Value Of tPSA Research Articles

The Predictive Value of tPSA, fPSA, fPSA/tPSA Combined with Ultrasound Parameters in Postoperative Gleason Grading of Prostate Cancer.

Prostate cancer (PCa) is a common malignant tumor in men. This study aimed to explore the predictive value of serum biomarkers combined with ultrasound parameters for postoperative Gleason grading in PCa. This study included 65 PCa patients who underwent transurethral resection of the prostate in our hospital from January 2021 to December 2023. Based on postoperative Gleason grading, the study subjects were divided into a Mild Group (n = 34) and a Severe Group (n = 31). Levels of serological biomarkers such as total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA), and fPSA/tPSA (the ratio of fPSA to tPSA), along with ultrasound (US) parameters, including prostate-specific antigen density (PSAD), intraglandular prostate-specific antigen density (IGPSAD), extraglandular prostate-specific antigen density (EGPSAD), and US score were compared between the two groups to evaluate their predictive values for postoperative Gleason grading. The fPSA, tPSA, fPSA/tPSA ratio, PSAD, IGPSAD, EGPSAD, and US scores in the Severe Group were significantly different from those in the Mild Group (p < 0.05). The combined evaluation of fPSA, tPSA, fPSA/tPSA, PSAD, IGPSAD, EGPSAD, and US score for predicting postoperative Gleason grading in PCa patients revealed an area under the curve (AUC) of 0.947, indicating a better predictive performance. The AUC of multi-parameter union was significantly higher than that of individual parameters and serum indicators union (fPSA, tPSA and fPSA/tPSA) (p < 0.05). The combined use of multiple parameters (fPSA, tPSA, fPSA/tPSA, PSAD, IGPSAD, EGPSAD and US Score) shows better predictive performance than individual testing. The combined application has high predictive value in postoperative Gleason grading of PCa. These findings can effectively guide clinical decision-making and optimize diagnostic strategies for developing effective and targeted therapeutic interventions for PCa.

Does the hemodialysis program affect the prostate-specific antigen (PSA) serum levels in patients with end-stage renal disease (ESRD)? A cross-sectional descriptive study.

This study aims to investigate the effect of high-flux membrane hemodialysis on total prostate-specific antigen (tPSA) serum levels in hemodialysis patients and to evaluate the clinical significance of any observed changes. A cross-sectional descriptive study was conducted involving 75 hemodialysis patients at An-Najah National University Hospital. tPSA and hematocrit (Hct) serum levels were measured before and after one hemodialysis session. The correlation between changes in tPSA and Hct levels was analyzed using the Statistical Package for Social Sciences (SPSS). The mean age of the patients was 54.25 ± 15.27 years, with a mean hemodialysis duration of 40 ± 38 months. The mean tPSA levels before and after hemodialysis were 0.95 ± 0.81 ng/ml and 1.15 ± 0.96 ng/ml, respectively. Significant increases were observed in both tPSA (t = -3.264, p = 0.002) and Hct levels (t = -7.861, p < 0.001). The percentage changes in tPSA and Hct were 20% and 12%, respectively, with no significant correlation between the changes (r = 0.152, p = 0.215). Hemodialysis significantly elevates tPSA serum levels; however, no significant correlation was found between changes in tPSA and Hct. None of the patients showed clinically significant elevations in tPSA that would necessitate prostate biopsy. Therefore, high-flux membrane hemodialysis does not appear to compromise the diagnostic value of tPSA in hemodialysis patients.

Survival Analysis and a Novel Nomogram Model for Progression-Free Survival in Patients with Prostate Cancer.

Background This study sought to perform a survival analysis and construct a prognostic nomogram model based on the Gleason grade, total prostate-specific antigen (tPSA), alkaline phosphate (ALP), and TNM stage in patients with prostate cancer (PCa). Methods The progression-free survival (PFS) of 255 PCa patients was analyzed in this study. The prognostic value of tPSA and ALP was evaluated using the Kaplan-Meier survival curves and Cox regression analysis, and a nomogram model based on the Gleason grade, tPSA, ALP, and TNM stage was further established for PFS prediction in PCa patients. Results PCa patients with different Gleason grades, tPSA and ALP levels, and TNM stages presented distinct PFS. The Gleason grade, tPSA, ALP, and TNM stage were four independent prognostic indicators. The C-index of the established nomogram was 0.705 for PFS in the test cohort and 0.687 for the validation cohort, and the calibration curves indicated a good consistency between predicted and actual PFS in PCa patients. Conclusion The data of this study demonstrated that the Gleason grade, tPSA, ALP, and TNM stage of PCa patients are independently correlated with PFS, and a nomogram model based on these indicators may be valuable for the PFS prediction in PCa patient.

A Nomogram for Predicting Pelvic Lymph Node Metastasis in Prostate Cancer

<i>Background</i>: Prostate cancer (PCa) is prone to lymph node metastasis. In this report, the authors described a model predictive of the probability of lymph node metastasis in prostate cancer patients. <i>Methods</i>: Two-hundred seventy-eight middle-high-risk PCa patients who received laparoscopic radical prostatectomy (LRP) combined with extended pelvic lymph node dissection (e-PLND) in our hospital were selected as the subjects and the authors performed a retrospective analysis. According to the postoperative pathological results, the patients were divided into a pelvic lymph node metastasis group (n=100) and a non-pelvic lymph node metastasis group (n=178). Univariable and multivariable logistic regression analyses were performed to identify independent risk factors for pelvic lymph node metastasis from PCa. Finally, a clinical prediction model nomogram was further established and verified, and a calibration plot was drawn to verify the accuracy of the model. <i>Results</i>: The TPSA level, FPSA level, PI-RADS score, biopsy ISUP classification and Gleason score of the two groups were statistically different (P<0.05), and there was no statistical difference between the age groups (P>0.05). Receiver operating characteristic curve (ROC) showed that the best diagnostic cut-off value of TPSA was 77.45 ng/ml (AUC=0.785, 95%CI: 0.729-0.842), and the best diagnostic cut-off value of FPSA was 0.085 ng/ml (AUC=0.282, 95%CI: 0.215-0.348). Univariable and multivariable logistic regression analyses showed that, TPSA level (OR=1.00, 95%Cl: 1.000-1.006, P<0.05), FPSA level (OR=0.00, 95%Cl: 0.000-0.089, P<0.01), PI-RADS score (OR=9.26, 95%CI: 5.278-16.248, P<0.01) and biopsy ISUP grade (OR=1.69, 95%CI: 1.163-2.450, P<0.01) were independent predictors of pelvic lymph node metastasis. <i>Conclusions</i>: The nomogram established in this study has a good predictive ability for pelvic lymph node metastasis in patients with PCa, and can provide a reference for the selection of clinical treatment options.

Serum Total and Free Prostate Specific Antigen Levels as Novel Biomarker in Patients with COVID-19

Objectives: This study aimed to evaluate the diagnostic value of TPSA and FPSA for early detection of COVID-19 and compare it with a control group. Methods: This is a retrospective study of 146 patients from the Respiratory Clinic in Sebha city, 73 of whom have COVID-19 PCR-confirmed and 73 who do not have COVID-19 (group control). Results: The mean and standard division age in the PCR-confirmed COVID-19 group was 61.51±16.40. In the PCR-confirmed COVID-19 group, the mean and standard division serum biomarker level for TPSA was 0.51±.26 ng/ml, and 0.57± 0.32 for FPSA. Conclusion: For the biomarkers TPSA and FPSA, there were no significant differences between the control and PCR-confirmed COVID-19 groups. These findings suggest that the tumor biomarker may be ineffective in detecting COVID-19.

GC-MS-based metabolomics reveals new biomarkers to assist the differentiation of prostate cancer and benign prostatic hyperplasia

Lack of efficient noninvasive biomarkers for differentiating prostate cancer (PCa) and benign prostate hyperplasia (BPH) is a serious concern for men’s health worldwide. In this study, we aimed to improve the diagnostic capability of the existing noninvasive biomarkers for PCa. GC-MS-based untargeted metabolomics was employed to analyze plasma samples for 41 PCa patients and 38 BPH controls. Both univariate and multivariate statistical analyses were performed to screen for differential metabolites between PCa and BPH, followed by the selection of potential biomarkers through machine learning. The chosen candidate biomarkers were then verified by targeted analysis and transcriptome data. The results showed that twelve metabolites were significantly dysregulated between PCa and BPH, three metabolites including L-serine, myo-inositol, and decanoic acid could be potential biomarkers for discriminating PCa from BPH. Most importantly, ROC curve analysis demonstrated that the involvement of the three potential biomarkers has increased the area under the curve (AUC) value of cPSA and tPSA from 0.542 and 0.592 to 0.781, respectively. Therefore, it was concluded that the involvement of L-serine, myo-inositol, and decanoic acid can largely improve the diagnostic capability of the commonly used noninvasive biomarkers in the clinic for differentiating PCa from BPH.

P039 - Prognostic value of tPSA’s early response in elderly patients with metastatic castration-resistant prostate cancer in treatment with Enzalutamide

P039 - Prognostic value of tPSA’s early response in elderly patients with metastatic castration-resistant prostate cancer in treatment with Enzalutamide

Value of semi-quantitative indices of 68Ga-PSMA-11 PET/CT in differential diagnosis of malignant and benign prostate lesions

Objective To evaluate the value of semi-quantitative indices of 68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT in differentiating malignant and benign prostate lesions. Methods From November 2017 to June 2018, 30 patients (age: 52-86 years) who underwent 68Ga-PSMA-11 PET/CT imaging in the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed, and the serum total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) were examined within 1 week before PET/CT imaging. Semi-quantitative indices of 68Ga-PSMA-11 PET/CT on prostate lesions were measured by automatic segmentation algorithm method, including PSMA-related lesion volume (VPSMA), maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak) and total lesion uptake value of PSMA (TLUPSMA). The indices were compared between malignant and benign prostate lesions, and the optimal cut-off values for differentiating malignant and benign prostate lesions were obtained by receiver operating characteristic (ROC) curve analysis. Results According to the pathological results, 19 patients had malignant lesions and 11 were with benign diseases. The differences of tPSA, SUVmax, SUVmean, SUVpeak and TLUPSMA between malignant and benign prostate lesions were statistically significant (u values: 17.00-48.00, all P 0.05). The optimal cut-off value of tPSA was 18.30 μg/L for differentiating malignant and benign prostate lesions, with sensitivity of 13/17 (PSA of 2 patients were missing), specificity of 9/11 and area under curve (AUC) of 0.743. The optimal cut-off values of SUVmax, SUVmean and SUVpeak were 5.50, 3.09 and 3.56, respectively, with all corresponding sensitivity of 18/19, all specificity of 9/11, and AUC of 0.902, 0.907 and 0.919, respectively. The optimal cut-off value of TLUPSMA was 54.81 cm3, with sensitivity of 14/19, specificity of 9/11 and AUC of 0.804. Conclusion The semi-quantitative indices of 68Ga-PSMA-11 PET/CT are valuable for differentiating malignant and benign prostate lesions, in which SUVpeak is superior to other indices. Key words: Prostatic neoplasms; Prostate-specific membrane antigen; Isotope labeling; Gallium radioisotopes; Positron-emission tomography; Tomography, X-ray computed; Diagnosis, differential

The value of NLR combined T-PSA in the diagnosis of prostate cancer

Objective The aim of our study was to explore the relationship between prostate cancer and four serum markers, including Prostate specific antigen (PSA), Beta 2 Microglobulin (β2M), Neutrophil-to-lympochyte ratio (NLR) and Lactic dehydrogenase (LDH), and their variation rules in development of prostate cancer. Then to find one or more markers that can increase the sensitivity and specificity of diagnosis to provide reference for clinic. Methods A total of 149 prostate cancer patients, 40 patients with benign prostatic hyperplasia, 80 healthy subjects in our hospital were analyzed, and subsequent the T-PSA, F-PSA, β2M, LDH and NLR were measured. The correlation between these markers and prostate cancer as well as its different types and Gleason score was assessed statistically. We determined the cut-off point of the NLR and T-PSA according to the specificity and sensitivity levels derived from area under receiver operator characteristic (ROC) curve. Results The level of T-PSA was significantly higher in patients of prostate cancer and benign prostatic hyperplasia, and the level of NLR was higher only in patients of prostate cancer. Based on the area under ROC, the cut-off value of T-PSA was determined to be 4.625 ng/ml, and NLR was 2.11, and combined NLR and T-PSA can increase the specificity of diagnose. There is a statistical difference in Gleason scores in patients with different NLR of prostate cancer (P=0.030). Conclusions It could increased the specificity when combined NLR and T-PSA to diagnose prostate cancer. And NLR has positive correlation with the prognosis of patients of prostate cancer as well. Key words: Prostatic neoplasms/DI; Prostate-specific antigen; Neutrophils; Lymphocytes

The diagnostic value of prostate health index for prostate cancer

Objective To investigate the role of prostate health index(PHI)in prostate cancer detection with a serum prostate specific antigen(PSA) level of 4- 10μg/L and negative digital rectum examination(DRE). Methods In a prospective study from October 2013 to October 2014, the clinical data of 101 old men were analyzed. All the 101 cases were DRE(-), had the serum PSA level of 4- 10μg/L and received prostate biopsy guided by transrectal ultrasound,including 16 cases of prostate cancer and 85 cases of benign prostate diseases.Serum total PSA(tPSA), free PSA(f PSA)and proPSA(p2PSA) were detected and% f PSA,% p2PSA and PHI were calculated. Using prostate biopsy for the definite diagnosis of prostate cancer, receiver operating characteristic curves (ROC)of PHI,% p2PSA, p2PSA,% f PSA and tPSA were established and the areas under the curve(AUC) were calculated.The diagnostic value of PHI,% p2PSA, p2PSA,% fPSA and tPSA, and the value of PHI for predicting aggressive prostate cancer were analyzed. Results In the prostate cancer group, average tPSA, fPSA, p2PSA,% fPSA,% p2PSA and PHI were 6.94, 1.27μg/L, 21.49 ng/L, 18.71%, 1.59% and 41.51 respectively, which were different from those in the noncancer group(6.68, 1.34μg/L,13.37 ng/L,20.42%, 1.05% and 27.18).The AUCs of PHI,% p2PSA,% f PSA and tPSA for diagnosis of prostate cancer were 0.777, 0.769, 0.681, 0.590 and 0.580 respectively.In the prostate cancer group with Gleason score≥7, the PHI value was higher than that of the group with Gleason score≤6(P< 0.05). Conclusion PHI can improve the diagnosis accuracy of prostate cancer in patients with the serum PSA level of 4- 10μg/L and DRE(-). PHI has the diagnostic value better than tPSA,% f PSA, p2PSA or% p2PSA.PHI value is positively associated with the aggressive prostate cancer. Key words: Prostate cancer; Prostate health index; Prostate specific antigen

The usefulness of complexed prostate–specific antigen in predicting metastasis in patients with prostate cancer

Objective To determine the value of complexed prostate–specific antigen (cPSA) in predicting metastasis in patients with prostate cancer. Methods From January 2012 to April 2014, the clinical data of 74 patients with newly diagnosed prostate cancer in our hospital was retrospective reviewed. The prostate cancer was diagnosed by transrectal ultrasound guided biopsy and postoperative pathologic diagnosis. The patients were divided to 2 groups according to metastases status. There were 38 patients in the group of metastasis and 36 patients in the group of without metastasis. In metastasis group, the bone metastasis was found in 36 cases. There is only one case with lung metastasis and one case with lymph node metastasis. In the group without metastasis, the T stages classification were T1–T2 in 17 cases and T3–T4 in 19 cases. While, 10 cases with T1–T2 stage and 28 cases with T3–T4 stage were confirmed in the group with metastasis. There was no statistical significance of T stages and mean age in two groups (P>0.05). The level of cPSA in the serum was detected by chemiluminescent immunoassay, the level of tPSA, fPSA were detected by electro–chemiluminescent immunoassay. fPSA/tPSA, cPSA/tPSA were evaluated and the corresponding specificity were calculated. The correlation of age with tPSA, cPSA were analysed. The differences in PSA, fPSA/tPSA, cPSA/tPSA were compared between metastasis and non–metastasis group. ROC curve analysis was used to determine the diagnostic value of cPSA and tPSA, In the meantime, area of ROC curves were compared by Z test. Results The age was not related to the value of tPSA (r=–0.09, P=0.12) and cPSA (r=–0.38, P=0.14). The median levels of tPSA, fPSA, and cPSA are 29.88μg/L, 2.18 μg/L and 18.86 μg/L in the group without metastasis, respectively. The median levels of tPSA, fPSA, and cPSA were 410.05 μg/L, 51.50 μg/L and 290.40 μg/L in the group with metastasis, respectively. Significant differences of those results could be found in two groups (P 0.05). The area under the curve of tPSA and cPSA were 0.83 (95%CI 0.73–0.93) and 0.82 (95%CI 0.73–0.92) respectively. Analysis of ROC curves showed that the AUC for cPSA is not significant different from tPSA (Z=1.64, P=0.10). The specificity of cPSA was 22.2% which is higher than that of tPSA (19.4%) at a sensitivity of 92.1% in predicting metastasis comparing with the patients without metastasis. The sensitivity could reach to 90.0% when the cut off value of tPSA was 9μg/L or the cut off value of cPSA was 7 μg/L. Conclusions In our study, a preliminary validation that cPSA is useful for predicting the metastasis in patients with prostate cancer was made. Key words: Prostate cancer; Metastases; Complex prostate–specific antigen

Role of TPSA, F/T and PSAD in diagnosis of prostate cancer

Objective To investigate the diagnostic value of serum TPSA, the ratio of free PSA(FPSA)and TPSA(F/T) and PSAD in prostate cancer(PCa).Methods The serum TPSA and PSAD levels and the ratio of F/T of 467 patients with BPH,116 patients with PCa and 50 healthy men as normal control were determined, analyzed and compared. Results Serum TPSA of PCa (53.26±33.10) were significantly higher than that of BPH (8.12±9.70) (P ＜0.01), and normal control (1.51 ±1.17) (P ＜0.01); Serum PSAD of PCa[(1.59±1.46) ng·ml-1·cm-3] were significantly higher than that of BPH [(0.14±0.17) ng·ml-1·cm-3] (P ＜0.01),and normal control [(0.08±0.07) ng·ml-1·cm-3] (P ＜0.01); F/T of PCa (0.22±0.16) was significantly lower than that of BPH (0.27±0.15) and normal control (0.36±0.14) (P ＜0.01). When TPSA was limited specificity at 4 ～10 ng/ml, F/T of PCa (0.18±0.13) were significantly lower than that of BPH (0.27±0.14), (P ＜0.05), PSAD of Pca [(0.21 ±0.07) ng· ml -1· cm -3] were significantly higher than that of BPH [(0.11 ±0.06) ng· ml-1· cm-3], (P ＜0.001). When F/T was 0.16, PSAD used 0.15 as the critical value, the sensitivity, specificity of diagnostic value and positive prediction value were 81.6 ％, 78.2 ％, 96.1％ and 53.8 ％, 76.9 ％, 97.9 ％, respectively;And the diagnostic efficiency was the highest. Conclusion F/T and PSAD have valuable role as the diagnose marker of PCa. When PSA level between 4 ng/ml and 10 ng/ml, F/T ratio and PSAD are of significant value to differentiate PCa from BPH patients. Key words: Prostatic neoplasms; Prostate specific antigen; Prostate hyperplasia; Diagnosis

Spotlight

Zhong et al., pp. 2125–2131 It is thought that only a minority of cells within any tumor have the ability to self-renew. In the context of retinoblastoma (RB), the consensus view is that RB cells originate from retinal stem cells (RSC) or multipotent primitive retinoblasts. There is, however, no direct evidence that tumorigenic RSCs actually exist within RBs. Previously, Zhong et al. had successfully cultivated stem-like cells from human RBs. In this report they have taken the results a step further by investigating whether these retinal stem-like cells (RSLCs) have the potential to reproduce the parental tumor in vivo. Using tumor tissues from eight patients with either differentiated or nondifferentiated RB, primary cell cultures were generated under conditions that favored stem cell growth. All tumor-derived cultures developed nonadherent neurospheres that could be passaged many times. These cells were found to be capable of self-renewal and expressed neural stem cell markers such as pax6, nestin and Bmi-1. RSLCs also exhibited an impressive degree of multipotentiality, forming neurons and glial cells – among others – though they fell short of the full cellular repertoire of RSCs. After intraocular (I.O.) injection of four of the RB primary cultures into NOD/SCID mice, the mice developed tumors within 2–12 weeks. Interestingly, these xenograft tumors were very similar to their parental tumor cells. To further confirm that these xenografts contain RSLCs, single tumor cells were isolated from the xenograft tumors and reinjected I.O. into new animals, which in turn developed RB-like tumors. These findings strongly suggest that RB derives from RSLCs. In addition to furthering our understanding of RB tumorigenesis, this model could be useful in developing new therapeutic approaches for the disease. Vickers et al., pp. 2212–2217 Total prostate specific antigen (tPSA) levels can be raised in benign prostate disease, particularly in older patients, complicating its usefulness as a predictor of prostate cancer. Previous studies have shown that levels of human kallikrein-2 (hK2) and the ratio of free to total PSA (%fPSA) may also reflect underlying prostate malignancy. In this study, Vickers et al., wanted to determine whether the combination of these biomarkers could offer a better means of detecting prostate cancer and whether the biomarkers vary as a function of age. Using blood samples from a very large (13,600) cohort of men between the ages of 44 and 50 and 59 and 61 and data from the Swedish Cancer Registry, the authors determined odds ratios and the predictive probability of the various biomarkers in over 500 prostate cancer patients. They found that the predictive value of tPSA is inversely associated with age but not with time of diagnosis. The predictive value of %fPSA combined with hK2 was inversely related to the time of diagnosis but not modified by age. Using tPSA, %fPSA and hK2 compared to tPSA alone enhanced prediction levels in older patients but not younger ones. The results from this study importantly show the value of screening younger men (<50) for PSA and that combined biomarker testing may be needed to detect prostate malignancy more accurately in older subjects. Inskip et al., pp. 2233–2240 Mortalities associated with childhood cancers have decreased over the last few decades. However, the aggressive nature of the treatments means that patients are subsequently at risk of developing new primary cancers. Setting up a large-scale follow-up of childhood cancer survivors is not an easy task. In this report, Inskip et al. use a US population-based cancer registry — SEER – which contains data on nearly 26,000 childhood cancer survivors from 1973–2002, to determine new malignancy risk in childhood cancer patients. Using observed to expected ratios and regression analysis, the cancer survivors were found to have an almost 6-fold increased risk of developing a new primary cancer compared to the general population. The degree of risk and nature of the second cancer was highly dependent on the first type of cancer the patient had suffered from. Hodgkin lymphoma (HL), retinoblastoma, primitive neuroectodermal tumor and Ewing sarcoma were the cancers associated with the highest risk of developing a second primary cancer. The most likely subsequent cancers were female breast, CNS, bone, thyroid, soft tissue, melanoma and acute nonlymphocytic leukemia (ANLL). The mode of original cancer treatment also had an influence on subsequent cancer development. Patients who had received radiotherapy were more likely to develop a solid tumor, whereas patients treated with chemotherapy were at higher risk of developing ANLL. This thorough study gives a comprehensive analysis of the new malignancy risks facing survivors of childhood cancer. This perspective and future follow-up studies will be important to help monitor patients and evaluate the risks associated with changing cancer treatments.

The predictive value of prostate cancer biomarkers depends on age and time to diagnosis: Towards a biologically‐based screening strategy

Both benign and malignant prostate diseases elevate total prostate-specific antigen (tPSA), and the incidence of benign disease increases markedly with age. There is evidence, however, that free-to-total PSA ratio (%fPSA) and human kallikrein 2 (hK2) more closely reflect the malignant process. We tested the hypothesis that tPSA levels are more strongly predictive of cancer in younger when compared to older men, whereas %fPSA and hK2 are more strongly predictive in men tested closer to diagnosis. The study included 13,676 men age >/= 44 in Sweden, where PSA screening was uncommon during the study period. fPSA, tPSA and hK2 were measured in archived plasma collected during 1974-1986 in 501 men subsequently diagnosed with prostate cancer up to 1999 and in 1,292 matched controls. The predictive value of tPSA was lower in older men (p = 0.003) but was not strongly affected by time to diagnosis (p = 0.3); the predictive value of hK2 was higher closer to diagnosis (p < 0.0005) but was not modified by age (p = 0.7). A model including tPSA, fPSA and hK2 was superior (p = 0.02) to tPSA alone in older (AUC 0.819 vs. 0.794), but not in younger men (0.758 vs. 0.759). Total PSA can be used as a single marker at early middle age to predict long-term risk of prostate cancer and thus to determine intensity of subsequent screening. In contrast, %fPSA and hK2 add important predictive value in older men and much closer to diagnosis. Strategies for prostate cancer screening should be based on thorough understanding of the interaction of kallikrein-related biomarkers with prostate pathobiology.

Long-Term Prediction of Prostate Cancer Up to 25 Years Before Diagnosis of Prostate Cancer Using Prostate Kallikreins Measured at Age 44 to 50 Years

We examined whether prostate-specific antigen (PSA) forms and human kallikrein 2 (hK2) measured at age 44 to 50 years predict long-term risk of incident prostate cancer. From 1974 to 1986, 21,277 men age 50 years in Malmö, Sweden, enrolled onto a cardiovascular study (74% participation). The rate of PSA screening in this population is low. According to the Swedish Cancer Registry, 498 were later diagnosed with prostate cancer. We measured hK2, free PSA, and total PSA (tPSA) in archived blood plasma from 462 participants later diagnosed with prostate cancer and from 1,222 matched controls. Conditional logistic regression was used to test for association of prostate cancer with hK2 and PSA forms measured at baseline. Median delay between venipuncture and prostate cancer diagnosis was 18 years. hK2 and all PSA forms were strongly associated with prostate cancer (all P < .0005). None of the 90 anthropometric, lifestyle, biochemical, and medical history variables measured at baseline was importantly predictive. A tPSA increase of 1 ng/mL was associated with an increase in odds of cancer of 3.69 (95% CI, 2.99 to 4.56); addition of other PSA forms or hK2 did not add to the predictive value of tPSA. tPSA remained predictive for men diagnosed > or = 20 years after venipuncture, and the predictive value remained unchanged in an analysis restricted to palpable disease. A single PSA test at age 44 to 50 years predicts subsequent clinically diagnosed prostate cancer. This raises the possibility of risk stratification for prostate cancer screening programs.

866: Value of T-PSA and %F-PSA as a Preoperative Predictive Marker for Pathological Stage and Biochemical Recurrence in Low PSA Prostate Carcinomas

866: Value of T-PSA and %F-PSA as a Preoperative Predictive Marker for Pathological Stage and Biochemical Recurrence in Low PSA Prostate Carcinomas

Value of Free Prostate-Specific Antigen (Hybritech Tandem-R) in Symptomatic Patients Consulting the Urologist

Introduction: Prostate-specific antigen (PSA) is a widely used tumor marker in the detection and follow-up of adenocarcinoma of the prostate. Selection of candidates for prostate biopsies is hampered by the lack of specificity resulting in a large number of unnecessary biopsies. The intention of our study was to compare the percent free PSA (f-PSA; Hybritech Tandem-R) with total PSA and age-specific PSA reference values to evaluate the clinical benefit in detecting patients with prostate cancer (PC) in a selected group of patients consulting the urologist. The question was whether cutoff points are influenced by this selection of patients. Methods: A total of 188 patients, 114 with benign prostate hyperplasia (BPH) and 74 with PC were selected. It is a selected group of patients consulting the urologist. Diagnosis was confirmed in the BPH and PC groups by either ultrasound-guided biopsy or transurethral resection of the prostate or suprapubic adenomectomy or cystoprostatectomy. Total PSA (t-PSA) and f-PSA of all patients were measured before any manipulation by Tandem-R assay for f-PSA and Tandem-E assay for t-PSA (Hybritech). Mean values of age, prostate volume, t-PSA, f-PSA, percent f-PSA were compared in patients with BPH and PC by Mann-Whitney U test. The sensitivity and specificity of t-PSA and age-specific PSA were compared to the sensitivities and specificities of different cutoff points of percent f-PSA. Results: The mean value of t-PSA, f-PSA and percent f-PSA in patients with BPH (n = 114) and PC (n = 74) were statistically significantly different. At PSA levels between 4 and 10 ng/ml 19% of negative biopsies could be avoided by the use of percent f-PSA (cutoff point 25%). There was no additional benefit of age-specific PSA. At a PSA of <4 ng/ml 6 of 7 PCs could be diagnosed by percent f-PSA (cutoff point 25%), whereas only 1 patient would be diagnosed by age-specific PSA. Conclusion: Percent f-PSA seems to decrease the biopsy rate at PSA levels from 4 to 10 ng/ml without missing a relevant number of cancers and to increase the detection rate at PSA <4 ng/ml. Our data indicate that it might be necessary to choose high cutoff points (25%; Tandem-E and R assay, Hybritech) in a selected study population consulting the urologist with large glands and a high prevalence of disease. However, this situation is not comparable to testing of screening populations. No benefit of age-specific PSA could be observed in this study.

Improved discrimination of prostate cancer and benign prostatic hyperplasia by means of the quotient of free and total PSA.

The value of t-PSA (total prostate specific antigen) and of the quotient of free and t-PSA (% f-PSA) for the discrimination of BPH (benign prostatic hyperplasia) and PC (prostate cancer) as well as possible influencing factors were subject to examination under study conditions. The sera of 210 patients (131 BPH, 79 PC patients) were examined by means of the Immulite test; thereof 76 male patients (47 BPH, 29 PC patients) were found to have a t-PSA-value between 4 and 10 ng/ml (grey area). Apart from the age and the findings of rectal digital examination, we recorded the prostate volume, indications of non-specific increases in PSA and for PC patients also the TNM-G stage. For patients with prostate cancer the quotient of f- and t-PSA was significantly lower (median: 0.08) than compared to patients with BPH (median: 0.22) (p<0.001). Also in the grey area the quotient was significantly lower in patients with malignant diagnosis (median: 0.12) than for patients with a non-malignant diagnosis (median: 0.21) (p<0.001). ROC curves were prepared in order to compare the capability of discrimination of the two parameters. At this point, the better discrimination potential of the quotient in the grey area became evident. Due to the fact that priority was given to the detection of carcinoma, the threshold value was defined at a level at which high sensitivity (90%) is existent in combination with an acceptable specificity (approx. 50%). The resultant values are for the total PSA area 0.21, for the grey area 0.19 as a cut-off. Neither the age, nor the prostate volume, nor urinary tract infections had any influence upon the quotient. There was also no correlation between the stage or the grading of the tumour and the percentage of the f-PSA. The quotient alleviates the discrimination between BPH and PC, in particular in the diagnostically problematic grey area. Thus, it can serve as an aid for the decision "biopsy or re-biopsy". As there is currently no standardized method for the application of % f-PSA, there is a requirement for further examination under homogeneous criteria.