Biomedical subjects

Robert W Veltri

Publications and source records attributed to Robert W Veltri.

At least 19 recordsLinked to original sources

PubMed2006

Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial.

CONTEXT: Prostate safety is a primary concern when aging men receive testosterone replacement therapy (TRT), but little information is available regarding the effects of TRT on prostate tissue in men. OBJECTIVE: To determine the effects of TRT on prostate tissue of aging men with low serum testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial of 44 men, aged 44 to 78 years, with screening serum testosterone levels lower than 300 ng/dL (<10.4 nmol/L) and related symptoms, conducted at a US community-based research center between February 2003 and November 2004. INTERVENTION: Participants were randomly assigned to receive 150 mg of testosterone enanthate or matching placebo intramuscularly every 2 weeks for 6 months. MAIN OUTCOME MEASURES: The primary outcome measure was the 6-month change in prostate tissue androgen levels (testosterone and dihydrotestosterone). Secondary outcome measures included 6-month changes in prostate-related clinical features, histology, biomarkers, and epithelial cell gene expression. RESULTS: Of the 44 men randomized, 40 had prostate biopsies performed both at baseline and at 6 months and qualified for per-protocol analysis (TRT, n = 21; placebo, n = 19). Testosterone replacement therapy increased serum testosterone levels to the mid-normal range (median at baseline, 282 ng/dL [9.8 nmol/L]; median at 6 months, 640 ng/dL [22.2 nmol/L]) with no significant change in serum testosterone levels in matched, placebo-treated men. However, median prostate tissue levels of testosterone (0.91 ng/g) and dihydrotestosterone (6.79 ng/g) did not change significantly in the TRT group. No treatment-related change was observed in prostate histology, tissue biomarkers (androgen receptor, Ki-67, CD34), gene expression (including AR, PSA, PAP2A, VEGF, NXK3, CLU [Clusterin]), or cancer incidence or severity. Treatment-related changes in prostate volume, serum prostate-specific antigen, voiding symptoms, and urinary flow were minor. CONCLUSIONS: These preliminary data suggest that in aging men with late-onset hypogonadism, 6 months of TRT normalizes serum androgen levels but appears to have little effect on prostate tissue androgen levels and cellular functions. Establishment of prostate safety for large populations of older men undergoing longer duration of TRT requires further study. Trial Registration clinicaltrials.gov Identifier: NCT00161304.

Adult↗

PubMed2006

Alterations in nuclear structure and expression of proPSA predict differences between native Japanese and Japanese-American prostate cancer.

OBJECTIVES: To differentiate the benign and/or malignant epithelial cells in prostate cancer (PCa) glands of native Japanese (NJ) and Japanese-American (JA) men using biomarkers. METHODS: Tissue microarrays from radical prostatectomy specimens of cancerous and adjacent benign areas from 25 NJ and 25 JA prostate glands were studied. Image analysis was used to quantify total prostate-specific antigen (PSA) and proPSA immunohistochemical staining, as well as the variance of several morphometric features from Feulgen-stained epithelial cell nuclei. Logistic regression analysis was applied to determine whether quantitative nuclear grade (QNG) calculations and PSA immunohistochemical staining could differentiate the two test groups. RESULTS: The QNG model differentiated changes in the benign epithelium of the two Japanese groups with an area under the receiver operating characteristic curve of 84% and accuracy of 82% (P = 0.0001). A second QNG model differentiated changes in the malignant epithelium of the two groups with an area under the receiver operating characteristic curve of 84% and accuracy of 76% (P = 0.0023). Logistic regression models combining proPSA immunohistochemical data and QNG from either benign or malignant tissue components yielded areas under the receiver operating characteristic curve of 96% and 91% (P <0.0001) for differentiation of the JA and NJ groups, respectively. CONCLUSIONS: Unique nuclear morphometric alterations demonstrated by QNG combined with proPSA immunohistologic localization independently predicted for significant differences between NJ and JA men with PCa. These preliminary observations indicate a basis for biologic and molecular alterations in the benign adjacent and malignant epithelium between these two groups.

Asian↗

PubMed2006

Urinary markers in the detection of bladder cancer: what's new?

PURPOSE OF REVIEW: Bladder cancer is one of the most common genitourinary malignancies and is a potentially life-threatening diagnosis. For many patients, however, the diagnosis of bladder cancer entails a lifetime of vigilant, costly, and invasive surveillance for recurrent and/or progressive disease. In the context of relative limitations of the current standard of cystoscopy and cytology, there has been burgeoning activity in the development of novel molecular urine-based markers for bladder cancer detection. RECENT FINDINGS: A large number of candidate bladder cancer biomarkers have emerged as our understanding of the molecular pathogenesis of the disease has evolved. Many of these are in the relatively earlier phases of development but several have received the approval of the United States Food and Drug Administration for clinical use and are already being applied to patients in clinical practice. SUMMARY: Urine-based markers for bladder cancer detection represent an area of substantial innovation and discovery with potentially profound scientific, clinical, and economic implications. As more of these tests become standardized and undergo evaluation in large multicenter trials, it is conceivable that a novel marker or panel of markers will emerge as a major enhancement to the current standard of care.

Biomarkers, Tumor↗

PubMed2006

Immunohistochemical staining of precursor forms of prostate-specific antigen (proPSA) in metastatic prostate cancer.

Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.

Acid Phosphatase↗

PubMed2004

Natural history of disease progression in patients who fail to achieve an undetectable prostate-specific antigen level after undergoing radical prostatectomy.

BACKGROUND: To the authors' knowledge, the natural history of disease progression to distant metastasis is unknown in men who fail to achieve an undetectable prostate-specific antigen (PSA) level after radical retropubic prostatectomy (RRP),. The authors assessed the clinical outcome of men with a persistently detectable PSA level after RRP for clinically localized prostate carcinoma. METHODS: Between 1989 and 2002, 160 men failed to achieve an undetectable PSA level (>/= 0.1 ng/mL) after undergoing RRP for clinically localized prostate carcinoma. No patient received adjuvant therapy before documented metastasis. The Kaplan-Meier method was used to estimate distant metastasis-free survival. Univariate and multivariate Cox proportional hazards regression was used to assess the ability of clinical and pathologic variables to predict distant metastasis-free survival. RESULTS: The probability of distant metastasis-free survival at 3 years, 5 years, and 10 years was reported to be 68%, 49%, and 22%, respectively. Seventy-five men (47%) developed distant metastases after RRP (median time to metastases of 5.0 years; range, 0.5-13 years). The combination of RRP Gleason score, seminal vesicle status, and lymph node status resulted in 3 risk groups for the prediction of distant metastasis-free survival (hazards ratio [HR] = 1.6; P < 0.01). The slope of PSA changes approximately 3-12 months after RRP at a cutoff value >/= 0.05 was found to be even more predictive of distant metastasis-free survival (HR = 2.9; P < 0.01). CONCLUSIONS: Many patients remained free of metastatic disease for an extended period despite failing to achieve an undetectable PSA level after undergoing RRP for clinically localized prostate carcinoma. However, other patients experienced rapid disease progression to distant metastasis. The authors defined clinical (PSA slope) and pathologic (Gleason score) prognostic variables to help identify those patients with a higher risk of developing distant metastasis after undergoing RRP.

Adult↗

PubMed2004

Ability to predict metastasis based on pathology findings and alterations in nuclear structure of normal-appearing and cancer peripheral zone epithelium in the prostate.

PURPOSE: Malignant transformation in the prostate produces significant alterations in glandular architecture (Gleason grade) and nuclear structure that provide valuable prognostic information. Normal-appearing nuclei (NN) adjacent to cancer may also have altered functions in response to malignancy. We studied NN adjacent to peripheral zone (PZ) prostate cancer (PCa), as well as the PZ cancer nuclei (CaN) using quantitative image cytometry. The nuclear structure information was combined with routine pathological findings to predict metastatic PCa progression and/or death. EXPERIMENTAL DESIGN: Tissue microarrays of normal-appearing and cancer areas were prepared from 182 pathologist-selected paraffin blocks. Feulgen-stained CaN and NN were captured from the tissue microarrays using the AutoCyte Pathology Workstation. Multivariate logistic regression was used to calculate quantitative nuclear grade (QNG) solutions based on nuclear morphometric descriptors determined from NN and CaN. Multivariate logistic regression and Kaplan-Meier plots were also used to predict risk for distant metastasis and/or PCa-specific death using QNG solutions and routine pathology. RESULTS: The pathology model yielded an area under the receiver operator characteristic curve of 72.5%. The QNG-NN and QNG-CaN solutions yielded an area under the receiver operator characteristic curve of 81.6 and 79.9%, respectively, but used different sets of nuclear morphometric descriptors. Kaplan-Meier plots for the pathology variables, the QNG-NN and QNG-CaN solutions, were combined with pathology to defined three statistically significantly distinct risk groups for distant metastasis and/or death (P < 0.0001). CONCLUSIONS: Alterations in cancer or normal-appearing nuclei adjacent to peripheral zone cancer areas can predict PCa progression and/or death. The QNG-NN and QNG-CA solutions could be combined with pathology variables to improve the prediction of distant metastasis.

Adult↗

PubMed2004

Prostate cancer in native Japanese and Japanese-American men: effects of dietary differences on prostatic tissue.

OBJECTIVES: To investigate the relationship between diet and prostate cancer (CaP) among native Japanese (NJ) and second-generation or third-generation Japanese-American (J-A) men--focusing on the effects of animal fat and soy on prostatic tissues. METHODS: The subjects were 50 Japanese men undergoing radical prostatectomy, 25 NJ living in Nagoya, Japan and 25 U.S.-born J-A men, living in Los Angeles, California. A priori, the NJ men were believed to be a low-fat, high-soy group and the J-A men, a high-fat, low-soy group. The studies included postoperative measurements of diet (Block questionnaire), body fat (bioimpedance), blood, urine, and prostatic biomarkers in malignant and adjacent normal tissue, using a tissue microarray made from the original paraffin blocks. RESULTS: The NJ and J-A men were similar in age (65 to 70 years old; P <0.05), prostate-specific antigen level (7.1 to 8.6 ng/mL), prostate volume (35 to 38 cm3), and Gleason score (5.6 to 6.6), but their body composition differed. J-A men had more body fat (24% versus 19%), higher serum triglyceride levels (245 versus 106 mg/dL), lower estradiol levels (27 versus 31 ng/mL), and much lower urinary soy-metabolite levels (1:3) than NJ men (P <0.02). In both NJ and J-A groups, expression of numerous tissue biomarkers separated normal from CaP tissue, including markers for apoptosis (Bcl-2, caspase-3), growth factor receptors (epidermal growth factor receptor), racemase, 5-lipoxygenase, kinase inhibition (p27), and cell proliferation (Ki-67; all P <0.02). Furthermore, within both normal and CaP tissues, caspase-3 and 5-lipoxygenase were expressed more in NJ than in J-A men (P <0.01). Nuclear morphometry showed that the chromatin in each of the four groups (normal versus CaP, NJ versus J-A) was different (area under the curve 85% to 94%, P <0.01), despite fundamental genetic homogeneity. CONCLUSIONS: NJ and J-A men, products of similar genetics but differing environments, were shown to have differences in body composition that could influence CaP evolution. The CaP specimens from the NJ and J-A men were histologically similar, but tissue biomarker expression, especially of lipoxygenase and the caspase family, suggested differing mechanisms of carcinogenesis. Differences in nuclear morphometry suggested the additional possibility of gene-nutrient interactions.

Adenocarcinoma↗

PubMed2003

Quantitative alterations in nuclear structure predict prostate carcinoma distant metastasis and death in men with biochemical recurrence after radical prostatectomy.

BACKGROUND: Microscopic histologic grade has been the best predictor of prostate carcinoma (PCa) progression in men after surgical therapy. The ability to predict accurately, at the time of surgery, which patients are likely to develop metastatic PCa would enable optimization of disease management with adjuvant therapy. The authors assessed the ability of pathologic, nuclear morphometric, and chromatin parameters to predict metastatic PCa progression and/or death in 227 men with biochemical recurrence and long-term follow-up after undergoing radical prostatectomy. METHODS: Multivariate logistic regression (LR) was used to calculate quantitative nuclear grade (QNG) solutions using the variances of 60 nuclear morphometric descriptors (NMDs) of nuclear size, shape, DNA content, and chromatin organization that predicted distant metastasis and/or PCa-specific death. An LR model also was generated to predict this outcome using a combination of pathologic variables and the best QNG solution. Cox proportional hazards models were generated, and Kaplan-Meier plots were used to display three risk groups based on pathology, QNG, and a combination of these variables. RESULTS: A multivariate LR model using pathology retained lymph node (LN) status, seminal vesicle status, and prostatectomy Gleason score, yielding an area under the curve-receiver operator characteristic (AUC-ROC) of 75% with an accuracy of 59% at 90% sensitivity. The best QNG solution used the variance of 25 NMDs, yielding an AUC-ROC of 84% and an accuracy of 70% at 90% sensitivity. The combined pathology-QNG model retained LN status, prostatectomy Gleason score, and QNG, yielding an AUC-ROC of 86% with an accuracy of 76% at 90% sensitivity. The Cox proportional hazards models produced the following significant univariate and multivariate hazard ratios: QNG, 3.5 and 2.9, respectively; LN, 2.7 and 1.8, respectively; and prostatectomy Gleason score, 2.8 and 2.1, respectively. CONCLUSIONS: Alterations in the structure of tumor nuclei measured by computer-assisted image analysis were strong predictors of PCa progression and death in men with long-term follow-up who had biochemical recurrence after undergoing radical prostatectomy. QNG solutions can serve as a new supplemental biomarker for accurate prediction of PCa progression at the time of surgery.

Adenocarcinoma↗

PubMed2003

Quantitative biopsy pathology for the prediction of pathologically organ-confined prostate carcinoma: a multiinstitutional validation study.

BACKGROUND: Quantitative biopsy pathology with prostate specific antigen significantly improves the prediction of pathologic stage in patients with clinically localized prostate carcinoma (PCa). The authors recently reported a computational model for predicting patient specific likelihood of organ confinement of PCa using biopsy pathology and clinical data. The current study validates the initial models and presents an new, improved tool for clinical decision making. METHODS: The authors assessed 10 biopsy pathologic parameters and 2 clinical parameters using data from two institutions. Of 1287 patients, 798 men had pathologically organ confined (OC) PCa, 282 men had nonorgan-confined disease with capsular penetration (NOC-CP) only, and 207 men showed seminal vesicle or lymph node invasion (NOC-AD) after undergoing pelvic lymphadenectomy and radical prostatectomy. Patient input data were evaluated by ordinal logistic (OLOGIT) and neural network (NN) models; and the likelihood of developing OC, NOC-CP, or NOC-AD disease was calculated for the combined and separate data sets and was compared with the results from original presentation. In addition, a new two-output model was constructed (OC/NOC-CP vs. NOC-AD). RESULTS: The three-output OLOGIT and NN models predicted OC disease with 95.0% and 98.6% accuracy, respectively, for the combined data set and with 93.0% and 98.6% accuracy, respectively, on subset analysis. The combined accuracy for predicting OC, NOC-CP, and NOC-AD disease in the entire validation set was 66.7% for OLOGIT model and 66.0% for the NN model. The two-output OLOGIT and NN models correctly predicted 94.9% and 100.0% of all OC/NOC-CP disease, respectively. CONCLUSIONS: Both computation models predicted OC PCa with an accuracy of 93.0-98.6% when they were validated with two different data sets. The OLOGIT and NN-based, two-output model permitted an appropriate treatment decision for 85.2-90.2% of patients. These data support the use of quantitative pathology and clinical data-based decision modeling to manage patients with clinically localized PCa.

Biopsy↗

PubMed2003

Extended peripheral zone biopsy schemes increase cancer detection rates and minimize variance in prostate specific antigen and age related cancer rates: results of a community multi-practice study.

PURPOSE: We assessed the impact of age and prostate specific antigen (PSA) on extended systematic biopsy schemes for detecting prostate carcinoma and better characterized these tumors as a function of patient age and PSA. MATERIALS AND METHODS: We retrospectively reviewed the records of 2,299 consecutive patients who underwent initial systematic biopsy performed by 167 community based urologists. A total of 12 systematic biopsies of the peripheral zone were obtained in all patients. Various biopsy schemes were then created and cancer detection rates were calculated. Data analyses were stratified by patient age and PSA. RESULTS: On biopsy 1,020 patients (44.4%) had cancer. Detection rates increased with increasing patient age. Increasing age and PSA were associated with larger, higher grade tumors. Overall and unique site specific cancer detection rates were highest for laterally directed biopsies and the apical biopsy of the standard sextant scheme. The 12 site biopsy scheme outperformed all other schemes in patients with PSA 7 ng./ml. or less and in those 60 years or younger. The variation in age related and PSA related detection rates was greatest for the standard sextant scheme and this variability decreased for extended biopsy schemes. CONCLUSIONS: This multi-practice community based study confirms the inadequacy of sextant biopsies and emphasizes the need for extended peripheral zone sampling of the lateral aspect of the prostate. Generally increasing patient age and PSA were associated with larger, higher grade tumors. Extended biopsy schemes minimize PSA and age related detection rates.

Age Factors↗

PubMed2003

Evaluation of DD23 as a marker for detection of recurrent transitional cell carcinoma of the bladder in patients with a history of bladder cancer.

OBJECTIVES: To determine whether DD23 increases the sensitivity of urinary-based detection of transitional cell carcinoma (TCC) recurrence. The murine monoclonal antibody DD23 recognizes a 185-kDa tumor-associated antigen that is expressed in human bladder cancer cells in vitro and in vivo but is not detected in normal urothelium. METHODS: Using alcohol-fixed urinary cytology, matched voided urine and bladder wash specimens were evaluated for the contribution of DD23 antigen expression in the detection of recurrent TCC. The selected patient population had a history of bladder cancer, and urine cytology analysis was performed in a single commercial reference laboratory. DD23 antigen expression in a cohort of 81 patients was compared with urine cytology findings, and the sensitivity and specificity for each urine-based test was determined. The presence of recurrent disease was determined by positive pathologic biopsy. RESULTS: The 81-patient cohort produced 151 urine specimens for which both biopsy and cytology information were obtained. Of these specimens, 64 were confirmed by a tissue diagnosis for TCC recurrence. These biopsy-proven recurrences were used as the dependent variable to assess the accuracy of cytology testing. For the detection of TCC, the DD23 antigen had a sensitivity of 70.3% and a specificity of 59.8%. Combined with cytopathologic findings, DD23 enhanced the sensitivity for the detection of TCC from 43.8% (cytology alone) to 78.1%. For low-grade TCC (n = 20) DD23 enhanced the sensitivity from 20.0% (cytology alone) to 55.0%. For high-grade TCC (n = 25), DD23 enhanced the sensitivity from 64.0% (cytology alone) to 76.0%. In patients with a prior history of intravesical treatment, DD23 had a sensitivity of 94.7% and a specificity of 33.3% compared with a sensitivity of 52.6% and a specificity of 83.3% for cytology. CONCLUSIONS: DD23 antigen expression can be used as an adjunct to cytopathologic evaluation to enhance the sensitivity of urinary cytology detection of TCC. In addition, DD23 does not appear to lose sensitivity in patients with a prior history of bladder cancer treated with intravesical agents.

Administration, Intravesical↗

PubMed2003

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.

Adenocarcinoma↗

PubMed2003

Can prostate specific antigen derivatives and pathological parameters predict significant change in expectant management criteria for prostate cancer?

PURPOSE: A prior report established that pretreatment criteria based on clinical and biopsy pathology parameters can predict men who harbor small volume prostate cancer who might be followed expectantly. However, some of these men will exhibit disease progression with time and will need definitive therapy. To detect those in whom disease may progress, repeat prostate biopsies are performed at yearly intervals. Therefore, we determined whether biomarkers could be used to determine those in whom disease is likely to progress and thus those who require definitive therapy. MATERIALS AND METHODS: Initial and repeat biopsy information along with transrectal ultrasound measurements of gland volume, total prostate specific antigen (PSA), %free PSA (%fPSA) and total PSA velocity were evaluated in 78 men, 45 from the prior study, in whom disease was being managed expectantly. Univariate and multivariate logistic regression analyses determined variables that predicted a favorable tumor burden based on biopsy pathology status at each subsequent repeat biopsy. A Cox proportional hazards model was produced using 67 of 78 evaluable cases having adequate temporal data to predict hazard ratios for conversion from favorable to unfavorable tumor burden status. RESULTS: At time zero for 78 patients %fPSA, total PSA, and gland volume univariately and multivariately differentiated unfavorable and favorable tumor burden groups (p <0.05). The receiver operator characteristic area under the curve (ROC-AUC) was 83%. At the first followup biopsy 17 of 67 (25.4%) men converted to unfavorable tumor burden status. The %fPSA, PSA velocity and gland volume univariately distinguished these 2 groups (p <0.05) with 82% ROC-AUC. At second repeat biopsy 6 of 36 (16.7%) men converted to unfavorable tumor burden status and the ROC-AUC was 76%. Of the 14 men who had a third repeat biopsy all demonstrated favorable tumor burden status. A Cox proportional hazards model stratified the 67 of 78 men into high (48) and low risk (19) groups based on %fPSA at a 20% cutoff (p <0.01). Classification and regression tree analysis using logistic regression multivariately selected variables predicted favorable tumor burden status with an accuracy that ranged from 75% to 84% during our study. CONCLUSIONS: PSA velocity, %fPSA and gland volume information improves the prediction of men undergoing expectant management who are more likely to have small volume disease based on a 12-core biopsy interpretation within the time of our observations. %fPSA proved to be a valuable marker to stratify the 2 risk groups. Therefore, based on these factors it may be possible to consider deferment of repeat prostate biopsy until adverse results are detected. This rational approach to the management of prostate cancer in older men with small volume cancer seems to be a reasonable strategy.

Aged↗

PubMed2003

Comparison of total prostate-specific antigen and derivative levels in a screening population of black, white, and Korean-American men.

Numerous studies have assessed serum total PSA (tPSA) levels among different races. We extended the serum biomarker profiling using prostate-specific antigen (PSA) derivatives in age-matched screening populations that included white, black, and Korean-American patients. The median ages were 61 years for white and black patients and 63 years for Korean-American patients. Serum samples from 70 men in each ethnic group were analyzed using 3 different tPSA assays (Tosoh AIA 600II, Bayer Immuno-1, Roche Elecsys 2010). The percentage of free PSA (fPSA) was measured directly by Roche Elecsys 2010 immunoassay and then calculated from complexed PSA (cPSA) and tPSA results determined with the Bayer Immuno-1. The percentage of cPSA was determined using cPSA and tPSA assayed by the Immuno-1 method. Statistical analyses included nonparametric Kruskal-Wallis and analysis of variance (ANOVA) evaluations. There were no differences noted in the tPSA values based on ANOVA among the 3 races irrespective of the assay platform methodology employed. Also, the PSA derivatives, percentages of fPSA and cPSA, evaluated using the Kruskal-Wallis test, showed no significant differences for either derivative assayed on 2 different assay platforms among the 3 groups. In a contemporary screening population comparing tPSA, percentage of fPSA, and percentage of cPSA levels in 3 races, there were no significant differences identified among the groups.

Black or African American↗

PubMed2003

Modern Tumor Marker Discovery in Urology: Surface Enhanced Laser Desorption and Ionization (SELDI).

During the last two decades, biomarker research has benefited from the introduction of new proteomic analytical techniques. In this article, we review the application of surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopy in urologic cancer research. After reviewing the literature from MEDLINE on proteomics and urologic oncology, we found that SELDI-TOF is an emerging proteomic technology in biomarker discovery that allows for rapid and sensitive analysis of complex protein mixtures. SELDI-TOF is a novel proteomic technology that has the potential to contribute further to the understanding and clinical exploitation of new, clinically relevant biomarkers.

Journal Article↗

PubMed2002

Cost-benefit analysis of total, free/total, and complexed prostate-specific antigen for prostate cancer screening.

Refinements in prostate-specific antigen (PSA) through the use of its derivatives have augmented early detection rates of prostate cancer. However, these improvements are coupled with relatively large increases in unit cost per detected cancer. We used decision-analytic modeling to determine the most appropriate PSA derivative for population-based screening. We constructed a decision-analytic model to determine the PSA derivative with the highest cost-benefit ratio for prostate cancer screening. We defined 5 screening strategies: total PSA (tPSA) 4.0 ng/mL; free PSA/tPSA (f/tPSA) in conjunction with tPSA; and complexed PSA (cPSA) 3.8, 3.4, and 3.0 ng/mL. Prostate cancer prevalence, false-positive rates, and false-negative rates for each test strategy were calculated from a database of 2138 men. The direct costs were obtained from literature review and our department of clinical chemistry. The derivative cPSA with a positive threshold of 3.8 ng/mL was the dominant strategy. The average cost of screening was 138.93 dollars. The strategy of tPSA became dominant when the cost of cPSA was >35.00 dollars or the cost of a prostate biopsy was <67.30 dollars. To match the false-negative rate of tPSA 4.0 ng/mL, a cPSA threshold of 3.0 ng/mL is necessary (sensitivity 92.5%). At this level, the marginal cost increase over tPSA is 9.40 dollars. The dominant strategy for population-based prostate cancer screening is use of cPSA with a positive threshold of 3.8 ng/mL. The use of cPSA with a threshold of 3.0 ng/mL identifies a similar number of cancers with fewer biopsies than tPSA at 4.0 ng/mL.

Aged↗

PubMed2002

Impact of age on total and complexed prostate-specific antigen cutoffs in a contemporary referral series of men with prostate cancer.

Age-specific prostate-specific antigen (PSA) cutoffs were previously suggested and were found to miss significant cancers in older men. We assessed the influence of an age-adjusted PSA cutoff to optimize the diagnostic performance (sensitivity and specificity) of complexed PSA (cPSA) and total PSA (tPSA) in the differentiation of benign disease from prostate cancer using a contemporary referral patient cohort. The cPSA and tPSA values were determined using the Bayer Immuno 1 system. The diagnostic utility of tPSA and cPSA was assessed using a diverse contemporary test population consisting of sera prospectively collected between June 1999 and October 2000 from 3597 men who recently underwent 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 (NEM; N = 2189) or prostate cancer (n = 1408). All serum samples had tPSA values between 2.0 and 20.0 ng/mL. The mean tPSAs (ng/mL) for the NEM and prostate cancer groups were 7.1 +/- 3.2 and 7.3 +/- 3.3, respectively (P = 0.026). The mean cPSAs (ng/mL) for the NEM and prostate cancer groups were 5.6 +/- 2.7 and 6.0 +/- 2.9, respectively (P <0.001). As the tPSA increased from 2.0 to 10.0 ng/mL, the cancer detection rate remained relatively constant at approximately 39% when evaluated using increments of 2.0 ng/mL for tPSA. For fixed sensitivities of 80%, 85%, 90%, and 95%, as the age range increased (45 to 59, 60 to 69, 70 to 79, >or=80), the tPSA and cPSA assay cutoffs required to sustain the specified sensitivity level markedly increased, with the exception of the 95% sensitivity level, where the cutoffs only slightly increased between the age ranges of 45 to 69 and >or=70. Overall, cPSA showed a marginal improvement in specificity versus tPSA across all age groups at all sensitivity levels. In this community referral population, the cancer detection rate remained fairly constant over the tPSA range of 2.0 to 20.0 ng/mL. This study demonstrated that to maintain a given sensitivity level for cPSA and tPSA in the age ranges studied, continuous upward adjustment of the cutoffs was required as age increased.

Age Factors↗

PubMed2002

Saw palmetto alters nuclear measurements reflecting DNA content in men with symptomatic BPH: evidence for a possible molecular mechanism.

OBJECTIVES: To examine the nuclear chromatin characteristics of epithelial cells, looking for an SPHB-mediated effect on nuclear DNA structure and organization. Saw palmetto herbal blend (SPHB) causes contraction of prostate epithelial cells and suppression of tissue dihydrotestosterone levels in men with symptomatic benign prostatic hyperplasia, but a fundamental mechanism remains unknown. METHODS: A 6-month randomized trial, comparing prostatic tissue of men treated with SPHB (n = 20) or placebo (n = 20), was performed. At baseline, the two groups were similar in age (65 versus 64 years), symptoms (International Prostate Symptom Score 18 versus 17), uroflow (maximal urinary flow rate 10 versus 11 mL/s), prostate volume (59 versus 58 cm(3)), prostate-specific antigen (4.2 versus 2.7 ng/mL), and percentage of epithelium (17% versus 16%). Prostatic tissue was obtained by sextant biopsy before and after treatment. Five-micron sections were Feulgen stained and quantitatively analyzed using the AutoCyte QUIC-DNA imaging system. Images were captured from 200 randomly selected epithelial cell nuclei, and 60 nuclear morphometric descriptors (NMDs) (eg, size, shape, DNA content, and textural features) were determined for each nucleus. Logistic regression analysis was used to assess the differences in the variances of the NMDs between the treated and untreated prostate epithelial cells. RESULTS: At baseline, the SPHB and placebo groups had similar NMD values. After 6 months of placebo, no significant change from baseline was found in the NMDs. However, after 6 months of SPHB, 25 of the 60 NMDs were significantly different compared with baseline, and a multivariate model for predicting treatment effect using 4 of the 25 was created (P <0.001). The multivariate model had an area under the receiver operating characteristic curve of 94% and an accuracy of 85%. CONCLUSIONS: Six months of SPHB treatment appears to alter the DNA chromatin structure and organization in prostate epithelial cells. Thus, a possible molecular basis for tissue changes and therapeutic effect of the compound is suggested.

Aged↗