The effect of prostate volume, age, total prostate specific antigen level and acute inflammation on the percentage of free serum prostate specific antigen levels in men without clinically detectable prostate cancer

PURPOSE: We determine the influence of age, prostate volume, total serum prostate specific antigen (PSA) level and histological evidence of acute inflammation in biopsy specimens on the percent free serum PSA level in men without clinically detectable prostate cancer. MATERIALS AND METHODS: We studied 70 men with total PSA levels of 2.6 to 9.9 ng./ml. who had undergone at least 3 sets of prostate biopsies that were negative for cancer as part of our PSA based prostate cancer screening program. Total and free PSA levels were measured using Hybritech immunoassays. Prostate volume and the presence of acute inflammation were determined from the most recent transrectal ultrasonography and prostate needle biopsy. RESULTS: Percent free PSA levels correlated significantly with age (r = 0.48, p = 0.0001) and prostate volume (r = 0.44, p = 0.0002) but not with total PSA (r = 0.04, p = 0.7). The mean percent free PSA did not differ for those with or without acute inflammation. Multivariate regression models demonstrated that age and prostate volume were significant predictors of percent free PSA. CONCLUSIONS: Among men without detectable prostate cancer and a total PSA level between 2.6 and 9.9 ng./ml. percent free serum PSA was higher in older men and in men with a larger prostate gland but was not influenced by total PSA level or the presence of acute inflammation in the prostatic biopsy specimen.     

Early detection of recurrent prostate cancer with an ultrasensitive chemiluminescent prostate-specific antigen assay

OBJECTIVES: Treatment failure after radical prostatectomy is most commonly heralded by an increase in serum prostate-specific antigen (PSA) to detectable levels. We evaluated the clinical utility of an ultrasensitive chemiluminescent PSA assay. METHODS: We evaluated the assay in banked sera obtained from 170 men after radical prostatectomy. Controls consisted of 142 females, 29 men who had undergone cystoprostatectomy without evidence of prostate cancer, and 25 men without evidence of recurrent disease at least 5 years after prostatectomy for organ-confined disease. Lead time to diagnosis of recurrence was based on comparisons with the IMx or Tandem E assays using a cutoff of 0.1 ng/mL (100 pg/mL). RESULTS: The biologic level of detection of this assay is 8 pg/mL. Serum PSA levels were undetectable in 82.4% of females, 86.2% of the cystoprostatectomy patients, and 96% of the radical prostatectomy controls. After radical prostatectomy, PSA levels were undetectable at last check in 104 of 168 (61.9%) men. In the 24 men with prostate cancer recurrence, the enhanced sensitivity of 8 pg/mL provided a mean lead time based on conservative calculations of 12.7 to 22.5 months over conventional assays. Thirty-four of the 41 men with detectable PSA levels and no evidence of disease recurrence had PSA levels of 30 pg/mL or less. CONCLUSIONS: PSA levels are undetectable in most men who do not have recurrence of disease after radical prostatectomy. Low but detectable serum PSA levels less than or equal to 30 pg/mL can be produced by nonmalignant sources of PSA. PSA assays with enhanced sensitivity can detect recurrent prostate cancer with significant lead time over conventional assays.     

Androgen receptor gene CAG repeat length varies in a race-specific fashion in men without prostate cancer

OBJECTIVES: Preliminary studies suggest that black men have shorter androgen receptor CAG repeat length compared with non-Hispanic whites. Because decreased CAG repeat length (in particular less than 20 repeats) may be associated with increased prostate cancer risk, these findings are potentially important in providing a hypothesis to explain the increased risk of prostate cancer in black men. METHODS: CAG repeat length in the androgen receptor (exon one) was determined by a polymerase chain reaction method in 130 non-Hispanic white and 65 black men. All men had prostate-specific antigen levels less than 4 ng/mL and normal digital rectal examinations. Men self-classified themselves into racial categories by a standardized questionnaire. RESULTS: For whites, the mean +/- SD, median, and range of CAG repeat length were 21.0+/-3.0, 21, and 9 to 28, respectively. For blacks, the mean +/- SD, median, and range of CAG repeat length were 19.0+/-3.0, 19, and 13 to 26, respectively. The mean and median CAG repeat length in blacks were statistically significantly shorter than in whites. Black men were twice as likely as whites to have fewer than 20 CAG repeats (56.9% versus 28.5%, P = 0.0001). CONCLUSIONS: These data unequivocally demonstrate that androgen receptor gene CAG repeat length varies in a race-specific manner in men without evidence of prostate cancer.     

Faecal pollution of ocean swimming pools and stormwater outlets in eastern Sydney

BACKGROUND: We evaluated routine transition zone biopsies for the detection of prostate cancer. METHODS: Systematic sextant transrectal biopsies, including 2 systematic transition zone biopsies (sextant biopsy group), were performed on 196 consecutive patients. Biopsies were based on indications from digital rectal examination and/or a serum PSA level greater than 4.0 ng/mL. During the same period, 21 patients with persistently elevated PSA levels and earlier negative systematic biopsies also had the sextant biopsy (re-biopsy group). The sextant biopsy group was compared with 124 cases in our previous cancer detection program who had systematic quadrant biopsies targeted to the peripheral zone (quadrant biopsy group). RESULTS: Between the sextant and quadrant biopsy groups, the difference in rate of cancer detection was not significant statistically. Of the sextant biopsy group, 64 (33%) demonstrated malignancy, including 9 (4.6%) with cancer found exclusively in the peripheral zone and 55 (28%) both in the peripheral and transition zones. No cancer was found exclusively in the transition zone. Of the re-biopsy group, all 4 cancers (19%) were detected in the transition zone, 2 of them exclusively in the transition zone. CONCLUSION: Routine transition zone biopsies did not increase the detection rate of prostate cancer. Systematic transition zone biopsies proved useful to the patients with persistently elevated PSA values and negative results in previous systematic peripheral zone biopsies.     

The clinical utility of measuring free-to-total prostate-specific antigen (PSA) ratio and PSA density in differentiating between benign prostatic hyperplasia and prostate cancer

OBJECTIVE: To evaluate the role of free-to-total prostate-specific antigen ratio (f/tPSA), prostate volume and PSA density in differentiating between men with prostate cancer and benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study comprised 51 patients who were assessed after transurethral electroresection of the prostate (16 with prostate cancer and 35 with BPH). Patients with a tPSA of < or = 4.0 ng/mL and > or = 30.0 ng/mL were excluded from the analysis. Total and fPSA were measured using an immunoradiometric assay and prostate volume was determined by transrectal ultrasonography. The incidence of prostate cancer and BPH was then compared with the PSA variables to determine specificity and predictive value. RESULTS: Most patients with BPH had a tPSA of 4.0-6.0 ng/mL; no patients with BPH had a tPSA of > 20.0 ng/mL. Most patients with prostate cancer had a f/tPSA of 6-10%. The area under the receiver operating characteristic curve for f/tPSA was significantly greater than that for tPSA (P < 0.003). CONCLUSIONS: The measurement of f/tPSA and PSA density increase the specificity of the differential diagnosis between BPH and prostate cancer.     

The predictive value of race as a clinical prognostic factor among patients with clinically localized prostate cancer: a multivariate analysis of positive surgical margins

OBJECTIVES: Several investigators have reported that African-American men with clinically localized prostate cancer have poorer survival than do white men. In addition, prostate cancer in African-American men is commonly diagnosed at a more advanced stage of disease. Is race or ethnicity predictive of outcome of clinically localized prostate cancer? It has been reported that the presence of positive surgical margins significantly influences time to progression independently of other prognostic factors. Therefore, we have elected to conduct a multivariate analysis of clinical factors including race as potential predictors of positive surgical margin outcome. METHODS: We studied 369 consecutive men (120 African-American and 249 white) who had radical prostatectomies at a single institution. Comparisons by race of Gleason score, stage, presence of positive surgical margins, and mean preoperative prostate-specific antigen (PSA) level were carried out. RESULTS: Our data demonstrate that African-American men have more pathologically locally advanced prostate cancer than do white American men: 69% among blacks compared with 57% among whites. However, the difference in rate of positive surgical margins between blacks and whites is statistically significant: 58% among blacks versus 40% among whites (P = 0.002). Four factors were predictive of positive surgical margins: preoperative PSA level, race, clinical stage, and Gleason score. CONCLUSIONS: We have demonstrated that race is an independent predictor of positive surgical margins among patients with clinically localized prostate cancer and should be included in treatment decisions. In addition, the risk of positive surgical margins increases noticeably when PSA is greater than 10 ng/mL.     

Finasteride and flutamide as potency-sparing androgen-ablative therapy for advanced adenocarcinoma of the prostate

OBJECTIVES: Androgen ablation with luteinizing hormone-releasing hormone (LHRH) agonists, orchiectomy, or oral estrogens has significant untoward sexual side effects. We evaluated a combination of finasteride and flutamide as potency-sparing androgen ablative therapy (AAT) for advanced adenocarcinoma of the prostate. In addition, we evaluated whether finasteride provided additional intraprostatic androgen blockade to flutamide. METHODS: Twenty men with advanced prostate cancer were given flutamide, 250 mg orally three times daily. Serum prostate-specific antigen (PSA) values were measured weekly. At a nadir PSA value, finasteride, 5 mg orally every day, was added. PSA values were then measured weekly until a second nadir PSA value was achieved. Sexual function was evaluated at baseline, at the second nadir PSA value, and every 3 months thereafter. Testosterone, dihydrotestosterone (DHT), and dehydroepiandrostenedione (DHEA) levels were measured at baseline and at the first and second nadir PSA values. RESULTS: The median follow-up period was 16.9 months. Therapy failed in 1 patient with Stage D2 disease at 12 months, but an additional response to subsequent LHRH agonist therapy was observed. One patient developed National Cancer Institute grade 3 diarrhea and was withdrawn from the study. Seven of 20 men developed mild gynecomastia, and 3 of 20 developed mild transient liver function test elevations. Mean PSA levels were 94.6 +/- 38.2 ng/mL at baseline and 7.8 +/- 2.7 and 4.7 +/- 2.2 ng/mL at the first and second PSA nadir values, respectively (P = 0.034). Mean percent decline in PSA value from baseline was 87.0 +/- 3.1% with flutamide alone and 94.0 +/- 1.9% with both flutamide and finasteride (P = 0.001). Eleven of 20 men were potent at baseline. At the second nadir PSA value, 9 (82%) of 11 were potent, whereas 2 (18%) of 11 were impotent. With longer follow-up (median 16.4 months), 6 (55%) of 11 men were potent, 2 (18%) of 11 were partially potent, and 3 (27%) of 11 were impotent. With flutamide alone, testosterone rose a mean of 77 +/- 14.7% of baseline (P = 0.0001), DHEA fell a mean of 32.4 +/- 4.6% (P = 0.0001), and DHT was unchanged. With the addition of finasteride, testosterone rose another 14 +/- 6% (P = 0.06, not significant), DHEA was unchanged, and DHT fell a mean of 34.8 +/- 4.7% (P = 0.0009). CONCLUSIONS: Finasteride and flutamide were safe and well tolerated as AAT for advanced prostate cancer. Finasteride provided additional intraprostatic androgen blockade to flutamide, as measured by additional PSA suppression. Sexual potency was preserved initially in most patients, although there was a reduction in potency and libido in some patients on longer follow-up. Further evaluation of this therapy is needed.     

Reference ranges for serum prostate-specific antigen in black and white men without cancer

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.     

G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension

OBJECTIVES: To evaluate the response of testicular androgen ablation in patients with advanced prostate cancer with a biochemical recurrence after finasteride or combined finasteride and flutamide therapy. METHODS: Eighteen hormone na?ve men with advanced prostate cancer (10 with detectable prostate-specific antigen [PSA] levels after radical prostatectomy, 4 with rising PSA levels after definitive radiation therapy, and 4 with Stage D2 disease) were treated with finasteride (5 mg/day) alone or in combination with flutamide (250 mg three times a day). All men experienced an initial reduction in serum PSA, but later had treatment failure with two consecutive rising PSA measurements. All men were then treated with testicular androgen ablation (bilateral orchiectomy in 15 and luteinizing hormone-releasing hormone analogue in 3). RESULTS: Overall, serum PSA declined by more than 80% in 15 (83%) of 18 and to undetectable levels in 14 (78%) of 18. With a median+/-semi-interquartile range follow-up of 22+/-14.5 months from the initiation of hormone therapy, 12 (67%) of 18 currently have undetectable PSA levels. Two men having rising serum PSA levels above 100 ng/mL and 1 man has died from complications of metastatic prostate cancer. CONCLUSIONS: Testicular androgen ablation effectively lowers serum PSA levels in most men with advanced prostate cancer who have experienced a biochemical recurrence despite initial response and subsequent relapse on finasteride or combined finasteride and flutamide therapy.     

Numerical chromosomal aberrations in transition-zone carcinomas of the prostate

PURPOSE: Prostatic carcinomas arising in the transition zone (TZ) are thought to differ from the more frequent cancers of the peripheral zone (PZ) with regard to morphology and biologic behavior. It is unclear, however, whether the differences are reflected in genetic alterations. MATERIALS AND METHODS: We assessed numerical aberrations of chromosomes 7, 8, 10, 17, and X with interphase cytogenetics in 10 radical-prostatectomy specimens containing exclusively TZ cancers larger than 0.5 cm.3 and in 10 additional specimens containing both TZ and PZ cancers larger than 0.5 cm.3 each. RESULTS: Of the 20 TZ carcinomas, 9 were completely disomic, 5 were at least focally tetrasomic but not aneusomic, and 6 were focally aneusomic. Ploidy correlated well with tumor volume (p = 0.0083), grade (p = 0.0064) and surgical margins (p = 0.0141) but not with preoperative prostate-specific antigen. A strong correlation was observed between the presence of low grade tumor (Gleason grade 4 or 5) and a nondiploid chromosomal status (p = 0.0001). In 10 cases there were also foci of PZ cancer larger than 0.5 cm.3, of which 4 were disomic, 3 were tetrasomic at the most, and 3 were aneusomic. The mean tumor volumes of disomic and aneusomic cancers differed significantly between TZ and PZ carcinomas (p = 0.0336 and 0.0476, respectively). CONCLUSIONS: Numerical chromosomal instability parallels tumor progression in TZ carcinomas of the prostate. However, our results indicate that PZ and TZ cancers differ in that the latter can reach larger volumes before histological dedifferentiation and aneusomy occur.     

Do prostate specific antigen and prostate specific antigen density enhance the detection of prostate carcinoma after initial diagnosis of prostatic intraepithelial neoplasia without concurrent carcinoma?

BACKGROUND: Prostatic intraepithelial neoplasia (PIN) is considered to be a precursor of prostate carcinoma in which serum levels of prostate specific antigen (PSA) have been correlated with PIN grades. The aim of this study was to determine whether PSA and prostate specific antigen density (PSAD), obtained at the time of initial diagnosis of PIN without concurrent carcinoma, can be used as predictive factors to discriminate patients with subsequent cancer on repeat biopsy. METHODS: We studied, retrospectively, the records of 93 patients with PIN (low and high grade) without concurrent carcinoma at the time of their first needle biopsy. We assessed the relationship between initial PIN grade, PSA, and PSAD with later detection of carcinoma on repeat biopsy. Patients were divided into 3 subgroups for analysis according to their initial PSA level (0-4, 4.1-10, >10 ng/mL). RESULTS: Carcinoma detection rate on repeat biopsy was 13.3% for patients with low grade PIN and 47.7% for patients with high grade PIN (P < 0.006). High grade PIN was frequently associated with subsequent carcinoma whatever the PSA level (33.3-61.9%). Low grade PIN was associated with subsequent carcinoma in 42.8% of the cases when PSA was greater than 10 ng/mL. When PSA was between 4 and 10 ng/mL, low grade PIN carcinoma was found on repeat biopsies in only 10.7% of the cases (P = 0.05). In none of the PSA subgroups did PSAD enhance later cancer detection. CONCLUSIONS: For patients with high grade PIN, the incidence of subsequent carcinoma is high, whatever the PSA values. For these cases repeat biopsies should be recommended. Patients with low grade PIN and PSA greater than 10 ng/mL should have repeat biopsies because the incidence of subsequent carcinoma is high and comparable to high grade PIN. PSAD did not provide additional information.     

Prevalence and predictors of a positive repeat transrectal ultrasound guided needle biopsy of the prostate

PURPOSE: We determined the prevalence of and risk factors for carcinoma in patients with 1 previously negative prostate biopsy. MATERIALS AND METHODS: Transrectal ultrasound guided prostate needle biopsies were repeated in 130 men. Risk factors analyzed included age, pathological result of initial biopsy, inter-biopsy interval, prostate specific antigen (PSA), PSA density, PSA velocity, digital rectal examination, abnormal transrectal ultrasound and family history of prostate cancer. RESULTS: A total of 39 patients (30%) had positive biopsies for cancer. Univariate analysis revealed that PSA more than 20 ng./ml. and abnormal transrectal ultrasound were more frequent in men with positive second biopsies. Using multivariate logistic regression analysis only PSA more than 20 ng./ml. was a significant risk factor (adjusted odds ratio 4.48, 95% confidence interval 1.02 to 20.1). We determined the incidence of carcinoma in patients who represent the lowest risk group as defined by PSA less than 10 ng./ml., PSA density less than 0.15 mg./ml./cm.3, PSA velocity less than 0.75, ng./ml. per year, no prostatic intraepithelial neoplasia plus negative transrectal ultrasound, digital rectal examination and family history. Of 21 patients who fit this cohort 5 (23.8%) had carcinoma on repeat biopsy. CONCLUSIONS: A significant false-negative rate for initial transrectal ultrasound guided prostate biopsies exists. Baseline risk in lowest risk patients is sufficiently high such that one cannot define a subset of patients for whom repeat biopsy is unnecessary. We recommend repeat biopsy in all patients who meet the criteria for a transrectal ultrasound guided biopsy and in whom the initial biopsy is negative.     

Exposure of hepatic sinusoidal mononuclear cells to UW solution in situ but not ex vivo induces apoptosis

OBJECTIVES: To determine the influence of race or ethnicity on serum prostate-specific antigen (PSA) levels and PSA density (PSAD) in a population of healthy men without clinically evident prostate cancer. METHODS: This retrospective study was conducted between January 1988 and January 1993. The serum PSA levels were measured in 859 men (586 African Americans, 142 whites, and 131 Hispanics) who were participants in a prostate cancer screening program or had urinary symptoms suggestive of prostate gland pathology. All men underwent a detailed clinical examination, including digital rectal examination, serum PSA determination, and transrectal ultrasound (TRUS). None of the subjects included had clinical or TRUS evidence of prostate cancer (furthermore, 283 men were pathologically proved to be cancer-free by prostate biopsies). Serum PSA levels and PSA densities as a function of each individual's ethnic background were determined. RESULTS: The mean serum PSA level in African Americans was 2.1 ng/mL, which was significantly higher than that of whites (mean PSA of 1.53 ng/mL) and Hispanics (mean PSA of 1.83 ng/mL) (P = 0.003). Similar differences among the three groups were observed in PSA density (the mean PSAD was 0.078, 0.057, and 0.065 for African Americans, whites, and Hispanics, respectively). A separate analysis for the biopsy-negative men was performed, and the findings were consistent with the observations for the entire study group. After adjustment for age and prostate volume, the differences remained statistically significant. CONCLUSIONS: Among men without evidence of prostate cancer, African Americans have higher serum PSA levels and PSA densities than do whites or Hispanics. Race or ethnicity was an independent factor that affected serum PSA levels even after adjustment for age and prostate volume.     

The early detection of prostate carcinoma with prostate specific antigen: the Washington University experience

BACKGROUND: It is not yet known whether screening for the detection of early prostate carcinoma will reduce mortality rates. However, data are available to assess intermediate outcomes from screening, including the performance characteristics of the screening tests and shifts in disease stage. METHODS: Approximately 30,000 community volunteers (mean age 60 years; <5% nonwhite) were enrolled in 1 of 3 screening studies. Volunteers were screened with PSA or PSA in combination with digital rectal examination at 6-month intervals, and prostatic biopsy was recommended for those with results suspicious for cancer. Based on a first-time screen, the current study reports screening test results, the proportion of men recommended to undergo biopsy, the proportion who actually underwent biopsy, and the carcinoma detection rates for each study, stratified by initial PSA level. The authors also report the pathologic features of screen-detected carcinomas for a subset of men who underwent radical prostatectomy and for whom complete embedding and microscopic examination of the surgical specimen was performed. RESULTS: Approximately 10% of the volunteers had PSA levels >4.0 ng/mL and 3-10% had digital rectal examination results suspicious for cancer. Overall, 9-20% of volunteers were recommended to undergo biopsy and 8-13% actually underwent the procedure. The positive predictive value for carcinoma detection ranged from 25-33% across studies. In the subset of men for whom surgical specimens were completely embedded, the majority of tumors detected had the clinicopathologic features of significant carcinoma (<10% possibly harmless). CONCLUSIONS: The intermediate outcomes for screening with PSA and/or PSA in combination with digital rectal examination are encouraging. In community volunteers these screening tests demonstrated reasonable positive predictive value and detected carcinomas at an earlier stage. The majority of screen-detected tumors had the pathologic characteristics of medically significant carcinoma.     

Evaluation of transition zone biopsy in systematic prostate biopsy

We evaluated the systematic biopsies performed on 83 patients suspected of having prostate cancer. In the systematic biopsy, 6 cores were from the peripheral zone and 2 cores from the transition zone. Cancer was detected in 25 patients (30.1%). The percentage of patients who had abnormal digital rectal examination and transrectal echo findings, average PSA and PSA density, and the number of examinations which suggested cancer were higher in the cancer group than in the non-cancer group, although the mean prostate volume was smaller. Cancer was more frequently detected in the peripheral zone than in the transition zone. Cancer was detected only in the transition zone in only 1 of the 25 cancer patients. We conclude that biopsy of the transition zone to all the patients is not always needed in systematic biopsy.     

Free-to-total prostate-specific antigen (PSA) ratio improves the specificity for detecting prostate cancer in patients with prostatism and intermediate PSA levels

OBJECTIVE: To investigate the clinical significance of the free-to-total prostate-specific antigen (PSA) ratio in improving the specificity of PSA measurement for detecting prostate cancer within the diagnostic intermediate range (4-10 ng/mL total PSA) in patients referred for the treatment of urinary symptoms. PATIENTS AND METHODS: Serum samples were obtained from 333 consecutive patients with obstructive and irritative urinary symptoms. Of these men, 114 had total PSA levels of 4-10 ng/mL; 22 had prostate cancer (group 1) and 71 had benign prostatic hyperplasia (BPH, group 2). Group 3 consisted of 21 patients with BPH and a chronic indwelling catheter. The concentrations of free and total PSA (ProStatus, Wallac Oy, Turku, Finland) and PSA complexed to alpha-1-antichymotrypsin were measured and the free-to-total PSA ratio calculated. All patients under 70 years of age or with suspicious findings on digital rectal examination or transrectal ultrasonography underwent ultrasound-guided sextant prostate biopsies. Of the 114 patients, 105 (92%) underwent transurethral resection of the prostate and six (5%) radical retropubic prostatectomy. RESULTS: Patients in group 1 had significantly lower median free PSA concentrations (0.78 ng/mL vs 1.13 ng/mL, P < 0.001) and a lower free-to-total PSA ratio (12.1% vs 19.9%, P < 0.001) than those in group 2. The differences were similar between group 1 and group 3 (median free PSA in group 3, 1.06 ng/mL, P = 0.03, and free-to-total PSA ratio 18.7%, P = 0.007). There were no significant differences between patients in groups 2 and 3. The free-to-total PSA ratio had a higher specificity than total PSA at all sensitivity levels, e.g. a threshold free-to-total PSA ratio of 0.20 detected 91% of cancers and spared 48% (group 2) or 46% (group 3) from unnecessary biopsies. The area under the receiver operating characteristic curve for group 1 vs group 2 was 0.56 (total PSA) and 0.78 (free-to-total PSA ratio) and for group 1 vs group 3 was 0.56 (total PSA) and 0.81 (free-to-total PSA ratio). CONCLUSION: In those patients with extensive symptoms from BPH and requiring surgical treatment, the free-to-total PSA ratio improves the specificity for detecting prostate cancer in the diagnostic 'grey zone' of 4-10 ng/mL total PSA. This improvement occurred in patients with or without a chronic indwelling catheter for urinary retention.     

Race, prostate cancer survival, and membership in a large health maintenance organization

BACKGROUND: Population-based cancer registry data have shown that black men with prostate cancer have poorer stage-specific survival than white men, while studies in equal-access health care systems have not found racial differences in stage-specific survival. This study was designed to test the hypothesis that black men and white men with prostate cancer have equal stage-specific survival in equal-access health care systems. METHODS: We conducted a cohort study using cancer registry data from all incident cases of prostate cancer occurring in a five-county San Francisco Bay Area region. Incident cases occurred among members (5263 cases, from January 1973 through June 1995) and nonmembers (16,019 cases, from January 1973 through December 1992) of the Kaiser Permanente Medical Care Program, a large health maintenance organization. Death rate ratios (DRRs, black men versus white men) for Kaiser members and nonmembers were computed for all stages combined (adjusting for age and stage) and for each stage (adjusting for age). RESULTS: Among Kaiser members, adjusted DRRs comparing black men with white men were as follows: all stages combined, 1.28 (95% confidence interval [CI] = 1.14-1.44); local stage, 1.23 (95% CI = 1.01-1.51); regional stage, 1.30 (95% CI = 0.97-1.75); and distant stage, 1.27 (95% CI = 1.07-1.50). Corresponding DRRs for nonmembers were as follows: all stages combined, 1.22 (95% CI = 1.14-1.30); local stage, 1.24 (95% CI = 1.09-1.41); regional stage, 1.48 (95% CI = 1.29-1.68); and distant stage, 1.01 (95% CI = 0.91-1.12). CONCLUSIONS: These results show poorer prostate cancer survival for black men compared with white men in an equal-access medical care setting. The findings are most consistent with the hypothesis of increased tumor virulence in blacks.     

Relation between literacy, race, and stage of presentation among low-income patients with prostate cancer

PURPOSE: Diagnosis of advanced prostate cancer is a major health problem, especially among low-income men. Opportunities vary for early detection of prostate cancer for low-income black and white men because of financial, cultural, and social factors. In this study, we evaluated the association of poor literacy skills with higher rates of presentation of advanced stages of prostate cancer among low-income black and white men who received care in equal-access medical systems. PATIENTS AND METHODS: Literacy and stage at diagnosis of prostate cancer were evaluated in 212 low-income men who received medical care in Shreveport, LA, and Chicago, IL. The patients' literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine (REALM), an individually administered reading screening test designed specifically for use in the medical setting. Logistic regression models were used to evaluate predictors of metastatic disease at presentation as a function of patient age, race, literacy, and city. RESULTS: Whereas black men were almost twice as likely to present with stage D prostate cancer (49.5% v 35.9%; P < .05), they were significantly more likely to have literacy levels less than sixth grade (52.3% v 8.7%; P < .001). However, after adjustment for differences in literacy, age, and city, race was not a significant predictor of advanced-stage prostate cancer. CONCLUSION: Low literacy may be an overlooked but significant barrier to the diagnosis of early-stage prostate cancer among low-income white and black men. The development of culturally sensitive, low-literacy educational materials may improve patient awareness of prostate cancer and improve the frequency of diagnosis of early-stage cancer.     

Influence of age on serum prostate specific antigen concentration

322 men who had not prostatic diseases were selected at random for defining the characteristics of serum prostate specific antigen (PSA) in order to use PSA more appropriately in detecting clinically significant prostate cancer. The serum PSA concentration is correlated with patient age (r = 0.301; P < 0.0001), PSA is increased with age. The recommended upper limits (mean +2 standard deviations) for serum PSA for men aged 20-49 years was 2.71 ng/ml; for 50-59 years, 5.01ng/ml; for 60-69 years, 6.05 ng/ml; and for greater than or equal to 70 years, 7.92 ng/ml. Our findings led to proposals for using age-specific PSA reference range instead of a single reference range for men of all age groups. These age-specific reference ranges have the potential to increase the specificity of using PSA for detecting prostate cancer.     

Evaluation of the digital rectal examination as a screening test for prostate cancer. Rotterdam section of the European Randomized Study of Screening for Prostate Cancer

BACKGROUND: The utility of digital rectal examination (DRE) as a screening test for early detection of prostate cancer has not been established. Therefore, we evaluated the usefulness of DRE as a stand-alone screening test and in conjunction with measured serum prostate-specific antigen (PSA) levels of 0-3.9 ng/mL and transrectal ultrasonography (TRUS). METHODS: Our study population consisted of 10,523 men aged 54-76 years who were randomly assigned to the screening arm of the Rotterdam, The Netherlands, section of the European Randomized Study of Screening for Prostate Cancer. The underlying prevalence of detectable prostate cancer was estimated by logistic regression analysis and used for calculating the sensitivity of DRE as a test. Pathologic characteristics of 105 radical prostatectomy specimens were used to determine the aggressiveness of the tumors diagnosed (and missed) by DRE. RESULTS: The overall detection rate for prostate cancer in this population when serum PSA measurement, DRE, and TRUS were used was 4.5%, and the detection rate with DRE alone was 2.5%. The positive predictive value of DRE ranged from 4% to 11% in men with PSA levels of 0-2.9 ng/mL and from 33% to 83% in men with PSA levels of 3.0-9.9 ng/mL or more. Most tumors detected by DRE in men with PSA levels of less than 4.0 ng/mL were small (mean volumes = 0.24-0.83 mL), and most were well differentiated (Gleason scores of 6 or less). Minimal, moderate, and advanced cancers were seen in 42%, 42%, and 16% of men, respectively, with a PSA level of 4.0 ng/mL or less. DRE alone allowed detection of 264 (55.8%) of 473 cancers; 82 (17.3%) of the 473 cancers would have remained undetected by PSA-based screening alone (i.e., no follow-up procedures for PSA values of 0-3.9 ng/mL). CONCLUSIONS: For PSA values of 0-3.9 ng/mL, the positive predictive value and sensitivity of DRE, tumor volume, and tumor grade were strongly dependent on PSA level. DRE has a poor performance in low PSA ranges.