The percentage of free prostatic-specific antigen is also useful in men with normal digital rectal examination and serum prostatic-specific antigen between 10.1 and 20 ng/ml

OBJECTIVE: The percentage of free prostatic-specific antigen (PSA) has been introduced as a tool to avoid unnecessary biopsies in men with normal digital rectal examination (DRE) and serum PSA between 4.1 and 10 ng/ml. In this series we also analyze its utility in men with normal DRE and serum PSA between 10.1 and 20 ng/ml. MATERIALS AND METHODS: A series of 1149 consecutive men with normal DRE and serum PSA between 4.1 and 20 ng/ml submitted for the first ultrasound guided sextant biopsy is analyzed. In 921 (80.2%) the serum PSA was from 4.1 to 10 ng/ml and in 228 (19.8%) from 10.1 to 20 ng/ml. Total and free serum PSA determinations were done by the inmunoradiometric assays Tandem and Tandem free PSA (Hybritech Inc.). RESULTS: The overall detection rate of prostate cancer was 27.9%. In the group of men which serum PSA ranged from 4.1 to 10 ng/ml the rate of detection was 25.4% and 37.7% when it was between 10.1 and 20 ng/ml. Using 25% or less of percent free PSA as a criterion for performing prostatic biopsy it would have detected 95.3% and 95.4% of the prostate cancers, respectively. The rate of unnecessary avoided biopsies would be 17.5% when serum PSA ranged from 4.1 to 10 ng/ml and 17.6% between 10.1 and 20 ng/ml. CONCLUSIONS: This prospective study demonstrates that the percentage of free PSA seems to have similar utility when serum PSA levels are between 4.1 and 10 ng/ml and between 10.1 and 20 ng/ml, at the time of the first prostatic biopsy indication.     

Robustness of free prostate specific antigen measurements to reduce unnecessary biopsies in the 2.6 to 4.0 ng./ml. range

PURPOSE: Prostate specific antigen (PSA) cutoffs lower than 4.0 ng./ml. are being evaluated more frequently but lower PSA cutoffs increase the number of prostatic biopsies. PSA exists in several forms free and complexed to proteins. Percent free PSA is lower in men with prostate cancer. Accordingly, free PSA and complexed PSA have been used to distinguish between cancer and benign disease in the diagnostic gray zone of 4 to 10 ng./ml. to eliminate unnecessary biopsies. There are limited data on the robustness of free PSA measurements in the 2.6 to 4.0 ng./ml. total PSA range. MATERIALS AND METHODS: We evaluated percent free PSA measurements to discriminate between cancer and benign conditions in 965 consecutive volunteers in a prostate cancer screening study who underwent prostatic biopsy for a PSA of 2.6 to 4.0 ng./ml. and had benign digital rectal examination. RESULTS: Overall 25% of men had cancer detected. A 25% free PSA cutoff detected 85% of cancers and avoided 19% of negative (cancer-free) biopsies, while a 30% free PSA cutoff detected 93% of cancers and avoided only 9% of negative biopsies. Of those men who underwent radical prostatectomy 132 (80%) had pathologically organ confined tumors. Only 5% of these tumors fulfilled the published pathological criteria for possibly clinically unimportant tumors. CONCLUSIONS: Percent free PSA provides risk assessment but does not eliminate many unnecessary prostatic biopsies while maintaining a high sensitivity in the narrow total PSA range of 2.6 to 4.0 ng./ml.     

Percent free prostate specific antigen in the total prostate specific antigen 2 to 4 ng./ml. range does not substantially increase the number of biopsies needed to detect clinically significant prostate cancer compared to the 4 to 10 ng./ml. range

PURPOSE: Percent free prostate specific antigen (PSA) is useful to select patients for prostate biopsy with total PSA 4 to 10 ng./ml. However, 20% of men with PSA between 2.6 and 4 ng./ml. harbor significant prostate cancer and percent free PSA has been suggested to aid in the decision to biopsy in this total PSA range as well. Concerns exist that the number of biopsies needed to detect 1 cancer in this range may be inappropriately high. In a prospective referral population we evaluated sensitivity and specificity of various percent free PSA cutoffs and determined the biopsy-per-cancer ratio in the PSA 2 to 4 ng./ml. range in men with a benign digital rectal examination, and report on the biological nature of the detected cancers based on Gleason score. Results were compared to those obtained from a reference group of patients (PSA 4 to 10 ng./ml., benign digital rectal examination) from the same prospective referral cohort. MATERIALS AND METHODS: Total PSA and free PSA were measured and percent free PSA was calculated. Of the initial 1,602 men 756 had a benign digital rectal examination and PSA 4 to 10 ng./ml., and 219 had a benign digital rectal examination and PSA 2 to 4 ng./ml. Sensitivity, specificity, the number of true positive (evidence of cancer) and false-positive (no evidence of cancer) biopsies were determined. The ratio of true positive biopsies-to-all biopsies performed was used to determine the biopsy-per-cancer ratio. Gleason score of the detected cancers was evaluated. The procedure was repeated for the PSA 4 to 10 ng./ml. range. RESULTS: In the PSA 4 to 10 ng./ml. range a sensitivity of 63.7% to 92.5% with a specificity of 57.5% to 18.7% was found when percent free PSA was 18% to 25%. On average 3 biopsies were needed to detect 1 cancer. When PSA was 2 to 4 ng./ml. sensitivity was 46.3% to 75.6% and specificity was 73.6% to 37.6% when the same percent free PSA cutoff was examined. Calculation of the biopsy-per-cancer ratio for various percent free PSA cutoffs revealed that 3 to 5 biopsies were needed to find 1 cancer. Of 41 cancers detected in the PSA 2 to 4 ng./ml. range 6 had a Gleason score 5. The majority (28 of 41) of cases had a Gleason score of 6. Gleason score was 7 in 5 patients and 8 in 1. CONCLUSIONS: In the PSA 4 to 10 ng./ml. range high sensitivity for prostate cancer detection is critical and 3 biopsies are needed to detect 1 cancer. In the PSA 2 to 4 ng./ml. range a percent free PSA cutoff of 18% to 20% detected about 50% of cancers while sparing up to 73% of unnecessary biopsies with a biopsy-to-cancer ratio of 3 to 4:1. Percent free PSA can be applied to the PSA 2 to 4 ng./ml. range to detect prostate cancer and only moderately increases the number of biopsies needed to detect 1 significant cancer compared to the greater than 4 to 10 ng./ml. range.     

f/tPSA比值对tPSA值为2.6～4.0ng/ml前列腺癌的诊断意义

目的探讨利用血清游离前列腺特异性抗原(fPSA)和总前列腺特异性抗原(tPSA)的比值(f/tPSA),提高tPSA2.6～4.0ng/ml前列腺癌的诊断率的价值。方法对117例tPSA在2.6～4ng/ml可疑前列腺癌患者行直肠B超引导下前列腺穿刺活检,对患者血清tPSA,fPSA及f/t PSA值及其他临床病理资料进行统计学分析。结果经病理诊断良性前列腺增生(BPH)82例和前列腺癌35例,35例癌中Gleason score≤4分共6例(17%),Gleason score5-7分和8-10分别为22例(63%)和7例(20%)。前列腺癌的f/tPSA明显高于BPH(P＜0.01),以f/tPSA0.22为界值,诊断癌的特异性为83%,敏感性为71%,阳性预测值为68%。结论f/t PSA作为一项辅助检查可提高tPSA 2.6～4.0ng/ml前列腺癌的诊断率。     

Repeating the measurement of prostate-specific antigen in symptomatic men can avoid unnecessary prostatic biopsy

OBJECTIVES: To report the 2-year clinical and biochemical follow-up of symptomatic men who had a high prostate-specific-antigen (PSA) level, for whom our policy has been to avoid biopsy in those with a normal repeat PSA, as minimizing negative prostate biopsies is an important goal in managing men with a high PSA, where the decision for biopsy based on one high value may be inappropriate. PATIENTS AND METHODS: In all, 101 men (median age 72 years, range 47-85) referred to a urology department over 1 year with a PSA level above the age-specific reference range (but < 50 ng/mL) had a repeat PSA measurement. Those with a normal PSA and a normal digital rectal examination (DRE) were not biopsied. Their follow-up included a symptom review, DRE and PSA measurements. RESULTS: Of the 101 men, 67% presented with LUTS, 11% with symptoms of urinary infection, 8% with haematuria and 9% for screening. In 35 patients the repeat PSA level was normal; in three of these 35 prostate cancer was diagnosed after biopsy because of an abnormal DRE, three were lost to follow-up and one died from unrelated causes. Thus 28 patients were available for review at 2 years. In 23 (82%) the PSA remained within the normal range. In 66 of the 101 men the repeat PSA was abnormal. Cancer was diagnosed in 28 and the remaining 36 with no cancer were managed by PSA review; 30 were reviewed at 2 years and in half of them the PSA level returned to normal. CONCLUSIONS: In symptomatic men referred with a raised PSA level and who have a normal DRE and normal repeat PSA, prostatic biopsy can be safely avoided.     

The utility of free to total PSA ratio for detecting prostate cancer in Japanese men with total PSA between 2.1 and 10 ng/ml

We sought to determine whether the free to total prostate specific antigen (PSA) ratio in men with "gray zone" total PSA could accurately indicate the presence or absence of cancer, thus reducing the number of unnecessary biopsies without lessening the chance of detecting early stage prostate cancers. In 137 patients with total PSA levels between 2.1 and 10.0 ng/ml, we examined total PSA, free to total PSA ratio, PSA density (PSAD), and prostatic volume measured by transrectal ultrasound, and used these features to predict histologic features determined following sextant biopsy and/or surgery of the prostate. Of 137 patients with intermediate PSA levels, 25 (18%) had cancer. With a free to total PSA cut-off of 20%, cancer would not have been detected in 4 of the 25 patients (84% sensitivity), and 36% of the unnecessary negative biopsies would have been successfully avoided (p < 0.0005). With a PSAD cut-off of 0.15, cancer would have been missed in 4 of the 25 patients (84% sensitivity) and a 50% reduction in unnecessary negative biopsies would have been possible (p < 0.0005). Of 41 patients with large prostatic glands (>40 cm(3)), cancer was detected in only one, compared with 24 (25%) of 96 patients with small glands (<40 cm(3)) (p = 0.002). The results of receiver operating characteristic analysis indicated that PSAD, free to total PSA ratio, and prostatic volume would be effectively applicable to the diagnosis of cancer (areas under the curve: 0.7562, 0.7564, and 0.7693, respectively). At 100% sensitivity, specificity was highest for PSAD used in conjunction with ratio of free to total PSA. All patients with cancer had PSAD > 0.15 and/or free to total PSA < 15%. Patients with PSAD < 0.15 and free to total PSA ratio > 15% had no cancer (p < 0.0001). By this procedure, a 48% (54 of 112) reduction in the number of unnecessary biopsies would have been possible. Use of the free to total PSA ratio, measured with the AxSYM system, can significantly reduce unnecessary negative biopsies in patients with intermediate levels of PSA. Prostatic volume data can enhance the usefulness of this ratio for diagnosing prostate cancer.     

(I) Re: prostate specific antigen velocity in men with total prostate specific antigen less than 4 ng/ml

This study analyses the prostate-specific antigen (PSA) determinations of 11,709 men with two or more PSA measurements within approximately 12 mo, an initial PSA of <4 ng/ml, and using biopsy indications of PSA > or 2.5 ng/ml or > or =4.0 ng/ml. The authors found that PSA velocity (PSAV) thresholds in the range of 0.4 ng/ml/yr should be used to help guide the need for biopsy in men with a total PSA level <4 ng/ml. Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) was 0.68 for PSAV and 0.87 when total PSA was included in addition to PSAV.     

Percent free prostate specific antigen and cancer detection in black and white men with total prostate specific antigen 2.5 to 9.9 ng./ml

PURPOSE: The ratio of free-to-total prostate specific antigen (PSA), or percent free PSA, is a useful adjunct to total PSA for estimating the risk of prostate cancer when total PSA is 2.5 to 9.9 ng./ml. Relationships between cancer detection and total PSA are influenced by race but to our knowledge relationships between cancer detection and percent free PSA have not been studied. MATERIALS AND METHODS: A total of 222 black and 298 white consecutive and evaluable men with total PSA 2.5 to 9.9 ng./ml. underwent prostate biopsy for suspected cancer at a Veterans Affairs Medical Center. Clinical measurements included digital rectal examination, total and free serum PSA, prostate volume, PSA density and Gleason score of malignant biopsy specimens. RESULTS: Median percent free PSA was 14.1 (range 3.6 to 49.2) in 201 men with prostate cancer and 21.9 (range 5.7 to 83.3) in 319 without detectable cancer (p <0.0001). Significant racial differences in demographic characteristics and clinical measurements were limited to total PSA, which was higher in black men (p = 0.03). Cancer was detected in 156 black (47%) and 206 white (33%) men (p = 0.001). Areas under receiver operating characteristics curves for percent free PSA and total PSA were 0.66 and 0.58, respectively, for black men (p = 0.15), and 0.76 and 0.58, respectively, for white men (p <0.00001). Percent free PSA was 35.2 in black men and 29.2 in white men, and specificity was 9.1% and 28.7%, respectively, when sensitivity for percent free PSA was set at 95%. Of 156 black and 206 white men with percent free PSA less than 25, 83 (53%) and 85 (41%), respectively, had detectable cancer (p = 0.03). Of 66 black and 92 white men with percent free PSA 25 or greater 21 (32%) and 12 (13%), respectively, had detectable cancer (p = 0.005). CONCLUSIONS: Our study demonstrates racial differences in relationships between percent free PSA and cancer detection in men with suspected prostatic carcinoma and total PSA 2.5 to 9.9 ng./ml. Clinical application of the commonly used percent free PSA cutoff of less than 25 to determine the advisability of prostate biopsy may lead to under diagnosis of early stage prostate cancer in black men, who are at greater risk of morbidity and mortality from disease than white men.     

Characteristics of prostatic cancer in men with a serum prostate-specific antigen level of < or =4.0 ng/ml

Fifteen out of 140 men (median age 67 years, range 62-75) had a serum prostate-specific antigen (PSA) level of < or = 4 ng/ml before radical prostatectomy which was performed without preoperative neoadjuvant hormonal therapy between 2001 January and 2004 September. Demographic and clinical data were analyzed. Pathological specimens were evaluated by routine hematoxylin and eosine staining and immunohistochemistry with anti-PSA antibody, for both pathological staging and grading, and for the presence of PSA production. Pathological data were compared between patients with PSA < or = 4 ng/ml and those with 4 < PSA < or = 10 ng/ml. Clinically insignificant cancer was defined as a cancer volume of < 0.5 ml and the Gleason score < or = 6. The median PSA level was 3.0 ng/ml (range 1.4-3.9). Thirteen tumors (87%) were pT2. One tumor had a Gleason score of 7 and 14 tumors had a final Gleason score of < or = 6. Nine (60%) tumors were clinically insignificant. Comparison of pathological variables, PSA < or = 4 ng/ml cancer had a significantly lower Gleason score (p = 0.0029), and a smaller cancer volume (p = 0.0451) than 4 < PSA < or = 10 ng/ml cancer. All tumors were stained strongly for PSA. During a median follow-up of 24 (9-36) months, no patient showed elevated PSA (PSA > or = 0.1 ng/ml). Most prostate cancers in men with a PSA level of < or = 4 ng/ml were pT2, and about half of them were clinically insignificant. All cancers produced PSA.     

Probability of prostate cancer at various levels of per cent free prostate specific antigen in Japanese men with total PSA of 4.1-10.0 ng/ml

Estimates for the likelihood of prostate cancer at different levels of per cent free prostate specific antigen (PSA) were derived from experience with consecutive Japanese male patients with intermediate total PSA values who underwent ultrasound-guided biopsies and/or transurethral resection of the prostate. Receiver operating characteristic (ROC) curve analysis showed that in patients with a total PSA of 4.1-10.0 ng/ml, per cent free PSA identified those with prostate cancer better than did total PSA; per cent free PSA also proved superior in the subgroup whose glands appeared benign on palpation. The probabilities of prostate cancer at per cent free PSA values of 10-15, >15-20, >20-26 and >26% were 58.3, 40.8, 25.3, 14.3 and 7.6%, respectively, when analyzed without regard to findings on palpation. In patients with palpably benign glands, the corresponding values were 55.3, 35.4, 19.6, 9.7, and 4.6%, respectively. These probabilities are lower than those reported in Western countries, probably reflecting both different patterns of practice and racial differences. Race-specific assessment is recommended before applying a clinical test.     

Clinical value of human glandular kallikrein 2 and free and total prostate-specific antigen in serum from a population of men with prostate-specific antigen levels 3.0 ng/mL or greater

OBJECTIVES: To investigate the clinical value of human glandular kallikrein 2 (hK2) compared with free (f) and total (t) prostate-specific antigen (PSA) in the early detection of prostate cancer (PCa). METHODS: In PCa screening conducted in 1995 to 1996 in G?teborg, Sweden, 5853 of 9811 randomly selected men (aged 50 to 66 years; median 61) accepted PSA testing; those with tPSA levels of 3. 0 ng/mL or greater were offered digital rectal examination, transrectal ultrasound, and sextant biopsies. Serum from 604 of 611 biopsied men (18% with positive digital rectal examinations, tPSA range 3.0 to 220 ng/mL, 144 men with PCa) was analyzed for hK2 (research assay) and tPSA and fPSA (Prostatus). Sera were stored at -20 degrees C for a maximum of 2 weeks for tPSA and fPSA and 3 years for hK2. RESULTS: hK2 levels and hK2 x tPSA/fPSA values were significantly elevated in men with PCa. Receiver operating characteristic data revealed that the area under the curve for hK2 x tPSA/fPSA was significantly greater than that for tPSA and greater, but not significantly greater, than that for percent fPSA. Also, the cancer-detecting sensitivity was significantly improved (P <0.05) using hK2 x tPSA/fPSA compared with tPSA and percent fPSA at specificity levels of 75% to 90%. At 75% specificity, a sensitivity of 74% was obtained compared with 64% or 54% using percent fPSA or tPSA; at 90% specificity, the corresponding sensitivity level was 55%, 41%, and 36%, respectively. CONCLUSIONS: Discrimination of men with and without PCa in a randomly selected population was improved by measuring hK2 in addition to tPSA and fPSA.     

Complexed prostate specific antigen (PSA) reduces unnecessary prostate biopsies in the 2.6-4.0 ng/mL range of total PSA

OBJECTIVE: To compare the performance of complexed prostate-specific antigen (cPSA) to total PSA (tPSA) and percentage free PSA (f/tPSA) in the diagnosis of prostate cancer for the tPSA range 2.6-4.0 ng/mL. PATIENTS AND METHODS: Consecutive men scheduled for prostate biopsy were enrolled prospectively at 14 different sites in two multicentre studies in Europe and the USA. Serum obtained before biopsy was tested with the ACS:180 and Immuno 1 tPSA and cPSA assays (Bayer Diagnostics, Tarrytown, NY, USA) and the Access fPSA and tPSA assays (Beckman, Inc., San Diego, CA, USA). Receiver operating characteristics (ROC) curves were generated to compare the diagnostic performance of tPSA, cPSA and f/tPSA. RESULTS: Of 316 men with a tPSA of 2.6-4.0 ng/mL, 82 (26%) were diagnosed with prostate cancer on biopsy. ROC analysis of all 316 men showed an area under the curve (AUC) for cPSA of 0.63, significantly greater than the AUC for tPSA of 0.56 (P = 0.008). At a sensitivity of 95%, threshold values of 2.3 ng/mL for cPSA and 2.73 ng/mL for tPSA provided specificities of 20.1% and 9.8%, respectively. f/tPSA was only available for 205 of the 316 (65%) men and the AUC for cPSA was 0.63, and did not significantly differ from the f/tPSA AUC of 0.64 (P = 0.58). CONCLUSIONS: As a single test, cPSA provides improved specificity over tPSA and comparable specificity to f/tPSA for detecting prostate cancer, and may reduce the number of unnecessary prostate biopsies in the 2.6-4.0 ng/mL tPSA range.     

Influence of prostate volume and percent free prostate specific antigen on prostate cancer detection in men with a total prostate specific antigen of 2.6 to 10.0 ng/ml

PURPOSE: Percent free prostate specific antigen and prostate specific antigen density have been independently shown to increase the specificity of prostate cancer screening in men with prostate specific antigen levels between 4.1 and 10.0 ng/ml. Recent data suggest the total prostate specific antigen cutoff for performing a biopsy should be 2.6 ng/ml. We assessed the influence of percent free prostate specific antigen and prostate volume on cancer detection in men with a prostate specific antigen between 2.6 and 10.0 ng/ml. MATERIALS AND METHODS: From 1991 to 2005 all transrectal ultrasound guided prostate biopsies (5,587) for abnormal digital rectal examination and/or increased age specific prostate specific antigen were evaluated. A total of 1,072 patients with a prostate specific antigen between 2.6 and 10.0 ng/ml and any percent free prostate specific antigen were included in study. The cancer detection rate was calculated for each percent free prostate specific antigen/volume stratum. RESULTS: Prostate cancer was detected in 296 patients (27.6%). The mean age and prostate specific antigen of the patients with benign pathology and prostate cancer were similar. Mean percent free prostate specific antigen was 17.5% and 14.1% (p>0.05), and the mean volume was 62.0 and 46.0 cc (p=0.001), respectively. The strongest risk factors for a positive biopsy were percent free prostate specific antigen (odds ratio 0.004, p<0.001), volume (OR 0.977, p<0.001) and digital rectal examination (OR 1.765, p=0.007), but not total prostate specific antigen (p=0.303). When stratified by volume and percent free prostate specific antigen, distinct risk groups were identified. The probability of detecting cancer inversely correlated with prostate volume and percent free prostate specific antigen. CONCLUSIONS: In men with prostate specific antigen levels between 2.6 and 10.0 ng/ml, the probability of detecting cancer was inversely proportional to prostate volume and percent free prostate specific antigen. This table may assist in predicting patient risk for harboring prostate cancer.