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Background: Selecting appropriate candidates for postprostatectomy radiotherapy is challenging, because adverse pathological features cannot accurately predict clinical recurrence. Biomarkers that identify residual disease activity may assist clinicians when counseling patients on the risks, benefits and costs of secondary treatment. NADiA ProsVue PSA slope results ≤2.0 pg ml(-1) month(-1) are predictive of a reduced risk of clinical recurrence; however, its clinical utility has not yet been studied., Methods: We prospectively enrolled men treated by radical prostatectomy in a multicenter, institutional review board-approved clinical trial. At postsurgical follow-up, investigators (N=17) stratified men into low-, intermediate- or high-risk groups for prostate cancer recurrence based on clinicopathological findings and other factors. Investigators documented their initial treatment plan for each subject and serially collected three serum samples for ProsVue testing. After the ProsVue result was reported, investigators recorded whether or not the initial treatment plan was changed. The proportion of cases referred for secondary treatment before and after ProsVue was reported, and the significance of the difference determined., Results: Complete assessments were reported for 225 men, 128 (56.9%) of whom were stratified into intermediate- and high-risk groups. Investigators reported that they would have referred 41/128 (32.0%) at-risk men for secondary treatment. However, after results were known, they referred only 15/128 (11.7%) men. The difference in proportions (-20.3%, 95% confidence interval (CI) -29.9 to -10.3%) is significant (P<0.0001). Odds of a referral was significantly reduced after results were reported (odds ratio 0.28, 95% CI 0.15-0.54, P<0.0001)., Conclusions: Knowledge of a ProsVue result had significant impact on the final treatment plan. A ProsVue result ⩽2.0 pg ml(-1) month(-1) significantly reduced the proportion of men at risk of recurrence who otherwise would have been referred for secondary treatment.

We hypothesized that factors beyond pathological stage, grade, PSA and margin status would be important predictors of biochemical recurrence (BCR) after radical prostatectomy (RP). A cohort of 3194 patients who underwent RP between 1988 and 2007 and who had neither neoadjuvant therapy nor postoperative adjuvant hormonal therapy was retrieved from the Duke Prostate Center database. Age, prostate-specific antigen (PSA), pathological Gleason score (pG), lymph node status, seminal vesicle invasion (SVI), extracapsular extension (ECE), positive surgical margin (PSM) status, year of surgery, race, adjuvant radiation therapy (XRT), percent tumor involvement in the RP specimen and prostate weight were evaluated as possible predictors of BCR in multivariate Cox regression analysis. BCR was defined as a PSA of 0.2 ng ml(-1) or higher at least 30 days after surgery. A nomogram was developed from the Cox model. Predictive accuracy was obtained by calculating bias-corrected Harrell's c and by bootstrap calibration. In multivariate analysis, PSA (hazard ratio 1.39 (95% confidence interval 1.29-1.51)), ECE (1.22 (1.04-1.44)), pG score (1.38 (1.14-1.68), 2.23 (1.76-2.84), 2.69 (2.12-3.40) for pG 3+4, 4+3, >7, respectively), SVI (1.72 (1.40-2.12)), PSM (2.05 (1.73-2.42)), year of surgery (0.65 (0.54-0.77)), African-American race (1.37 (1.13-1.66)), adjuvant XRT (0.19 (0.11-0.34)) and prostate weight (0.83 (0.76-0.92)) were identified as independent predictors of BCR (P< or =0.018 for all factors). Predictive accuracy of the nomogram was 0.75. Race and prostate weight were independent predictors for BCR after RP. By incorporating these variables, we developed a nomogram, which provides a highly accurate means for estimating risk of BCR after RP.

The use of prostate specific antigen (PSA) in the 1990s has brought on a stage migration of prostate cancer. Despite that, many men have still presented with metastatic prostate cancer in the past decade. The use of primary hormone therapy in the PSA era at a tertiary care Army Medical Center is studied in this paper. Charts were reviewed of 135 men who were diagnosed with metastatic prostate cancer and treated with hormone therapy as a primary treatment between 1989 and 1995. Statistical analysis was used to determine significant predictor variables on the time to disease progression. In univariate analysis clinical stage, pretreatment alkaline phosphatase and nadir PSA values were significant predictors of time to progression. Race and type of treatment were not. In multivariate analysis the relative risk of progression was 3.2 for patients with an alkaline phosphatase >252 and 16.5 for patients with a nadir >2.0. This study supports the argument that racial disparities in prostate cancer outcomes are due to access to care. Furthermore, the survival rate for patients with D-2 disease is better than in the pre PSA studies. Clinical stage, pretreatment alkaline phosphatase and PSA nadir can be used to predict response for those men presenting with metastatic prostate cancer.

The purpose of this investigation was to examine changes in pretreatment prostate-specific antigen (PSA), stage, and grade over the past decade as a function of race and geographic region. A multiinstitutional database representing 6,790 patients (1,417 African-American, 5,373 white) diagnosed with nonmetastatic prostate cancer between 1988 and 1997 was constructed. PSA, stage, and grade data were tabulated by calendar year and region, and time trend analyses based on race and region were performed. There was an overall decline of PSA of 0.8%/year, which was significant (P = 0.0001), with a faster rate of decline in African-Americans (1.9%/year) than for whites (0.6%/year). The odds ratio (OR) for a stage shift was 1.09, which was significant (P < 0.0001), and this shift was greater in whites. The OR for an overall grade shift was 1.15, which was significant (P < 0.0001). Although grade and PSA trends were similar for the different regions, there were significant regional differences in stage trends. The implications are that the face of prostate cancer has changed over the past decade; i.e., the distributions of stage, grade, and PSA (the most important prognosticators) have changed. In addition, the countenances of that face are different for whites and African-Americans. For African-Americans, this is good news: the stage, grade, and PSA distributions are more favorable now than before. For whites, the trends are more complex and more dependent on region. These findings should be used for future clinical and health-policy decisions in the screening and treatment of prostate cancer., (Copyright 2001 Wiley-Liss, Inc.)

Background: The objective was to compare the changes in pathologic and clinical data over time for African-American (AA) and white men with prostate carcinoma undergoing radical prostatectomy in an attempt to determine the early impact of prostate specific antigen (PSA)., Methods: Data from 195 AA and 587 white men who underwent radical prostatectomy from 1988 to 1999 in an equal access, tertiary, military medical facility were collected. Statistical analysis was used to determine the significance of the changes in the rates of extracapsular extension (ECE), positive margins, pretreatment PSA levels, and age at the time of surgery for each race over time., Results: Comparing 1988-99 results, the authors found that the percentage of AA men with ECE decreased from 100% to 34.8% (P = 0.007), and for white men from 56.9% to 43.2% (P = 0.269). The percentage of AA men with positive margins decreased from 100% to 26.1% (P < 0.0001), and for white men from 41.2% to 27.0% (P = 0.021). Mean age at surgery decreased from 66.6 to 59.9 years for AA men (P < 0.001) and from 65.9 to 61.1 years for white men (P < 0.001). Also, PSA levels decreased from 10.1 to 6.6 ng/dL for white men (P < 0.001) and from 16.5 to 6.5 ng/dL for AA men (P < 0.001)., Conclusions: The authors believe that the decrease in ECE and positive margins in AA men is primarily because of PSA testing, coupled with improved public awareness and equal access to care. It appears reasonable to recommend PSA testing in AA men, who have historically experienced poor outcomes from prostate carcinoma., (Copyright 2001 American Cancer Society.)

Purpose: Biostatistical models to predict stage or outcome in patients with clinically localized prostate cancer with pretreatment prostate specific antigen (PSA), Gleason sum on biopsy or prostatectomy specimen, clinical or pathological stage and other variables, including ethnicity, have been developed. However, to date models have relied on small subsets from academic centers or military populations that may not be representative. Our study validates and updates a model published previously with the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE, UCSF, Urology Outcomes Research Group and TAP Pharmaceutical Products, Inc.), a large multicenter, community based prostate cancer database and Center for Prostate Disease Research (CPDR), a large military database., Materials and Methods: We validated a biostatistical model that includes pretreatment PSA, highest Gleason sum on prostatectomy specimen, prostatectomy organ confinement status and ethnicity, including white and black patients. We then revised it with the Cox regression analysis of the combined 503 PSA era surgical cases from the CPDR prospective cancer database and 1,012 from the CaPSURE prostate cancer outcomes database., Results: The original equation with 3 risk groups stratified CaPSURE cases into distinct categories with 7-year disease-free survival rates of 72%, 42.1% and 27.6% for low, intermediate and high risk men, respectively. Parameter estimates obtained from a Cox regression analysis provided a revised model equation that calculated the relative risk of recurrence as: exponent (exp)[(0.54 x Race) + (0.05 x sigmoidal transformation of PSA [PSA(ST)]) + (0.23 x Postop Gleason) + (0.69 x Pathologic stage). The relative risk of recurrence, as calculated by the aforementioned equation, was used to stratify the cases into 4 risk groups. Very low-4.7 or less, low-4.7 to 7.1, high-7.1 to 16.7 and very high-greater than 16.7, and patients at risk had 7-year disease-free survival rates of 85.4%, 66.0%, 50.6% and 21.3%, respectively., Conclusions: With a broad cohort of community based, academic and military cases, we developed an equation that stratifies men into 4 discrete risk groups of recurrence after radical prostatectomy and confirmed use of a prior 3 risk group model. Although the variables of ethnicity, pretreatment PSA, highest Gleason sum on prostatectomy specimen and organ confinement status on surgical pathology upon which the model is based are easily obtained, more refined modeling with additional variables are needed to improve prediction of intermediate risk in individuals.

Purpose: It has been shown that black men with clinically localized prostate adenocarcinoma treated with radical prostatectomy have poorer disease-free and disease specific survival than white men with similar tumors. These findings suggest that a potentially more aggressive variant of prostate cancer exists in black men. Because prostate specific antigen (PSA) velocity at tumor recurrence is a good indicator of disease aggressiveness, we determine whether there was evidence that PSA velocity at biochemical recurrence after radical prostatectomy is faster in black men., Materials and Methods: Our retrospective data search at 2 university centers resulted in 127 white and 37 black men with clinical stage cT1 to 2 prostate adenocarcinoma who underwent radical prostatectomy between 1990 and 1994 and had evidence of biochemical recurrence (PSA greater than 0.2 ng./ml.) on followup available for analysis. No neoadjuvant or adjuvant treatments were given before or after radical prostatectomy, and all PSA relapses and subsequent treatments were recorded. PSA velocity modeling was performed in patients before any form of treatment for PSA failure. Preoperative PSA, Gleason score and pathological stage were also included in the model to assess the impact on PSA velocity after recurrence., Results: Our data suggested that PSA velocity at tumor recurrence was related to preoperative PSA on a continuous scale (p = 0.063). However, in our analysis there was little evidence that race had any effect on PSA velocity at tumor recurrence in our patient cohort (p = 0.58). Likewise, little difference in PSA velocity was seen in regard to Gleason score (p = 0.89) or pathological stage (p = 0.23) in these patients. With data on 37 black men available for analysis it was likely that only large or extreme trends could be detected. Results could be used to estimate required sample sizes for assessment of less extreme trends., Conclusions: Our data on tumor growth rate at recurrence, as reflected by PSA velocity kinetics, do not support the hypothesis that prostate tumors in black men are necessarily more aggressive due to enhanced growth. Further studies comparing the molecular and biological differences between prostate cancers in black and white males are needed to clarify reasons for the apparent differences in initial presentation, as compared to that at tumor recurrence in these 2 groups.

Prostate-specific antigen (PSA) testing could be used to identify men who are at higher future risk of developing clinical prostate cancer or to diagnose prostate cancer earlier in high-risk groups, such as black men or those with a family history of the disease. These cohorts then could be offered chemopreventive clinical trial participation opportunities. The Physicians' Health Study and other longitudinal studies have shown that even between a PSA level of 1.0 and 4.0 ng/mL, the risk of future prostate cancer is incrementally increased. Department of Defense Studies of young men between 15 and 45 show that normal men have very low PSA values. Using a threshold PSA even as low as 1.5 ng/mL for men in their fifth decade is well beyond the 95th percentile of "normal" PSA. Young black men between 40 and 49 years old have a higher risk of prostate cancer than white men and should be pursued for chemoprevention studies. PSA is not perfect. Benign prostatic hyperplasia and inflammation (and, perhaps, other factors) can confound the use of PSA thresholds to identify men for chemoprevention or early detection. Certain chemopreventive agents may affect PSA physiology without affecting the disease process itself creating a meaningless epiphenomenon. Young black men may not generally be receptive to PSA testing or chemopreventive trials.

Objectives: To determine the prostate-specific antigen (PSA) levels and PSA change over time in young white and black men 20 to 45 years old., Methods: The Department of Defense Serum Repository, a serum bank that stores all residual serum from the military human immunodeficiency virus screening program at -25 degrees C, was sampled to obtain a total of 588 black and 588 white subjects 20 to 45 years old. This was a retrospective study with only demographic data available on the studied subjects. The samples used for this study were collected between June 24, 1988 and June 12, 1996. Individuals with a history of prostate disease were excluded by query of a centralized Department of Defense diagnosis database. Three serum specimens evenly distributed over a mean of 6 years were selected for each individual to determine the free and total PSA levels and PSA velocity. The Hybritech Tandem-E PSA assay was used for the total PSA measurement, and the Hybritech Tandem-R assay was used for the free PSA measurement., Results: The baseline serum PSA levels differed by race (P = 0.04). The median (25th, 75th percentile) baseline serum PSA levels for black men 20 to 29, 30 to 39, and 40 to 45 were 0.38 ng/mL (0.26, 0.61), 0.45 ng/mL (0.32, 0. 67), and 0.52 ng/mL (0.37, 0.73), respectively. The median baseline serum PSA levels for the same decade groups in white men were 0.38 ng/mL (0.27, 0.57), 0.45 ng/mL (0.28, 0.68), and 0.40 ng/mL (0.26, 0. 64), respectively. The PSA velocity was higher in white men than in black men (mean 2.8%/yr and 1.6%/yr, respectively, P = 0.032)., Conclusions: These results suggest that although black men 20 to 45 years old have higher baseline serum PSA levels than white men of the same age, the PSA velocity is greater in young white than in young black men. Additional work is needed to determine the clinical significance of these findings.

Recurrence after local prostate cancer treatment detectable only by a rise in serum prostate specific antigen (PSA) is a very common problem facing clinicians. Given that the majority of these men are relatively young and otherwise healthy, treatment of PSA-only recurrence requires approaches that not only improve survival but also preserve quality of life. For radical prostatectomy patients, a PSA-only recurrence is broadly defined as persistent or rising PSA in the postoperative period. For radiation-treated patients, the 1997 American Society for Therapeutic Radiology and Oncology guidelines specify three consecutive elevations of PSA after the post-treatment nadir PSA is achieved. Traditional hormonal therapy is the mainstay of systemic treatment for PSA-only recurrence, although nontraditional approaches such as intermittent and oral-only hormonal therapy are under study.

Purpose: Introduction of the prostate specific antigen (PSA) serum marker for prostate cancer and the subsequent PSA era from 1988 to the present have dramatically altered the diagnosis of the disease. The early to mid 1990s diagnosis boom resulted in a huge increase in clinically localized and early stage disease treatments. Radical prostatectomy rates increased from 17.4 to 54.6/100,000 between 1988 and 1992, and age adjusted rates increased 2 to 4-fold for men in the fifth and sixth decades of life. Since the late 1990s clinicians have been seeing the effects of this diagnosis and localized treatment boom, in that many men each year are experiencing PSA only disease recurrence. Given that the majority are relatively young and otherwise healthy, treatment of PSA only recurrence requires approaches that not only improve survival, but also preserve quality of life. A comprehensive overview of the definition of PSA only recurrence, staging controversies and the wide variety of treatments to be considered is provided., Materials and Methods: A literature review and overview of the topic of PSA only recurrence after prior clinically localized prostate cancer treatment were performed., Results: For radical prostatectomy cases PSA only recurrence is broadly defined as any elevation of PSA postoperatively. For radiation treated patients the 1997 American Society for Therapeutic Radiology and Oncology guidelines specify 3 consecutive elevations of PSA after posttreatment PSA nadir is achieved. As localized treatment series in the PSA era have matured, and database and statistical support have improved, a number of useful models to predict PSA only recurrence have emerged. These models are based on traditional prognostic markers, such as pretreatment PSA, and grade and stage of disease as well as emerging molecular and cellular biomarkers. Although bone scans and pelvic computerized tomography are commonly used for re-staging at PSA only recurrence, recent study suggests that their value is limited unless PSA recurrence exceeds 30 to 40 ng./ml. 111Indium capromab pendetide radionuclide scan, which has been approved for radical prostatectomy PSA only recurrence, may be helpful to determine cases best suited for salvage radiotherapy versus systemic hormonal therapy, although more study is needed. Treatment of PSA only recurrence is divided into 2 main categories of salvage local treatments and systemic therapy. The principal dilemma is the inability to determine definitively whether PSA only recurrence is solely due to local progression or distant micrometastases. External beam radiation is the main local salvage treatment for radical prostatectomy recurrence, and cryotherapy, salvage prostatectomy and salvage brachytherapy are options for radiation recurrence. Proper patient selection is critical to the success of all salvage local treatments. Traditional hormonal therapy is the mainstay of systemic treatment for PSA only recurrence, although nontraditional approaches, such as intermittent and low dose hormonal therapy, are under study. Emerging chemopreventive agents, such as vitamins, minerals and other supplements, may have a future role in treatment., Conclusions: PSA only recurrence after prior local prostate cancer treatment remains a common problem facing clinicians.

Purpose: Although black men with and without prostatic carcinoma in general have higher levels of prostate specific antigen (PSA) than other racial groups, the cause is unknown. Previous studies have shown that black men produce greater PSA per cc of benign gland volume. We determined whether prostatic inflammation varied by race and could account for the racial difference in PSA among prostate cancer patients., Materials and Methods: Between April 1993 and February 1997, 238 patients underwent radical prostatectomy for clinically localized prostate cancer at Walter Reed Army Medical Center and whole mounted specimens were processed at the Armed Forces Institute of Pathology. Cases were reviewed by 2 pathologists (W. Z. and I. A. S.) blinded to clinical information, and scored for inflammation as 0--rare; 1--mild, 10 to 15 small foci; 2--moderate, greater than 15 foci with a large area or greater than 20 small foci; 3--marked, greater than 20 small foci with a large area, and 4--diffuse, multiple large areas. The extent of inflammation was correlated to pretreatment PSA and other variables., Results: A total of 181 white and 57 black men were evaluated. Of the patients 28 were excluded from analysis due to prior hormonal therapy. The percentage of patients with inflammation scores from 1 to 4 was higher among white (113 of 161, 70.2%) than black (30 of 49, 61.2%) men but this difference was not significant (p = 0.299) and the extent of inflammation was not significantly related to racial variation in serum PSA., Conclusions: To our knowledge no significant racial difference exists in the extent of inflammatory infiltrate, and inflammation was not the etiology of the racial difference in serum PSA levels in this clinically localized prostate cancer cohort.

Purpose: Black men with and without prostate cancer in general have higher prostate specific antigen (PSA) before screening and treatment than other racial groups. A preliminary study suggested that higher PSA levels may be primarily due to greater tumor burden. We compared PSA and 3-dimensional (D) tumor volume in a consecutive cohort of black and white radical prostatectomy patients in an equal access military health care setting to determine racial differences in these parameters., Materials and Methods: Prospective data collection, 2.25 mm. step section whole mount specimen processing and 3-D tumor volume assessment were performed in 226 patients with clinical stage T1-T3 prostate cancer undergoing radical prostatectomy at our center between April 1993 and March 1997. Of the patients 25 were excluded from further analysis because of neoadjuvant hormone treatment, T3 disease or Asian race. A total of 155 white and 46 black patients were compared., Results: There was no significant racial difference in the distribution of patients by age, clinical stage, pathological stage, Gleason sum or benign prostate gland volume. A significant racial difference was noted for pretreatment PSA and 3-D tumor volume. PSA values were higher in black men than in white men, and the racial difference remained statistically significant in multivariate analysis adjusting for 3-D tumor volume, benign gland volume, age, stage and Gleason sum., Conclusions: Racial difference in PSA persists, despite rigorous covariate adjustment, and further study is needed to explain this PSA difference.

Patients whose only sign of recurrence after local therapy for prostate cancer is a rising prostate-specific antigen level (PSA-only recurrence) have become more common. We have developed two models to predict PSA-only recurrence after radical prostatectomy, one using traditional factors (race, sigmoidal transformation of PSA, postoperative Gleason sum, and organ confinement) and a second using traditional clinical and pathologic variables combined with molecular biomarker levels. Treatment options for patients with PSA-only recurrence include observation, radiation therapy for patients who have undergone surgery, salvage surgery or cryotherapy for patients who have received radiotherapy, and traditional or nontraditional hormonal therapy. Radiation for PSA-only recurrence is likely to benefit men who have no adverse pathology, a low PSA level at recurrence, and PSA recurrence after the first year. Salvage radical prostatectomy and cryotherapy pose a relatively high risk of incontinence and other morbidity and should be reserved for carefully selected patients with a high likelihood of organ-confined disease. Hormonal therapy is probably the single most beneficial treatment for PSA-only recurrence. Nontraditional low-dose oral hormonal therapy and intermittent hormonal therapy are gaining in popularity, although their long-term efficacy is unknown. More clinical trials are needed to fine-tune prognostic models and to determine the best treatments, alone or in combination, for PSA-only recurrence.

Objectives: The reverse transcriptase-polymerase chain reaction (RT-PCR)-prostate-specific antigen (PSA) assay to detect presumed occult micrometastatic prostate cancer has been controversial, and this molecular staging has been thought to be clinically useful by some groups but not others., Methods: We used a sensitive nested RT-PCR assay with specific primers derived from the PSA sequence and a very stringent two-step PCR protocol with denaturing temperature of 94 degrees C annealing and extension temperature of 68 degrees C. This method enabled us to detect PSA-expressing LNCaP prostate cancer (PC) cells as low as one cell of 10 million lymphocytes (1/10(7)). Ninety-six patients with PC were studied, including 85 before radical prostatectomy (RP), and 22 controls, including healthy men and women and men with benign prostatic hyperplasia., Results: In 85 patients undergoing RP, a minimum of two independent RT-PCR-PSA assays detected circulating prostate cells preoperatively in 27 patients (31.8%). Of 12 patients with locally advanced or advanced stage cancer, RT-PCR-PSA was positive in 5 (41.7%); of the 22 controls, no patient was RT-PCR-PSA positive. In 10 randomly selected cases, the RT-PCR product was confirmed as PSA by DNA sequencing. Of the 27 patients undergoing RP who were RT-PCR positive, 11 (40.7%) had non-organ-confined disease (pT3a or greater), and of the 58 patients who were RT-PCR negative, 32 (55.2%) had non-organ-confined disease. Patients with RT-PCR positive results also had lower margin positivity (9 of 27, 33.3%) than did patients with RT-PCR negative results (21 of 58, 36.2%). Finally, at a mean follow-up of 25.7 months, 5 (18.5%) of 27 RT-PCR positive patients had recurrence (PSA) compared with 14 (24.1%) of 58 RT-PCR negative patients., Conclusions: On the basis of this blinded study, RT-PCR for PSA-expressing cells in 85 patients before RP is not related to clinical stage, age, race, grade, Gleason sum, serum PSA or prostatic acid phosphatase, tumor volume, or tumor multifocality. RT-PCR positivity did not predict pathologic stage or early PSA recurrence. A standardized RT-PCR assay needs to be developed to account for interlaboratory discrepancies.

Purpose: The reverse transcriptase polymerase chain reaction (RT-PCR) assay for prostate specific antigen (PSA) expressing cells in the blood circulation has been under intense investigation since 1992. Although it has been suggested that this technology could be used as molecular staging for occult prostatic hematogenous metastases, we have been unable to confirm RT-PCR PSA positivity of peripheral blood to predict stage or recurrence in radical prostatectomy cases. We performed bone marrow RT-PCR PSA assay on a large cohort of radical prostatectomy cases and evaluate the use of this assay in improving prostate cancer staging and detecting early recurrence., Materials and Methods: Unilateral anterior iliac crest bone marrow aspirates were performed on 116 patients immediately before radical prostatectomy between February 1995 and September 1997. Radical prostatectomy specimens were processed as whole mounts. A sensitive nested RT-PCR assay with specific primers derived from the PSA sequence was used, which enabled us to detect PSA expressing LNCaP prostate cancer cells at the sensitivity of 1 cancer cell per 10 million lymphocytes (1/10(7)). A minimum of 3 RT-PCR PSA reactions were performed on all patients and at least 2 positive tests were required to define positivity. Patients were followed for PSA recurrence (mean followup 14.7 months)., Results: PSA expressing cells were detected in bone marrow of 51 of 116 patients (44.0%) when at least 2 of 3 RT-PCR PSA assays per patient were positive. A much higher rate of RT-PCR PSA positivity was noted (77/116 patients, 66.3%) when any RT-PCR PSA positivity was considered. In 10 randomly selected cases the RT-PCR product was confirmed as PSA by deoxyribonucleic acid sequencing. Of 51 bone marrow RT-PCR positive cases 25 (49%) had organ confined disease and 26 (51%) had nonorgan confined disease. Similarly, bone marrow RT-PCR PSA was not associated with age, race, grade, pretreatment PSA or prostatic acid phosphatase value, clinical stage or margin status. However, the 2-year disease-free survival was 96.6% in RT-PCR negative patients versus 77.5% in RT-PCR positive patients (p = 0.054), and bone marrow RT-PCR PSA was an independent prognostic factor in multivariate analysis including PSA, Gleason grade and pathological stage., Conclusions: Bone marrow RT-PCR PSA positivity in this study did not predict pathological stage, grade or margin positivity as determined from whole mount prostate cancer specimens. Furthermore, no relationship with age, grade or serum markers and bone marrow RT-PCR PSA positivity was noted. However, bone marrow RT-PCR PSA was associated with early disease recurrence. Further studies and longer followup are warranted to define the metastatic potential of the PSA expressing cells in the bone marrow of prostate cancer patients.

Objectives: To assess the ability of pretreatment and post-treatment prostate-specific antigen (PSA) measurements, clinical tumor stage, tumor grade, Gleason sum, race, age, and radiation dose to predict the recurrence of prostate cancer following external beam radiation therapy (XRT) since the introduction of PSA as a tumor marker at one tertiary care center., Methods: The recurrence of prostate cancer among 371 evaluable patients of 389 patients treated with XRT at Walter Reed Army Medical Center was analyzed using Kaplan-Meier survival methodology and Cox multivariable regression models. Serologic (PSA) recurrence was determined using three consecutive rises in PSA after a nadir value. Clinical recurrence was defined as local recurrence (palpable or positive biopsy) and/or distant (radiographically evident) recurrence. Mean and median follow-up is 40.2 and 39.4 months, respectively (range 3.0 to 89.5), and minimum follow-up is 18 months for patients who were alive at the time of analysis. No patient received adjuvant hormonal therapy. Potential prognostic factors evaluated are pretreatment PSA, PSA nadir, age, race, clinical tumor stage, tumor grade, Gleason sum, and radiation dose., Results: Of the 371 evaluable patients, 125 had disease recurrence. The Kaplan-Meier 5-year disease-free survival (DFS) rates for significant pretreatment variables in univariate analyses are as follows: pretreatment PSA less than 4 (79%), 4.1 to 10 (67%), 10.1 to 20 (57%), 20.1 to 50 (27%), and more than 50 (0%); for clinical tumor Stage T1a-T1c (84%), T2a-T2c (51 %), and T3-T4 (29%); for tumor grade well (58%), moderate (58%), and poor (30%). Four-year DFS rates for Gleason sum are 2 to 4 (82%), 5 (72%), 6 (56%), and 7 to 10 (48%). In multivariable Cox regression analysis with backward elimination of nonsignificant variables, age, race, tumor grade, and radiation dose were eliminated, leaving pretreatment PSA, clinical tumor stage, and Gleason sum as significant prognostic factors. Analysis of a Cox model that included nadir PSA as a time-dependent variable showed it to be the strongest prognostic factor variable in the analysis., Conclusions: XRT remains a suitable treatment modality for patients with pretreatment PSA less than 20.0, clinical tumor Stages T1-T2, and Gleason sum 2 to 6 prostate cancer. Patients achieving a nadir value less than 0.5 have more durable treatment outcomes.

Objectives: To determine the age- and race-specific prostate-specific antigen (PSA) distributions in healthy men in central South Carolina and to compare these to data from other studies., Methods: Two thousand ninety-two black men aged 40 to 69 years and white men aged 50 to 69 years from the general population in 11 counties of central South Carolina participated in a prostate cancer educational program. Seventy-two percent of the participants were black-about double the proportion in the general population-and 63% of the men (1319 of 2092) subsequently obtained a PSA determination from their own physician. The distribution of serum PSA was compared with distributions from the Olmsted County study and from the Walter Reed Army Medical Center/Center for Prostate Disease Research study., Results: Older men without cancer had higher PSA levels. Regression analyses yielded an associated increase of about 3.3% per year. Reference ranges for normal PSA in men without cancer (based on their sample 95th percentiles) were zero to 1.9, 3.8, and 5.7 ng/mL in black men aged 40 to 49, 50 to 59, and 60 to 69 years, and zero to 2.7 and 4.9 mg/mL in white men aged 50 to 59 and 60 to 69 years, respectively., Conclusions: Reference ranges for normal serum PSA levels should take into account the population from which they are derived and to which they will be applied. Reference ranges that are useful in the general population can differ from those that are appropriate in a hospital setting. For the general population in central South Carolina, reference ranges for serum PSA levels are lower than previously published reference ranges, particularly among black men.

Background: Higher preoperative prostate specific antigen (PSA) levels are associated with higher pathologic stage and grade in patients undergoing radical prostatectomy (RP). In earlier studies, serum prostate specific membrane antigen (PSMA) elevations were associated with clinical progression and hormone-refractory carcinoma. The goal of this study was to evaluate the serum markers PSMA, free PSA (FPSA), free:total PSA ratio (F:TPSA), and total PSA (PSA) in men undergoing RP., Methods: Serum was obtained from 63 patients undergoing RP for clinically localized (T1c, T2) prostate carcinoma. Serum PSA and FPSA were determined by Hybritech Tandem-E(R) and Tandem-R(R), respectively, and PSMA was determined by Western blot analysis. Serum values for these markers were compared with the pathologic stage, surgical margin status, Gleason sum, prostate size (as calculated via reconstruction and transrectal ultrasound), tumor size based on pathologic assessment of the whole mount, and World Health Organization (WHO) grade of the prostatectomy specimen. Markers were also compared against demographic information and the patients' age and race., Results: There was a weak correlation between serum PSA and positive surgical margins, higher Gleason sum, and WHO grade (P < 0.05). Receiver operating characteristic curve (ROC) analysis comparing sensitivity and specificity of the markers to positive and negative margins as well as seminal vesicle invasion demonstrated PSA and FPSA predictive ability for seminal vesicle invasion. The area under the curve for PSA and FPSA in this case was 0.7318 and 0.7432, respectively. There was also a weak correlation between the FPSA level and margins, with a low ROC area under the curve of 0.6789. The FPSA cannot distinguish the more advanced stage of disease. There was no significant correlation between F:TPSA and PSMA with regard to the study variables in predicting organ confinement. High PSMA levels only correlated with higher stage and were maximal in pT4a classified disease., Conclusions: Higher PSA and FPSA levels are likely to be associated with more locally advanced disease. Total PSA was the best marker. However, the cutoff values necessary for significant accuracy between PSA and FPSA are not of clinical usefulness due to the lack of specificity and sensitivity of the markers at those cutoffs. F:TPSA and PSMA levels as currently measured are of limited value in discriminating more aggressive disease in patients with clinically localized CaP.

Background: Clinical and pathological staging of prostate cancer has been, and remains, problematic. Since prostate-specific antigen (PSA)-detected tumors are often discerned during "screening," what are their significance?, Methods: We analyzed 67 consecutive patients with stage T1c prostate cancer undergoing radical prostatectomy at our institution from August 1, 1991-September 12, 1995, and who had whole-mount specimen processing. Diagnosis was determined in all cases by transrectal ultrasound-guided biopsy., Results: The mean age of our patients was 63 years, and the mean PSA at time of diagnosis was 8.6 ng/ml (median, 7.2 ng/ml). There was organ-confined cancer in 31/67 (46%) patients; 17/67 (25%) had periprostatic fat infiltration, and of these 5(7%) had seminal vesicle involvement. Thirty-one of 67 (46%) had positive surgical margins. Twenty-two (33%) had a Gleason sum of > or = 7 in the final pathological specimen. Insignificant tumors (dominant tumor volume < 0.20 cc) were found in only 4 cases. Smaller tumors were more likely to be found when the PSA was < 10 ng/ml. Multifocal disease was found in 64/67 (96%) prostate specimens., Conclusions: This study adds impetus to the growing realization that nonpalpable prostate cancer, detected because of elevated PSA, is rarely insignificant. Our findings add further emphasis to the fact that patients diagnosed by PSA elevation have, for the most part, significant cancer that should be treated aggressively.

Purpose: While prostatic manipulation and surgery have been shown to increase serum prostate specific antigen (PSA), the influence of ejaculation on serum PSA remains controversial. We examined the effect of ejaculation on serum PSA levels., Materials and Methods: We evaluated 100 men 25 to 35 years old with no history of surgery or inflammatory disease of the urogenital tract. Serum PSA was evaluated 1 and 24 hours after ejaculation, and serum testosterone and seminal fluid PSA levels were determined., Results: In all men a baseline PSA level was detected. There were no statistically significant changes in serum PSA and testosterone 1 and 24 hours after ejaculation. Mean PSA concentration was significantly higher in seminal plasma than in serum. However, we did not observe a correlation between serum and seminal plasma PSA levels., Conclusions: Based on our data ejaculation does not affect serum PSA concentration in young men, and there seems to be no physiological relationship between ejaculation and PSA level.

Objectives: We prospectively evaluated whether free PSA improves the specificity of PSA and can be useful as a clinical guide to avoid repeat prostate biopsies in patients with persistent PSA elevations, normal digital rectal examinations, and previous negative prostate biopsies., Methods: Sixty-seven men with persistent PSA elevations (median 9.5, range 4.1-24.8 ng/mL), normal digital rectal examinations and two or more prior sextant biopsies (mean 2.8) had serum collected for measurement of total and free PSA. All patients were rebiopsied to determine the receiver operating characteristics of total PSA versus percent free PSA for prostate cancer detection., Results: The study biopsy identified 11 prostate cancer cases. The median percent free PSA was significantly higher at 18.0% among men without prostate cancer compared to 6.7% in men with prostate cancer (P < 0.00005). When sensitivity was plotted against 1-specificity, the area under the receiver operating characteristic curve for percent free PSA was 0.93, compared to 0.69 for free PSA density, 0.66 for PSA density, and 0.51 for PSA. In patients with elevated total PSA levels, normal digital rectal examinations and two prior negative sets of sextant prostate biopsies, a cutoff of 10% free PSA would maintain sensitivity at 91% with a corresponding specificity of 86%., Conclusions: Selective measurement of percent free PSA can significantly improve the specificity of prostate cancer screening with PSA. A low percent free PSA (< 10%) appears to be a powerful predictor of prostate cancer even after two negative prostate biopsies.

Background: The detection of prostate cancer by screening for prostate-specific antigen (PSA) in serum is improved when age-specific reference ranges are used, but these ranges have been derived from white populations. We determined the distribution of PSA and age-specific reference ranges in black men both with and without prostate cancer., Methods: From January 1991 through May 1995, we measured serum PSA in 3475 men with no clinical evidence of prostate cancer (1802 white and 1673 black) and 1783 men with prostate cancer (1372 white and 411 black). We studied the data as a function of age and race to determine the usefulness of measuring PSA in diagnosing prostate cancer., Results: Serum PSA concentrations in black men (geometric mean in controls, 1.48 ng per milliliter; in patients, 7.46) were significantly higher than those in white men (geometric mean in controls, 1.33 ng per milliliter; in patients, 6.28). The values in the controls correlated directly with age. The area under the receiver-operating-characteristic curve was 0.91 for blacks and 0.94 for whites. If traditional age-specific reference ranges were used in screening black men, with the test specificity kept at 95 percent, 41 percent of cases of prostate cancer would be missed. For the test to have 95 percent sensitivity among black men, the following normal reference ranges should be used: for men in their 40s, 0 to 2.0 ng of PSA per milliliter (test specificity, 93 percent); for men in their 50s, 0 to 4.0 ng per milliliter (specificity, 88 percent); for men in their 60s, 0 to 4.5 ng per milliliter (specificity, 81 percent); and for men in their 70s, 0 to 5.5 ng per milliliter (specificity, 78 percent)., Conclusions: Serum PSA concentrations can be used to discriminate between men with prostate cancer and those without it among both blacks and whites. Over 40 percent of cases of prostate cancer in black men would not be detected by tests using traditional age-specific reference ranges, which maintain specificity at 95 percent. In this high-risk population, the alternative approach--maintaining sensitivity at 95 percent--may be used with acceptable decrements in specificity.

Background: Prostate-specific antigen (PSA) is a most valuable tool for the early detection of prostate cancer; however, it has a high false-positive rate as presently used in prostate cancer screening programs. Patients with persistent PSA elevations, normal digital rectal examinations, and multiple negative biopsies present a clinical dilemma. We prospectively evaluated whether free PSA improves the specificity of PSA and can be useful as a clinical guide to avoid repeat prostate biopsies in a group of such patients., Methods: Sixty-seven men with persistent PSA elevations (mean 9.6 ng/mL; range 4.1-24.8 ng/mL), normal digital rectal examinations, and two or more prior sextant biopsies (mean 2.8), had serum collected for measurement of total and free PSA. All patients were rebiopsied to determine the receiver-operating characteristics (ROC) of total PSA vs. percent free PSA for prostate cancer detection., Results: This study by biopsy identified 11 new prostate cancer cases. The median percent free PSA was significantly higher at 18.1% among men without prostate cancer, compared to 6.4% in men with prostate cancer (P < 0.00005). When sensitivity was plotted against I-specificity, the area under the receiver-operating curve (ROC) for percent free PSA was 0.95, compared to 0.75 for free PSA density, 0.59 for PSA density, and 0.54 for PSA. In patients with elevated total PSA levels, normal digital rectal examinations, and two prior sets of negative sextant prostate biopsies, a cutoff of 10% free PSA would maintain sensitivity at 91% with a corresponding specificity of 86%., Conclusions: Selective measurement of percent free PSA in cases of uncertain diagnosis can significantly improve the specificity of prostate cancer detection compared to total PSA alone. A low percent free PSA (< 10%) appears to be a significant predictor of prostate cancer even after two or more negative prostate biopsies.

Objective: To determine if African-American men with newly diagnosed prostate cancer (PC) have higher pretreatment serum prostate-specific antigen (PSA) values after adjustment for clinical stage, age, and tumor grade, and to determine if any difference detected is related to tumor volume difference., Design: Consecutive case series of newly diagnosed PC patients between January 1990 and September 1994 and cohort analytic study of PC patients treated by radical prostatectomy (RP) and who had whole-mount pathologic tumor volume assessment between May 1993 December 1994., Setting: Tertiary care military medical center., Patients: A total of 541 evaluable newly diagnosed PC patients (408 white and 133 black) having pretreatment PSA assessment at one laboratory; 91 patients undergoing RP had whole-mount tumor volume analysis., Interventions: Medical record review for pretreatment PSA value, race, tumor grade, clinical stage, and age, as well as whole-mount pathologic assessment of RP specimen and measurement of tumor volume., Main Outcome Measures: The PSA differences between black and white PC patients with adjustments for age, biopsy tumor grade (Gleason score), and clinical stage (TNM stage); PSA differences between black and white PC patients undergoing RP with adjustment for age, RP grade, clinical stage, and tumor volume., Results: The mean (geometric) PSA value for 133 black men was 14.00 ng/mL compared with 8.29 ng/mL for 408 white men (P < .001). The black patients had higher PSA values across all stage, grade, and age categories. The racial difference in PSA levels remained statistically significant when stage, grade, and age were simultaneously controlled for (P < .001). Multivariable odds ratio testing revealed that even after adjustment for stage, grade, and age, black patients were 2.2 times as likely as white patients to have a PSA value greater than 10.0 ng/mL (95% confidence interval, 1.3 to 3.6). Tumor volume (geometric mean) was 5.42 cm3 and 2.10 cm3 for black and white RP patients, respectively (P = .002). Across all clinical stages (T1a to T3), black men had tumor volumes 1.3 to 2.5 times greater than those of white men. Multivariable analysis of covariance revealed that tumor volume and stage of disease were important predictors of PSA level, but race, grade, and age were not. (The percentage of white and black patients whose cancer was detected by screening [75.4% vs 70.4%] or who had symptoms [37.7% vs 29.6%] was not significantly different.), Conclusions: As a group, African-American men with newly diagnosed PC have higher PSA values at initial diagnosis than white men. This PSA difference appears to be due to larger tumor volumes within clinical (TNM) stage categories among black patients. Elevated PSA value was a surrogate for larger tumor volume in this cohort of black men. This stage-for-stage tumor volume disparity even in an equal-access health care environment should prompt further study of screening behavior and/or biological differences of PC in the black population.

Objective: To test the hypothesis that prostate cancer lymph node (LN) micrometastases, undetected by standard histology, might be found using sensitive immunohistologic methods and may correlate to preoperative prostate-specific antigen (PSA) levels., Method: Archival paraffin blocks of pelvic lymphadenectomy specimens from radical prostatectomy were blindly submitted for immunostaining using pan-cytokeratin monoclonal antibody SB-3, as well as antibodies directed against PSA. Automated immunostaining was performed on a Ventana Medical Systems 320 immunostainer. As a positive control, 7 cases with known nodal metastases by standard histology were blindly analyzed and all has detectable micrometastases by this methodology., Results: For 13 patients with PSA < 10.1 (8%) had LN micrometastases detected. For 10 patients with PSA between 10 and 20 and for 9 patients with PSA > 20, no occult metastases were detected. We did find previously undetected prostate cancer (CaP) LN micrometastases in 1 of 32 (3%) clinically localized prostate cancer patients who had undergone radical prostatectomy. In many LNs, cytokeratin stains cross-reacted and stained individual plasma cells, whereas in the positive metastatic case, a cluster/nest of CaP cells were reactive. To the unfamiliar observer, the pitfall of false-positive results because of nonspecific cytokeratin staining must be considered. These results are in exact agreement with another recent study which also found only a 3 percent incidence of unsuspected pelvic lymph node micrometastases in clinically localized CaP utilizing similar methods., Conclusions: Our hypothesis was not substantiated: LN micrometastases were uncommon and did not correlate to serum PSA. Unlike studies with breast cancer, occult micrometastatic nodal disease not appreciated by standard methods appears to be uncommon in clinically localized prostatic carcinoma.

Background: Gonadotropin releasing hormone (GnRH) antagonists suppress follicle-stimulating hormone (FSH) to lower levels than GnRH agonists. This may partially explain the differences between these agents on prostate cancer outcomes. In this post-hoc analysis, FSH and prostate specific antigen (PSA) responses and the impact of cross-over from leuprolide to degarelix were evaluated from a 1-year comparative study (CS21) and its extension study (CS21A). Materials and methods: Overall, 610 patients were enrolled in CS21, wherein PSA and FSH levels were evaluated monthly. CS21A evaluated 386 patients, including those previously treated with degarelix (n = 251) who continued to receive degarelix, and those previously treated with leuprolide (n = 135) who crossed-over to receive degarelix. PSA and FSH levels were evaluated in CS21A for 3 months after cross-over. The associations between measurements were assessed using Spearman's correlation coefficient. The impact of class variables on FSH suppression were evaluated using Analysis of Variance. Results: Rapid PSA and FSH suppression was observed and maintained in the degarelix arm (CS21 and CS21A), while patients on leuprolide experienced rising PSA during CS21. Patients crossed-over from leuprolide to degarelix achieved a suppression of FSH and a significant PSA decrease. PSA and FSH levels were significantly (p < .05) correlated at months 1, 3, 6, 12 and 13 in the degarelix arm. Conclusions: Significant FSH suppression with GnRH antagonists may explain its advantage over GnRH agonists in terms of better prostate cancer control. The effect of profound FSH suppression is analogous to the need for profound testosterone suppression for tumor control. [ABSTRACT FROM AUTHOR]

Traces the causes of prostate cancer in African American males. Concept of race and prostate cancer; Screening for prostate cancer in African American men; Advantages and disavantages of population-based screening; Proper use of prostate specific antigen in African American men.

Combination hormonal therapy, comprising a luteinising hormone-releasing hormone analogue (LHRHa) with an antiandrogen, is widely used in the treatment of advanced prostate cancer. There is ongoing debate regarding the use of combination hormonal therapy as opposed to LHRHa monotherapy. The pivotal consideration is whether there are adequate benefits with combination hormonal therapy in terms of increased survival and decreased disease progression to outweigh the increased risk of adverse events and additional cost. The most recent meta-analysis by the Prostate Cancer Trialists'Collaborative Group indicates a small but statistically significant survival benefit with combination hormonal therapy using nonsteroidal antiandrogens. It is, however, noteworthy that combined conclusions derived from such meta-analyses may not apply across each of the individual antiandrogens. Individual studies have reported differences between antiandrogens in terms of both tolerability and efficacy-for example, bicalutamide has been shown to be better tolerated than flutamide, and may be associated with improved survival. In addition, it is essential that treatment decisions are taken in consultation with the patient. Owing to an increasing proportion of cases presenting with early-stage disease, combination hormonal therapy is increasingly used in the neoadjuvant or adjuvant setting with radiotherapy and, in cases of prostate-specific antigen recurrence after prior localised therapy. Further data are awaited to optimise the use of combination hormonal therapy in these new settings.Prostate Cancer and Prostatic Diseases (2004) 7, S2-S7. doi:10.1038/sj.pcan.4500741 [ABSTRACT FROM AUTHOR]