), may improve the discrimination between PCa and BPH. An immunoassay specific for f-PSA is reported with very low cross-reactivity (0.7%) to PSA-ACT. Serum specimens from BPH and PCa patients (determined by biopsy) with PSA levels from <1 to >100 ng/ml were tested. No f-PSA was detected in serum specimens from normal females (N = 50). Low levels (0–0.3 ng/ml) were detected in specimens from healthy males (N = 60). In specimens from PCa and BPH patients, the f-PSA to total PSA ratio (f/t) was found to range from 1% to higher than 60%. While maintaining an 80% sensitivity for cancer, the f/t ratio improved specificity to approximately 80%, as compared to 55% for total PSA alone. The receiver operating characteristics (ROC) curve analysis of the f/t ratio displayed a greater area under the plot (0.84) compared to total PSA alone (0.745). The results demonstrate that the f/t ratio significantly increases specificity for PCa detection compared to total PSA alone, showing the potential clinical value of the f-PSA immunoassay. © 1996 Wiley-Liss, Inc.     

Role of tissue polypeptide specific antigen in the detection of prostate cancer

OBJECTIVE: The aim of the present study was to evaluate the role of tissue polypeptide specific antigen (TPS) in the diagnosis of different stages of prostatic cancer (CaP) and to compare the diagnostic efficacy of serum TPS in respect to total prostate-specific antigen (tPSA) and free/total (f/t) PSA ratio. PATIENTS AND METHODS: Patients with BPH (n = 58), localized CaP (n = 37) and metastatic CaP (n = 16) were compared by measuring serum TPS, tPSA and f/t PSA ratio. RESULTS: Serum TPS was significantly increased only in patients with metastatic CaP (p < 0.05) and TPS levels was not significantly different between patients with BPH and localized CaP. Both f/tPSA and tPSA showed better sensitivity, specificity and receiver operating curve analysis in the differential diagnosis of BPH and localized CaP. CONCLUSION: In conclusion, serum TPS measurement was found to be significantly increased in metastatic prostatic carcinoma cases but was not useful in the early detection of prostatic carcinoma. Although there are several studies demonstrating the usefulness of TPS in the differential diagnosis of prostate cancer, there is increasing evidence for the use of this molecule in the late period of the disease or as an adjunct to other molecules in the detection of recurrences.     

Current usefulness of free/total PSA ratio in the diagnosis of prostate cancer at an early stage

The aim of our study was to evaluate five different free/total PSA (f/t PSA) kits for the diagnosis of early stage prostate cancer. We compared the PSA density and the f/t PSA ratio to differentiate between benign prostatic hyperplasia (BPH) and prostate cancer. This prospective study included a total of 120 patients with suspected prostate cancer (PSA between 4 and 15 ng/ml) observed over a period of 30 months. All patients had a blood test as well as a prostate biopsy prior to inclusion. Serum immunoassay total-PSA (t PSA) and free-PSA (f PSA) were carried out using five different assay kits: IMX Abbott (A), Kryptor Brahms (B), Immulite DPC (D), IRMA Immunotech (I) and IRMA DiaSorin (S). The results were compared to determine sensitivity, specificity, threshold values, and to differentiate between BPH and cancer. No difference was found between assay reproducibility and variation in the assays, however, only a slight variation was observed in the mean t PSA values, whereas a significant difference was found with f/t PSA. Receiver operating curves were generated for t-PSA and f/t PSA. The area under the curves did not show any significant differences for either t PSA or f/t PSA. A low comparative variability between the five kits tested for tPSA was observed, which suggest that the f/t PSA ratio has no current usefulness in the initial diagnosis of prostate cancer, particularly in patients with larger prostates. Furthermore, no prognostic value was found for surgically positive margins in radical prostatectomy. The named authors wrote this article with the participation of the Members of the Normandy Urological Association     

Measurement of serum zinc improves prostate cancer detection efficiency in patients with PSA levels between 4 ng/mL and 10 ng/mL

Aim： To investigate whether the measurement of serum zinc may improve the detection of prostate cancer （PCa） in men who had total prostate-specific antigen （PSA） levels higher than 4.1 ng/mL. Methods： A mass screening for PCa of 3940 men over 50 years old was undertaken using total serum PSA. Of the 190 men （4.8 %） with elevated PSA, 143 （3.6 %） underwent a transrectal ultrasonography （TRUS）-guided biopsy of the prostate, and 42 men （1% of total and 29.3 % of men undergoing biopsy） were found to have cancer. The areas under the receiver operating characteristic curves （ROC-AUC） were used to compare the diagnostic power of cancer detection by means of serum zinc, and free PSA/total PSA ratio （fit）. Results： The men with levels of serum zinc that ranged from 40 ng/mL-60 ng/mL, had an age-adjusted odds ratios（OR） of 5.0. A cutoff value of 100 gg/mL for-serum zinc concentration provided a sensitivity of 90.5 % and a specificity of 32.7 % in elevated PSA range, and a sensitivity of 93.3 % and specificity of 27.1% in gray zone, respectively. In the gray zone ranges of 4.1 ng/mL-10.0 ng/mL, the ROC-AUC for zinc was 73.0 % higher than 62.7 % of f/t PSA ratio and 56.7 % of total PSA. Conclusion： PCa displays a lower serum zinc concentration. The measurement of zinc levels improves PCa detection in the gray zone compared with the f/t PSA ratio and total PSA. （Asian J Androl 2005 Sep; 7： 323-328）     

Serum human glandular kallikrein (hK2) and insulin-like growth factor 1 (IGF-1) improve the discrimination between prostate cancer and benign prostatic hyperplasia in combination with total and %free PSA

BACKGROUND: There is growing evidence describing an association of hK2 and IGFs with cancer. The aim of this study is to investigate the differences in serum levels of hK2 and IGFs in a large group of patients with benign prostatic hyperplasia (BPH) or prostatic carcinoma (CaP) and to examine the value of these variables, as well as their various combinations with PSA, for discriminating between these two clinical entities. METHODS: Human glandular kallikrein 2 (hK2), insulin-like growth factor-1 (IGF-1), free and total PSA concentrations were measured with non-competitive immunological procedures. Receiver operating characteristic (ROC) analysis as well as univariate and multivariate logistic regression analysis were performed to investigate the potential utility of the various markers and their combinations for discriminating between BPH and CaP. RESULTS: hK2 and IGF-1 concentrations were increased in CaP patients, in comparison to BPH patients. hK2/free PSA and free/total PSA ratios (area under the curve, AUC = 0.70) were stronger predictors of prostate cancer than the IGF-1/total PSA ratio (AUC = 0.56) in the group of patients with total PSA <4 microg/L. The hK2/free PSA ratio (AUC = 0.74) was found to have significant discriminatory value in patients with total PSA within the "gray zone" (4-10 microg/L). Multivariate logistic regression models confirmed the observed relationships and identified IGF-1/free PSA and hK2/free PSA as independent predictors of CaP. CONCLUSIONS: hK2/free PSA and IGF-1/free PSA ratios may be useful adjuncts in improving patient selection for prostate biopsy.     

Effect of transrectal ultrasonography of the prostate on serum prostate-specific antigen levels and free/total prostate-specific antigen ratio

To study the effect of transrectal ultrasonography (TRUS) on serum total prostate-specific antigen (PSA), free PSA and free/total (f/t) PSA ratio and to determine the reliability of serum total and free PSA levels and f/t PSA ratio after such interventions, serum free and total PSA levels and f/t PSA ratios were determined before, immediately after and 24 h after TRUS in 44 patients who were referred to our department by their general practitioner for prostate screening. The duration of TRUS procedure and prostate volume and age were evaluated to determine whether the serum PSA levels following TRUS had changed. The total PSA and free PSA levels and f/t PSA ratio did not show any significant rise immediately after DRE and TRUS. The duration of the TRUS procedure did not appear to affect the PSA values. Age and prostate volume were not correlated with the PSA levels. Our findings revealed no significant changes in f/t PSA ratio and serum free and total PSA level, suggesting that serum free and total PSA levels and f/t PSA ratio may be more reliable parameters in the early period after TRUS.     

f/t PSA比值、PSA密度、PSA移行带密度在tPSA灰区前列腺偶发癌诊断中的意义

【摘要】 目的： 探讨血清f/t PSA比值、PSA密度、PSA移行带密度在tPSA位于灰区时前列腺癌诊断中的意义。方法： tPSA位于4～10ng/ml的前列腺增生患者112例,术前经前列腺穿刺活检均证实为前列腺增生,行TURP术后病理证实21例为前列腺偶发癌患者。回顾性分析该21例前列腺偶发癌患者和其余前列腺增生患者间的血清f/t PSA比值、PSA密度、PSA移行带密度,并进行统计学分析,以了解其在tPSA灰区前列腺偶发癌诊断中的意义。结果：前列腺偶发癌组和BPH组血清f/t PSA比值分别为0.13±0.03、0.21±0.04;PSAD分别为0.20±0.05 ng/ml2 、0.12±0.04 ng/ml2;PSATZ分别为0.38±0.06 ng/ml2 、 0.21±0.05 ng/ml2;两组在以上三个检测指标上差异具有显著性(P<0.05)。以0.15 ng/ml2为截断点则PSAD 灵敏性为76.115%,特异性为69.146%;以0.35 ng/ml2为截断点则PSATZ 灵敏性为60.642%,特异性为93.943%。结论：f/t PSA比值、PSAD、PSATZ对前列腺偶发癌的诊断具有重要价值,其中尤以PSATZ更具预测价值。     

A comparison of the free fraction of serum prostate specific antigen in men with benign and cancerous prostates: the best case scenario

Purpose

In most previous studies of free-to-total serum prostate specific antigen (PSA) ratios, the specimens from patients with prostate cancer or those with benign prostatic hyperplasia (BPH) have not been highly characterized. We compared preoperative sera from post-radical prostatectomy patients with clinically significant cancers of at least 2 cm.³ to sera from those with BPH and large, biopsy negative prostates.

Materials and Methods

We used 2 different time resolved immunofluorometric assays for free and total PSA, and a combination of a chemoluminescent immunoassay for free PSA detection with an immunoradiometric assay for total PSA to measure free and total PSA. The serum ratios of free-to-total PSA in these assays were compared to those obtained previously from gel filtration studies. Sera from 51 men with prostate cancer volumes of 2 to 18 cm.³ were compared to those from 48 men with BPH and a mean prostate volume of 78 plus/minus 7 cm.³. The respective mean serum PSA levels plus or minus standard deviation were 10.0 plus/minus 6.3 and 8.9 plus/minus 7.2 ng./ml.

Results

Monoclonal assays for free PSA confirmed the previous study with gel filtration. For PSA 4 to 10 ng./ml., 94 to 95 percent of the men with prostate cancer were correctly diagnosed, with a cutoff of less than 15 percent for free-to-total PSA on immunofluorometric assay and less than 14 percent for chemoluminescent immunoassay with immunoradiometric assay. However, 46 percent (immunofluorometric assay) and 36 percent (chemoluminescent immunoassay and immunoradiometric assay) of men with BPH did not have enough free PSA for diagnosis of BPH (that is 36 to 46 percent false-positive rate).

Conclusions

For total PSA 4 to 10 ng./ml., the sensitivity of approximately 15 percent free-to-total PSA for prostate cancer is high (94 to 95 percent) but 36 to 46 percent of men with BPH and a large gland will not be correctly identified. For PSA 2 to 4 ng./ml., no ratio of percent free-to-total PSA discriminated BPH from prostate cancer.     

Preoperative serum prostate specific antigen levels between 2 and 22 ng./ml. correlate poorly with post-radical prostatectomy cancer morphology: prostate specific antigen cure rates appear constant between 2 and 9 ng./ml.

PURPOSE: Serum prostate specific antigen (PSA) is widely used as a guide to initiate prostatic biopsies and to follow men older than 50 years old with and without prostate cancer. However, benign prostatic hyperplasia (BPH) is a common cause of serum PSA values between 2 and 10 ng./ml. A better understanding of the relationships among serum PSA, prostate cancer and BPH is important. MATERIALS AND METHODS: A total of 875 men underwent radical prostatectomy at our institution between December 1984 and January 1997. Of these men 784 had a serum PSA of 2 to 22 ng./ml., including 579 with the largest cancer located in the peripheral zone of the prostate. Of the 579 men 406 had serum PSA followups for greater than 3 years after radical prostatectomy. We examined Pearson correlations (R2) between preoperative serum PSA, and the volume of Gleason grades 4/5 and 3 to 1 cancer in 784 men, separating peripheral zone from transition zone cancers. We used broken line regression with break points of 7 and 9 ng./ml. preoperative PSA to summarize the relationship of each PSA doubling to 5 different morphological variables in 579 men with peripheral zone cancer. A 9 ng./ml. break point was used for prostate weight. Trend summaries with a local regression line for the relationships between 6 morphological variables and PSA were superimposed on full scatterplots of the 579 men with PSA less than 22 ng./ml. Cox proportional hazard models were used to examine 5-year PSA failure-free probabilities based on 406 men with minimal PSA followups greater than 3 years at break points of 7 to 9 ng./ml. PSA. RESULTS: Pearson correlation between cancer volume and preoperative serum PSA in 875 men was weak (r2 = 0.27) and driven by large cancers with serum PSA greater than 22 ng./ml. For peripheral zone cancer the overall R2 x 100 for 641 men with low and high grade cancer was 10% and only 3% for low grade cancer, that is almost no PSA produced by these peripheral zone cancers enters the serum. All morphological variables changed at rates of doubtful medical significance below a PSA of 7 to 9 ng./ml. but at rates that were significantly worse above 9 ng./ml. R2 for these relationships was never greater than 15%. Large individual morphological variations at all levels of PSA emphasize the serious limitation of PSA as a predictor of prostate cancer morphology. Below 9 ng./ml. prostate weight increased by 21% for each doubling of PSA but above 9 ng./ml. the increase was only 4.8%. CONCLUSIONS: Preoperative serum PSA has a clinically useless relationship with cancer volume and grade in radical prostatectomy specimens, and a limited relationship with PSA cure rates at preoperative serum PSA levels of 2 to 9 ng./ml. Trend summaries for prostate weight on broken line regression showed that below 9 ng./ml. BPH is a strong contender for the cause of PSA elevation, constituting the primary cause of the over diagnosis of prostate cancer.     

RATIO OF FREE-TO-TOTAL PROSTATE SPECIFIC ANTIGEN IN SERUM CANNOT DISTINGUISH PATIENTS WITH PROSTATE CANCER FROM THOSE WITH CHRONIC INFLAMMATION OF THE PROSTATE

Purpose

We demonstrate the effect of chronic inflammation of the prostate on the ratio of free-to-total prostate specific antigen (PSA) in serum calculated as a percentage of free PSA and, therefore, that percentage of free PSA is an unspecific means to distinguish among prostate cancer, chronic prostatitis and benign prostatic hyperplasia (BPH).

Materials and Methods

Total, free and percentage of free PSA was measured in 66 men with prostate cancer, 119 with BPH and 17 with asymptomatic chronic prostatitis. In all patients the diagnosis was histopathologically confirmed by microscopic examination of prostatic specimens after sextant biopsy, transurethral prostatic resection or prostatectomy.

Results

The median values of total, free and percentage of free PSA were 4.11 micro g./l., 0.75 micro g./l. and 20.4% in patients with BPH, 10.0 micro g./l., 0.84 micro g./l. and 8.5% in those with prostate cancer, and 7.60 micro g./l., 1.23 micro g./l. and 10.6% in those with chronic prostatitis. Patients with prostate cancer and chronic prostatitis had a significantly lower percentage of free PSA than those with BPH. Receiver operating characteristics curve analysis showed that percentage of free PSA as a discriminator between prostate cancer and BPH was not suitable for differentiating between prostate cancer and chronic prostatitis.

Conclusions

Chronic prostatitis is not characterized by elevated total PSA concentrations alone but also by a decreased percentage of free PSA, a tendency similar to that in prostate cancer. This unspecific change in percentage of free PSA must be considered to interpret the percentage of free PSA correctly.