Can complexed prostate specific antigen enhance prostate cancer detection in Japanese men?

BACKGROUNDS: The aim of this study is to ascertain whether Bayer complexed PSA (cPSA) and volume referenced cPSA could enhance the detection of prostate cancer in Japanese men. METHODS: A total of 214 Japanese men whose serum total PSA (tPSA) values ranged from 1.2 ng/ml to 4600 ng/ml were enrolled from two institutions. Serum samples for tPSA, free PSA, PSA-alpha-1-antichymotripsin (PSA-ACT) and cPSA (ADVIA-Centaur) were obtained in all cases. In addition, total gland (TGV) as well as transition zone volume (TZV) were determined in all cases who underwent untrasound guided prostate biopsy (sextant and two additional transition zone biopsies). Biopsy outcome was correlated to the following parameters: tPSA, cPSA, PSA-ACT, free to total (F/T) PSA ratio, 2 complex to total (C/T) PSA ratios and 6 volume referenced parameters. RESULTS: Prostate cancer was detected in 85 of 214 patients (40%). The area under the receiver operating characteristic curve in non-volume referenced variables was highest for cPSA (0.736), followed by PSA-ACT (0.735), tPSA (0.722), F/T PSA ratio (0.613) and C/T PSA ratio (0.591). Comparing tPSA with the cutoff value of 4.0 ng/ml, the cutoff value with a 2.8 ng/ml of cPSA detected one more positive biopsy patient, decreasing one more cancer missed case and 8 more false positive cases. At sensitivities of 85% to 95% in men with tPSA between 4.00 and 10.00 ng/ml (n = 116), there were no significant differences in the corresponding specificities between tPSA and cPSA, or between cPSA and PSA-ACT. At sensitivities of 90% to 95%, the corresponding specificities of PSA-ACT adjusted for transition zone volume revealed best performance. As for the performance in men with a tPSA less than 4.0 ng/ml, the specificities of cPSA performed best, and differed significantly from PSA-ACT and F/T PSA at sensitivities of 80% to 90%. CONCLUSION: Bayer cPSA could replace the first screening test by total PSA and can enhance cancer detection, compared with PSA-ACT. However, cPSA did not provide additional value in differentiating cancer from non-cancer cases in men with a tPSA between 4.00 and 10.00 ng/ml.     

Predictors of prostate cancer on repeat prostatic biopsy in men with serum total prostate-specific antigen between 4.1 and 10 ng/mL

OBJECTIVES: We determine whether the different molecular forms of prostate-specific antigen (PSA) and other PSA variables can predict prostate cancer in men undergoing repeat prostate needle biopsy. METHODS: Between 1997 and 2001, repeat biopsy was performed in 97 patients who had undergone prior negative prostate biopsy. The ability of total PSA (tPSA), complexed PSA (cPSA), free PSA (fPSA), free-to-total PSA (fPSA/tPSA), free-to-complexed PSA (fPSA/cPSA), complexed-to-total PSA (cPSA/tPSA), tPSA density (tPSAD), cPSA density (cPSAD), transition zone tPSA density (tPSATZ) and transition zone cPSA density (cPSATZ) was assessed by univariate and multivariate analyzes as well as receiver operating characteristics (ROC) curves. RESULTS: Prostate cancer on repeat biopsy was detected in 24% of subjects (23 of 97) who had a negative initial biopsy. The PSA parameters cut-off to ensure a 96% sensitivity of cancer detection, were 29% using fPSA/tPSA, 32% using fPSA/cPSA, 0.18 ng/mL/cc using tPSATZ and 0.16 ng/mL/cc using cPSATZ. The fPSA/tPSA would have prevented 32% of negative biopsies, the fPSA/cPSA 28%, the tPSATZ 23% and the cPSATZ 30%. ROC curve analysis fPSA/tPSA, fPSA/cPSA ratios, tPSATZ and cPSATZ were significantly better predictors of repeat biopsy results than tPSA or cPSA, but there was no significant difference in the ROC curves among these four PSA parameters. In the multivariate logistic regression analysis these four PSA parameters were significant predictors for cancer detection in the repeat biopsy group (P < 0.001). CONCLUSION: fPSA/tPSA ratio, fPSA/cPSA ratio, tPSATZ and cPSATZ enhance the specificity of PSA testing compared to tPSA or cPSA when determining which patients should undergo repeat biopsy.     

PSA-related markers in the detection of prostate cancer and high-grade disease in the contemporary era with extended biopsy

OBJECTIVE: To determine the relationship of total PSA (tPSA), percent free PSA (%fPSA), and complexed PSA (cPSA) with prostate cancer detection and the diagnosis of poorly-differentiated cancers in the contemporary era. METHODS: We retrospectively reviewed the clinical and pathological records of 292 men who met the following inclusion criteria: (1) tPSA 2.5 to 10 ng/ml; (2) initial biopsy only; (3) extended biopsy scheme (>or=10 peripheral zone cores); (4) no previous prostate surgeries. The ability of PSA-related markers to detect cancer was determined by area under the receiver operating characteristics curve analysis (AUC-ROC). Various clinically relevant % fPSA cutoffs and cPSA ranges were analyzed to determine the association with poorly-differentiated cancers. RESULTS: Cancer was detected in 126 (43%) men, with mean Gleason score of 7. The cancer detection rates for various cutoffs of tPSA, cPSA and % fPSA were very similar. On ROC analysis for cancer diagnosis, the AUCs for tPSA, % fPSA, and cPSA were 0.53, 0.54, and 0.52, respectively. Men with % fPSA <15 were more likely to have poorly-differentiated cancer than those with % fPSA >or=15 (66% vs. 41%, P < 0.005). Similarly, cPSA ranges (2-4, 4.1-6, and >6) were associated with the detection of poorly-differentiated cancers (37%, 57%, and 80% P < 0.003). CONCLUSIONS: With the use of extended prostate sampling in the contemporary screening population, the addition of cPSA and % fPSA does not enhance the diagnostic performance of tPSA. However, the significant association between cPSA and poorly-differentiated cancers suggests that this may be a more useful initial test for prostate cancer screening.     

Comparative evaluation of various prostate specific antigen ratios for the early detection of prostate cancer

OBJECTIVE: To compare the performance of various ratios using total prostate specific antigen (PSA), complexed PSA (cPSA) and free PSA (fPSA) in the early detection of prostate cancer. PATIENTS AND METHODS: The study included 535 consecutive patients evaluated at a prostate cancer detection clinic between January 1998 and October 1999. Patients had blood samples drawn before transrectal ultrasonography and prostate biopsy to measure PSA, cPSA and fPSA. Receiver operating characteristic (ROC) curves (sensitivity vs 1 - specificity) were used to evaluate the performance of PSA, cPSA, f/tPSA, cPSA/tPSA, fPSA/cPSA, tPSA/prostate volume (PV), fPSA/PV, and cPSA/PV. The areas under the curve (AUC) were calculated for each ratio. The performance of each ratio over all patients or in those with a tPSA of 4-6 or 4-10 ng/mL were evaluated. RESULTS: Of the 535 patients, 204 (38%) had biopsy-confirmed prostate cancer. The AUC obtained with tPSA alone was 0.64; when measured for all patients the cPSA/PV (0.78), PSA/PV (0.77), f/tPSA (0.76) and fPSA/cPSA (0.75) performed better than tPSA alone. Furthermore, in patients with a tPSA of 4-10 ng/mL, tPSA/PV (0.72), cPSA/PV (0.71), f/tPSA (0.69), fPSA/cPSA (0.69) and cPSA/tPSA (0.62) performed better than tPSA alone (0.52). Finally, in patients with a tPSA of 4-6 ng/mL, PSA/PV and cPSA/PV performed better than the other ratios. CONCLUSIONS: The use of PSA ratios gives a higher sensitivity and specificity for detecting prostate cancer than the use of tPSA alone.     

The significance of the free-to-complexed prostate-specific antigen (PSA) ratio in prostate cancer detection in patients with a PSA level of 4.1-10.0 ng/mL

OBJECTIVE: To compare the ratio of free prostate specific antigen (fPSA), total PSA (tPSA) and complexed PSA (cPSA, measured using a novel immunoassay) with other variables used to detect prostate cancer in patients with intermediate serum PSA levels of 4.1-10.0 ng/mL. PATIENTS AND METHODS: From July 1997 to August 1998, 140 consecutive patients were assessed; all had intermediate serum PSA levels and/or abnormal findings on a digital rectal examination. All patients underwent transrectal ultrasonography (TRUS)-guided biopsy, and the prostate and transition zone volumes were determined by TRUS. Free and tPSA were measured using the Tandem-R assay (Hybritech Corp., San Diego, CA). PSA complexed with alpha1-antichymotrypsin (cPSA) was measured using an appropriate assay. The ability of cPSA, free-to-total PSA ratio (f/tPSA), free-to-complexed PSA ratio (f/cPSA), tPSA density of the whole prostate (PSAD), of the transition zone (tPSATZ), and cPSA density of the whole prostate (cPSAD) and of the transition zone (cPSATZ) to improve the power of PSA in detecting prostate cancer was evaluated using receiver operating characteristic (ROC) curves. Results Of the 140 patients, 126 had histologically confirmed benign disease and 14 had prostate cancer. The cPSA alone had better specificity for detecting prostate cancer than had tPSA alone but the difference was not significant. The area under the ROC curve for f/cPSA was larger than those for all other variables. With a 93% sensitivity for detecting prostate cancer, a f/cPSA threshold of 25% would result in fewer unnecessary biopsies (40% f/cPSA specificity) than with all other PSA variables. The difference in the resolution was significant between f/cPSA and tPSA, cPSA, tPSAD and tPSATZ, but not with f/tPSA, cPSAD or cPSATZ. In patients with a prostate volume of < 30 mL, the cPSATZ showed better specificity for prostate cancer than tPSA alone. CONCLUSION: Measuring the level of cPSA and its derivatives may provide better differentiation of prostate cancer and benign disease than tPSA alone in patients with a tPSA level of 4.1-10.0 ng/mL.     

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.     

Use of various combinations of free, complexed and total prostate-specific antigen levels as predictors of the pathologic stage of prostate cancer

BACKGROUND: The efficacy of various combinations of total, free and complexed prostate-specific antigen (PSA) levels were assessed to predict the pathologic stage of prostate cancer. METHODS: Total PSA (tPSA), free PSA (fPSA) and complexed PSA (cPSA) levels were measured preoperatively in 52 patients with clinical localized prostate cancer who had undergone radical prostatectomy. Pathologic stages were classified as: organ-confined (n = 27); capsular penetration (n = 14); seminal vesicle involvement (n = 8); involvement of the surgical margins (n = 10); and lymph node involvement (n = 3). RESULTS: The fPSA/tPSA and fPSA/cPSA ratios significantly differed between patients with organ-confined disease and non-organ-confined disease (P = 0.035, P = 0.033, respectively) and between those with favorable versus unfavorable pathology (P = 0.001, P = 0.014, respectively), but tPSA, cPSA, fPSA and the cPSA/tPSA ratio did not. Using a fPSA/tPSA cutoff level of 11%, the prediction of organ-confined disease would increase from 52 to 67% and the rate of predicting favorable pathology would increase from 42 to 62%. A fPSA/cPSA cutoff level of 12% would increase the rate of predicting organ-confined disease to 79% and the rate of predicting favorable pathology would increase to 69%. The positive predictive value of the fPSA/cPSA ratio was higher than that of the fPSA/tPSA ratio, although the receiver operating characteristic curve of the fPSA/cPSA ratio was not different from that of the fPSA/tPSA ratio. CONCLUSION: Although there was no predictive difference found between fPSA/tPSA and fPSA/cPSA ratio, both ratios may help predict the pathologic stage of prostate cancer.     

Complexed prostate specific antigen improves specificity for prostate cancer detection: results of a prospective multicenter clinical trial

PURPOSE: Complexed (c) prostate specific antigen (PSA) has been shown to enhance specificity for prostate cancer (CaP) detection over total PSA (tPSA), although a large multi-institutional prospective evaluation was required to confirm these findings. We compared the clinical performance of cPSA with tPSA as a first line test for CaP detection and secondarily to determine if PSA ratios, namely percent free PSA (fPSA) and percent cPSA, can provide further enhancement in diagnostic performance over cPSA or tPSA. MATERIALS AND METHODS: Consecutive men scheduled for initial biopsy of the prostate were enrolled prospectively at each of 7 university centers and community based urology practices. Serum was collected and tested with the Immuno 1 (Bayer Diagnostics, Tarrytown, New York), tPSA and cPSA, and Access (Beckman, Inc., San Diego, California) fPSA and tPSA methods. RESULTS: A total of 831 patients were evaluated, of whom 313 (37.5%) were diagnosed with CaP. ROC curve analysis performed from the results of all samples and those within the clinically relevant cPSA ranges of 1.5 to 3.2, 1.5 to 5.1, 1.5 to 8.3 and 3.2 to 8.3 ng/ml (tPSA 2 to 4, 2 to 6, 2 to 10 and 4 to 10 ng/ml, respectively) indicated a significant improvement in the AUC ROC curve for cPSA compared with tPSA (p < or =0.001). Using cutoff points that provide a sensitivity of 80% to 95% for CaP detection within the 1.5 to 8.3 ng/ml cPSA range cPSA provided a statistically significant enhancement in specificity over tPSA of 6.2% to 7.9%. Within the cPSA range of 1.5 to 3.2 ng/ml using a cutoff point of 2.5 ng/ml for tPSA and 2.2 ng/ml for cPSA provided a specificity of 21.2% and 35%, respectively, and 85% sensitivity for CaP detection. PSA ratios provided no further enhancement in specificity over cPSA within these ranges. CONCLUSIONS: The use of cPSA as a single test provided improved specificity over tPSA. Percent fPSA and percent cPSA offered little to no additional benefit in the differentiation of benign and malignant disease at clinically relevant cPSA concentrations.     

New insights into the diagnostic accuracy of complexed and total prostate specific antigen using discordance analysis characteristics

PURPOSE: Comparison of diagnostic performances of total and complexed prostate specific antigen (tPSA, cPSA) using ROC curve analysis resulted in controversial interpretations. To overcome the biases due to analysis of subgroups selected by concentration ranges of only 1 marker the novel approach named discordance analysis characteristics is presented. MATERIALS AND METHODS: DAC method includes only patients who are discordantly categorized by the tests under investigation using cutoffs with identical sensitivity. Within those patients parameters describing diagnostic accuracy are calculated. The systematic nature of the results is confirmed by varying the cutoffs. DAC method is demonstrated considering the example of cPSA and tPSA data from 2 prostate cancer studies with a total of 1,624 patients (study A and B, of 283 and 565 with as well as 417 and 359 men without prostate cancer, respectively). PSA concentrations were measured using the Bayer assays. RESULTS: The DAC method proved that cPSA outperformed tPSA regarding the criteria diagnostic specificity and positive predictive value. Among discordantly tested patients cPSA detected patients with an about 2-fold higher risk to have prostate cancer and with a 3.6 to 5.5-fold better specificity than tPSA. Using cPSA instead of tPSA more than 10% of unnecessary biopsies could be avoided in the tPSA range of 3 to 5 ng/ml. CONCLUSIONS: The superior diagnostic performance of cPSA in comparison with tPSA warrants the recommendation to use cPSA as initial test in prostate cancer diagnostics. The DAC method is generally recommended to replace comparative ROC analyses of subgroups to evaluate the diagnostic usefulness of markers.     

Comparisons of the various combinations of free, complexed, and total prostate-specific antigen for the detection of prostate cancer

OBJECTIVES: We compared the ability of three prostate-specific antigen (PSA) ratios - free-to- total PSA ratio (fPSA/tPSA), free-to-complexed PSA ratio (fPSA/cPSA), and complexed-to-total PSA ratio (cPSA/tPSA) - to distinguish prostate cancer from benign prostatic hyperplasia (BPH). METHODS: We tested 258 consecutive patients who underwent transrectal ultrasound-guided prostate needle biopsy because of an abnormal digital rectal examination or a Tandem-R PSA of >4.1 ng/ml. Free PSA (fPSA) and total PSA (tPSA) were measured by Tandem-R assay. alpha(1)-Antichymotrypsin-complexed PSA (cPSA) was measured by Markit-M PSA-ACT assay. RESULTS: Of the 258 patients, 204 had BPH, and 54 had prostate cancer. The specificity at 96% sensitivity for fPSA/tPSA, fPSA/cPSA, and cPSA/tPSA was 23, 25, and 33%, respectively. Of 162 patients with tPSA between 4.1 and 10.0 ng/ml, 132 had BPH and 30 had prostate cancer. The specificity at 96% sensitivity for f/tPSA, f/cPSA and c/tPSA was 32, 44, and 41%, respectively. There was no significant difference in the area under the receiver-operating characteristic curves among fPSA/tPSA, fPSA/cPSA, and cPSA/tPSA in the overall PSA range or in tPSA between 4.1 and 10.0 ng/ml. CONCLUSION: fPSA/tPSA, fPSA/cPSA, and cPSA/tPSA did not differ in their ability to distinguish prostate cancer from BPH.     

Complexed prostate specific antigen density is better than the other PSA derivatives for detection of prostate cancer in men with total PSA between 2.5 and 20 ng/ml: results of a prospective multicenter study

PURPOSE: This prospective, multicenter study was initiated to evaluate the diagnostic performance of PSA, free/total PSA (f/tPSA) and complexed PSA (cPSA) with volume-based parameters for early detection of prostate cancer in patients with PSA between 2.5 and 20 ng/ml. MATERIALS AND METHODS: 408 subjects with serum PSA values between 2.5 and 20 ng/ml regardless of digital rectal examination (DRE) were included in to the study. The diagnostic validity, sensitivity, specificity and cut-off values were evaluated by Receiver Operating Characteristic (ROC) curve analysis. RESULTS: Of 408 patients 77 (18.9%) were positive for prostate cancer. Digital rectal examination was non-suspicious in 86% (351/408) of the patients. Area under curve (AUC) values for cPSA were better than PSA and f/tPSA in patients with PSA values of 2.5-10 ng/ml and 4-10 ng/ml, as well as the whole group. Furthermore, on ROC curve analysis cPSAD was the best predictor of prostate cancer for all PSA ranges regardless of the DRE findings except PSA values between 2.5 and 4 ng/ml. The cut-off value of cPSAD at 90% sensitivity was 0.06 ng/ml/cm(3) with a 35.3% specificity saving 126 unnecessary biopsies in the whole group. CONCLUSION: cPSA might be a better initial test than PSA for prostate cancer detection and measurement of cPSA alone and its derivatives obviate the need for additional fPSA testing.     

Percent-free prostate specific antigen is elevated in men on haemodialysis or peritoneal dialysis treatment.

BACKGROUND: Men with chronic renal failure evaluated for transplantation are often tested for prostate specific antigen (PSA) to detect prostate cancer. PSA occurs in several different molecular forms in serum: free PSA (fPSA) and complexed PSA (cPSA), the sum of which corresponds to total PSA (tPSA). In addition to tPSA, percent fPSA to tPSA (%fPSA) is widely used to enhance discrimination of benign disorders from prostate cancer. The low molecular mass of fPSA suggests elimination by renal glomerular filtration and that renal failure may significantly influence %fPSA. We evaluated whether established reference levels for %fPSA are applicable also to patients treated with haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). METHODS: The study included 20 men on intermittent haemodialysis with low-flux membranes and 25 men on CAPD, without known history of prostate cancer. The control group included 3129 men without known prostate cancer. We analysed fPSA and tPSA in serum by dual-label immunofluorometric assays, from which we calculated %fPSA and cPSA. Serum levels of different PSA forms were adjusted for age and presented as geometric means. RESULTS :Percent fPSA was significantly higher in patients on either haemodialysis (39.5%) or CAPD (39.6%) compared with controls (28.1%). Haemodialysis patients, but not CAPD patients, had significantly higher mean levels of fPSA. Levels of tPSA and cPSA for haemodialysis or CAPD patients did not differ significantly compared with controls. CONCLUSIONS: Recommended reference ranges for %fPSA, based on men with normal renal function, do not apply to uraemic men on dialysis. In these men, a high %fPSA should not be considered as a sign of benign disease. This is clinically important in the evaluation of dialysis patients for transplantation, as %fPSA is often used as a tool for detection of prostate cancer.     

Use of prostate-specific antigen (PSA) isoforms for the detection of prostate cancer in men with a PSA level of 2-10 ng/ml: systematic review and meta-analysis

OBJECTIVE: Measurement of serum prostate-specific antigen (PSA) for the detection of prostate cancer has poor specificity in men with PSA levels between 2 and 10 ng/ml. It has been suggested that measurement of the ratio of free to total PSA (f/tPSA) or complexed PSA (cPSA) might offer an improvement. We performed a systematic review and meta-analysis to evaluate the diagnostic performance of these tests among men with PSA levels between 2 and 10 ng/ml. METHODS: Data on sensitivity and specificity were extracted from 66 eligible studies. Likelihood ratios and summary receiver operating characteristic curves were estimated and possible sources of heterogeneity between studies examined. RESULTS: Use of the f/tPSA or the cPSA test improved diagnostic performance among men with a total PSA (tPSA) of 2-4 or 4-10 ng/ml compared to tPSA alone. The diagnostic performance of the f/tPSA test was significantly higher in the tPSA range of 4-10 ng/ml compared to a tPSA range of 2-4 ng/ml (p < 0.01); at a sensitivity of 95%, the specificity was 18% in the 4-10 ng/ml tPSA range and 6% in the 2-4 ng/ml tPSA range. Among studies that measured both isoforms, the diagnostic performance of the f/tPSA test and the cPSA was equivalent in both PSA ranges. CONCLUSIONS: The use of the f/tPSA or cPSA test among men with PSA levels between 2 and 10 ng/ml can reduce the number of unnecessary biopsies whilst maintaining a high cancer detection rate.     

Derivatives of prostate‐specific antigen as predictors of incidental prostate cancer

OBJECTIVE

To search for an optimal derivative of prostate‐specific antigen (PSA) identifying patients at risk of incidental prostate cancer.

PATIENTS AND METHODS

In all, 693 patients who underwent transurethral resection of the prostate (TURP) with a normal digital rectal examination, no history of prostate cancer and a PSA level of 2.5–10 ng/mL were studied. The total PSA (tPSA), percentage of free/total PSA (%fPSA), complexed PSA (cPSA), PSA density, cPSA density and the ratio of fPSA to cPSA were measured. Specificity, sensitivity, positive and negative predictive values were determined for all possible threshold values indicating the risk of incidental prostate cancer (T1a or T1b). Furthermore, the patients were subdivided according to age and the presence of an indwelling transurethral catheter. The areas under the receiver operating characteristic curves (AUC) were compared.

RESULTS

In the whole sample, the %fPSA was the best test predicting all incidental prostate cancers (AUC 0.618, reference: tPSA 0.494), whereas cPSA density was the best predictor of T1b disease (AUC 0.720, reference: tPSA 0.548). Stratification by age did not meaningfully alter the results, the presence of a transurethral catheter, however, was associated with a superiority of tests based on fPSA (AUC 0.620–0.670) compared with tests based on tPSA or cPSA (AUC 0.421–0.581).

CONCLUSION

Replacing tPSA by PSA derivatives (%fPSA or cPSA density) and stratifying by the presence of an indwelling transurethral catheter may improve the prediction of the risk of incidental prostate cancer and spare unnecessary biopsies before TURP in the tPSA range 2.5–10 ng/mL.     

Effect of hemodialysis on serum complexed prostate-specific antigen levels

OBJECTIVE: The measurement of prostate-specific antigen (PSA) is a useful tool in the screening and follow-up of prostate cancer, but its diagnostic validity is uncertain in hemodialysis patients. The aim of this study was to evaluate the effects of hemodialysis on serum complexed PSA (cPSA) levels. MATERIAL AND METHODS: A total of 36 men (mean age 62.54+/-8.20 years) with end-stage renal disease were enrolled in a prospective study. Serum total PSA (tPSA), free PSA (fPSA) and cPSA, and hematocrit levels were measured before and immediately after dialysis using low-flux membranes in the serum and in the dialysis ultrafiltrate. RESULTS: After hemodialysis, cPSA, fPSA and the fPSA:tPSA ratio increased significantly (p<0.05). However, there was no significant increase in tPSA. fPSA, cPSA and tPSA were not detected in ultrafiltrate. Hematocrit levels increased significantly (p<0.0001) due to hemoconcentration. Of patients with initial serum tPSA and cPSA values and fPSA:tPSA ratios below the cut-off values, none had a post-hemodialysis value greater than the cut-off point. There were weak correlation between the difference in values after and before hemodialysis of hematocrit and cPSA (p=0.035), and between the percentage change in levels before and after hemodialysis of hematocrit and cPSA (p=0.041). CONCLUSIONS: Hemodialysis induced elevations in all forms of PSA, but tPSA was the least affected form. cPSA did not show any diagnostic superiority over other forms of PSA. Thus, serum tPSA remains a reliable parameter for follow-up of prostate cancer in uremic patients receiving long-term dialysis. However, further research is needed to explain the pathophysiology of alterations in the concentrations of different forms of PSA.     

Effect of prostate manipulation on the serum levels of complexed prostate-specific antigen and total prostate-specific antigen

BACKGROUND: Recently there has been considerable interest in complexed prostate-specific antigen (cPSA) as an alternative to total PSA (tPSA). Data regarding the variations of cPSA are limited. We performed a prospective study using different forms of prostate manipulation to demonstrate and compare variations between cPSA and tPSA. METHODS: The study included 113 men, 34 of whom had a digital rectal examination, 28 had a flexible cystoscopy, 17 had a rigid cystoscopy, 21 had a prostate biopsy, and 13 underwent a transurethral resection of the prostate (TURP). Blood samples were taken before and after manipulation for measurement of tPSA and cPSA. RESULTS: There was a statistically significant difference in the cPSA and tPSA before and after manipulation, with the exception of cystoscopy. On review of the data, it was clear that not all changes were clinically significant. The mean differences were greater for tPSA than for cPSA for all procedures. This was most apparent following prostate biopsy and TURP. Regression analysis also showed that cPSA and tPSA were affected differently by prostate manipulation. CONCLUSION: Our results demonstrate that cPSA is less prone to variations when compared to tPSA.     

血清结合PSA对前列腺疾病诊断价值的探讨

目的 :探讨血清中结合前列腺特异性抗原 (cPSA)在前列腺癌 (PCa)诊断中的临床价值。　方法 :用磁微粒子免疫化学发光法测定 110例良性前列腺增生 (BPH)病人和 78例PCa病人cPSA、tPSA ,并计算cPSA/tPSA比值。　结果 :cPSA及cPSA/tPSA比值可有效地区分BPH和PCa(P <0 .0 0 5 ) ,尤其是在诊断灰值区 (tPSA为 4～10 μg/L)时效果更显著。在以tPSA≤10 .0 μg/L和cPSA/tPSA≥0 .78为筛选界值联合对PCa进行筛选时 ,临床概率敏感度为 97.8%,特异性为 95 .8%,阴性预示值为 81.9%,阳性预示值为 96 .5 %。　结论 :cPSA的引入及cPSA/tPSA比值的应用 ,对PCa的诊断具有重要临床意义 ,尤其是在tPSA的诊断灰值区。     

Contemporary use of complexed PSA and calculated percent free PSA for early detection of prostate cancer: impact of changing disease demographics

Objectives. To assess the diagnostic performance of complexed prostate-specific antigen (cPSA), total PSA (tPSA), and calculated free/total PSA (f/t PSA) ratios in the differentiation of benign disease from prostate cancer (CaP) using a contemporary patient cohort.Methods. The cPSA, tPSA, and calculated fPSA values were determined using the Bayer Immuno-1 system. To validate our calculated f/t PSA ratio, we also retrospectively measured fPSA using the Abbott AxSYM immunoassay system in archival pretreatment sera obtained between 1990 and 1997 from 362 men with clinically and biopsy-confirmed benign prostatic hyperplasia (n = 179) or CaP (n = 183). The diagnostic utility of tPSA, cPSA, and the calculated f/t PSA ratio was assessed using a contemporary test population consisting of sera prospectively collected between June 1999 and June 2000 from 3006 men who had recently undergone a systematic biopsy by urologists in clinical practices throughout the United States. This contemporary patient sample had biopsy diagnoses of either no evidence of malignancy (n = 1857) or CaP (n = 1149). All serum samples had tPSA values between 2.0 and 20.0 ng/mL.Results. The measured versus calculated f/t PSA ratios had a Pearson’s correlation coefficient of 0.9130 in the retrospectively studied population of 362 men. The areas under the receiver operating characteristic curves (ROC-AUCs) for the measured and calculated f/t PSA ratios were indistinguishable (69.6% versus 69.2%, respectively). In the contemporary population (n = 3006), the ROC-AUC for tPSA, cPSA, and the calculated f/t PSA ratio was 52.2%, 53.9%, and 58.4%, respectively. We also compared the diagnostic performance using published cutoffs for tPSA (greater than 4.0 ng/mL), cPSA (greater than 3.8 ng/mL), and the f/t PSA ratio (greater than 15% and greater than 25%) in tPSA reflex ranges of 2 to 20 ng/mL and 2 to 10 ng/mL. We found that both cPSA and the f/t PSA ratio (greater than 25% cutoff) outperformed tPSA and yielded similar results in terms of biopsies spared and cancers missed.Conclusions. The calculated f/t PSA ratio and cPSA perform equally well in terms of the improvement of specificity in the discrimination of benign disease and CaP. The f/t PSA ratio and cPSA provide clinical benefits over the use of tPSA alone, such as an increased sparing of unnecessary biopsies performed with a manageable degree of risk of delayed cancer detection.     

Comparison of the clinical validity of free prostate-specific antigen, alpha-1 antichymotrypsin-bound prostate-specific antigen and complexed prostate-specific antigen in prostate cancer diagnosis

OBJECTIVE: To evaluate the diagnostic utility of free prostate specific antigen (fPSA), alpha-1- antichymotrypsin-bound PSA (PSA-ACT), complexed PSA (cPSA), and including their associated ratios to total PSA (tPSA) in serum for discrimination between prostate cancer (PCa) and benign prostatic hyperplasia (BPH). METHODS: A total of 166 white men (age: 65-88 years) with a tPSA between 2 and 20 microg/l were retrospectively analysed. Serum concentrations of tPSA, fPSA, PSA-ACT and cPSA were measured in 118 untreated PCa patients and 48 patients with BPH. The tPSA and cPSA concentrations were measured with the Bayer Immuno 1 system (Bayer Diagnostics, Tarrytown, USA). The Elecsys system 2010 (Roche Diagnostics, Mannheim, Germany) was used for determination of tPSA and fPSA. The PSA-ACT assay is a newly, developed prototype assay on the ES system (Roche Diagnostics, Mannheim, Germany). RESULTS: For statistical analysis only patients with tPSA between 2 and 20 microg/l were enrolled. The median concentrations of tPSA (Bayer: PCa 7.36 microg/l, BPH 4.03 microg/l; Roche: PCa 7.75, BPH 4.13), PSA-ACT (PCa 6.98, BPH 3.18) and cPSA (PCa 6.46, BPH 3.20) were significantly different. The median ratios of fPSA/tPSA (PCa 12.8 vs. BPH 22.4%), PSA-ACT/tPSA (PCa 89.8 vs. BPH 76.1%) and cPSA/tPSA (PCa 90.5 vs. BPH 81.7%) were significantly different between PCa and BPH patients. Using the areas under the curves, receiver operating characteristics analysis (tPSA: 2-20 microg/l) for discrimination between PCa and BPH showed that the ratios fPSA/tPSA (area under the curve: 0.77), PSA-ACT/tPSA (0.72) and cPSA/tPSA (0.78) were significantly different from tPSA (Bayer: 0.53; Roche: 0.55). PSA-ACT (0.64) and cPSA (0.59) alone were not significantly different from tPSA. The calculated ratios fPSA/tPSA, PSA-ACT/tPSA and cPSA/tPSA were not significantly different. CONCLUSION: The determination of PSA-ACT or cPSA and the associated ratios do not improve the diagnostic impact to discriminate between PCa and BPH compared to fPSA/tPSA ratio. The ratios PSA-ACT/tPSA or cPSA/tPSA can be considered to be alternative tools of fPSA/tPSA.     

血清tPSA、PSAD及Gleason评分在前列腺癌分期中的应用价值

目的:探讨血清前列腺特异性抗原(PSA)系列及穿刺组织活检Gleason评分在前列腺癌病理分期的预测价值。方法:回顾性分析我院1999～2008年病理证实为前列腺腺癌的124例患者资料,将该124例患者根据术后病理、骨扫描和CT或MRI结果分为A、B两组。骨扫描、CT、MRI或术后证实为有周围浸润或远处转移者归为A组;无周围浸润且无远处转移者归为B组。比较两组之间以上各指标的差异。通过多因素回归分析筛选前列腺癌病理分期的影响因子。运用工作特征曲线(ROC曲线)比较各指标的预测价值。结果:tPSA、穿刺活检Gleason评分值A组明显高于B组(P<0.05);多元Logistic回归分析中,仅tPSA进入模型,被认为是最主要的预测因子。ROC曲线对前列腺病理分期预测效力比较:联合分析tPSA与穿刺活检Gleason评分预测效果明显高于其他指标,工作特征曲线下面积(AUC)从大到小依次为Gleason评分+tPSA>tPSA>PSAD+tPSA+Gleason评分。结论:tPSA依然是临床上对前列腺癌病理分期较好的预测因素;联合穿刺组织活检Gleason评分,可以提高预测准确度,对指导临床治疗和预后有重要意义。