Examination of the 3 molecular forms of serum prostate specific antigen for distinguishing negative from positive biopsy: relationship to transition zone volume

PURPOSE: We evaluated the relative usefulness of total, free and complexed serum prostate specific antigen (PSA), and their ratios for distinguishing positive from negative biopsy of prostates in a university referral practice. MATERIALS AND METHODS: We compared 90 consecutive men who had 2 sets of 6 negative systematic biopsies with 70 who had at least 5 mm. of prostate cancer in systematic biopsies during the same period at our institution. Total prostate and transition zone volumes were determined by transrectal ultrasound. The Bayer, DPC and Hybritech assays were performed to measure total, free and complexed serum PSA. Receiver operating characteristics curves were constructed for all forms of serum PSA and their ratios as well as prostate size to distinguish true positive (sensitivity) from false-positive (1 minus specificity) fractions. RESULTS: Complexed PSA was only marginally better than total serum PSA. Free-to-total, complexed-to-total and prostate size had highly significant areas under the curves of greater than 80%. Free PSA only was better than complexed or total PSA. When factored by prostate volume, total PSA performed as well as the PSA ratios, and transition zone volume was consistently better than total prostate volume. DPC free-to-total ratios were equivalent to Hybritech ratios in all respects. CONCLUSIONS: Complexed PSA is only marginally better than total PSA for distinguishing negative from positive biopsy of prostates. It is inferior to free PSA and far less useful than free-to-total or complexed-to-total ratios. Prostate size is a decisive variable in men in whom we avoided the expected 25% false-negative biopsy rate in terms of specificity and hopefully avoided insignificant cancer in terms of sensitivity. In the future the performance of PSA serum markers should be related to a transition zone volume of less than 20, 20 to 60 and greater than 60 gm. when comparing assays to each other.     

Improving prostate cancer detection with an extended-core transrectal ultrasonography-guided prostate biopsy protocol

OBJECTIVE: To investigate whether taking two transition zone (TZ) and four lateral peripheral zone (PZ) biopsies in addition to routine parasaggital sextant biopsies would improve detection rates in men with suspected prostate cancer. PATIENTS AND METHODS: The study included 493 consecutive men (mean age 68.7 years, sd 8.2) with elevated serum prostate-specific antigen (PSA) levels and/or abnormal findings on a digital rectal examination who underwent transrectal ultrasonography-guided prostate biopsy. In addition to sextant biopsies, six further biopsies were obtained, two from the TZ (mid-gland) and four from the lateral PZ (base and mid-gland). Pathological findings for the additional biopsies were compared with those of the sextant regions. RESULTS: Prostatic adenocarcinoma was diagnosed in 164 of the 493 (33%) men biopsied. Men with cancer were older, had smaller prostates and higher median PSA levels than men with negative biopsies. Sextant biopsies were positive for cancer in 133 of 164 (81%) men. All three sets of biopsies were positive in 53 (32%) cases. In 50 (30%) men both the sextant and lateral PZ biopsies were positive, while in six (4%) men, both sextant and TZ biopsies were positive. Thirty-one (19%) tumours were not detected by sextant biopsies, 10 (6%) where the lateral PZ biopsies alone were positive, 17 (10%) where the TZ biopsies alone were positive and four (3%) where both the TZ and lateral PZ together were positive. There were no differences in median PSA concentration, total prostate volume or TZ volume between men with an isolated TZ cancer and men with cancer elsewhere in the prostate. However, 77% of men with TZ cancer had a PSA of > 10 ng/mL, compared with 60% of men with cancer at other sites within the prostate (P = 0.015). CONCLUSION: An extended-core biopsy protocol significantly improves the detection rate for prostate cancer when compared with the standard sextant biopsy protocol alone. Routine TZ biopsies should be considered for men with serum PSA levels of >10 ng/mL.     

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.     

Expectant management of nonpalpable prostate cancer with curative intent: preliminary results

PURPOSE: We evaluate a strategy of expectant management for men with stage T1c prostate cancer. MATERIALS AND METHODS: A total of 81 men (median age 65 years, range 52 to 72) with stage T1c prostate cancer who were thought to have small volume prostate cancer based on needle biopsy findings and prostate specific antigen (PSA) density were followed for more than 1 year with semiannual PSA and digital rectal examination, and annual prostate biopsies (median followup 23 months, range 12 to 58). A recommendation for treatment was made if disease progression was indicated by unfavorable followup needle biopsy findings (Gleason pattern 4 or 5, greater than 2 biopsy cores with cancer, greater than 50% involvement of any core with cancer). Curable disease was defined on pathological examination of radical prostatectomy specimens as 1) organ confined cancer of Gleason score 7 or less, 2) cancer with extraprostatic extension of Gleason score 7 (3+4) or less with negative margins, seminal vesicles and lymph nodes, or 3) cancer of Gleason score 6 or less regardless of margin status or extraprostatic extension if negative seminal vesicles and lymph nodes. RESULTS: Of the 81 men 25 (31%) had progression of disease at followup. PSA density was statistically significantly higher (p = 0.01) and the percentage of free PSA was statistically significantly lower (p = 0.04) in men with compared to those without disease progression. Disease progression occurred in 22 of 39 men (56%) with every followup biopsy showing cancer compared to 3 of 42 (2%) men with 1 or more negative followup biopsies (p <0.001). Of the 25 men with progression 13 underwent radical prostatectomy and 12 of 13 (92%) had curable cancers. CONCLUSIONS: Expectant management with curative intent may be a reasonable alternative for carefully selected older men who are thought to have small volume cancers.     

Predictors of prostate cancer on repeat transrectal ultrasound-guided systematic prostate biopsy

BACKGROUND: We analyzed the outcome of repeated transrectal ultrasound (TRUS)-guided systematic prostate biopsy in Japanese men whose clinical findings were suspected of prostate cancer after previous negative biopsies. METHODS: Between January 1993 and March 2002, 1045 patients underwent TRUS-guided prostate biopsy. Among them, 104 patients underwent repeat biopsy due to indications of persistent elevated serum prostate-specific antigen (PSA), abnormal digital rectal examination (DRE) or TRUS, increased PSA velocity, and/or previous suspicious biopsy findings. Several clinicopathological factors were evaluated for their ability to predict the detection of prostate cancer on repeat biopsy. RESULTS: Prostate cancer was detected in 22 of 104 patients (21.2%) who underwent repeat biopsies. PSA concentration and PSA density at both the initial and repeat biopsies, and PSA velocity in men with positive repeat biopsy were significantly greater than those in men with negative repeat biopsy. The incidence of abnormal findings in DRE and TRUS at initial biopsy in men with positive repeat biopsy was also significantly higher than that in men with negative repeat biopsy. However, neither the presence of prostatic intraepithelial neoplasia nor number of biopsy cores at initial biopsy had a significant association with the results of the repeat biopsy. Furthermore, multivariate analysis revealed that PSA and PSA density at both the initial and repeat biopsies, PSA velocity, and DRE and TRUS findings at initial biopsy were independent predictors of malignant disease on repeat biopsy. CONCLUSION: Despite an initial negative biopsy, repeat TRUS-guided biopsy should be carried out to exclude prostate cancer in cases of suspicious clinical findings, such as elevated PSA or PSA-related parameters, or abnormal findings of DRE or TRUS.     

Follow-up of men with elevated prostate-specific antigen and one set of benign biopsies at prostate cancer screening

OBJECTIVE: To study the follow-up of men with elevated prostate-specific antigen (PSA) (>3 ng/ml) after one benign set of sextant biopsies. From the G?teborg branch of the European Randomised Study of Screening for Prostate Cancer (ERSPC). METHOD: 456 men with one set of benign sextant biopsies were followed every second year for 4 years with PSA determinations. In cases of elevated PSA, transrectal ultrasound (TRUS) guided sextant biopsies were suggested. Digital rectal examination (DRE), prostate volume, PSA, PSA density (PSAD) and the ratio between free and total PSA (PSA F/T) were recorded. RESULTS: Complete data were available for 322 men. 3 groups were identified. In 84/322 (26%) men cancer was found ("cancer" group). 182/322 (56%) had benign biopsies ("benign" group) and 56/322 (17%) had normalised PSA ("normalised PSA" group). Median prostate volumes were 36, 46, and 33 cc respectively in the three groups. DRE and/or TRUS were abnormal in only 30% of the men in all groups. Cancer was not found in any prostate >70 cc volume. In prostates of <20 cc either cancer was found or PSA was normalised. The "normalised PSA" group had initial PSA, PSAD and PSA F/T similar to cancer, normalising during follow-up. CONCLUSIONS: Patients with one negative sextant biopsy still have a high likelihood of cancer, especially men with persistently elevated PSA and small prostates (<20 cc) while the majority of men with large prostates (>70 cc) have PSA elevation due to benign prostate hyperplasia (BPH) and not to cancer.     

Prevalence of undiagnosed prostate cancer in men with erectile dysfunction

OBJECTIVE: To explore the prevalence of prostate cancer in men presenting with erectile dysfunction (ED). PATIENTS AND METHODS: In a prospective study, 127 men with ED of at least 6 months duration underwent screening for prostate cancer using prostate specific antigen (PSA) and a digital rectal examination (DRE). Men with a high PSA level (> 4 ng/mL) had sextant biopsies taken under sedoanalgesia. The serum testosterone level was measured in all the men. RESULTS: Twenty-six men were aged < 50 years and all had a normal PSA level; of 101 men aged > 50 years, 20 had an abnormal PSA. The detection rate for prostate cancer using PSA and DRE was 5%, which was not significantly higher than in the general population. All the detected cancers were clinically significant (> T2a, Gleason grade > 4). Two of the five men diagnosed with prostate cancer were Afro-Caribbean. Of the 127 men, 31% had a low serum testosterone level, but there was no association between testosterone and PSA levels. CONCLUSIONS: Prostate cancer is no more common in men with ED than in the normal male population. Therefore, routine screening for prostate cancer in men with ED is not indicated.     

Free and total prostate-specific antigen levels in saliva and the comparison with serum levels in men

OBJECTIVE: We investigated free and total prostate-specific antigen (PSA) levels and free/total (f/t) ratio in the fasting saliva and compared them with the serum levels in normal individuals, in patients with benign prostatic hyperplasia (BPH) and prostate cancer. Our aim was to determine free and total PSA and f/t ratio in saliva and to improve and simplify the differentiation between BPH and prostate cancer by using saliva as an alternative to serum. METHODS: Serum and fasting saliva concentrations of free and total PSA were measured in 35 men with BPH, 16 men with stage D prostate cancer, and 25 healthy men. Serum and fasting saliva samples were collected at the same time and were analyzed on the same day at our laboratory with microparticle enzyme immunoassay technology. RESULTS: For the total of 76 men, there was a significant correlation between free and total PSA levels in each sample (r = 0.97 for serum and r = 0.44 for saliva, p<0.001). Although there was a significant difference between three groups for serum-free and total PSA levels and serum f/t ratios, no significant difference was determined between groups for salivary free and total PSA levels and salivary f/t ratios. No correlations were found between patient age and salivary PSA levels. CONCLUSIONS: Fasting salivary free and total PSA levels are not effected by high serum levels of prostatic origin. Although there was a significant difference between mean serum and salivary levels of free and total PSA in each group, the f/t ratio of saliva was very close to the serum ratio of normal subjects. Determination of free and total PSA in saliva to improve and simplify the differentiation between prostate cancer and BPH is not suitable for use as alternative measurement of serum.     

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.     

Effectiveness of percent free prostate specific antigen as a predictor of prostate cancer detection on repeat biopsy

BACKGROUND: The aim of this study was to identify predictors that can increase the accuracy of detecting prostate cancer on subsequent biopsies. METHODS: Between 1998 and 2003, a total of 235 men with prostate specific antigen (PSA) levels between 4.0 and 20 ng/mL underwent one or more systematic needle biopsies of the prostate. Of these men, 73 (31.1%) underwent one repeat biopsy and 26 (11.1%) underwent two or more repeat biopsies. We evaluated the results of prostate biopsies in relation to the morbidity of prostate cancer detected on repeat biopsies. RESULTS: Of the 73 men who underwent repeat biopsy, 16 (21.9%) had prostate cancer. Twenty-six men with one negative re-biopsy underwent two or more repeat biopsies, and five of these patients were found to have early stage prostate cancer. On repeat biopsy, there was a significant difference in percent free PSA between the cancer-detected group and the no-cancer-detected group (P < 0.01). A receiver operating characteristics (ROC) curve gave an optimal cut-off value for percent free PSA of 11%, demonstrating a significant difference in the cancer detection rate on repeat biopsy (P = 0.0009). Analysis of the data for re-biopsies showed that cancer-detected cases showed a raised PSA value and a simultaneously reduced percent free PSA (these differences were statistically significant). CONCLUSIONS: A low percent free PSA level increased the probability of a positive result in repeat biopsy. An increase in the accuracy of detecting cancer, especially on repeat biopsy, will promote the detection of more early stage prostate cancer.     

Strategies combining total and percent free prostate specific antigen for detecting prostate cancer: a prospective evaluation

PURPOSE: Determining total prostate specific antigen (PSA) in plasma can often identify men who are subsequently diagnosed with prostate cancer. However, excess false-positives create large financial and psychological burdens in prostate cancer screening. The percent free PSA is lower when prostate cancer is present, although to our knowledge no large prospective analyses to date have evaluated whether adding testing for free PSA may decrease false-positives, while maintaining or perhaps improving the detection of potentially curable tumors. MATERIALS AND METHODS: We measured total and percent free PSA in banked plasma samples from the Physicians' Health Study in 430 men who were later diagnosed with prostate cancer and 1,642 age matched controls who were not diagnosed with prostate cancer during a 12-year observation period. We calculated the number of cancers detected and the number of false-positives for various strategies of combined free and total PSA levels, and compared them to the use of total PSA alone. RESULTS: Total PSA with a cutoff of 4 ng./ml. detected 149 cases but also yielded 144 false-positives. A strategy that applied percent free PSA to men with total PSA 4 to 10 ng./ml. detected 133 to 140 cancers and decreased false-positives to 83 of 117 depending on the percent free PSA cutoff used. As the percent free PSA cutoff was lowered from 25% to 20%, additional undetected cancers did not occur until year 9 of followup and the 20% cutoff decreased false-positives and, thus, potential negative biopsies, by 42%. Percent free PSA was superior to total PSA for discriminating cases from controls within the total PSA range of 4 to 10 or 3 to 10 ng./ml. (p <0.0001). A percent free PSA cutoff of 20% in men with total PSA 3 to 10 ng./ml. detected 10% more cancers with 12.5% fewer false-positives than the conventional strategy of total PSA greater than 4 ng./ml. Cancers missed by combined total and free PSA testing had longer intervals between blood sampling and diagnosis, and a greater likelihood of later diagnosis at an organ confined stage. CONCLUSIONS: These results demonstrate that in a prospective setting with long-term followup free PSA strategies can be identified that decrease unnecessary biopsies, while preserving or even improving cancer detection. Thus, total and free PSA can be combined without the need to weigh subjectively the trade-offs and relative costs of false-negative and false-positive results.     

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.     

Determination of the percentage of free prostate-specific antigen helps to avoid unnecessary biopsies in men with normal rectal examinations and total prostate-specific antigen of 4-10 ng/ml

OBJECTIVE: To assess the usefulness of measuring the percentage of free prostate-specific antigen (PSA) in serum to reduce the number of prostate biopsies in men with serum PSA levels between 4 and 10 ng/ml and benign prostate examinations. MATERIALS AND METHODS: The percentage of free PSA (Immulite((R))) in serum was analyzed prospectively in 180 men with benign digital rectal examinations and total PSA serum levels of between 4 and 10 ng/ml. All patients underwent ultrasound-guided sextant prostatic biopsies. Sensitivity, specificity and positive and negative predictive values were calculated as well as the percent of patients in which biopsies could have been avoided for various cutoff values of the percentage of free PSA as an indicator for biopsy. Influence of age in the determination of cut points was evaluated. RESULTS: Cancer was detected in 22.2% (40/180) of the patients. Mean percentage of free PSA was 13.4% in patients with cancer and 18.9% in patients with benign prostatic hyperplasia (p = 0.001). Using a percentage of free PSA cutoff of 22% or less as a criterion for performing prostatic biopsy would have detected 95% of cancers, avoided 25% of benign biopsies and yielded a positive predictive value of 29% in patients who underwent biopsy. Mean percent of free PSA values increased as mean subject age increased, influencing the calculation of cut points, sensitivity and specificity. Leaving the cut point constant across all age groups will oblige older patients to undergo an increased number of unnecessary biopsies, although allowing for higher sensitivity in younger men. CONCLUSIONS: Measurement of the percentage of free serum PSA improves specificity of prostate cancer detection in patients with elevated total serum PSA levels and benign prostate examinations. Subject age seemed to influence the determination of optimal cut points.     

Head-to-head comparison of the Montreal nomogram with the detection of primary malignant circulating prostate cells to predict prostate cancer at initial biopsy in Chilean men with suspicion of prostate cancer

IntroductionThe limitations of total serum prostate-specific antigen (PSA) level values remain problematic. Nomograms may improve the predictive value of a positive prostate biopsy (PB) finding. We compare in a prospective study of Chilean men suspicious of having prostate cancer (PC), owing to an elevated total serum PSA or abnormal digital rectal examination finding or both, the use of the online Montreal nomogram for the detection of primary malignant circulating prostate cells (mCPCs) to predict a positive PB finding.Methods and patientsConsecutive men suspicious of PC underwent 12-core transrectal ultrasound PB; their age, total serum PSA levels and percent free PSA values, and Montreal nomogram scores were registered. Immediately before the PB, an 8-ml blood sample was taken to detect primary mCPCs. Mononuclear cells were obtained by differential gel centrifugation and identified using double immunomarcations with anti-PSA and anti-P504S. Biopsies were classified according to presence of cancer/no cancer. The test results for the detection of mCPC were stated as negative/positive, and the total number of cells/8 ml of blood was registered. Areas under the curve for total serum PSA level, percent free PSA value, Montreal score, and detection of mCPCs were calculated and compared. Diagnostic yields, the number of possible biopsies that could be avoided, and the number of clinically significant cancers that would be missed were calculated.ResultsOverall, 607 men underwent biopsy, where 197 (32.5%) had cancer. These men were significantly older, had higher total serum PSA level and Montreal score, and lower percent free PSA value. The values for area under the curve were 0.56 for total PSA level, 0.78 for percent free PSA, 0.78 for Montreal score, and 0.84 for mCPC detection; mCPC detection had a significantly superior prediction value (P = 0.018). Using cutoff values of percent free PSA<10%, Montreal score>50%, and≥1 mCPC detected, mCPC detection had a higher diagnostic yield. Of the 197 cancers, 41 complied with the criteria for active surveillance; percent free PSA and the Montreal score missed a higher number of significant cancers when compared with mCPC detection.ConclusionsPrimary mCPC detection outperformed the use of percent free PSA and the Montreal nomogram in predicting clinically significant PC at initial PB.     

Necessity of repeat biopsies in men for suspected prostate cancer

Background: The indications for repeat prostate needle biopsy in men whose initial biopsy results revealed no evidence of cancer are not defined. Methods: We retrospectively studied 218 consecutive cases of men undergoing prostate biopsies for suspected cancer. Men in whom cancer was found on repeat biopsy were compared with others with regard to age, digital rectal examination, serum prostate-specific antigen (PSA) concentration, prostate volume, PSA density, PSA slope and the frequency of prostatic intraepithelial neoplasia (PIN) on initial prostate biopsy. Results: Of the 114 cancers detected, 99 (87%) were diagnosed on initial biopsy and 15 (13%) were diagnosed on repeat biopsy. Mean PSA concentration and mean PSA density were significantly higher in patients with cancer on initial biopsy than on repeat biopsy (P < 0.05), but they were similar among patients with and without cancer on repeat biopsy. The PSA slope showed a more progressive increase in patients with cancer on repeat biopsy than in those patients without cancer at 6 month intervals. Of the 218 patients undergoing prostate biopsy, seven (3.2%) were identified with high grade PIN but without concurrent prostate cancer. Prostate cancers were detected in two of these seven patients (29%) on repeat biopsy. Conclusions: Serum PSA levels and PSA density did not provide useful predictive information about the indications of repeat biopsy. We conclude that men with a more progressive increase in PSA levels at 6 months intervals and high grade PIN on prostate needle biopsy should undergo repeat sampling to exclude missed cancer.     

Predictors of first repeat biopsy cancer detection with suspected local stage prostate cancer

PURPOSE: We determine demographic and tumor related predictors of repeat biopsy cancer detection in men with suspected stage T1c-2 prostate cancer. MATERIALS AND METHODS: The study population included 298 consecutive men with suspected stage T1c-2 prostate cancer who had a benign prostate biopsy at 1 institution between January 1, 1992 and April 1, 1999 and underwent 1 repeat biopsy. Mean age plus or minus standard deviation was 66.8+/-6.7 years for 133 black (55%) and 165 white (45%) patients. Clinical measures included determination of high grade prostatic intraepithelial neoplasia in benign biopsy specimens, Gleason score of malignant biopsy specimens, prostate specific antigen (PSA), PSA density, annualized interbiopsy PSA change, percent free PSA (201 cases) and PSA velocity (171). RESULTS: Cancer was detected on repeat biopsy in 80 cases (27%). Significant differences between patients with benign and malignant repeat biopsies included age (p = 0.001), PSA density (p = 0.0001), percent free PSA (p = 0.0001) and PSA velocity (p = 0.009). High grade prostatic intraepithelial neoplasia in an initial benign biopsy was not predictive of cancer in repeat biopsy (p = 0.12). Multiple logistic regression analysis of all cases showed that age (p = 0.002) and PSA density (p = 0.0002) were independent predictors of cancer. Subset multiple logistic regression analysis modeled with age, PSA density and percent free PSA demonstrated that age (p = 0.002) and percent free PSA (p = 0.0001) were significant independent predictors of malignancy. Subset multiple logistic regression analysis modeled with age, PSA density, percent free PSA and PSA velocity revealed that age (p = 0.02) and percent free PSA (p = 0.0003) were significant independent predictors of cancer. There were no significant differences between the Gleason scores of cancers detected on repeat biopsy compared to 587 stage T1c-2 cancers detected on initial biopsy during the study period (p = 0.09). PSA, PSA density, percent free PSA and PSA velocity were not significantly different among men without a cancer diagnosis who had high grade neoplasia in 1 or 2 benign biopsies. CONCLUSIONS: Greater than 25% of this population of select patients with suspected stage T1c-2 prostate cancer had malignancy detected on repeat biopsy. Percent free PSA was the most powerful predictor of cancer. High grade prostatic intraepithelial neoplasia was not a predictor of repeat biopsy cancer detection and PSA functions were similar among men without cancer who did and did not have high grade neoplasia in 1 or more benign biopsies. This finding suggests that high grade prostatic intraepithelial neoplasia may not be a reliable indicator of clinically significant existing prostate cancer.     

Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia

OBJECTIVES: To assess the utility of prostate-specific antigen (PSA) as a predictor of prostate volume by characterizing the relationship between prostate volume and serum PSA in men with symptomatic benign prostatic hyperplasia (BPH) and no evidence of prostate cancer, stratified by decade of life. METHODS: Placebo-controlled multicenter trials in patients with BPH and a safety study in normal young men provided baseline measurements of serum PSA and prostate volume. The analyses included patients with a baseline prostate volume measured by either transrectal ultrasound (TRUS) or magnetic resonance imaging and baseline serum PSA. A common central laboratory was used for all but one of the individual studies; both laboratories used the Hybritech method. Patients 80 years of age or older were excluded. Patients with a baseline serum PSA greater than 10 ng/mL were excluded to reduce the likelihood of including occult prostate cancer cases. The patients in the BPH trials were screened at baseline by digital rectal examination (DRE) and serum PSA. Those with suspicious findings underwent TRUS-guided biopsy; only patients with negative biopsies are included in these analyses. RESULTS: The analyses included 4627 patients, 4448 from the BPH trials and 179 from the safety study. The men in the BPH trials were older (mean age+SE, 63.7+0.10 years) than the men in the safety study (mean age + SE, 30.8+/-0.43), had larger prostates (mean volume+/-SE, 43.7+/-0.38 mL versus 26.3+/-0.49 mL in the safety study), and had higher serum PSA values (mean+/-SE, 2.6+/-0.03 ng/mL versus 0.7+/-0.39 ng/mL in the safety study). The relationship between prostate volume and serum PSA was evaluated using only the BPH trial data. Prostate volume and serum PSA have an age-dependent log-linear relationship (ie, their logarithms are linearly related, and the parameters of the relationship depend on age). Older men tend to have a steeper rate of increase in prostate volume with increasing serum PSA (P < 0.00 for differences between slopes), and there was a slight tendency for PSA density to increase with age. Receiver operating characteristic (ROC) curves were constructed to evaluate the ability of serum PSA to predict threshold prostate sizes in men with BPH. The ROC curve analyses revealed that PSA had good predictive value for assessing prostate volume, with areas under the curve ranging from 0.76 to 0.78 for various prostate volume cutoff points (30, 40, and 50 mL). Conclusions. Prostate volume is strongly related to serum PSA in men with BPH and no evidence of prostate cancer, and the relationship depends on age. Since treatment outcome or risk of long-term complications depend on baseline prostate volume, serum PSA can estimate the degree of prostate enlargement sufficiently accurately to be useful for therapeutic decision making. To achieve a specificity of 70% while maintaining a sensitivity between 65% and 70%, approximate age-specific criteria for detecting men with prostate glands exceeding 40 mL are PSA > 1.6 ng/mL, >2.0 ng/mL, and >2.3 ng/mL for men with BPH in their 50s, 60s, and 70s, respectively.     

Serum testosterone levels in African-American and white men undergoing prostate biopsy

Objectives. Because androgen levels are known to influence prostate growth, we performed a prospective analysis of serum testosterone levels in all African-American and white men who underwent transrectal ultrasound-guided prostate biopsies to evaluate an abnormal digital rectal examination (DRE) and/or serum prostate-specific antigen (PSA) level greater than 4 ng/mL.Methods. From June 1996 through July 1998, we evaluated 453 men (189 African-American and 264 white men) who underwent prostate needle biopsy because of an abnormal DRE or serum PSA greater than 4 ng/mL, or both. All men had morning serum testosterone levels determined just before undergoing prostate needle biopsy. Serum testosterone levels were compared on the basis of the prostate biopsy result (positive or negative for prostate cancer) and by race.Results. A total of 453 men underwent prostate biopsy and had morning serum testosterone levels available for comparison. Of the 264 white men who underwent biopsy, 88 (33%) were found to have prostate cancer compared with 67 (35%) of 189 African-American men who underwent biopsy. In the white men without cancer, the mean serum testosterone level was 380.19 ng/dL; those with prostate cancer had a mean serum testosterone level of 419.52 ng/dL. The mean serum testosterone level in African-American men without cancer was 424.30 ng/dL; it was 386.55 ng/dL in those with prostate cancer. There was no statistical difference in serum testosterone levels based on biopsy result or race.Conclusions. Although several studies have suggested that African-American men have higher serum testosterone levels than white men, these differences were noted only in men 40 years of age or younger. As was noted in our study, after age 40, African-American and white men have comparable serum testosterone levels. In addition, although prostate growth is androgen dependent, we found no difference in serum testosterone levels in men with and without prostate cancer.