Follow-up ProstaScint scans verify detection of occult soft-tissue recurrence after failure of primary prostate cancer therapy

BACKGROUND: A reliable imaging modality is required to uncover occult soft- tissue recurrence after failure of primary prostate cancer therapy. This retrospective study was done to evaluate the ability of the (111)Indium-labeled monoclonal antibody (ProstaScint(R)) scan in detection of prostatic bed recurrence and/or metastases to regional and/or distant lymph nodes. METHODS: One hundred sequential patients were evaluated with repeated ProstaScint(R) scans because of evidence of recurrence during the course of their disease. These 100 patients were followed closely from November 1994 and April 1999, and had concurrent bone scans and serum prostate-specific antigen (PSA) evaluations. They have had hormone therapy (n = 53) and/or experienced a rising PSA after radical prostatectomy (n = 38) or after radiation therapy (n = 56). Scan images were scored 0-3, where score 0 = negative, score 1= prostate bed uptake, score 2 = regional lymph node uptake, and score 3 = distant lymph node uptake. In each patient, the uptake of the follow-up scan(s) was compared to that of the initial scan. RESULTS: The median age was 70 years (range, 45-87), and 23 patients had a positive bone scan. The average PSA was 40.5 ng/ml (standard deviation, 223.5). There was 257 scans representing 100 patients. All patients had at least 2 scans, 35 patients had 3 scans, and 11 patients had 4 scans. No individual exhibited detectable adverse clinical reactions during or after the scan. The findings of the initial and consecutive scans were anatomically consistent in 79%, whereas in 21% there were skip metastases. In 24 patients the lesions progressed by scan and PSA, 10 patients showed progression of scan but no PSA progression, 49 patients showed no change, and 17 patients showed a remission related to adjuvant therapy. CONCLUSIONS: The consistency on repeating the scan (79%) and the high percentage of patients showing persistent uptake at the prostate bed (43%) as well as the percentage of detection of regional nodes (20%) and distant nodes (32%) reflects the importance of using the ProstaScint(R) scan in finding occult recurrences after primary treatment failure of prostate cancer. These results are similar to those reported earlier in autopsy series studies in similar populations.     

The prognostic value of different forms of prostate specific antigen and their ratios in patients with prostate cancer

OBJECTIVE: To assess the prognostic value for patient survival of different forms of PSA and ratios thereof, before treatment for prostate cancer, by considering the forms and ratios both as independent markers and by comparing them with other commonly used prognostic markers, e.g. tumour grade, local stage (T-stage) and absence or presence of skeletal metastases (M-stage). PATIENTS AND METHODS: Blood samples were collected consecutively from men diagnosed with prostate cancer at our department in 1988. From this group, 66 men were followed until death, or for >/=9 years. Twenty-five patients died from their prostate cancer and 21 from other causes during the follow-up period. Forty-eight patients received hormonal treatment, whereas 18 remained untreated or received no treatment for their cancer before they died from other causes. Assays measuring the serum levels of free prostate specific antigen (fPSA), PSA complexed to alpha1-antichymotrypsin (PSA-ACT), and total PSA (tPSA) were used to calculate the percentage of free to total PSA (f/tPSA) fPSA/ACT and ACT/tPSA at diagnosis. Based on the initial levels or ratios of the PSA forms, the patients were divided into three numerically comparable groups (tertiles) for survival analysis. Prognostic factors predicting patient survival were evaluated using univariate (Kaplan-Meier life-tables with the log-rank test) and multivariate techniques (Cox proportional hazards regression model). RESULTS: Univariate analysis using the log-rank test showed that the serum level of each molecular form of PSA, i.e. tPSA (P=0.001), PSA-ACT (P<0.001) and fPSA (P<0.001), as well as grade (P<0.001), T-stage (P=0.00355) and M-stage (P<0.001), provided statistically significant prognostic information. Log-rank tests showed that none of the ratios, i.e. f/tPSA, fPSA/ACT and ACT/tPSA, were informative of prognosis (P>0.05). However, in a multivariate analysis regression model, not only M-stage (risk ratio 4.2; P=0. 026) and grade (risk ratio 2.6; P=0.022), but also f/tPSA (risk ratio 1.8; P=0.037), provided significant prognostic information. CONCLUSION: The values of tPSA, fPSA and PSA-ACT, as well as grade and T- and M-stage, are all independent prognostic factors of prostate cancer survival. In a multivariate analysis, not only M-stage and grade but also f/tPSA provided significant prognostic information.     

The impact of a negative (111)indium-capromab pendetide scan before salvage radiotherapy

PURPOSE: We determined the prognostic role, if any, of the ProstaScint (111)indium-capromab pendetide scan before salvage radiotherapy for biochemical recurrence after RP for localized prostate cancer. MATERIALS AND METHODS: We reviewed the records of 649 patients who underwent a ProstaScint scan from 1998 to 2004. A total of 44 patients were identified who had biochemical recurrence after RP and underwent a ProstaScint scan immediately before salvage radiotherapy. All patients received salvage radiotherapy to the prostatic bed unless pelvic lymph node uptake was identified on the scan, resulting in initial whole pelvic radiotherapy with 45 Gy, followed by a conformal boost to the prostate bed in 6. The median salvage radiotherapy dose to the prostate bed was 72 Gy. Patient demographics, pathological information, PSA values and ProstaScint results were collected retrospectively. The majority of ProstaScint scans were digitally fused with noncontrast pelvic computerized tomography images for interpretation. PSA progression after radiotherapy was defined using American Society for Therapeutic Radiation and Oncology criteria. RESULTS: At a mean followup of 22 months 43 of 44 patients (97%) experienced a PSA decrease after salvage radiotherapy with a mean PSA nadir of 0.16 ng/ml compared to a mean pre-radiotherapy PSA of 1.7 ng/ml. Of the 44 patients 15 (34%) showed post-radiotherapy PSA progression. When the entire cohort was analyzed, patients with negative ProstaScint scans had statistically lower post-radiotherapy PSA progression rates than patients with positive scans (1 of 10 or 10% vs 14 of 34 or 41%, p = 0.026). Patients with negative ProstaScint results were also statistically more likely to have a pre-radiotherapy PSA of less than 1.0 ng/ml (p = 0.005), no seminal vesicle involvement (p = 0.006), a greater mean PSA doubling time (p = 0.008) and received no hormone therapy (p = 0.003). When patients with pre-radiotherapy PSA less than 1.0 ng/ml were analyzed, a negative ProstaScint scan suggested but did not provide a statistically significant advantage over pre-radiotherapy PSA alone for predicting post-radiotherapy PSA progression (1 of 9 or 11% for negative vs 5 of 15 or 33% for positive scans, p = 0.20). CONCLUSIONS: Our early experience supports an improved prognosis in patients receiving salvage pelvic radiotherapy for biochemical recurrence after RP who have a negative pre-radiotherapy ProstaScint scan. However, this finding is not necessarily independent of pre-radiotherapy PSA.     

Broadening the criteria for avoiding staging bone scans in prostate cancer: a retrospective study of patients at the Royal Marsden Hospital

OBJECTIVE: To determine if it is possible to exclude staging bone scans in a greater proportion of patients if more consideration is given to T stage and Gleason score, as recent guidelines from the National Institute of Clinical Excellence state that routine staging bone scans for prostate cancer are unnecessary in patients with a prostate specific antigen level (PSA) of < 10 ng/mL and Gleason scores of < 8. PATIENTS AND METHODS: We identified a cohort of consecutive patients with untreated prostate cancer who had a staging isotope bone scan between 1 January 1995 and 31 December 2000, who were not on hormone therapy, who had their PSA estimated within 30 days of the scan, and who had histologically confirmed prostate cancer on biopsy reviewed at the Royal Marsden. Data were analysed according to Gleason score, major Gleason grade, clinical T-stage and PSA level. RESULTS: In all, 420 patients were identified who fulfilled the criteria for inclusion; 67 scans (16%, 95% confidence interval, CI, 13-20%) were positive. Of the 187 scans taken in patients with a PSA level of 相似文献   

Evaluation of preoperative ProstaScint scans in the prediction of nodal disease

Diagnostic methods are limited for detecting microscopic soft tissue metastases in patients with prostate cancer. Previous studies using (111)Indium Capromab Pendetide (ProstaScint scan) analyzed patients with extensive localized tumor (prostate specific antigen (PSA) >20 ng/ml) not optimal for surgical therapy. We evaluated the role of the ProstaScint trade mark scan in a preoperative population to provide histological documentation and to assess its utility in a surgical population. A total of 22 preoperative patients, underwent a ProstaScint scan. The mean preoperative PSA was 16.0 ng/ml (range 3.9-33 ng/ml). The mean Gleason score at biopsy was 6.9 (range 6-9). Each patient underwent a radical retropubic prostatectomy and bilateral pelvic lymph node dissection, which included resection of both obturator and common iliac lymph nodes. Histologic analysis of the resected lymph nodes provided the standard of comparison with the ProstaScint scan. The results of the scan and pathology for all 22 patients were compared with the bilateral obturator and iliac nodes, creating 88 data points. Nine areas (10%) were positive on the scan. One of these (11%) was a true positive while the other eight (89%) were false positives. Seventy-nine areas (90%) were negative on scan results. Of these, five areas (6%) were false negatives and 74 areas (94%) were true negatives. The scan yielded a sensitivity of 17%, specificity of 90%, negative predictive value (NPV) of 94% and a positive predictive value (PPV) of 11%. The high false positive rate and low PPV of ProstaScint scans overestimates metastatic lymph nodes disease, and is not useful when used preoperatively.     

Three new serum markers for prostate cancer detection within a percent free PSA-based artificial neural network

BACKGROUND: We aimed to evaluate the value of macrophage inhibitory cytokine 1 (MIC-1), human kallikrein 11 (hK11) migration inhibitor factor (MIF) in comparison to prostate-specific antigen (PSA) and % fPSA and also to develop a % fPSA-based ANN with the new input factors to determine whether these additional markers can further eliminate unnecessary prostate biopsies. METHODS: Serum samples from 371 patients with prostate cancer (PCa, n=135) or benign prostate hyperplasia (BPH, n=236) within the PSA range 0.5-20 microg/L were analyzed for total PSA, free PSA, MIC-1, hK11, and MIF. 'Leave one out' ANN models with these variables and prostate volume were constructed and compared to logistic regression (LR) and all single parameters. RESULTS: The discriminatory power of MIC-1, hK11, and MIF was less than that for PSA despite significant differences in BPH compared to PCa patients. At 90% and 95% sensitivity, the artificial neural networks (ANNs) were only significantly better than % fPSA if prostate volume was included. CONCLUSIONS: ANNs with the novel input factors of MIC-1, MIF, and/or hK11 and additional use of prostate volume demonstrated significant advantage compared with % fPSA and tPSA and may lead to a reduction in unnecessary prostate biopsies.     

The criteria for avoiding unnecessary computerized tomography and bone scan in staging patients with newly diagnosed prostate cancer: retrospective study of patients at Matsusaka Chuo General Hospital

PURPOSE: Staging for prostate cancer often includes computed tomography (CT) and bone scan in Japan. We examined the criteria of avoiding unnecessary CT and bone scan for the prostate cancer patients at Matsusaka Chuo General Hospital. SUBJECTS AND METHODS: 211 patients were newly diagnosed at our institution between 1998 September and 2004 April. We reviewed data from 208 patients who had a staging CT and bone scan. The data was analysed using Gleason score, clinical T-stage and serum prostatic specific antigen (PSA) level. RESULTS: CT detected lymphadenopathy in 19 patients (9.1%), Bone scan detected bone metastasis in 31 patients (14.9%). However there was no lymphadenopathy detected by CT in the patients with 20 ng/ml or less. In the analysis using PSA and Gleason score, there was no bone metastasis detected by bone scan in the patients with PSA level of 20 ng/ml or less and Gleason sum 7 or less. In the analysis using PSA and clinical local stage there was no bone metastasis detected by bone scan in the patients with PSA level of 20 ng/ml or less and localized lesion (cT1-2). CONCLUSION: In a new proatate cancer patient CT and bone scan can be avoidable by PSA level of 20 ng/ml or less and cT1-2 or less and Gleason sum 7 or less.     

The role of 111indium-capromab pendetide imaging for assessing biochemical failure after radical prostatectomy

PURPOSE: Conventional imaging modalities, such as computerized tomography and magnetic resonance imaging, lack sensitivity and specificity for detecting recurrent prostate cancer after radical surgery. We evaluated the role of the indium-capromab pendetide scan, otherwise known as the ProstaScint (Cytogen Corp., Princeton, New Jersey) scan, in this setting. MATERIALS AND METHODS: A retrospective review was performed of 42 patients undergoing ProstaScint imaging for biochemical progression after radical prostatectomy. Of these patients 16 (38.1%) subsequently completed a course of salvage radiation therapy. RESULTS: Median prostate specific antigen (PSA) immediately prior to ProstaScint imaging was 1.2 ng/ml (range 0.2 to 4.8). Abnormal accumulation on the ProstaScint scan was detected in 36 patients (85.7%). Of the 16 patients undergoing salvage radiation therapy 15 had uptake isolated to the prostatic fossa on ProstaScint imaging. Ten of these 15 patients (66.7%) achieved undetectable PSA after radiation therapy, while 5 (33.3%) had little or no response. Using American Society for Therapeutic Radiology and Oncology criteria 3 of 10 responders had relapse after an average of 9 months. The remaining 7 patients remained biochemically free of disease at last followup. CONCLUSIONS: ProstaScint imaging is capable of detecting recurrent prostate cancer at low PSA levels. However, only 7 of 15 men (46.7%) with ProstaScint uptake isolated to the prostatic fossa showed a durable response to salvage radiation therapy. Based on these findings patients might be better treated based on the rate of increase in PSA rather than on routine scanning with this test.     

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.     

Comparison of predictive accuracy for pathologically organ confined clinical stage T1c prostate cancer using human glandular kallikrein 2 and prostate specific antigen combined with clinical stage and Gleason grade

PURPOSE: Previously human glandular kallikrein 2 (hK2) has been implicated to predict pathologically organ confined prostate cancer (PCa) in patients with stage T2 disease. Now we evaluated the usefulness of hK2, as measured by 2 entirely different immunoassay designs, to enhance the discrimination of pathologically organ from nonorgan confined clinical stage T1c PCa. MATERIALS AND METHODS: A consecutive series of pretreatment serum from 148 men with clinical stage T1c PCa was used in 2 equally sensitive and specific methods to measure total hK2 with independent reagents and entirely different assay designs. Total prostate specific antigen (tPSA) and free PSA (fPSA) were measured and percent fPSA was calculated. We determined the algorithm, hK2*tPSA/fPSA, from data generated by each hK2 assay, calculated means, medians and ranges for each analyte and algorithm, and calculated the significance of differences on univariate analysis. Using pretreatment PSA, clinical stage and biopsy Gleason grade we then developed a multivariate logistic regression base model to predict organ confined cancer and we compared predictions of the base model supplemented by the different hK2 measurements. RESULTS: hK2 and hK2 based algorithms obtained by each hK2 assay were significantly different for pT2a/b vs pT3a or greater PCa (p = 0.034 to 0.0001) compared to tPSA (p = 0.06), fPSA (p = 0.90) or percent fPSA (p = 0.059). However, AUC (0.67 to 0.70) calculated by ROC analysis of the 4 models containing hK2 derived information was not significantly larger than that of the base model (AUC = 0.64, p = 0.52). CONCLUSIONS: The current data confirm that hK2 alone or hK2*tPSA/fPSA measured by 2 immunoassays is significantly lower in men with pT2a/b vs pT3a or greater PCa compared to tPSA, fPSA or percent fPSA on univariate analysis of a validation set of clinical stage T1c prostate cancer treated at an American center of excellence for prostate cancer surgery. However, the incorporation of preoperative hK2 into multiparameter predictive models for pT2 cancers did not increase predictive accuracy in this cohort of men.     

Evaluation of proprostate specific antigen for early detection of prostate cancer in men with a total prostate specific antigen range of 4.0 to 10.0 ng/ml

PURPOSE: In contemporary screening populations a major drawback of prostate specific antigen (PSA) is its relative lack of specificity, especially in the range of 4 to 10 ng/ml, where prostate cancer is found 25% of the time. ProPSA is a derivative of free PSA (fPSA) consisting of the truncated forms (eg [-2]proPSA, [-4]proPSA or the full-length [-7]proPSA). There is increasing evidence that proPSA is associated preferentially with prostate cancer. The objective of this study was to determine whether proPSA can influence the detection of early prostate cancer. MATERIALS AND METHODS: Archival serum samples obtained from 93 men who underwent a systematic 12-core prostate biopsy (total PSA range 4.0 to 10.0 ng/ml) were assayed for percent free PSA, total PSA and the 3 forms of proPSA (Hybritech Tandem Assays Beckman Coulter Access, Beckman Coulter, Inc., Brea, California). Free PSA, the cumulative sum of individual proPSA forms ([-2], [-4] and [-7], or sum-proPSA) and derivatives were determined. Of the 93 men assessed 41 (44%) had evidence of prostate cancer (76% Gleason 5/6, 19% Gleason 7 and 5% Gleason 8). Prostate volume was measured at systematic 12-core biopsy for the detection of prostate cancer. Results were analyzed using univariate and multivariate logistic regression (LR) nonparametric statistical methods. RESULTS: Using univariate LR, fPSA, percent fPSA (%fPSA), percent sum-proPSA and prostate volume significantly (p <0.05) differentiated men with prostate cancer from those with benign disease. However, applying stepwise backward multivariate LR, total PSA, %fPSA and sum-proPSA were retained and generated a receiver operator characteristic curve with an area under the curve of 76.6%. At 90% sensitivity these 3 variables collectively achieved a specificity of 44% for the detection of prostate cancer. Individually, the 3 retained variables had a specificity of 23% (total PSA), 33% (%fPSA) and 13% (sum-proPSA). CONCLUSIONS: Sum-proPSA, total PSA and %fPSA in combination improve the specificity of early prostate cancer detection in men with a total PSA of 4 to 10 ng/ml compared with the results of individual PSA molecular forms measured.     

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.     

PSA和SPECT骨显像在前列腺癌诊断治疗中的意义

目的：研究PSA、SPECT骨显像在前列腺癌诊断及治疗中的临床意义。方法：对100例经临床确诊的前列腺癌患者全部行血清PSA测定及全身骨显像。结果：发生骨转移的患者为81％,PSA≥20tμg／I．的患者发生骨转移的为60％。结论：血清PSA与骨显像联检对前列腺癌临床诊断、疗效观察及预后判定具有重要的指导意义。     

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.     

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.     

Prediction of bone metastases by combination of tartrate-resistant acid phosphatase, alkaline phosphatase and prostate specific antigen in patients with prostate cancer

Objective:   The clinical value of serum tartrate-resistant acid phosphatase (TRACP), prostate specific antigen (PSA), alkaline phosphatase (ALP), and prostatic acid phosphatase (PACP) for the prediction of bone metastases in prostate cancer were investigated.
Methods:   TRACP, PACP, ALP, and PSA serum levels were measured in 215 patients with prostate cancer, including 160 without and 55 with bone metastases. Correlation of serum marker levels with bone metastases was assessed using receiver operating characteristics (ROC) analysis. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for each serum marker. Multivariate stepwise logistic regression analysis was used to identify independent predictors for the presence of bone metastasis.
Results:   Mean serum TRACP, PACP, ALP, and PSA levels were significantly elevated in patients with bone metastases compared with those without ( P  < 0.05). PSA and PACP levels increased significantly with clinical stage of the disease, whereas TRACP and ALP levels only increased significantly in stage D2. Serum TRACP levels correlated significantly with extent of disease on bone scans. ROC analyses showed no significant differences in area under the curve for these markers. Logistic regression analysis demonstrated that PSA, ALP, and TRACP were significant predictors of bone metastasis. Predicted and observed risks of bone metastasis were well correlated when TRACP, ALP, and PSA were combined and bone scan could have been omitted in 70% of patients by assessing these three markers.
Conclusions:   Serum TRACP can be considered a useful predictor of bone metastases in prostate cancer. A combination of TRACP, ALP, and PSA can obviate the need for a bone scan in 70% of cases.     

Phase II prostate cancer vaccine trial: report of a study involving 37 patients with disease recurrence following primary treatment

BACKGROUND: A phase II trial was conducted to assess the efficacy of infusions of dendritic cells (DC) and two HLA-A2-specific prostate-specific membrane antigen (PSMA) peptides (PSM-P1 and -P2). This report describes the evaluation of 37 subjects admitted with presumed local recurrence of prostate cancer after primary treatment failure. METHODS: All subjects received six infusions of DC pulsed with PSM-P1 and -P2 at 6-week intervals. Clinical monitoring was conducted pre-, during, and post-phase II study. Data included: complete blood count, bone and total alkaline phosphatase, prostate markers, physical examination, performance status, bone scan, ProstaScint scan, and chest X-ray, as well as other assays to monitor cellular and humoral immune responses. RESULTS: One complete and 10 partial responders were identified from this group based on National Prostate Cancer Project criteria, or on a 50% reduction of prostate-specific antigen (PSA), or on a significant resolution in lesions (biopsy-proven when possible) on ProstaScint scan. CONCLUSIONS: About 30% of study participants in this group showed a positive response at the conclusion of the trial. This study suggests that DC-based cancer vaccines may provide an alternative therapy for prostate cancer patients whose primary treatment failed.     

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.     

Assay-specific artificial neural networks for five different PSA assays and populations with PSA 2–10 ng/ml in 4,480 men

Use of percent free PSA (%fPSA) and artificial neural networks (ANNs) can eliminate unnecessary prostate biopsies. In a total of 4,480 patients from five centers with PSA concentrations in the range of 2–10 ng/ml an IMMULITE PSA-based ANN (iANN) was compared with other PSA assay-adapted ANNs (nANNs) to investigate the impact of different PSA assays. ANN data were generated with PSA, fPSA (assays from Abbott, Beckman, DPC, Roche or Wallac), age, prostate volume, and DRE status. In 15 different ROC analyses, the area under the curve (AUC) in the PSA ranges 2–4, 2–10, and 4–10 ng/ml for the nANN was always significantly larger than the AUC for %fPSA or PSA. The nANN and logistic regression models mostly also performed better than the iANN. Therefore, for each patient population, PSA assay-specific ANNs should be used to optimize the ANN outcome in order to reduce the number of unnecessary biopsies.     

Effects of systematic 12-core biopsy on the performance of percent free prostate specific antigen for prostate cancer detection

PURPOSE: The performance characteristics of percent free (f) prostate specific antigen (PSA) for differentiating between benign prostatic hyperplasia and prostate cancer were originally established using primarily sextant biopsy. We determined whether the addition of 6 laterally directed cores to the traditional sextant prostate biopsy affects the performance of percent fPSA. MATERIALS AND METHODS: We retrospectively evaluated a cohort of 350 consecutive biopsies in men with negative digital rectal examinations and PSA between 4 and 10 ng/ml who underwent systematic 12 core biopsy (S12C) biopsy at Scott Department of Urology between March 1999 and January 2003. The effects of 6 additional, laterally directed biopsies on the sensitivity, specificity and area under the ROC curve for percent fPSA was evaluated in the 277 men in whom percent fPSA was measured. RESULTS: Cancers detected exclusively in the 6 laterally directed cores were associated with percent fPSA values similar to those in patients with a benign S12C biopsy. This resulted in a modest and yet predictable decrease in the sensitivity of percent fPSA at each biopsy threshold value without affecting specificity. There was a nonstatistically significant decrease in the area under the ROC curve with the addition of 6 laterally directed cores to sextant biopsy (medial sextant cores 0.66 vs S12C 0.60). CONCLUSIONS: The 12 core biopsy strategies have a higher cancer detection rate than sextant biopsies and they are gaining widespread acceptance. The addition of 6 laterally directed cores to traditional sextant biopsy may result in a modest decrease in the sensitivity of percent fPSA at each selected biopsy threshold without affecting specificity.